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Rabu, 29 Februari 2012

Can Vitamin D Treat Pain?

Women with dysmenorrhea who take a single high dose of vitamin D suffer much less menstrual pain and have no need of pain medications for any reason for up to 2 months, a new study has found.
“To our knowledge, this is the first study investigating the effect of a single high dose of vitamin D in primary dysmenorrhea,” wrote the study authors, led by Antonino Lasco, MD, from the Department of Internal Medicine, University of Messina, Italy.
“Our data support the use of cholecalciferol in these patients, especially when exhibiting low plasmatic levels of 25(OH)D [25-hydroxyvitamin D],” they write.
The study is published February 27 in the Archives of Internal Medicine.
Pain Trigger
Dysmenorrhea affects almost one half of menstruating women. The pelvic pain is believed to be triggered by excessive uterine production of prostaglandins, synthesized from omega-6 fatty acids before menses, that control vasoconstriction and uterine contractions.
According to the study authors, vitamin D may act as an anti-inflammatory and may regulate the expression of key genes involved in the prostaglandin pathway, causing decreased biological activity of prostaglandins.
The study included 40 women aged 18 to 40 years who had experienced at least 4 consecutive painful menstrual periods in the past 6 months and had a 25(OH)D serum level below the upper limit of the lowest quartile (<45 ng/mL). They were not taking calcium, vitamin D, oral contraceptives, or other medications, and they had not used an intrauterine contraceptive device during the previous 6 months.
The participants could use other means of birth control, however. They were also allowed to use nonsteroidal anti-inflammatory drugs (NSAIDs) as needed, but they had to record their use of these agents.
The women were randomly assigned to receive a single oral dose of 300,000 IUs of vitamin D (cholecalciferol) or placebo 5 days before the time they expected to begin their next menstrual period.
The primary outcome was intensity of menstrual pain as measured by a visual analog scale. The secondary outcome was use of NSAIDs.
After 2 months, baseline pain scores decreased 41% among women in the vitamin D group; there was no difference in scores among women taking placebo (P < .001). The greatest reduction in pain was among women in the vitamin D group who had the most severe pain at baseline (r = -0.76; P < .001)
During the study, none of the women in the vitamin D group needed NSAIDs to manage pain at 1 and 2 months, whereas 40% of those taking placebo used an NSAID at least once (P = .003).
Implications for Chronic Pain?
In an accompanying commentary, Elizabeth R. Bertone-Johnson, ScD, from the Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, and JoAnn E Manson, MD, from the Division of Preventive Medicine, Department of Epidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, said the study provides support for larger randomized trials of vitamin D for treating pain-related conditions in women.
Chronic widespread pain and fibromyalgia syndromes are more prevalent in women, "likely owing to the influence of sex steroid hormones," they write.
This future research, they write, must address several key issues.
"First, it is important to know how long reductions in pain associated with a single high-dose vitamin D therapy would persist and how often treatment would need to be repeated," the editorialists write. They point out that each dose would need to be effective for a lengthy period for average daily intake to remain below recommended upper limits.
Because many women will experience dysmenorrhea for several years until menopause, follow-up of participants in vitamin D trials must be extended to better evaluate adverse effects and to compare risks and benefits, they note.
The editorialists also note that it remains unknown whether vitamin D would improve dysmenorrhea pain in women with higher 25(OH)D levels.
"If these findings are confirmed in future randomized trials, vitamin D supplementation may become an important new treatment option for women who experience menstrual pain disorders," they conclude. "In the meantime, encouraging all women to obtain the recommended dietary allowance for vitamin D (≥600 IU/d for women of reproductive age), as well as screening for low serum 25(OH)D levels among women with other risk factors for vitamin D deficiency, would be a rational interim approach."
Pain Site
Approached for comment, Clifford Lo, MD, PhD, Director, Harvard Human Nutrition Program, and Medical Education Coordinator, Harvard Medical School Division of Nutrition, said that although the numbers were small, there was a convincing difference between the placebo and vitamin D groups in the study.
However, although it is plausible that vitamin D affects prostaglandins, the study did not specify which prostaglandin or which pain site might be involved, said Dr. Lo, whose research interests include vitamin D metabolism.
The study proposes an interesting possible mechanism, "but that's certainly not good enough for me to say that this is a good treatment for pain," said Dr. Lo. "It's very premature to say it's something we should use."
Pain associated with dysmenorrhea is generally subjective and not easily measured, he added. It is difficult to make conclusions about the effect an agent will have on pain when there is "no convincing biomarker" for the pain, as was the case with this study, said Dr. Lo.
The 300,000 IU dose of vitamin D used in the study is probably harmless if taken every month or 2, and even perhaps every week, but it could cause hypercalcemia if taken daily, said Dr. Lo. The typical vitamin D dose is 400 to 1000 IU/day.
Dr. Lo pointed out that because the participants in the study had vitamin D levels below 45 ng/mL, they were not exactly deficient in vitamin D to begin with. "Most people would say that you're not deficient until you're below 20 ng/ml," he said. "I would say that half the American population is below 30 ng/mL."
Arch Intern Med. 2012;172:366-367, 367-369.

Senin, 27 Februari 2012


Nyeri kepala dapat menyerang siapa saja tanpa terkecuali. Yang kadang-kadang dapat hilang dengan sendirinya. Nyeri kepala akan menimbulkan masalah bagi para penderita jika benar-benar mengalami kesakitan sehingga mengganggu keadaan atau kegiatan sehari-hari seperti yang dialami oleh penderita migren.1, 2, 3

Istilah migren berasal dari pemakaian kata hemicrania oleh Galen sekitar 200 M, untuk melukiskan suatu kelainan periodik yang terdiri atas nyeri hemikranial yang paroksimal serta mengganggu penglihatan, vomitus fotofobia, berulang dengan interval teratur dan mereda ketika keadaan sekeliling tenang.1, 2, 


   Epilepsi merupakan masalah penting baik dipandang dari sudut ilmu kedokteran maupun sosial, diperkirakan bahwa diseluruh dunia terdapat lebih dari dua puluh juta orang dengan epilepsi, akan tetapi hanya sebagian kecil para penderita tersebut yang telah dapat menikmati pengobatan secara optimal.

Flavanones in Citrus Fruit May Lower Stroke Risk

High intake of flavanones, a subclass of flavonoids found in the greatest concentrations in oranges and grapefruit, is associated with a 19% lower risk for ischemic stroke in women, a new analysis from the Nurses’ Health Study has shown. 

Although oranges are the best source of flavanones, North Americans tend to drink the juices of these fruits, lead author Aedín Cassidy, PhD, professor, nutrition, Norwich Medical School, University of East Anglia, Norwich, United Kingdom, told Medscape Medical News.

However, because commercial juices often contain sugar that may increase diabetes risk, she said, "our advice would be to eat more of the citrus fruits as opposed to product made from the citrus fruits."

Much of the recent evidence has focused on vitamin C, Dr. Cassidy added. "What we’re showing here is that there are other bioactive constituents in citrus fruits that may be responsible for this cardioprotective effect."
The results are published online February 23 in Stroke.

