Ivermectin treatment of onchocerciasis

Ivermectin is a recently developed macrocyclic lactone that has widespread antiparasitic activity. A series of clinical trials has shown that ivermectin is safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. The drug also temporarily interrupts production of microfilaria but has no known long-lasting effects on the adult worms. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement. At this dose, ivermectin causes minimal side effects and appears to be sufficiently free of severe adverse reactions to be used on a mass scale. Its use promises to revolutionise the treatment of onchocerciasis.     

Cognitive dysfunction in melancholia

Sixty-seven patients with melancholia and 42 normal controls were tested with a battery of neuropsychological tasks selected to assess regional cortical functioning in both hemispheres. Compared with controls, melancholics exhibited a pattern of bifrontal and right parietal impairment, which was independent of age, sex, handedness and drug administration. These findings confirm and extend prior studies and contrast with those we and others have reported in patients with schizophrenia.     

Immunohistochemical study of the local inflammatory response to chlamydial ocular infection

Immunohistochemical staining of conjunctival biopsies from cynomolgus monkeys (Macaca fascicularis) was performed after they received a single primary ocular infection, a single secondary challenge infection, or repeated ocular inoculations with Chlamydia trachomatis. T cells of the suppressor/cytotoxic (OKT8F) phenotype predominated regardless of the infection protocol, and perifollicular T lymphocytes of both the suppressor/cytotoxic and helper (OKT4A) phenotypes appeared in large numbers during the peak inflammatory reaction. In repeatedly inoculated monkeys, T cells and follicles persisted until cessation of reinfection. IgM-bearing B lymphocytes comprised the majority of cells within follicles, with smaller numbers of IgG- or IgA-positive B cells. The major difference in the response to the various infection protocols was the increased number and persistence of follicles with repeated reinoculation. The finding of large numbers of T-suppressor/cytotoxic and T-helper cells in the infected conjunctiva supports a role for cell-mediated immunity in the local response to C. trachomatis ocular infection.     

Postoperative splinting for isolated digital nerve injuries in the hand.

Digital nerve injuries in the hand are common and can result in significant impairment and functional restriction. Despite this, there is relatively little literature, particularly with respect to postoperative rehabilitation. Splinting after repair, purported to protect the repaired nerve from excessive stretch is still commonly used. Recent cadaveric studies indicate postoperative rehabilitation is not necessary with resection up to 2.5mm. A randomized controlled trial was therefore undertaken to determine whether splinting after isolated 5th degree digital nerve transection is in fact necessary. Twenty-six subjects were recruited over a two-year period and randomized to either three weeks of hand-based splinting or free active motion. ANCOVA indicated no differences in sensibility at six months between the two groups. Subjects also reported their greatest functional limitations were because of hyperesthesia. Although this study is underpowered, these limited results suggest splinting may not be required postoperatively.     

Predictors of non-spine fracture in elderly men: the MrOS study.

We examined determinants of nonvertebral fracture in elderly men from six U.S. communities followed an average of 4.1 years. Six clinical risk factors predicted fracture risk independent of hip BMD: tricyclic antidepressant use, previous fracture, inability to complete a narrow walk trial, falls in previous year, age > or =80 years, and depressed mood. INTRODUCTION: There are few prospective studies of fracture determinants in men. We examined the associations between a comprehensive set of clinical risk factors and risk of nonspine fracture in older men and whether determinants of fracture risk were independent of total hip BMD. MATERIALS AND METHODS: A total of 5995 men > or =65 years of age were recruited from six communities in the Unites States and followed prospectively for an average of 4.1 years. Baseline assessments of demographic, lifestyle, medical history, functional status, anthropometry, and cognitive, visual, and neuromuscular function were assessed by questionnaire or examination. Triannual mailed questionnaires ascertained incident fracture; reported fractures were adjudicated by physicians using medical records and X-ray reports. Proportional hazards models were used to develop multivariable models, selecting variables and controlling for BMD. RESULTS: Of 5876 men, 4.7% (N = 275) reported an incident nonspine fracture during follow-up (11.46/1000 person-years). Tricyclic antidepressant use (hazard ratio [HR], 2.36; 95% CI, 1.25-4.46), history of fracture at or after age 50 (HR, 2.07; 95% CI, 1.62-2.65), inability to complete a narrow walk trial (HR, 1.70; 95% CI, 1.23-2.34), falls in previous year (HR, 1.59; 95% CI, 1.23-2.05), age > or =80 years (HR, 1.33; 95% CI, 1.01-1.76), depressed mood (HR, 1.72; 95% CI, 1.00-2.95), and decreased total hip BMD (HR, 1.53; 95% CI, 1.34-1.74) were independently related to increased risk. Compared with having none (48.0% of men), having three or more of the clinical risk factors (4.9% of men) increased fracture risk 5-fold, independent of BMD. Having three or more risk factors and being in the lowest tertile of BMD was associated with a 15-fold greater risk than having no risk factors and being in the highest BMD tertile. CONCLUSIONS: Several clinical risk factors were independently associated with nonspine fractures in elderly men. The combination of multiple risk factors and low BMD was a very powerful indicator of fracture risk.     

Hormone therapy use after the Women's Health Initiative.

OBJECTIVE: To continue surveillance of hormone therapy (HT) use in an Australian population and to assess the impact of the Women's Health Initiative (WHI) and associated reports on HT use 16 months after the results of the WHI were first reported. METHODS: Data were obtained from the 2003 South Australian Health Omnibus Survey, which involves a representative, population face-to-face interview survey. Data were compared to five surveys undertaken between 1991 and 2000, which had consistent methods and quality-control procedures. A total of 907 interviews were conducted with women over 40 years in their own homes by trained health interviewers. RESULTS: In association with the timing of media reporting of the WHI, current HT use rates dropped from 28% in women over 50 years in 2000 to an estimated 10.2% in 2002. By October 2003, current use rates had returned to 18.8% in this age group. The media had been the main influence in the women's decision-making. Half of those who restarted therapy changed to another type of HT. Only 2.8% changed to an alternative/complementary therapy. CONCLUSIONS: Nearly two-thirds (64%) of those currently using HT in 2002 stopped therapy, mostly in response to the media reporting of the WHI. Nearly half of those who stopped HT in 2002 have since restarted. Media reporting greatly influences the use of hormonal therapies.     

Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers.

BACKGROUND & AIMS: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk, and none have reported associations on the basis of HOMA-IR. METHODS: We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n=29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin x fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. RESULTS: Median (interquartile range) values for serum insulin, glucose, and HOMA-IR were 4.1 (2.9-7.2) mIU/L, 101 (94-108) mg/dL, and 0.99 (0.69-1.98) for case subjects and 4.1 (2.7-6.1) mIU/L, 99 (93-107) mg/dL, and 1.02 (0.69-1.53) for non-case subjects, respectively. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03-3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06-3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92-3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend=.12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. CONCLUSIONS: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors.