Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions.

OBJECTIVES: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. METHODS: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). RESULTS: Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. CONCLUSIONS: Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study.

OBJECTIVE: To evaluate the effect of adalimumab on the frequency of anterior uveitis (AU) flares in patients with active ankylosing spondylitis (AS). METHODS: We determined the history of ophthalmologist-diagnosed AU in 1250 patients with active AS who were enrolled in a multinational, open-label, uncontrolled clinical study of treatment with adalimumab, 40 mg every other week for up to 20 weeks. All AU flares were documented throughout the adalimumab treatment period plus 70 days. We compared the rates of AU flares per 100 patient years (PYs) reported during the year before adalimumab treatment with rates during adalimumab treatment, in total and by patient subgroups. RESULTS: The AU flare rates before adalimumab treatment were 15/100 PYs in all patients (n = 1250), 68.4/100 PYs in 274 patients with a history of AU flares, 176.9/100 PYs in 106 patients with a recent history of AU flares, 192.9/100 PYs in 28 patients with symptomatic AU at baseline and 129.1/100 PYs in 43 patients with a history of chronic uveitis. During adalimumab treatment, the rate of AU flares was reduced by 51% in all patients, by 58% in 274 patients with a history of AU, by 68% in 106 patients with a recent history of AU, by 50% in 28 patients with symptomatic AU at baseline and by 45% in 43 patients with chronic uveitis. AU flares during adalimumab treatment were predominantly mild. Two patients with periods of high AS disease activity had new-onset AU during the treatment period. CONCLUSIONS: Results of this prospective open-label study suggest that adalimumab had a substantial preventive effect on AU flares in patients with active AS, including patients with a recent history of AU flares. Clinical trials: ClinicalTrials.gov Identifier: NCT00478660.

NIHSS applied to cerebral neurological dive injuries as a tool for dive injury severity stratification.

BACKGROUND: Evaluation via National Institutes of Health Stroke Scale (NIHSS) upon presentation in hospital triage following ischemic stroke is predictive of recovery or progression to neurological deficits. Cerebral injuries sustained while diving have symptoms similar to stroke. Applying the NIHSS to dive injuries may successfully summarize neurological dive injuries, providing a standardized tool for study of dive injury data. METHODS: We retrospectively determined NIHSS scores for a diverse population of 192 divers presenting to the University of Hawaii recompression chamber from 1983-2002, both prior to initial treatment and after all treatment. Spinal and vestibular decompression sickness cases were excluded. RESULTS: The performance of the NIHSS among this diving population was similar to its performance as an accepted tool in evaluation of ischemic stroke, although results are influenced by the abundance of mild injury cases in the data set. The estimated C-statistic with NIHSS predicting no observable deficit was 0.88, and predicting post NIHSS of 0-1 was 0.85 (vs. 0.86 when applied to stroke). Sensitivity for predicting recovery (NIHSS 0-1) at discharge was 0.99 (vs. 0.97 for stroke). CONCLUSIONS: The NIHSS applied to cerebral dive injuries has adequate predictive ability and correlates with other measures of dive injuries, while providing a standardized, more graduated scale. The NIHSS may be useful as a standardized measurement for evaluation of treatment regimens and adjunctive therapy for diving injuries.

Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort.

BACKGROUND: Antiretroviral therapy has improved survival for HIV-1-infected individuals. The neuroepidemiologic implications of HIV-1 in an aging population are not well known, particularly the prevalence of HIV-associated dementia (HAD). METHODS: The authors report a baseline cross-sectional analysis of 202 HIV-1-seropositive individuals enrolled into one of two groups of the Hawaii Aging with HIV Cohort: older (50 or more years old, n = 106) and younger (20 to 39 years old, n = 96). Neuropsychological, neurologic, medical, and laboratory data were obtained at enrollment. Participant cognitive status was classified (research case definitions) using American Academy of Neurology (1991) criteria in a consensus conference of physicians and neuropsychologists. RESULTS: HAD was more frequent in older (25.2%) compared to younger (13.7%) individuals (p = 0.041) corresponding to an OR of 2.13 (95% CI: 1.02 to 4.44) for the older compared to the younger group. After adjusting for education, race, substance dependence, antiretroviral medication status, viral load, CD4 lymphocyte count, and Beck Depression Inventory score, the odds of having HAD among individuals in the older group was 3.26 (1.32 to 8.07) times that of the younger group. CONCLUSIONS: Older age is associated with increased HAD in this HIV-1 cohort. Underlying mechanisms are unclear but do not appear related to duration of HIV-1 infection.

Symptomatic distal sensory polyneuropathy in HIV after age 50.