Cumulative Intake
This analysis used data from the Nurses’ Health Study on 69,622 participants who completed food-frequency questionnaires (FFQs) every 4 years. The 1990 FFQ was used as a baseline and included dietary intake data collected over the next 14 years.

Researchers used a state-of-the-art food database to examine 6 commonly consumed flavonoids: flavanones (including eriodictyol, hesperetin, and naringenin), anthocyanins, flavan-3-ols, flavonoid polymers, flavonols, and flavones. To arrive at intakes of individual compounds, they multiplied the sum of the consumption frequency of each food by the content of the specific flavonoid of a specified portion size. They averaged the intake for the current and preceding FFQ to determine the cumulative intakes (energy adjusted) for a given questionnaire cycle.

A diagnosis of stroke was confirmed from medical records. Researchers categorized strokes into ischemic, including embolic or thrombotic; hemorrhagic, including subarachnoid or intraparenchymal stroke; and unknown. Over the course of the study, 1803 strokes occurred; 943 of these were ischemic, 253 were hemorrhagic, and 607 were of unknown type.
The baseline median intake of total flavonoids (quintile 3) was 232 mg/d; the lowest intake (quintile 1) was 96.8 mg/d, and the highest (quintile 5) was 761.2 mg/d.

Tea was the main contributor to total flavonoid intake, with apples and oranges/orange juices also contributing significant amounts. Blueberries were the main source of anthocyanins, and oranges and orange juice were the main contributors to flavanone and flavone intake.

The study found that flavanone intake was inversely related to the risk for ischemic stroke. After adjustment for stroke risk factors, such as age, body mass index, physical activity, alcohol consumption, menopausal status, smoking, and history of type 2 diabetes, women in the top quintile of flavanone intake had a relative risk of 0.81 (95% confidence interval [CI], 0.66 - 0.99; P for trend = .04) compared with women in the bottom quintile. Further adjustment for calcium or magnesium intakes did not greatly alter the results.

Highest intake of citrus fruits/juices, which represent the main dietary source of flavanones, also tended to be associated with a reduced risk for ischemic stroke, with a relative risk of 0.90 (95% CI, 0.77 - 1.05).

Vitamin C
In this analysis, the addition of vitamin C to the statistical model did not substantially change the relationship between flavanones and ischemic stroke risk. "That’s not to say vitamin C isn’t important," stressed Dr. Cassidy. "We know that vitamin C may be one of the constituents responsible for the effect, but here’s some evidence that suggests that perhaps there are other components in citrus fruits that also may be responsible."
Animal and in vitro experiments have shown that the flavanones naringenin and hesperetin have anti-inflammatory and neuroprotective effects. "Some of these compounds can cross the blood-brain barrier so they are actually getting to the brain," said Dr. Cassidy.

There’s growing interest in the protective qualities of flavonoids, and with it progressively more sophisticated food databases that cover the wide range of flavonoids in the diet.

"About 5 years ago, people would have been publishing on flavonoids, but only on 2 or 3 of the subclasses," Dr. Cassidy noted. "Here we have an as-good-as-we-can-get database on 6 different subclasses. If you do large population-based study like this one, this can really help to generate hypotheses."

Using such a database can help further the understanding of possible mechanisms, dose effects, and optimal sources of various flavonoids, she added. The study found only a modest, and nonsignificant, inverse association between a higher intake of flavones and anthocyanins and the risk for total and ischemic stroke. There was no evidence of a link between flavones and stroke risk.

The lack of association between some flavonoids and stroke was somewhat surprising because there is evidence that dark chocolate, which contains these compounds, has positive effects on blood pressure, blood flow, and vascular and heart function, said Dr. Cassidy. "We assumed that they also may well have had effect on stroke risk, but we didn’t find that in these data sets."

The study found no association between any of the flavonoids and hemorrhagic stroke.

Diet Soda Tied to Heart Attack, Stroke Risks

Diet soda may benefit the waistline, but a new study suggests that people who drink it every day have a heightened risk of heart attack and stroke.
The study, which followed almost 2,600 older adults for a decade, found that those who drank diet soda every day were 44% more likely than non-drinkers to suffer a heart attack or stroke.

Of course, the findings, reported online January 27 in the Journal of General Internal Medicine, don't prove that the sugar-free drinks are actually to blame.

There may be other things about diet-soda lovers that explain the connection, researchers say.
"What we saw was an association," said lead researcher Dr. Hannah Gardener, of the University of Miami Miller School of Medicine. "These people may tend to have more unhealthy habits."

She and her colleagues tried to account for that, Gardener told Reuters Health.
Daily diet-soda drinkers did tend to be heavier and more often have heart risk factors like high blood pressure, diabetes and unhealthy cholesterol levels.

That all suggests that people who were trying to shed pounds or manage existing health problems often opted for a diet soda over the sugar-laden variety.

But even after the researchers factored in those differences -- along with people's reported diet and exercise habits -- they found that daily diet soda was linked to a 44% higher chance of heart attack or stroke.
Nevertheless, Dr. Gardener said, it's impossible for a study to capture all the variables that could be at work.

The findings do build on a few recent studies that also found diet-soda drinkers are more likely to have certain cardiovascular risk factors, like high blood pressure or high blood sugar.

This is the first study, Dr. Gardener said, to look at actual vascular events.
The findings are based on 2,564 New York City adults who were 69 years old, on average, at the outset. Over the next decade, 591 men and women had a heart attack, stroke or died of cardiovascular causes.

That included 31% of the 163 people who were daily diet-soda drinkers at the study's start. In contrast, 22% of people who rarely or never drank diet soda went on to have a heart attack or stroke.

There was no increased risk linked to less-than-daily consumption. Nor was regular soda tied to heart attacks and strokes.
If diet soda, itself, somehow contributes to health risks, it's not clear how, Dr. Gardener said.
There's research in rats suggesting that artificial sweeteners can end up boosting food intake and weight. But whether results in rodents translate to humans is unknown.
"I don't think people should change their behavior based on this study," Dr. Gardener said. "And I wouldn't advocate drinking regular soda instead."
Regular soda is high in calories, and for people who need to shed pounds, experts often suggest swapping regular soda for the diet version.
A study out this month found that the advice may be sound. Obese people who were randomly assigned to drink water or diet drinks in place of sugary ones lost about five pounds over six months.

Dr. Gardener said that further studies such as hers are still needed to confirm a connection between diet soda and cardiovascular trouble.

Kamis, 23 Februari 2012

Practice Guideline Effective in Community-Acquired Pneumonia

Use of a clinical practice guideline (CPG) for community-acquired pneumonia (CAP) led to increased use of ampicillin, which is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP, according to the results of a retrospective study reported in an article published online February 20 in Pediatrics

"[CAP] is a common pediatric illness caused by Streptococcus pneumoniae," write Ross E. Newman, DO, from the Department of Pediatrics, University of Missouri–Kansas City School of Medicine, Children's Mercy Hospitals and Clinics, and colleagues. "New pediatric Infectious Diseases Society of America CAP guidelines are now available recommending ampicillin as empirical treatment of children hospitalized with uncomplicated CAP."

