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Scabies infestation is a community health problem worldwide. This is particularly true in overcrowded and unhygienic areas. Seven dogs were experimentally infested with Sarcoptes scabiei freshly recovered from a patient. The dogs after infestation were treated with a mixture of ivermectin and clorsulon (Ivomec Super). The dose given to a single dog was 1 ml/50 kg body weight. This is equivalent to 200 mcg ivermectin and 2 mg clorsulon per Kg body weight. Five of the dogs (71.43%) were completely cured with 1 ml/50 Kg body weight. The remaining two dogs needed each, another injection of the same dose two weeks later. So, ivomec super is effective against the human strain of Sarcoptes scabiei in experementally infested dogs. A general discussion was given.

A differentiated approach toward treating secondary sulfanilamide resistance in patients with type II diabetes and proposed therapeutic regimens simple enough to be adopted in the management of the patients in question permit achieving satisfactory hypoglycemic effect maintaining an acceptable level of glucose in the blood.

In the winter of 1998/1999, sheep on a farm in the province of North Holland, The Netherlands, died from subacute and chronic liver fluke disease despite four previous treatments with triclabendazole (TCBZ). Faecal examinations of sheep and cattle on the farm showed high number of liver fluke eggs. In a randomised clinical trial, the fluke egg output was monitored weekly for 3 weeks in sheep which were treated with TCBZ or with closantel; in dairy cows treated with TCBZ or with clorsulon; and in heifers treated with TCBZ or clorsulon. The results showed a significant reduction of 99.7, 98.1 and 99.2%, respectively, in fluke egg output at 21 days in all non-TCBZ treated animals. TCBZ treatment produced percentage decreases of 15.3, 4.3 and 36.6%, respectively. These results are highly indicative of the presence of TCBZ-resistant Fasciola hepatica in sheep and cattle on this farm.

Two fasciolicide preparations have been compared in 130 rats experimentally infected with Fasciola hepatica. Parasitological, immunological, and biochemical parameters have been followed to monitor the efficacy of the treatments. While Fascinex (triclabendazole) efficiently cured both male and female rats when administered as soon as 4 weeks postinfection, treatment with Ivomec-D (clorsulon + ivermectin) displayed a low efficacy on either male or female rats at this time point (54 and 0%, respectively). Moreover, when administered 8 weeks postinfection, the Ivomec-D treatment proved highly efficient on male rats while it displayed little effect on the female population (100 and 53%, respectively). This unexpected result has been related to an overexpression of a P4503A isoform that is observed only in females that have been treated with Ivomec-D. The influence of this P4503A cytochrome on drug metabolism and the need for the incorporation of both genders in clinical trials are discussed.

The modes of action of fasciolicides are described. Closantel and other salicylanilides interfere with energy metabolism by uncoupling oxidative phosphorylation in the fluke. Other fasciolicides are believed to have a metabolic action-halogenated phenols (via uncoupling) and clorsulon (via inhibition of glycolysis)-but direct evidence is lacking. Benzimidazoles (in particular, triclabendazole) bind to fluke tubulin and disrupt microtubule-based processes. Diamphenethide inhibits protein synthesis in the fluke. Other potential drug actions may contribute to overall drug efficacy. In particular, a number of fasciolicides-salicylanilides, phenols, diamphenethide-induce a rapid paralysis of the fluke, so their action may have a neuromuscular basis, although the actions remain ill-defined. Resistance to salicylanilides and triclabendazole has been detected in the field, although drug resistance does not appear to be a major problem yet. Strategies to minimize the development of resistance include the use of synergistic drug combinations, together with the design of integrated management programmes and the search for alternatives to drugs, in particular, vaccines., (Copyright 1999 Harcourt Publishers Ltd.)

The paper is concerned with the problem of treatment of chronic infectious prostatitis. It is really a problem of today taking into account that it is most prevalent and difficult to deal with. Groups of drugs to be used for treatment are offered together with rational treatment schemes and drug routes. A treatment scheme is described for the most prevalent complication dysbacteriosis.

Background: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure., Methods: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability., Results: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05)., Conclusions: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.