OBJECTIVE: To determine if aging changes the frequency, severity, or manifestations of symptomatic distal sensory polyneuropathy (SxDSPN) in patients with HIV-1. METHODS: Prospective observations of 70 older (age < or = 50) and 56 younger (age 20 to 40) patients with HIV, and a control group of 48 older non-HIV patients, were conducted utilizing neurologic examination, neuropsychological testing, lumbar puncture, laboratory, and medical history. RESULTS: The frequency of SxDSPN among older HIV patients was 50.4%, compared to 19.6% among younger HIV patients (p < 0.001). SxDSPN among control patients occurred in 4.2%, similar to the general population. Older compared to younger HIV patients demonstrated more severe symptoms (p = 0.02) and greater deficits for vibration (p < 0.01). Increasing numbers of neuropathic comorbidities among older compared to younger HIV patients were associated with increasing severity of deficits to pinprick (p = 0.003). Dementia and SxDSPN coexisted in 36% of the older HIV patients and in none of the younger HIV patients (p = 0.021). Older HIV patients with nadir CD4 < or =200 cells/mL were 4.23 times as likely to have SxDSPN than older patients with nadir CD4 >200 cells/mL (p = 0.007). Vibratory deficits excessive to pinprick deficits predicted SxDSPN among older (OR 2.83) but not younger seropositive patients (p = 0.036). CONCLUSIONS: Age > or = 50 increases the frequency of SxDSPN, and is associated with both vibratory loss as the predominant sensory deficit and increased severity of pinprick loss among symptomatic patients with neuropathic comorbidities. SxDSPN is associated with both dementia and low nadir CD4 in HIV-positive patients aged 50 and greater.

[A severe traffic accident--250 years ago. Medical history presentation]. / Ein schwerer Verkehrsunfall--vor 250 Jahren. Eine medizinhistorische Darstellung.

During a scientific examination in July 1999 both crypts below the St. Martin's Church in Grünstadt, Germany, were opened and 9 coffins from the county family of Leiningen examined. This paper is concentrating on one of these persons: Georg Hermann (1679-1751), count of Leiningen-Westerburg-Altleiningen, who gave during the 18. century the city its barock character. He was also responsible for the rebuilding of the church. His skeleton revealed interesting pathological changes. Few years before his death the count had the accident to get run over by a heavy wagon which crushed the distal part of his legs. The fractures healed, but gave him an ancylotic and shortened left leg, which must have caused him a lot of suffering in his last years.

Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus.

BACKGROUND: Knowledge of the outcome of chronic hepatitis B virus (HBV) infection is limited. OBJECTIVE: To determine the incidence of and risk factors for adverse events (hepatocellular carcinoma and end-stage liver disease) and clearance of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) in carriers of HBV. DESIGN: Population-based cohort study of hepatitis B carriers who were observed for a median of 12.3 years as part of an active surveillance program to detect carriers with hepatocellular carcinoma. SETTING: 126 communities in Alaska. PATIENTS: 1536 Alaska Natives with chronic hepatitis B. MEASUREMENTS: Bivariate comparisons, multivariable models, and other statistical methods were used to examine the relationships of risk factors to outcomes and clearance of HBeAg and HBsAg. RESULTS: 1536 chronic HBV carriers were followed up for 19 430 person-years from their first HBsAg-positive test result. At the first serologic test, 641 were HBeAg positive and 893 were anti-HBe positive. Older carriers were more likely than younger carriers to clear HBeAg (P < 0.001). The observed probability of clearing HBeAg within 10 years of diagnosis was 72.5%. Clearance of HBsAg occurred in 106 (7%) of all carriers and was positively associated with older age and positive result on initial anti-HBe test. The incidence of adverse events was 2.3 per 1000 carrier-years, and the incidence of hepatocellular carcinoma was 1.9 per 1000 carrier-years (2.3 in men and 1.2 in women). Risk for hepatocellular carcinoma increased with age, among those of Yupik Eskimo ethnicity, and among carriers who reverted from anti-HBe to HBeAg. CONCLUSION: In HBsAg-positive carriers, observed clearance of HBeAg was more than 70% during the first 10 years of follow-up.

Cancer mortality among Alaska natives, 1994-1998.