The study goal was to assess the effect of implementing a CPG on antibiotic treatment of children hospitalized with CAP. The study sample consisted of patients admitted to a children's hospital from July 8, 2007, through July 9, 2009, and discharged with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), code for pneumonia (480–486). This period began 12 months before and ended 12 months after introduction of the CAP CPG. The investigators used 3-stage least squares regression analyses to evaluate the effect of their institution's antimicrobial stewardship program (ASP) and other hypothesized simultaneous associations.

Of 1033 patients included in the final analysis, 530 (51%) were admitted before CPG implementation, and 503 (49%) were admitted after CPG implementation. The most commonly prescribed antibiotic before CPG implementation was ceftriaxone (72%), followed by ampicillin (13%); ampicillin was the most commonly prescribed antibiotic after CPG implementation (63%).

The effect of the CPG was associated with a 34% increase in ampicillin use, and the combined effect of the CPG and ASP was associated with a 12% increase in amoxicillin use at hospital discharge and a 16% decrease in cefdinir and amoxicillin/clavulanate use (P < .001 for all). During both study periods, treatment failure was infrequent (1.5% before CPG implementation and 1% after CPG implementation).

"A CPG and ASP led to the increase in use of ampicillin for children hospitalized with CAP," the study authors write. "In addition, less broad-spectrum discharge antibiotics were used. Patient adverse outcomes were low, indicating that ampicillin is appropriate first-line therapy for otherwise healthy children admitted with uncomplicated CAP."

There was less compliance with other guideline recommendations, however. Obtaining blood cultures in all hospitalized children, for example, was recommended by the CPG, but the rate of blood culture draws in this population remained the same before and after the CPG (56% vs 54%; P = .4).

Limitations of this study include retrospective chart review, use of ICD-9 codes to identify patients with suspected uncomplicated CAP, and failure of the analysis to capture patients who experienced treatment failure and sought care at other institutions or had primary care physicians expand antimicrobial coverage for continued symptoms.

"Because CAP is a common pediatric condition, the use of a narrow-spectrum agent is important in preventing the further development of antibiotic resistance," the study authors conclude. "Second, although providers were willing to follow CPG recommendations for empirical antibiotic choices, other recommendations were not followed, including length of therapy and obtaining blood cultures. Finally, CPGs should be continually monitored and evaluated to ensure successful implementation, utilization, and revisions when required."

Three of the study authors were supported by a grant from the Agency for Healthcare Research and Quality.
Pediatrics. Published online February 20, 2012. Abstract

Senin, 20 Februari 2012

Hipertensi Ensefalopati

Latar Belakang

Hipertensi sampai saat ini merupakan masalah penting dalam dunia kesehatan karena prevalensinya yang tinggi dan komplikasi jangka panjang yang diakibatkannya. Budi Darmojo dalam laporan penelitiannya menyatakan bahwa 1,8–28,6% penduduk yang berusia di atas 20 tahun adalah penderita hipertensi, dan umumnya prevalensi hipertensi berkisar sekitar antara 8,6–10%. Dari penelitian yang ada terlihat kecenderungan bahwa masyarakat perkotaan lebih banyak menderita hipertensi dibanding masyarakat pedesaan. Jika dibanding antara wanita dan pria ternyata wanita lebih banyak menderita hipertensi. ( 1 )

Hipertensi apabila tidak ditangani dengan baik akan menyebabkan berbagai macam komplikasi. Apabila tekanan darah meningkat dengan cepat dapat terjadi kerusakan pada target organ yaitu otak, mata, jantung, ginjal, dan pembuluh darah lainnya yang dapat mengancam jiwa penderita, maka keadaan ini dikenal sebagai kegawat daruratan hipertensi atau hipertensi krisis. ( 2, 3 )

Nyeri Kepala Paska Trauma

Latar Belakang
Statistik negara-negara yang sudah maju menunjukkan bahwa trauma kapitis mencakup 26% dari jumlah segala macam kecelakaan, yang mengakibatkan seorang tidak bisa bekerja lebih dari satu hari sampai selama jangka panjang. Kurang lebih 33% kecelakaan yang berakhir pada kematian menyangkut trauma kapitis. Di luar medan peperangan lebih dari 50% dari trauma kapitis terjadi karena kecelakaan lalu-lintas, selebihnya dikarenakan pukulan atau jatuh. Orang-orang yang mati karena kecelakaan, 40%-50% meninggal sebelum mereka tiba di rumah sakit. Dari mereka yang dimasukkan ke rumah sakit dalam keadaan masih hidup 40% meninggal dunia dalam satu hari dan 35% meninggal dalam satu minggu perawatan.

Rhinitis Alergi

Rinitis alergi adalah penyakit/ kelainan yang merupakan manifestasi klinik reaksi hipersensitiv tipe I (Gell & Coombs) dengan mukosa hidung sebagai organ sasaran.
Berdasarkan sifat berlangsungnya, rinitis alergi dibedakan atas :
1. Rinitis alergi musiman (seasonal, hay fever, pollinosis). Hanya ada dinegara yang memiliki 4 musim. Alergen penyebabnya spesifik, yaitu tepung sari dan spora jamur.
2. Rinitis alergi sepanjang tahun (perennial)
Gejala keduanya hampir sama, hanya sifat berlangsungnya yang berbeda.
Gejala rinitis alergi sepanjang tahun timbul terus-menerus atau intermiten. Meskipun lebih ringan dibandingkan rinitis musiman, tapi karena lebih persisten, komplikasinya lebih sering ditemukan. Dapat timbul pada semua golongan umur, terutama anak dan dewasa muda, namun berkurang dengan bertambahnya umur. Faktor herediter berperan, sedangkan jenis kelamin, golongan etnis dan ras tidak berpengaruh.

Otitis Eksterna

Otitis eksterna adalah penyakit yang dapat diderita oleh semua orang dan berbagai usia. Otitis eksterna biasanya ditunjukkan dengan adanya infeksi bakteri pada kulit liang telinga tetapi dapat juga disebabkan oleh infeksi jamur. Meskipun demikian Otitis eksterna jarang menyebabkan komplikasi yang serius. Infeksi ini ditandai dengan rasa nyeri yang hebat (Waitzman, 2004).

Otitis eksterna juga sering dihubungkan dengan adanya proses dematologi lokal atau non infeksius. Gejala-gejala yang khas pada otitis externa adalah rasa tidak nyaman pada liang telinga yang ditandai dengan eritema dan discharge yang bervariasi (Sander, 2001).

Istilah otitis eksterna telah lama dipakai untuk menjelaskan sejumlah kondisi. Spektrum infeksi dan radang mencakup bentuk-bentuk akut atau kronis. Dalam hal infeksi perlu dipertimbangkan agen bakteri, jamur dan virus. Radang non-infeksi termasuk pula dermatosis, beberapa diantaranya merupakan kondisis primer yang langsung menyerang liang telinga. Shapiro telah menegaskan bahwa perbedaan antara otitis eksterna yang berasal dari dermatosis dengan otitis eksterna akibat infeksi tidak selalu jelas. Suatu dermatosis dapat menjadi terinfeksi setelah beberapa waktu, sementara pada infeksi kulit dapat terjadi reaksi ekzematosa terhadap organisme penyebab. Sekali lagi, anamnesis dan pemeriksaan yang cermat seringkali akan memberi petunjuk kearah kondisi primernya (Boies, 1997).