The North American llama and alpaca industries will probably continue to expand at a rate of 20-25% per year for at least the next one to two decades. As a result, while the total population will always be small relative to the cattle and swine industries, the total numbers of alpacas and llamas will be substantial. Accordingly, it is appropriate and timely to begin the process of getting drugs approved for usage in these species. Four drugs that warrant consideration for NRSP-7 evaluation and approval are: Ivermectin for the prevention of P. tenuis infections. Chlorsulon for the treatment of Fasciola hepatica infections. Ceftiofur sodium for the treatment of various bacterial infections. Omeprazole for the management and prevention of third compartment ulcers.

The production of superoxide by the peripheral blood neutrophils of 19 patients with active rheumatoid arthritis was measured during treatment with sulphasalazine (SASP). The response to drug treatment was determined by change in plasma viscosity, CRP, early morning stiffness and articular index over a 10-point scale. Of the 19 patients studied, eight were considered to have responded well to SASP and seven to have responded poorly or not at all. Over the treatment period, plateau levels of superoxide production fell in seven of the eight responders (P = 0.028) compared with a non-significant fall in 3/7 of the non-responder groups. The initial rate of superoxide production also fell in the responder group, but this was not statistically significant. Initial values in both the responder and non-responder groups were comparable with those seen for normal controls. Analysis of drug levels showed all patients to be compliant with drug treatment; however, drug levels and neutrophil activity were not correlated. Studies of the effect of SASP and sulphapyridine on superoxide production in vitro showed no difference between good and poor responders. These results suggest that there is no inherent difference between good and poor responders regarding the susceptibility of their neutrophils to SASP. SASP's action on neutrophils, therefore, appears not to be its main mechanism of disease-modifying activity in RA.

Purpose: Chloroquinoxaline sulfonamide (CQS) was one of the first agents identified by the human tumor colony-forming assay (HTCFA) as possessing antitumor activity in non-small-cell lung cancer (NSCLC). Prior phase I studies had suggested that plasma concentrations equivalent to those showing efficacy in the HTCFA could be reliably attained in humans. This phase II study assessed the antitumor activity of CQS while using an adaptive control pharmacokinetic modelling system to attain targeted plasma levels of this novel compound., Methods: A group of 20 patients with stage III or IV NSCLC received CQS as a 1-h weekly infusion at an initial dose of 2 g/m2. In all patients, 24-h plasma concentrations of CQS were measured. Patients with levels < 100 micrograms/ml had dose increases determined by their 24-h levels and pharmacokinetic parameters obtained from two prior phase I trials of this agent. These individuals had 24-h CQS levels repeated after their second weeks' treatment and doses were readjusted if the target concentration was not reached. Antitumor response assessment was made every 6 weeks., Results: Of the 20 patients, 18 attained the target plasma concentration, and 16 of these achieved this initially or with just one dose adjustment. No major objective antitumor responses were observed (major response rate 0%, 95% CI 0-17%). CQS was well tolerated with hypoglycemia being the most clinically significant toxicity., Conclusions: When given on this schedule CQS is inactive in NSCLC despite the fact that the target concentration was achieved in 90% of patients. The ability of the HTCFA to identify active agents remains unproved.

A group of 10 patients, nine of them seriously infected with Paracoccidioides brasiliensis (G1), received glucan (beta-1,3 polyglucose) as an immunostimulant intravenously once a week for one month, followed by monthly doses (10 mg) over an 11-month period, together with a specific anti-fungal agent as an immunostimulant. A second group of eight moderately infected patients (G2) was treated with only the anti-fungal agent. Among the patients in G1, there was only one case of relapse compared with five in G2. Values for the erythrocyte sedimentation rate (ESR) showed a significant difference (P < 0.001) post-treatment in G1 patients, when compared with the pretreatment levels. There was also a significant reduction (P < 0.001) in the level of serum antibodies to P. brasiliensis in the G1 patients in post-treatment examinations. The phytohemagglutinin (PHA) skin test showed a positive reaction among the patients in G1 (P < 0.01) post-treatment and there was a tendency towards an increase in the number of CD4+ T lymphocytes in both groups after treatment. The serum level of tumor necrosis factor (TNF) proved to be significantly higher (P < 0.02) in the G1 patients during treatment. In the G1 patients, the correlation between ESR and TNF tended to be negative whereas that between ESR and serum antibodies was positive. The present results indicate that the patients who received glucan, in spite of being more seriously ill, had a stronger and more favorable response to therapy.

Results are submitted of analysis of correlation between clinical efficacy of sulphanilamide drug preparations and endogenous reserves of insulin. As many as 102 patients with type II diabetes mellitus under varying efficacy of sulphanilamides, 15 patients with type I disease and 10 essentially healthy subjects were examined. Lack of effect from peroral therapy in case of secondary sulphanilamide resistance was found to be related to the insulin endogenous reserves diminution, which feature manifests itself by reduction of the body mass and therefore adipose tissue as well, in the human organism. The insulin-producing apparatus of beta-cells tends to get low in the glucose tolerance test, which fact is evidenced by lack of the blood glucose level control.

Female ICR mice, 5 to 6 weeks old, were exposed by stomach tube to 25 metacercarial cysts of Echinostoma caproni per mouse. At 14 days post-exposure, mice were fed by stomach tube clorsulon (1000 mg/kg, 500 mg/kg and 100 mg/ kg) or rafoxanide (50 mg/kg, 25 mg/kg and 5 mg/kg) dissolved in dimethylsulphoxide (DMSO) carrier and mebendazole (1000 mg/kg and 500 mg/ kg) or arprinocid (100 mg/kg and 50 mg/kg) suspended in a 2:1 polyethylene glycol (PEG)/DMSO carrier. All drugs were obtained from Merck Inc. (Rahway, New Jersey, USA) and only single dose regimes were used. Experimentally infected mice that served as controls received either DMSO or 2:1 PEG/DMSO carriers or were not given the carrier. Mice were necropsied 15, 16, 18 and 20 days postexposure to worms. Doses of 100 mg/kg of clorsulon and 50 mg/kg of rafoxanide were 100% effective in eliminating the echinostomes on day 1 post-administration of the anthelmintics. Mebendazole and arprinocid were ineffective in eliminating worms at 1 or 2 days post drug administration.

Female ICR mice, 5 to 6 weeks old, were exposed by stomach tube to 25 metacercarial cysts of Echinostoma caproni per mouse. At 14 days post-exposure, mice were fed by stomach tube clorsulon (1000 mg/kg, 500 mg/kg and 100 mg/kg) or rafoxanide (50 mg/kg, 25 mg/kg and 5 mg/kg) dissolved in dimethylsulphoxide (DMSO) carrier and mebendazole (1000 mg/kg and 500 mg/kg) or arprinocid (100 mg/kg and 50 mg/kg) suspended in a 2:1 polyethylene glycol (PEG)/DMSO carrier. All drugs were obtained from Merck Inc. (Rahway, New Jersey, USA) and only single dose regimes were used. Experimentally infected mice that served as controls received either DMSO or 2:1 PEG/DMSO carriers or were not given the carrier. Mice were necropsied 15v, 16, 18 and 20 days postexposure to worms. Doses of 100 mg/kg of clorsulon and 50 mg/kg of rafoxanide were 100% effective in eliminating the echinostomes on day 1 post-administration of the anthelmintics. Mebendazole and arprinocid were ineffective in eliminating worms at 1 or 2 days post drug administration.

Objective criteria of semen quality were evaluated in 60 men with positive culture of semen after treatment with two different antibiotics and compared with placebo. Group I received 160 mg trimethoprim and 800 mg sulfamethoxazole twice a day, group II received 250 mg ciprofloxacin twice a day, and group III received a placebo. No difference was recorded between antibiotic treatment and placebo in sperm quality but accessory gland function was modified.

The therapeutic efficacy of sulphachlorpyrazine and toltrazuril against experimentally induced Eimeria tenella infection was compared in battery and floor pen raised broiler chickens. In the battery studies, both drugs prevented coccidiosis-related mortality and decrease of weight gain to a similar degree, but toltrazuril was more effective in reducing intestinal lesions and faecal scores, when treatments were initiated 24 h postinfection. When medication was delayed until 72 h after inoculation, the sulphonamide proved to be more effective in preventing reduction of weight gain and intestinal lesions caused by the parasites. Under simulated use conditions both drugs showed an appropriate anticoccidial efficacy without major differences between them.