Although overall cancer mortality rates in the U.S. declined throughout the 1990s, Alaska Native rates increased. This study compares mortality patterns of Alaska Natives for the period, 1994-1998, and U.S. Whites, and examines changes in rates since 1960-1969. We used death certificate data and Indian Health Service population estimates to create age-adjusted mortality rates for Alaska Natives. We compared these rates to NCHS mortality for U.S. Whites. In all, 597 Alaska Natives died of cancer over the five-year period, 1994-1998, their age-adjusted average annual mortality rate (224.5 per 100,000) was thirty percent higher than that of U.S. Whites (166.7 per 100,000), a statistically significant excess (OR = 1.3, 95% CI: 1.2-1.4). Alaska Natives were forty percent more likely to die of lung cancer than U.S. Whites (OR = 1.4, 95% CI: 1.2-1.6). This population also demonstrated elevated mortality rates for several other smoking-related cancers. Also, Alaska Natives are at excess risk for nearly all cancers of the digestive system. Alaska Natives experienced the same or lower mortality rates for genitourinary cancers excluding cancer of the kidney. Smoking related cancers, and particularly, lung cancer, were the major contributors to the excess mortality rates. These data suggest that the burden of cancer on the Alaska Native healthcare system will continue to increase as the population ages. Intensified efforts to modify behavioral risk factors are needed.

[Alf Brodal--the great brain scientist]. / Alf Brodal--hjerneforsker av format.

The use of scientific methods in the investigation of the central nervous system began at the beginning of the twentieth century, as gifted scientists like Gustav Adolf Guldberg (1854-1908), Fridtjof Nansen (1861-1930), and Georg Herman Monrad-Krohn (1884-1964) took up their research work. Dr Monrad-Krohn's renowned textbook, the so-called "Blue Bible", appeared in 1914 and enhanced the reputation of Norwegian science among specialists internationally. More than any other Norwegian scientist, Professor Alf Brodal (1910-88) brought brain research to new heights. This article presents a portrait of him in relation to his area of research.

[Nose in the light of medical history]. / Nesen i medisinhistorisk lys.

Vanity, it seems, is one of the qualities that separate us from other species; indeed, we may said to possess it in excess. Decorating body and apparel with all kinds of objects in order to look attractive goes a long way back in time; even Stone Age man knew how to make himself look smart. This very human trait has not abated over the millennia, but the perception of what looks good has changed a great deal, just like fashion, and no part of the human body has probably been of such significance in this respect as the nose. This article presents a brief review of nasal fashion.

Cancer incidence in Alaska Natives thirty-year report 1969-1998.

The Alaska Native Tumor Registry includes data from 1969 to the present. This report provides incidence rates over the thirty year period, 1969 through 1998, and compares trends over time for Alaska Natives (AN) with those of US Whites and Blacks. To examine current rates, average annual age-adjusted incidence rates for AN for 1984-98 are compared with US Whites. Data from the registry document numerous differences in rates of occurrence of specific cancers compared to US Whites and Blacks. Studies of these differences may provide clues to the causes and risk factors for the cancers. Most importantly, these data show that although cancer was considered a rare disease in the Alaska Native population as recently as the mid-twentieth century, the incidence rate for all cancers combined among Alaska Natives is now as high as that of US Whites, and even higher in women. On the other hand, despite relative differences in rates, the most frequently diagnosed cancers among Alaska Natives are the same as US Whites. Cancers of the lung, colon/rectum, breast, and prostate are most frequently diagnosed among Alaska Natives and in the U.S. These four cancers comprise over 50% of all diagnosed invasive cancers. Cancer of the lung is almost entirely preventable by eradication of tobacco use. Screening and early detection have been proven to reduce mortality for cancers of the colon/rectum and breast. Primary and secondary prevention of these cancers could markedly improve morbidity and mortality.

Bronchiectasis in Alaska Native children: causes and clinical courses.

Although bronchiectasis has become a rare condition in U.S. children, it is still commonly diagnosed in Alaska Native children in the Yukon Kuskokwim Delta. The prevalence of bronchiectasis has not decreased in persons born during the 1980s as compared with those born in the 1940s. We reviewed case histories of 46 children with bronchiectasis. We observed that recurrent pneumonia was the major preceding medical condition in 85% of patients. There was an association between the lobes affected by pneumonia and the lobes affected by bronchiectasis. Eight (17%) patients had surgical resection of involved lobes. We conclude that the continued high prevalence of bronchiectasis appears to be related to extremely high rates of infant and childhood pneumonia. Pediatr Pulmonol. 2000;29:182-187. Published 2000 Wiley-Liss, Inc.

No seasonal variation of insulin sensitivity and glucose effectiveness in men.