Tumor Laring

Latar Belakang
Di Indonesia , tumor laring di pita suara suara mencapai 1 % dari semua keganasan. Selain rokok faktor resiko lain adalah alkohol, paparan radiasi, paparan bahan industri, faktor kekebalan tubuh serta faktor genetik.( 1 )
Seperti dikemukakan oleh dr Sri Susilawati memaparkan data di RS Ciptomangunkusumo, selama 5 tahun terakhir ada sekitar 144 kasus kanker laring. Penyakit itu telah menjadi pembunuh nomor tiga setelah nasofaring dan hidung atau sinus. Perbandingan antara pasien pria dan wanita adalah tujuh banding satu. Usia terbanyak 51 sampai 60 tahun.( 2 )


Latar Belakang

Tinnitus adalah bunyi abnormal yang didengar oleh penderita yang berasal dari dalam kepala.1 Menurut Tungland tinnitus adalah persepsi suara ketika tidak ada sumber suara.2 Menurut Richard kata tinnitus berasal dari kata latin tinnere yang berarti berdering atau deringan, sehingga disimpulkan tinnitus adalah persepsi suara yang tidak diinginkan dengan penyebab dari dalam kepala, biasanya terlokalisasi, dan jarang didengar oleh orang lain.3 Tinnitus dapat digambarkan sebagai telinga yang “berdering” dan berbagai suara didalam kepala yang terdengar tanpa adanya sumber suara dari luar.4 Tinnitus dapat didengar pada satu atau kedua telinga atau ditengah-tengah kepala ataupun bisa juga digambarkan tidak jelas lokasinya. Suara dapat terdengar lemah, sedang ataupun keras, dapat terdengan satu jenis atau pun lebih, dan serangan dapat terus menerus ataupun hilang timbul.5



Epistaksis atau perdarahan hidung sering ditemukan sehari-hari, dan hampir 90% dapat berhenti sendiri. Epistaksis bukan merupakan suatu penyakit, melainkan sebagai gejala dari suatu kelainan.3

Perdarahan dari hidung dapat merupakan gejala yang sangat menjengkelkan dan mengganggu. Ia dapat pula mengancam nyawa. Faktor etiologi harus dicari dan dikoreksi untuk mengobati epistaksis secara efektif. Perdarahan hidung tampak lebih sering terjadi pada masa awal kanak-kanak sampai pubertas. Walaupun pada kelompok usia tersebut biasanya tidak serius. Epistaksis berat atau yang mengancam jiwa tampaknya meningkat dengan bertambahnya usia.4

Epistaksis adalah masalah klinis yang berbahaya, terutama bila berasal dari posterior. Sembilan puluh persen epistaksis berasal spontan dari pleksus pembuluh darah superfisialis didalam septum anterior inferior, dan lebik mudah ditangani dibandingkan epistaksis posterior, yang 10% pasien dari pembuluh darah di dalam dinding hidung lateral dekat nasofaring dan disertai dengan mortalitas 4% sampai 5%.7

Otitis Media Kronik

Otitis media ialah peradangan sebagian atau seluruh mukoso telinga tengah, tuba Eustachius, antrum mastoid dan sel-sel mastoid. Otitis media terbagi atas otitis media supuratif dan otitis media supuratif dan otitis media non supuratif (=otitis media serosa, otitis media sekretoria, otitis media musinosa, otitis media efusi (OME).
Masing-masing golongan mempunyai bentuk akut dan kronis, yaitu otitis media supuratif akut (otitis media akut = OMA) dan otitis media supuratif kronis (OMSK). Begitu pula otitis media serosa terbagi menjadi otitis media serosa akut (barotrauma = aerotitis) dan otitis media serosa kronis. Selain itu terdapat juga otitis media spesifik, seperti otitis media tuberkulosa atau otitis media sifilitika. otitis media yang lain ialah otitis media adhesiva.

Kamis, 16 Februari 2012

Vitamin D and Chronic Rhinitis

Waleed M. Abuzeid; Nadeem A. Akbar; Mark A. Zacharek
Posted: 02/05/2012; Curr Opin Allergy Clin Immunol. 2012;12(1):13-17. © 2012 Lippincott Williams & Wilkins


Purpose of review To discuss the role of vitamin D in chronic rhinitis and chronic rhinosinusitis (CRS).

Recent findings Vitamin D has been shown to have an immunomodulatory effect with a significant impact on immune function. Specifically, vitamin D regulates the mechanisms which suppress the inflammatory response and direct the differentiation fate of immune cells. Vitamin D has been shown to play an important role in asthma, and the concept of the unified airway model allows the extrapolation of vitamin D as a critical player in chronic rhinitis and rhinosinusitis.

Summary Recent findings on the function of vitamin D may explain aspects of the pathophysiology of chronic rhinitis and CRS, and may help direct future treatment of these diseases.


The importance of vitamin D as an essential nutrient is well known, given its role in calcium and phosphate homeostasis. Over the past two decades, the influence of vitamin D on the immune system has become increasingly clear.[1] Recent work has elucidated that vitamin D harbors actions more akin to hormones and pro-hormones. The discovery of the vitamin D receptor (VDR) has stimulated more research into the nature of this vitamin which has, subsequently, been shown to be a steroid hormone. This steroid constitutes a component of a complex endocrine pathway termed the 'Vitamin D endocrine system'.[2] Investigators have found that vitamin D plays an integral role in the induction of cell differentiation, inhibition of cell growth, immunomodulation, and regulation of other hormonal systems.[3] This review seeks to highlight the recent research with respect to vitamin D and its role in chronic rhinitis and chronic rhinosinusitis (CRS).

Chronic Rhinitis and Chronic Rhinosinusitis Pathophysiology

The pathophysiology of CRS occurs, primarily, at the interface of the nasal mucosa with the external environment. The nasal mucosa is a highly specialized immunologic barrier that has evolved to process a constant load of foreign antigens with minimal collateral inflammation. Anatomically, the nasal mucosa consists of an epithelial layer of ciliated, pseudostratified, columnar cells. The cilia and tight junctions interconnecting the epithelial cells constitute a mechanical barrier to antigenic stimulation.[4]
Deep in the epithelium reside a variety of immune cells including lymphocytes and antigen-presenting cells (APCs), specifically dendritic cells and macrophages. These are key components of the acquired immune response.[4] The trigger for and modulation of the nasal acquired immune response has yet to be fully elucidated. Pattern-recognition receptors (PRRs), located in the cytoplasm and on the cell membrane, recognize antigens on microbial organisms. PRRs are also capable of detecting debris from necrotic cells, consequently triggering a process that culminates in the production of antimicrobial, antiviral, and antiproteinase products that facilitate pathogen clearance and help maintain the mechanical barrier.[4]
PRRs activate dendritic cells causing them to acquire chemokine receptors and to migrate to lymph nodes.[4] Similarly, various cytokines and microbial products induce a potent activating response on macrophages and these, in turn, produce both proinflammatory and anti-inflammatory mediators.[5] In the lymph nodes, the activated dendritic cells regulate the differentiation of naïve T cells towards a Th1 or Th2 phenotype.[5] This is largely based on the associated cytokine profile which is distinct between each type of T-helper response.[4] The drive towards either a Th1 or Th2 response is modulated by the type of triggering stimulus and by cues from the external environment.[5] In essence, APCs exert a profound regulating effect on the downstream inflammatory response of the sinonasal mucosa.

