Use of monoclonal antibodies in diagnosis of paracoccidioidomycosis: new strategies for detection of circulating antigens

The precise diagnosis of paracoccidioidomycosis, in most cases, is established by direct methods and indirect immunological tests. The latter method is reliant on the identification of the host's humoral responses, which are usually impaired or absent in patients with severe juvenile forms of the disease and in immunocompromised patients. Determining disease activity or assessing treatment responses by measuring antibody levels is difficult, since antibody titer may remain elevated or persist at stationary levels, even in the presence of clinical improvement. Consequently, there is a need for alternative tests aimed at the identification of circulating antigens. A modification of the standard hybridoma production method was used to raise a panel of murine monoclonal antibodies (MAbs) against the yeast form of Paracoccidioides brasiliensis. Of these, MAb PIB, directed against an 87-kDa determinant, was used to develop an inhibition ELISA (inh-ELISA) capable of detecting as little as 5.8 ng of circulating antigen per ml of serum. Sera from 46 patients with paracoccidioidomycosis or other mycoses and sera from healthy individuals were evaluated by the inh-ELISA; overall sensitivity was 80.4% (37 of 46 paracoccidioidomycosis patients tested positive), and specificity compared with that of normal controls from areas of endemicity was 81.4%. The inh-ELISA detected circulating antigen in 100% of patients with the acute form of paracoccidioidomycosis and in 83.3 and 60% of patients with the chronic multifocal and unifocal forms of paracoccidioidomycosis according to the patients' clinical presentation. These results indicate that the inh-ELISA with MAb PIB is effective in the detection of circulating antigen and that this test may be useful for monitoring responses to treatment and establishing disease prognoses.     

Acute alcohol tolerance in social drinkers: changes in subjective effects dependent on the alcohol dose and prior alcohol experience

There has been no systematic, large-scale statistical investigation of the link between gambling and suicide, despite the suggestion of such a link from small-scale case studies. This article examines whether gamblers or those associated with them are prone to suicide and whether gaming communities experience atypically high suicide rates. Las Vegas, the premier U.S. gambling setting, displays the highest levels of suicide in the nation, both for residents of Las Vegas and for visitors to that setting. In general, visitors to and residents of major gaming communities experience significantly elevated suicide levels. In Atlantic City, abnormally high suicide levels for visitors and residents appeared only after gambling casinos were opened. The findings do not seem to result merely because gaming settings attract suicidal individuals.     

Sexually transmitted infection as a cause of anal cancer

BACKGROUND: The incidence of anal cancer has increased in recent decades, particularly among women. To identify underlying risk factors, we conducted a population-based case-control study in Denmark and Sweden. METHODS: We conducted telephone interviews with 324 women and 93 men in whom invasive or in situ anal cancer was diagnosed between 1991 and 1994, 534 controls with adenocarcinoma of the rectum, and 554 population controls. The interviews covered a wide spectrum of possible risk factors for anal cancer. Odds ratios were calculated by logistic regression. Specimens of anal-cancer tissue and samples of rectal adenocarcinomas were tested for human papillomavirus (HPV) DNA with the polymerase chain reaction. RESULTS: Multivariate analysis revealed consistent and statistically significant associations between measures of sexual promiscuity and the risk of anal cancer in both men and women. There was a significant trend toward an association between higher numbers of partners of the opposite sex in women (P<0.001) and men (P<0.05) and strong associations with a variety of venereal diseases. In women, receptive anal intercourse, particularly before the age of 30 years, and venereal infections in the partner were also associated with an increased risk (odds ratios, 3.4 and 2.4, respectively). Fifteen percent of the men with anal cancer reported having had homosexual contact, as compared with none of the controls (P<0.001). High-risk types of HPV, notably HPV-16, were detected in 84 percent of the anal-cancer specimens examined, whereas all rectal-adenocarcinoma specimens tested were negative for HPV. CONCLUSIONS: Our study provides strong evidence that a sexually transmitted infection causes anal cancer. The presence of high-risk types of HPV, notably HPV-16 (which is known to cause cancer of the cervix), in the majority of anal-cancer tissue specimens suggests that most anal cancers are potentially preventable.     

Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine

Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60 degrees head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of treatment with L-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.     

MRI demonstration of impairment of the blood-CSF barrier by glucose administration to the thiamin-deficient rat brain

Contrast-enhanced T1-weighted spin-echo magnetic resonance imaging (MRI) has demonstrated that Gd-diethylenetriaminepentaacetate (Gd-DTPA), which normally does not cross the blood-brain or blood-CSF barriers, does so approximately 40 min after administration of glucose to a vitamin B1 deficient rat. The period of the onset of this blood-CSF or blood-brain barrier dysfunction coincides with our previous observations of accumulation of glutamate or glutamate derivatives following an equivalent glucose load under identical conditions of thiamin deficiency, consistent with a relationship between these two observations. The dysfunction was reversed when a thiamin deficient animal was made thiamin replete.