The identification of new chemotherapeutic agents for the treatment of non-small cell lung cancer should proceed in a structured, logical fashion. Agents should be evaluated on the basis of multiple objective and subjective end points. A 15% or greater major objective response rate, demonstrated in multiple single-agent phase II trials, is considered the lower limit for an agent to be deemed clinically active in this disease. A number of drugs previously have been identified in this category, including cisplatin, ifosfamide, mitomycin, paclitaxel, and the vinca alkaloids vinblastine and vindesine. Most of these conventional agents have been explored alone, in a variety of doses and schedules, and in combination. In the last several years clinical development has produced new agents, including chloroquinoxaline sulfonamide, docetaxel, edatrexate, gemcitabine, irinotecan, topotecan, and vinorelbine, which hold promise for more successful treatment of this lethal disease.

To define a maximum tolerable dose, chloroquinoxaline sulfonamide (CQS) was given as a 1-h infusion every 28 days to cancer patients for whom no effective standard therapy was available. Doses were escalated in cohorts of at least three patients each. Plasma for characterization of the pharmacokinetics of free and total CQS was obtained during and after the initial infusion and, when possible, during and after subsequent infusions of CQS if the dose had been reduced. A total of 101 courses of CQS in 55 patients were evaluated. Dose levels ranged from 18 to 3,700 mg/m2. The dose-limiting toxicity was hypoglycemia, first recognized at the 3,700-mg/m2 dose. When dose-limiting hypoglycemia was recognized, patients were entered at successively lower doses, with close monitoring of plasma glucose and insulin concentrations being done in 26 patients. Grade 1-3 hypoglycemia occurred within 4 h of the termination of CQS infusion and cleared by 24 h. Symptomatic hypoglycemia was more frequent at doses of CQS above 1,000 mg/m2. Concomitant administration of 5% glucose did not ameliorate the hypoglycemia associated with CQS doses of > 1,000 mg/m2. The total calorie intake, percentage of ideal body weight, or percentage of weight lost did not explain the incidence or severity of hypoglycemia in 12 patients in whom these data were obtained. Cardiac tachyarrhythmias occurred in 7 patients who received CQS at doses of > or = 1,000 mg/m2, and tachyarrhythmia was associated with hypoglycemia in 3 patients. Other toxicities were sporadic, but the frequency of toxicity was higher at CQS doses of > or = 1,000 mg/m2. These toxicities included fever, rash, lightheadedness, leukopenia, thrombocytopenia, alopecia, diarrhea, nausea, and vomiting. All toxicities were reversible. Mean peak plasma [CQS] and AUC increased with dose, with a suggestion that peak plasma [CQS] plateaued at higher doses. The decline in plasma [CQS] was fitted to a three-compartment, open linear model. The terminal half-life ranged from 28 to 206 h. Total body clearance ranged from 44 to 881 ml/h with no evidence of saturation. Urinary excretion of the parent compound in 24 h averaged < 5%. CQS not bound to plasma protein (free CQS) comprised 1%-17% of total plasma CQS and was not related to dose. A relationship was defined between the magnitude of hypoglycemia and CQS pharmacokinetic parameters. The percentage of decrease in plasma [glucose], i.e., (predose [glucose]-nadir [glucose]/predose [glucose]) x 100, correlated with both free and total peak plasma [CQS].(ABSTRACT TRUNCATED AT 400 WORDS)

A sulfanilamide resistant strain Ts-5 of Pseudomonas mallei was isolated in the experiments on sulfazine therapy of malleus. The spectrum and level of the strain cross resistance to sulfanilamides and trimethoprim were studied. The frequency of the SurTrr mutants of P. mallei was determined. Efficient antibacterial drugs for the therapy of malleus caused by the sulfanilamide resistant strain are recommended.

In a large pig production unit 60 postparturient sows were divided at random into 3 groups, each with 20 sows. Group 1 (20 sows) received 30 g Farmavet Trisulfa per os daily from the beginning of the postfarrowing period for 1 week. Group 2 (20 sows) received 30 g Farmavet Trisulfa per os daily from the beginning of the postfarrowing period for 1 week, and in addition were given 3 mg Gabbrostim 24-48 hours after farrowing in a single i.m. application. Group 3 (20 sows) untreated control. The following parameters were evaluated: A: number of weaned piglets per sow, B: weaning to service interval in days, C: return to oestrus in percent. Both groups 1 and 2 showed better results when compared to the control group. Group 2 was superior to group 1.

Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame. The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half-lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45-132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans. Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m2.

Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule.

The synthesis and Class III antiarrhythmic activity of a series of 4-[(methylsulfonyl)amino]benzamides and sulfonamides are described. Selected compounds show a potent Class III activity and are devoid of effects on conduction both in vitro (dog Purkinje fibers) and in vivo (anesthetized dogs). Compounds having a 2-aminobenzimidazole group were found to be the most potent, and one compound having this heterocycle (5, WAY-123,398) was selected for further characterization. Compound 5 was shown to have good oral bioavailability and a favorable hemodynamic profile to produce a 3-fold increase of the ventricular fibrillation threshold and to terminate ventricular fibrillation, restoring sinus rhythm in anesthetized dogs. Voltage-clamp studies in isolated myocytes show that 5 is a potent and specific blocker of the delayed rectifier potassium current (IK) at concentrations that cause significant prolongation of action potential duration.

The reproductive performance of beef cows and the weight gain of their calves was evaluated after oral administration of clorsulon or clorsulon in combination with the subcutaneous administration of ivermectin. One hundred and fifty pregnant cows harboring infections of Fasciola hepatica were assigned to one of three treatment groups: Group 1 comprising 50 unmedicated controls; Group 2, 50 cows treated with clorsulon orally at 7 mg kg-1; Group 3, 50 cows treated with clorsulon orally at 7 mg kg-1 and ivermectin subcutaneously at 200 micrograms kg-1. Weights and body condition scores of the cows were measured and fecal and blood samples were taken at trial initiation and days 158 and 270. Pregnancy status was also determined at day 270. Weights and body condition scores were measured for the calves at days 158 and 270. Adjusted 205 day weaning weight of the calves was calculated and analyzed for differences between treatment groups. Four sets of tracer calves were used periodically throughout the trial to monitor the helminth challenge to the herd. Both gastro-intestinal nematodes and liver flukes were transmitted to the tracer calves during the entire trial. Even in the face of continual helminth challenge, beef cows treated with combined clorsulon/ivermectin conceived approximately 2 weeks earlier than their untreated counterparts and their calves had better body condition scores and weights than untreated calves.

Azosemide, a novel loop diuretic that has been available for the past few years, acts qualitatively like thiazide, viz by prolonging the diuretic effect with, however, only a slight delay in the onset of diuresis, in combination with the quantitative effect of previous loop diuretics, i.e. large excretion volumes. On the basis of experience gained to date, specific indications will presumably be cardiac and renal edema and ascites, also as long-term treatment. Provided that no NaCl or volume deficiency presents, side effects are insignificant.

One particular case of thoracic actinomycosis is reported. The patient presented with a neurological picture mimicking a metastasis, as chest radiogram and CT-Scan indicated a primary pulmonary tumor. Diagnosis of actinomycosis was overlooked and final diagnosis was based on direct microscopy of lung tumor, which required a thoracotomy, without any resection. Antibiotic treatment with penicillin was successful as the cerebral lesion was completely cured within 2 months and the thoracic lesion reduced 2/3rd volume within the same delay. The importance of correct handling of tissue specimens and adequate informations to the microbiologist are emphasized. Another point of interest is that good clinical results can be expected from prolonged antibiotic treatment. Surgery must be reserved for diagnosis if no other means has been effective, for failure of medical treatment or for acute complications.

Preventing congenital toxoplasmosis is fundamental, and in France screening tests for primary infection are obligatory for pregnant women. All nonimmunized women should be encouraged to follow good dietary and general health rules until delivery. Nevertheless, the risk of seroconversion does exist but can be detected early through monthly serum tests. Spiramycin as initial treatment of maternal primary infection is an essential step in preventing parasite transmission to the fetus. Fetal antitoxoplasmosis antibodies and indirect signs of congenital abnormalities should be detected early by amniotic fluid and fetal blood tests before echographic evidence confirms the diagnosis. Pyrimethamine-sulfonamide therapy should be undertaken and modulated according to laboratory results in order to prevent or treat any possible fetopathy. Congenital toxoplasmosis can be prevented in utero through biological diagnosis and specific therapy.