Vitamin D and Immunomodulation

Vitamin D, as an immunomodulatory steroid hormone, directly affects dendritic cell, monocyte, macrophage, B cell, and T cell functions[5,6] (Fig. 1).

The VDR and vitamin D metabolizing enzymes are expressed by several cells of the immune system. For example, Th1 and Th2 cells are direct targets of the activated form of vitamin D, 1,25-dihydroxyvitamin D3, otherwise known as calcitriol. Indeed, activation of CD4+ T cells results in a five-fold increase in VDR expression, enabling calcitriol to regulate at least 102 identified genes.[7]
This regulatory effect has a downstream impact on the levels of circulating chemokines and cytokines. Th1 cells secrete interferon gamma (IFNγ), interleukin (IL)-2, IL-12, and tumor necrosis factor alpha (TNFα), all of which augment the cell-mediated defense against intracellular pathogens. Th2 cells express IL-4, IL-5, and IL-13, which further propagate the Th2 response. These Th2-derived cytokines modulate the immune response against parasites and are also associated with the regulation of atopy and asthma.[8,9] Vitamin D exerts a strong suppressive effect on the expression of IL-2 and IFNγ in a VDR-regulated mechanism. The suppression of IL-2 production, in turn, inhibits T-cell proliferation – indeed, addition of exogenous IL-2 can rescue T-cells from the antiproliferative effects of vitamin D.[1] Evaluation of T-lymphocyte subpopulations demonstrates that vitamin D blocks the induction of Th1 cytokines, especially IFNγ, while simultaneously enhancing Th2 responses through the enhancement of IL-4 production.[8,9] Overall, vitamin D decreases cell-mediated immune responses. This suppressive effect on humoral immunity is facilitated through the effect of vitamin D3 on APC. In APCs, calcitriol inhibits the production of IL-12, a cytokine that normally enhances the Th1 response.[10••] In effect, vitamin D acts as a physiologic 'brake' on humoral immunity.

Similarly, the innate immune system can also be inhibited by vitamin D. Here, vitamin D has been shown to inhibit the differentiation, maturation, and immune-stimulating ability of dendritic cells by downregulating the expression of MHC class II molecules.[1] Dendritic cells have important functions in maintaining both protective immunity and self-tolerance. Immature dendritic cells promote T-cell tolerance, whereas mature dendritic cells activate naive T cells. Physiologic levels of vitamin D inhibit the maturation of dendritic cells and maintain an immature and tolerogenic phenotype with inhibition of activation markers such as MHC class II, CD40, CD80, and CD86 and upregulation of inhibitory molecules. Vitamin D concurrently suppresses IL-12 and enhances IL-10 production in these dendritic cells.[10••]
The net response is a decrease in Th1 responses and proliferation of T regulator cells which act as a further 'check' on the immune response. The immune response is skewed towards a Th2 response with a significant suppression of the Th1 response.[8,9] Thus, vitamin D may have a suppressive effect on inflammation at the level of the nasal mucosa, potentially influencing the development and propagation of CRS. Interestingly, vitamin D has also been shown to have a stimulatory effect on monocytes in vitro, suggesting a complex role in immune hemostasis rather than a purely suppressive effect on the immune system.[1] The extent of this physiologic balance has yet to be fully elucidated.

Vitamin D and Cathelicidin

Vitamin D also influences the immune response through the regulation of cathelicidin, which is the only antimicrobial peptide produced by humans.[11] Cathelicidin is produced by neutrophils, macrophages, and the cells lining the epithelial surfaces of the skin, respiratory tract, and gastrointestinal tract – the sites which are constantly exposed to potential pathogens[10••] (Fig. 2).

Figure 2.  Vitamin D stimulates innate immunity and enhances antimicrobial activity via interaction with vitamin D receptor to upregulate the synthesis of the antimicrobial peptide cathelicidin. Reproduced with permission from [6].
Cathelicidin has a broad antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as certain viruses and fungi. Vitamin D treatment upregulated cathelicidin mRNA in several cell lines and primary cultures including keratinocytes, neutrophils, and macrophages.[12] Vitamin D levels were also found to be significantly lower in patients in the intensive care unit with sepsis when compared with healthy controls. In these patients, serum vitamin D directly correlated with serum cathelicidin, suggesting that systemic levels of cathelicidin may be regulated by vitamin D status, and that this may be important in the control of infections such as in CRS.[13]

Vitamin D and Chronic Rhinosinusitis

There currently exists a paucity of literature specifically evaluating the role of vitamin D in the pathophysiology of CRS. Recently, Mulligan et al. [5] were able to demonstrate several interesting trends with respect to vitamin D and CRS. They were able to show that patients with CRS and allergic fungal rhinosinusitis demonstrate insufficient levels of vitamin D (<32 ng/ml) when compared with controls (Fig. 3).

Figure 3.  Chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS) have insufficient levels of circulating 25-OH vitamin D3 (VD3). Compared with control and CRSwNP, AFRS and CRSwNP have significantly lower plasma VD3 levels. Reproduced with permission from [5].
Pinto et al. [14] explored the relationship of vitamin D levels in African American patients with CRS as compared to age and sex matched controls. This group found that vitamin D levels were significantly lower in the African American patients with CRS as compared with age and sex matched controls.

In the study by Mulligan and co-investigators,[5] an inverse relationship between vitamin D and the levels of various immune cells was established in CRS patients. In the subset of patients diagnosed with CRS with nasal polyposis or allergic fungal rhinosinusitis, lower levels of vitamin D correlated to elevated levels of dendritic cells as compared with controls. As discussed, dendritic cells play an important role in directing the differentiation of T-helper cells into Th1 or Th2 subtypes – without vitamin D, the inflammatory response is skewed towards a Th1 subtype promoting a chronic local inflammatory response. The investigators were also able to show that plasma levels of prostaglandin E2 and granulocyte monocyte-colony stimulating factor were upregulated in patients with CRS, and that these chemokine levels were inversely associated with serum vitamin D levels. Furthermore, an interesting correlation between serum levels of vitamin D and the severity of bone erosion on computed tomography scans was noted. Specifically, bone remodeling in patients with insufficient levels of serum vitamin D was significantly greater than in patients with adequate vitamin D levels. This is, perhaps, unsurprising given the well documented role of vitamin D in the regulation of calcium metabolism and bone homeostasis.