Insulin resistance is of pathogenetic importance for the development of non-insulin-dependent diabetes mellitus (NIDDM). However, not much is known about the variation in insulin sensitivity in the individual over longer periods. Consequently, we measured insulin sensitivity (Si) and glucose effectiveness (Sg) in healthy young men (N = 10) 5 times over a period of 15 months using a frequently sampled intravenous glucose tolerance test (FSIVGTT) with minimal-model analysis (study of seasonality). The maximal aerobic capacity (V(O2)max), fat-free mass, body mass index (BMI), and 24-hour ambulatory blood pressure (BP) were also assessed. Furthermore, we performed a study designed to evaluate the day-to-day variation in Si and Sg (study of day-to-day variation). Here, we studied Si and Sg in healthy young men (n = 8) within 2 weeks. In the study of seasonality, the coefficient of variation (CV) for Si was 24.0%, whereas the CV for Sg was 26.0%. Anticipating a seasonal variation in Si following a sine curve with a cycle length of 1 year and an unknown phase and amplitude, we tested this hypothesis with a multiple linear regression model that allows for different levels of Si between individuals, and failed to detect any impact due to this. Si (mean +/- SD, 1.17 +/- 0.28 x 10(-4) x min(-1) x pmol/L(-1), P = .38), Sg (0.023 +/- 0.006 min(-1), P= .71), fasting insulin (21.2 +/- 7.3 pmol/L, P= .98), V(O2)max (3.8 +/- 0.6 L/min, P= .13), and fat-free mass (64.9 +/- 2.5 kg, P = .92) were constant over time. In the study of day-to-day variation, we found a CV for Si of 17.3% and a CV for Sg of 23.3%. In conclusion, we found that the variations in Si and Sg were slightly higher than those found in studies performed to establish the day-to-day variation. However, no significant seasonal variation in Si and Sg was evident in this group of healthy young lean caucasian men. Consequently, indices of Si and Sg obtained at different times of the year appear comparable.

Epinephrine stimulates human muscle lipoprotein lipase activity in vivo.

Lipoprotein lipase (LPL) is involved in lipoprotein metabolism and nutrient partitioning in both adipose tissue and skeletal muscle, and LPL activity is regulated by various hormones and the nutritional state. However, the action of catecholamines has not been thoroughly investigated in humans. Therefore, the effects of exogenous epinephrine on skeletal muscle LPL (SM-LPL) activity and whole-body lipid oxidation were studied. Muscle biopsies were obtained from eight healthy subjects before, during, and after epinephrine infusion. Somatostatin was infused to suppress endogenous insulin production and insulin was infused at a constant rate to maintain basal insulin levels throughout the study. After an equilibrium period (120 minutes), epinephrine (0.05 microg/kg/min) was infused for another 120 minutes. Epinephrine stimulated SM-LPL activity by 21.8%+/-6.8% above basal levels from 1.44+/-0.25 to 1.69+/-0.28 micromol free fatty acid (FFA)/h/g muscle (P<.02), increased plasma FFA 270% from 0.147 to 0.544 mmol/L (P<.05), and increased lipid oxidation 45% from 4.37 to 6.36 mg/kg/min (P<.05). The increase in SM-LPL activity was positively correlated with the increase in whole-body lipid oxidation (R=.75, P<.05). Finally, lipid oxidation and SM-LPL activity were negatively correlated with whole-body glucose oxidation. Overall, the results demonstrate that epinephrine is able to stimulate SM-LPL activity in humans, and thus may have opposite effects on adipose tissue and SM-LPL activity.

Pap prevalence and cervical cancer prevention among Alaska Native women.

The goals of the Alaska Native Women's Health Project (WHP) were to determine the following: (1) Pap prevalence based on chart review before and during an intervention period; (2) the level of understanding of cancer and cancer screening services with emphasis on cervical cancer; (3) use and satisfaction with current health maintenance services; and (4) improvement in knowledge and cancer screening rates following intervention. A random sample of 481 Alaska Native (Eskimo, Aleut, Indian) women living in Anchorage were interviewed face to face about their understanding of cancer risk factors (tobacco use, sexually transmitted diseases (STDs), reproductive issues), cancer screening examinations (Pap test, breast self-examination (BSE), breast exam by a provider, mammography), and their attitudes about health care and health care services. Sixty-two percent of control women were documented to have had at least one Pap test within the 3-year period prior to the beginning of the study; however, only 9% were documented to have had annual Pap screening. The intervention included distribution of educational materials, counseling on any woman's health issue, special evening clinics, and reminders (mail/phone call) of scheduled Pap appointments.

[Health status in Norway around the year 1000]. / Helsetilstanden i Norge ved det forrige tusenårsskiftet.

One thousand years is a very long period, especially in relation to medical history. More than 30 generations have lived over this space of time, and their thoughts and attitudes and their views on hygiene, sickness and treatment are heterogeneous. This paper will discuss the state of health in Norway at the time of the turn of the first millennium--at a time when Norway underwent profound political, social and religious changes, as well as structure of diseases.