Rural campaign to diagnose and treat mucocutaneous leishmaniasis in Bolivia.

Mucocutaneous leishmaniasis (MCL) is endemic in the tropical Amazonian lowlands of Bolivia, an area that regularly receives influxes of migratory populations. In these new agricultural development areas, a campaign to diagnose and treat the disease was carried out between 1989 and 1992, in order to provide direct access to MCL treatment in the endemic areas at a standard equivalent to that offered in the urban centres in Bolivia. The campaign led to the creation of decentralized local centres for diagnosis and treatment of the disease. A campaign to inform the population about leishmaniasis was also undertaken and courses were run to educate medical and paramedical personnel. As a result of the campaign, 3285 cases of leishmaniasis were diagnosed, including 2152 cutaneous and 326 mucosal forms. Also, a total of 1888 cases were treated, 1677 of which cutaneous and 211, mucosal.     

Immunochemical and biochemical characterization of purified canine interferon-gamma. Production of a monoclonal antibody, affinity purification, and its effect on mixed lymphocyte culture and mixed lymphocyte kidney culture reactions.

We have advanced the hypothesis that the primary autolymphoproliferative response of dog T cells in mixed lymphocyte kidney cultures (MLKC) results from their recognition of tissue-specific (kidney-associated) antigen(s) presented in conjunction with class II MHC antigens. Lymphocyte culture-derived supernatants had been found previously to upregulate class II antigen expression on kidney cells and enhance T cell activation. In the present study we have isolated and characterized dog IFN-gamma, a class II-inducing substance that is secreted in the culture supernatant of activated T lymphocytes. Dog IFN-gamma was induced with A-23187 and PMA and purified stepwise using controlled-pore glass, Mono Q anion exchange chromatography, and Superose 6-gel filtration on FPLC. The purification resulted in two molecules of 42 Kd and 31 Kd molecular weights. An IgG1 monoclonal antibody was engendered to these molecules. With this mAb reagent, in immunochemical experiments, we have developed a sensitive ELISA and a method for purifying dog IFN-gamma by affinity chromatography. Species specificity studies indicated that purified dog IFN-gamma reacted with a polyclonal rabbit antihuman IFN-gamma, but not with a mAb to human IFN-gamma. However, the antidog IFN-gamma mAb that was generated also reacted with recombinant human IFN-gamma. In in vitro biological studies, the purified IFN-gamma (two mol. wt. species) upregulated the expression of canine class II MHC molecules on dog tubular epithelial cells and the dog kidney epithelial cell line (MDCK). The antidog IFN-gamma mAb blocked T cell proliferative response to kidney cell and, by inference, the interaction between endogenously released IFN-gamma in vitro with its cell surface receptor, thus inhibiting the induced upregulation of class II. Interestingly, although antidog IFN-gamma markedly blocked the MLKC (10 micrograms mAb/well), there was no effect on the allogeneic MLC. This observation indicates that the cytokine IFN-gamma may be a uniquely key substance amplifying the immune response of T cells to tissue-associated antigens on surrogate antigen-presenting cells that require induced upregulation of class II MHC antigen expression (MLKC), in contrast to reactions in which these antigens are already constitutively expressed on the antigen-presenting cells (mixed lymphocyte culture).     

Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor.

Depression is common in Parkinson's disease (PD) and affects 30 to 50% of all patients. In contrast to the wealth of research on depression in PD, little is known about the occurrence of depression in other movement disorders. The primary objective of the current study was to determine whether the high prevalence of depression symptoms seen in PD is also found in other movement disorders, by directly comparing rates of specific depression symptoms and depression severity across PD, dystonia, and essential tremor (ET). Three hundred and fifty-four patients with PD, 83 patients with dystonia, and 53 patients with ET completed the Beck Depression Inventory (BDI). We found no significant between-groups differences for depression severity, frequency, or endorsement of specific depression symptoms. Forty-eight percent of PD patients, 37.3% of dystonia patients, and 34% of ET patients were found to be at least mildly depressed (BDI score of 10 or higher). The most commonly endorsed symptoms were fatigability, difficulty with work, anhedonia, and sleep disturbance. Clinicians should be aware that depression is a frequent problem in dystonia and ET, in addition to PD, and inquire about depression symptoms in these patients so that they can be appropriately treated.     

Digitoxin elimination in healthy subjects taking ampicillin

The present study was carried out to evaluate the changes in digitoxin kinetics during ampicillin administration. Subjects were informed of the nature of the study and the treatment was applied to those who gave their written consent. Six healthy volunteers received a single oral dose of 1.0 mg of digitoxin. Three days later, they were given orally ampicillin trihydrate, 500 mg four times daily, for five consecutive days. Blood samples were taken at 24, 36, 48, 60, 72, 96, 120, 144, 168 and 192 hours after digitoxin. Compliance with ampicillin regimen was verified by fluorimetric measurement of serum ampicillin. Concentrations of serum digitoxin were determined by radioimmunoassay. The mean digitoxin elimination half-life changed from 162.8 +/- 12.9 h before to 181.3 +/- 10.1 h (mean +/- s.e. mean) after ampicillin. These differences were not significant. No consistent evidence of a kinetic interaction between digitoxin and the broad-spectrum antibiotic ampicillin was found.     

Effects of Carbetimer, a new antineoplastic drug, on bone metabolism

Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10-15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-alpha and IFN-gamma which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-alpha release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-gamma, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-gamma production.     

Invasive cancer of the prostate. Reconstruction of the lower urinary tract by prostatic resection and ureteral reimplantation into the bladder vault

Some prostatic cancers (T4) spread out along the ureters to the kidneys. Patients, usually arrive with terminal renal failure and bladder retention and have often fast-advancing cancer with massive nodes invading. T.U.R., reimplantation of the ureters into the bladder dome or into a pso?c bladder and the specific treatment of the cancer, have often permitted these patients to survive for some years without any dialysis. In these cases we often find very important lower limbs oedema. With lymphatic nodes radiotherapy and subcutaneous injections of heparin, these oedema may regress completely.     

Therapist features in sexual offender treatment: their reliable identification and influence on behaviour change

In the first of the two studies reported here, we established that trained judges could reliably identify 18 therapist features that occurred with reasonable frequency. In the second study 17 of these features were examined to determine how well they related to changes in sexual offenders with treatment. Five videotapes from each of five different prison programs were rated for the presence of these 17 features and correlational analyses examined their relationship with changes in 44 measures of treatment targets. The primary findings indicated that empathy and warmth displayed by the therapists and their directive and rewarding behaviours, were the features that most strongly predicted therapeutic benefits. The results are discussed in terms of their clinical and research implications. Copyright © 2002 John Wiley & Sons, Ltd.     

Do weekly and fast-rotating shiftwork schedules differentially affect duration and quality of sleep?

 Characteristics of shiftwork schedules can have distinct impacts on workers’ sleep. This report presents comparisons of the effects of two different shiftwork schedules on duration and quality of the main sleep episodes in comparable worker populations at two different petrochemical plants. No significant differences were found for sleep duration in comparing the two plants. However, within each plant’s shift cycles, morning and night shifts showed shorter sleep durations than all other workdays and days off. Quality of sleep was perceived as lowest for night shifts of both plant schedules, and of lesser quality for weekly than for fast-rotating shifts. These results support recommendations for reducing the number of consecutive nights of shiftwork. However, before recommending any optimal shift schedule, interactions of sleep duration and quality with shift schedules need much further evaluation. Received: 18 December 1995/Accepted: 18 July 1996