Although these results are extremely compelling, the Mulligan study suffers from a small sample size. Future work may extrapolate these data to a larger patient set, ideally through a prospective study, which would help clarify the role of vitamin D in the pathophysiology of CRS. Systemic vitamin D levels could, potentially, be added to the routine workup of patients suffering from CRS and these data could be used to help determine the disease severity and possibly even treatment. To this end, a recent Polish study[15] evaluated the role of vitamin D in the reduction of fibroblast proliferation in vitro from nasal polyps in patients with CRS. Tissue samples were subject to varying doses of calcitriol and a vitamin D analog, tacalcitol, with and without budesonide. A statistically significant decrease in fibroblast proliferation was noted with calcitriol and tacalcitol treatment. Furthermore, increasingly higher doses induced a greater suppressive effect on fibroblast proliferation. This study is a first step towards investigating the utility of topical vitamin D analogs for the treatment of CRS.



Early research suggests that vitamin D is involved in the pathophysiology of chronic rhinitis and CRS. However, this is an area that clearly requires further basic science and clinical research. Nonetheless, it is intriguing to consider the possibility that abnormal vitamin D blood levels – or even the local tissue concentration of vitamin D – could be a critical influencing factor in chronic rhinitis and CRS pathophysiology. The concept of the unified airway would suggest that similar associations from the asthma literature will be found with regards to allergic rhinitis, chronic rhinitis, and CRS. Randomized controlled trials are needed to further evaluate vitamin D and its relationship to allergic rhinitis, chronic rhinitis, and CRS. These findings may then direct researchers to pursue clinical trials aimed at evaluating vitamin D and its analogs as potential therapeutic interventions.




Rabu, 15 Februari 2012

More Evidence Links Low Vitamin D to Depression

A large cross-sectional study of adults suggests a link between low vitamin D levels and depressive symptoms, particularly in individuals with a history of depression.
Because the relationship between low vitamin D levels and depression was stronger in those with a prior history of depression, "it may be more of a marker for relapse than for new-onset," senior investigator E. Sherwood Brown, MD, PhD, head of the psychoneuroendocrine research program at the University of Texas Southwestern Medical Center, Dallas, told Medscape Medical News.

"Our findings suggest that screening for vitamin D levels in depressed patients — and perhaps screening for depression in people with low vitamin D levels — might be useful," Dr. Brown added in a university-issued statement.

The study was published in the November 2011 issue of Mayo Clinic Proceedings. It involved 12,594 participants (4005 women and 8595 men) from the prospective Cooper Center Longitudinal Study (CCLS). Participants' mean age was 51.7 years. A total of 1563 participants had a history of depression; 11,031 did not.

All participants completed baseline examinations that included measurement of serum 25-hydroxyvitamin D [25(OH)D] levels and an assessment using the Center for Epidemiologic Studies Depression Scale (CES-D). A CES-D score of 10 or higher was defined as evidence of depression.

According to the investigators, low vitamin D levels were common in the sample as a whole, with 50.7% of participants having levels in either the deficient range [25(OH]D < 20 ng/mL], according to Institute of Medicine recommendations, or the insufficient range [25(OH)D < 30 ng/mL]. Mean vitamin D levels did not differ significantly between those with and without a history of depression.

Biologically Plausible
In the overall sample, higher vitamin D levels were associated with a decreased risk for current depression, based on CES-D scores. The odds ratio [OR] was 0.92 (95% confidence interval [CI], 0.87 - 0.97; P < .002) for each 10 ng/mL increase in 25(OH)D.

When study participants with and without a history of depression were analyzed separately, the link was stronger in those with a prior history of depression (OR, 0.90; 95% CI, 0.82 - 0.98; P = .02) and was not significant in those without such a history (OR, 0.95; 95% CI, 0.89 - 1.02; P = .17).

It is biologically plausible that vitamin D could have a role in depression, Dr. Brown and colleagues note in their article. Vitamin D "appears to be important for brain health and may be involved in the pathogenesis of depression." Yet, studies to date have yielded conflicting results.

Three small clinical studies found an association between low 25(OH)D levels and depression, whereas the 5 population-based studies that have explored the association yielded more mixed results.

Positive studies include 1 involving 1282 older adults from Amsterdam that found 14% lower 25(OH)D levels in those with major and minor depression relative to control participants (Hoogendijk et al, Arch Gen Psych, 2008;65:508-512).

A British national survey of older adults showed clinical vitamin D deficiency [25(OH)D level < 10 ng/mL] was significantly associated with depressive symptoms, independent of age, sex, social class, physical health status, and season. Milder states of vitamin D deficiency were not strongly associated with depression in older adults (Psychosom Med , 2010;72:608-612.)

Largest Data Set to Date
Negative studies include 1 from China involving 3262 adults aged 50 to 70 years. In this study, depressive symptoms were less prevalent in those in the top tertile of 25(OH)D concentrations compared with those in the lowest tertile. The association disappeared, however, after controlling for geographic location (Pan et al, J Affect Disord, 2009;118:608-612).

Additionally, a study in 527 Japanese adults aged 21 to 67 years found no significant association between CES-D scores and 25(OH)D levels (Nanri et al, Eur J Clin Nutr, 2009;63:1444-1447).

A study of 3916 adults in the United States showed that 25(OH)D levels and parathyroid hormone levels were not significantly associated with depressive symptoms after adjusting for several potential confounding factors (Zhao et al, Br J Nutr, 20120;104:1696-1702).

The current study, Dr. Brown told Medscape Medical News, represents the largest data set to investigate this issue and, importantly, unlike prior studies, it included a subanalysis by history of depression.

"This subset analysis may shed light on why there were conflicting results in earlier studies because the populations were not assessed on the basis of prior history of depression," he and his colleagues write.

Nonetheless, he points out that "it's a cross-sectional study, and the old saying is true that correlation does not mean causation." Additional research is needed to determine the nature and direction of the association. "Right now, we don't really know whether low vitamin D makes you depressed or whether being depressed makes you have low vitamin D," Dr. Brown said.

"Studies looking at vitamin D supplementation in depressed people with low vitamin D to see if that in itself would help with depressive symptoms would help answer some of those questions," Dr. Brown commented.

Slow Acting
Vijay K. Ganji, PhD, RD, of the College of Health and Human Sciences, Georgia State University in Atlanta, who was not involved in the study, agrees. "We need more randomized trials to see if taking vitamin D really helps lowering the episodes of depression," he told Medscape Medical News.

To date, there have been only a few small trials of vitamin D supplementation in various depressed populations, with mixed results. In 2008, a placebo-controlled study from Norway found that supplementation with high doses of vitamin D (20,000 or 40,000 IU vitamin D per week) for 1 year seemed to ameliorate depressive symptoms in adults (Jorde et al, J Intern Med, 2008;264:599-609).

In 2009, in a study of 9 women with depressive symptoms and serum vitamin D levels < 40 ng/mL, vitamin D3 supplementation was associated with an increase in serum vitamin D levels (by 27 ng/mL on average) and a decline in depressive symptoms, as measured using the Beck Depression Inventory–II, of an average of 10 points (Shipowick et al, Appl Nurs Res, 2009).

Last year, however, as reported by Medscape Medical News, in a large study of women aged 70 years and older, those who received a high dose of vitamin D3 (500,000 IU) once a year for up to 5 years did not show any improvement in symptoms of depression (Sanders et al, Br J Psychiatry, 2011;198:357-364).

"One thing that complicates trials is that if you give someone vitamin D, it takes a long time for it to have much effect, as vitamin D levels go up and down very slowly; it probably wouldn't be a fast antidepressant," said Dr. Brown.

Dr. Brown reports that he has received research support from the National Heart, Lung, and Blood Institute, the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the Stanley Medical Research Institute, and AstraZeneca. Dr. Ganji has disclosed no relevant financial relationships.
Mayo Clin Proc. 2011;86:1050-1055. Abstract


No Cancer Protection With Vitamin B or Omega-3 Fatty-Acid Supplements

Vitamin B and omega-3 fatty-acid supplementation over a period of five years failed to reduce the incidence of cancer and cancer mortality in patients with cardiovascular disease, research shows [1]. The investigators did observe a statistically significant interaction by sex, however, with women taking omega-3 fatty acids at an increased for cancer and cancer mortality.

"People should be very careful when deciding to self-medicate with these dietary supplements because they are active substances," lead investigator Dr Valentina Andreeva (University of Paris, France) told heartwire . "The findings need to be confirmed and should be interpreted with caution, but there is some indication that they might have adverse effects. Taking these supplements without a physician's advice and over the long term might not be a good idea."
The researchers caution against reading too much into the increased cancer risk in women taking the omega-3 fatty acids, given that there were only 29 cancer cases in females, compared with the 145 cases that occurred in males, so the findings are preliminary and hypothesis-generating for future studies.

The SU.FOL.OM3 Study
Known as the Supplementation with Folate, Vitamins B6 and B12 and/or Omega-3 Fatty Acids (SU.FOL.OM3) trial and published online February 13, 2012 in the Archives of Internal Medicine, the study was designed as a secondary cardiovascular disease prevention study. The main results showed that treatment with vitamin B or omega-3 fatty acids had no effect of major vascular events. Given the availability of the data, the researchers examined the benefit of these supplements on cancer risk, because there is inconsistency across trials, with some studies suggesting a protective effect with omega-3 fatty acids and vitamin B and some studies showing a lack of benefit.

In SU.FOL.OM3, 2501 individuals aged 45 to 80 years old were randomized in a 2x2 factorial design to one of four study arms: 5-methlytetrahyrdofolate 0.56 mg, 3-mg vitamin B6, and 0.02-mg vitamin B12; eicosapentaenoic and docosahexaenoic acid 600 mg; B vitamins and omega-3 fatty acids; or placebo.

After five years of treatment with the supplements, new incident cancer was confirmed in 7.0% of patients, and death from cancer occurred in 2.3% of the study population. There were 47 deaths in men (2.4%) and 11 deaths in women (2.1%). In an age- and sex-adjusted multivariable model, there was no effect of the B vitamins on cancer incidence and cancer mortality, a lack of effect on cancer incidence and mortality in patients treated with omega-3 fatty acids, and a lack of effect in patients who received omega-3 fatty acids and B-vitamin supplementation.

The results confirm the findings of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a study reported by heartwire that showed the addition of folic acid and vitamin B did not have any effect on vascular events compared with placebo in a trial in more than 12 000 MI survivors.

There was a positive association observed in women who were treated with omega-3 fatty acids, with these women having a threefold greater risk of developing cancer (hazard ratio [HR] 3.02; 95% CI 1.33–6.89) and a fivefold increased risk of dying from cancer (HR 5.49; 95% CI 1.18–25.97). However, as the researchers point out, there were just 21 cases of cancer in the patients who received omega-3 fatty acids and eight cases among those assigned to the control group, resulting in very wide confidence intervals.

Andreeva said the five-year follow-up in SU.FOL.OM3 is short, but investigators hypothesized that if there were any adverse effects with the two supplements, the risk might be the promotion of preexisting clinical lesions. "We did not really expect it to show an effect on cancer initiation, given the decades it takes for cancer to develop," she said.

Sabtu, 11 Februari 2012

Probiotic Effects in Infants Last Until 4 Years of Age

Infants exposed to Lactobacillus rhamnosus through diet supplements from 35 weeks' gestation through 2 years of age had a significantly lower risk for eczema and rhinoconjunctivitis. The protective effect lasted until the children were at least 4 years of age, according to a study published online February 6 in Clinical and Experimental Allergy.

The researchers, led by Kristin Wickens, PhD, from the Wellington Asthma Research Group, Wellington School of Medicine and Health Sciences, University of Otago, New Zealand, and colleagues, followed 425 infants for 4 years after daily supplementation with L rhamnosus (HN001; 6 × 109 colony-forming units [cfu]/day), Bifidobacterium animalis subsp lactis (HN019; 9 × 109 cfu/day), or placebo. Mothers received supplements from 35 weeks' gestation until their child's birth, continuing to 6 months after birth if they were breast-feeding, and all infants received supplements from birth until age 2 years.

The cumulative prevalence of eczema by age 4 years was significantly reduced in the children taking HN001 (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.39 - 0.83) compared with in the children in the placebo group. The prevalence of rhinoconjunctivitis at age 4 years (relative risk, 0.38; 95% CI, 0.18 - 0.83) was also significantly reduced in the children in the HN001 group compared with in the children in the placebo group. HN019 did not affect the prevalence of any outcome relative to placebo.

"There have been a number of primary prevention studies investigating the effects of different species of probiotics taken by pregnant or breastfeeding mothers and/or their infants on the prevalence of eczema and sensitization by age 2 years. Reaching a consensus on the role of probiotics as primary preventers of allergic disease has been hampered by heterogeneity between studies in probiotic species and dose, duration and timing of intervention, and definitions of outcomes measured," the authors write.

The researchers previously published the initial results of their double-blind, randomized, placebo-controlled trial, in which they evaluated the effect of the probiotics on allergic disease and atopic sensitization in children in the first 2 years of life, in the October 2008 issue of the Journal of Allergy and Clinical Immunology (2008;122:788-794). That analysis demonstrated a 49% reduction in eczema prevalence in children receiving HN001 supplementation.

The current analysis demonstrates that the benefits of HN001 persist to age 4 years, despite cessation of therapy 2 years earlier, suggesting that this probiotic might be an appropriate preventative intervention for high-risk infants.

The researchers collected data regarding the presence (since the child turned 2 years old) of eczema and any history of asthma or hay fever. They assessed eczema severity using the Scoring Atopic Dermatitis (SCORAD) scale, with a cutoff of 10 or higher, and performed skin-prick tests on the child's forearm in accordance with the Australasian Society of Clinical Immunology and Allergy guidelines. They also evaluated the prevalence of current asthma symptoms, using standard International Study of Asthma and Allergies in Childhood questions.

In addition to significantly reducing the risk of eczema by 4 years of age, the use of the HN001 probiotic also provided some protection against SCORAD≥10, wheeze, and atopic sensitization by age 4 years. However, the protective effects did not reach statistical significance.

Fecal samples from a subset of children (n = 153) were analyzed using real-time polymerase chain reaction for the presence of L rhamnosus and B animalis. The researchers noted that HN019 was not detectable in the feces, but HN001 (or HN001-like strains) was detected in 33% of children.

The researchers had previously shown that there was no difference between study groups for sex, ethnicity, delivery, birth weight, length and head circumference, breast-feeding duration, smoking in pregnancy or in the household, pet ownership, family history of allergic disease, or antibiotic use before age 2 years.

Some of the children (24%) had received nonstudy commercially available probiotic supplements; however, exclusion of these children from the analysis did not alter relative risk estimates.

The authors acknowledge study limitations such as the unblinding of participants after 2 years of age, which may have biased responses to questions about eczema frequency and severity. The misclassification of infectious rhinitis as allergic rhinitis and asthma at 4 years of age may also have affected the results, but the authors report that this would not have had a significant effect on the study findings.

"Ours is the only study to separately evaluate two different probiotics, and show an effect for HN001 but not HN019. The different effects we found for each probiotic at age 2 years persisted to 4 years, highlighting the importance of the particular probiotic in allergic disease prevention. Another strength of our study is the high response rate (>86% of eligible infants in each group) and follow-up beyond infancy," Dr. Wickens and colleagues write.

"The precise pathways for effects [of probiotics] on allergic disease remain elusive and require more work, including the possibility that effects are mediated via epigenetic mechanisms," conclude the authors.

Clin Exp Allergy. Published online February 6, 2012. Abstract

Smoking Linked to Cognitive Decline in Men

Men who are currently smoking or those with a history of smoking may be at risk for cognitive decline as they transition from midlife to older age, new research suggests.

In a cohort study of more than 7,000 people (mean age at first assessment, 56 years), investigators found that men who continued to smoke over the next decade showed a significantly more rapid decline in cognition than men who never smoked.

Men who had recently quit smoking also showed some cognitive decline, especially in executive functioning tasks. In long-term ex-smokers, the degree of cognitive decline was similar to the decline seen in those who had never smoked.
"There is increasing evidence that smoking is a risk factor for dementia, but its impact on cognitive decline, and particularly on cognitive decline in early old age, has been unclear," lead author Séverine Sabia, PhD, research associate in the Department of Epidemiology and Public Health at the University College London, told Medscape Medical News. 
However, results from this study showed that male smokers who were in their 50s "had a cognitive decline as fast as nonsmokers 10 years older than they were," said Dr. Sabia.

In addition, she noted that the fact that no residual detrimental effects of smoking on cognitive decline was observed 10 years after smoking cessation "should encourage people to stop smoking as early as possible."

The study was published online February 6 in the Archives of General Psychiatry.
Doubling of Dementia Cases
According to the investigators, there were approximately 36 million cases of dementia worldwide in 2010 — a number that is projected to double by 2020.
"Smoking is a possible risk factor for dementia, although its impact may have been underestimated in elderly populations because of the shorter life span of smokers," write the researchers.

For this analysis, investigators examined a cohort of 5099 men and 2137 women who participated in the Whitehall II study, which includes employees of the British Civil Service.

All participants underwent their first cognitive assessments between 1997 and 1999, followed by examinations between 2002 and 2004 and between 2007 and 2009.

The assessments comprised 5 different cognitive tests, including examinations of memory, vocabulary, and executive function. The results were then combined to form a global cognitive score for each participant.

In addition, smoking status was recorded over the entire study period.
Results at the 10-year follow-up showed that men who were currently smokers had a faster decline in global cognition score (mean difference, -0.09; 95% confidence interval [CI], -0.15 to -0.03) and in executive function (mean difference, -0.11; 95% CI, -0.17 to -0.05) than men who had never smoked.

Men who had recently quit smoking also showed a greater decline in executive function compared with the men who had never smoked (mean difference, -0.08; 95% CI, -0.14 to -0.02).

No Association in Women
There were no significant differences in cognitive decline between the male long-term ex-smokers and those who had never smoked, nor was an association found between smoking status and cognitive decline in the women who were assessed.

Several possible reasons cited by Dr. Sabia for this last finding included the fact that the sample had significantly fewer women than men (only 262 of the women were current smokers at the time of the first cognitive assessment) and that "it is possible that smoking behavior is differently associated with other behaviors in men and women."

"For example, we found that current male smokers drank much more alcohol than female smokers (23 vs 10 drinks/week). More research is needed to understand this difference before drawing conclusions," she reported.
Nevertheless, at least for men, "it is increasingly recognized that age-related cognitive pathologies such as dementia result from long-term processes, perhaps beginning as long as 20 to 30 years before the clinical diagnosis of dementia," write the investigators.

"Our study illustrates the importance of examining risk factors for cognitive decline much earlier in the life course.... Public health messages on smoking should continue to target smokers at all ages," they add.

Positive Message
"What makes this study stand out is that they were looking at cognitive function over 10 years," Rachel Whitmer, PhD, epidemiologist at the Kaiser Permanente Division of Research in Oakland, California, told Medscape Medical News.
"This was looked at in people who we would consider to be 'young-old' and not very elderly. And that's a very important question to tackle when you're thinking about the influence of smoking on cognitive function or dementia or other diseases that manifest late in life," said Dr. Whitmer.

She added that although she was "a little surprised" to see the results' gender differences, she was not surprised to find that smoking was associated with a greater 10-year cognitive decline in the men.

"I also think there are some really nice implications for a public health message about not only not smoking but that if you do smoke, quitting has positive effects on disease and cognitive abilities."

Dr. Whitmer, who was not involved in this research, was principal investigator for a recent study published in the Archives of Internal Medicine that looked at the association between smoking in midlife and the long-term risks for dementia, Alzheimer's disease, and vascular dementia.

"In our study, we were able to retrospectively go back and look at data over 30 years and then follow our people going forward. We found that the smokers had about a 2-fold greater risk for dementia; and the risk was even greater in the heavy smokers," she explained.

"Even though it was looking at different outcomes, this new study supports the same body of evidence that smoking is bad for the brain."
Dr. Whitmer added that it will be exciting for the investigators to continue following the cohort to measure the association between smoking patterns over the long term and actual dementia.

"I think the take-home message from these types of studies is that clinicians need to realize that smoking elevates not only risk for dementia but that people also don't perform as well," she said.

"And patients need to hear that smoking can really affect the brain — but quitting can have good effects even up to 10 years later. It's a really positive message."

The study was funded by the National Institute on Aging, the Academy of Finland, the Bupa Foundation, and the British Heart Foundation; by a European Young Investigator Award from the European Science Foundation; and by grants from the National Institutes of Health and the British Medical Research Council. The study authors and Dr. Whitmer have disclosed no relevant financial relationships.
Arch Gen Psychiatry. Published online February 6, 2012. Abstract