A dose titration study was undertaken to determine the efficacy of clorsulon against the adult stage of Fasciola hepatica in goats. Thirty-nine goats were experimentally infected with metacercariae of F hepatica. At 14 weeks after infection, each goat was assigned randomly to 1 of 5 groups. Goats in groups 1 to 4 received a single oral administration of clorsulon at dosages of 3.5, 7, 11, and 15 mg/kg of body weight, respectively. The fifth group of goats (control group) was infected with F hepatica, but were not treated with clorsulon. Postmortem examination of goats at 3 weeks after treatment revealed mean reductions in numbers of flukes of 83, 98, 99, and 100% for groups 1 to 4, respectively. Mean percentage of reduction in eggs following treatment of groups was 82, 98, 100, and 100%, respectively. The clinical effects of clorsulon in 24 goats that were not infected with F hepatica were studied. Goats in groups 1 to 3 received a single oral administration of clorsulon at dosages of 7, 21, and 35 mg/kg, respectively, every other day for a total of 3 doses/goat. Group-4 goats (control group) received a vehicle placebo. Goats in group 3 were subject to postmortem examination at 14 days after dosing. Abnormal signs or lesions that could be attributed to clorsulon were not found in any goat.

Hemocoagulation was examined in 477 diabetes mellitus patients. Whatever the disease type, severity, duration and the intensity of microvascular complications, diabetes mellitus was discovered to be marked by the development of chronic intravascular blood microcoagulation associated with primary hyperactivation of the platelet component of hemostasis. The use of the new antiaggregation agents tiklid and diabeton allows an appreciable decrease of the activity of platelet microthrombus formation whereas the administration of the common sugar-reducing antidiabetic therapy favours the maintenance of its high level.

Newly detected noninsulin--dependent diabetes mellitus is shown to have changes in phospholipid structure of erythrocytic membranes: a fall in total phospholipids, sphingomyelin, phosphatidylcholine, phosphatidic acid, a trend to increasing lysophosphatidylcholine. The shifts go in parallel with lipid peroxidation activation. Carbohydrate metabolism compensation is not enough to eradicate the shifts. The process is also dependent on the properties of a sugar-reducing drug. Diabeton is recommended as beneficial in this respect, while metformin is efficient in combinations.

National adverse drug reaction registers in Sweden and the United Kingdom provided data on the type, severity and frequency of reported adverse reactions attributed to sulfa drugs. Reactions to the ten principal drugs were examined in terms of their half-lives and usual indications for use. Of 8339 reactions reported between 1968 and 1988, 1272 (15%) were blood dyscrasias, 3737 (45%) were skin disorders, and 578 (7%) involved the liver. These side-effects occurred with all types of sulfa drugs investigated, although at different relative rates, and 3525 (42%) of them were classified as serious. The overall case fatality rate (CFR) was 1:15 serious reactions, and was highest in patients with white blood cell dyscrasias (1:7). Drugs with longer elimination half-lives had higher CFRs, particularly for fatalities after skin reactions. In Sweden, the estimated incidences of serious reactions were between 9 and 33 per 100,000 short-term users of sulfa drugs (two weeks), between 53 and 111 among those on malaria prophylaxis, and between 1744 and 2031 in patients on continuous therapy. For dapsone, the incidence appeared to increase with higher doses. Our results indicate that sulfa drugs with short elimination half-lives deserve to be considered for use in combination with proguanil or chlorproguanil for malaria chemotherapy and possibly prophylaxis. The smaller risk of adverse reactions associated with lower-dose dapsone suggests that it should also be evaluated as a potentially safe alternative.

Dermatitis herpetiformis, pemphigus vulgaris, and bullous pemphigoid are uncommon, but not rare, blistering diseases. Accurate diagnosis is essential so that prognosis can be estimated and proper treatment begun. The systemic drugs used in treatment can cause major complications, and careful monitoring is vital. Management is best achieved with a team approach consisting of a primary care physician and a dermatologist.

A modification of the standard World Health Organisation 7--day in vivo test was used to assess the parasitologic and, to limited extent, the clinical response of children less than 5 years of age to defined oral dosages of chloroquine and pyrimethamine-sulphadoxine during the 14 days following the initiation of treatment. The study took place in Jato-Aka, a rural community in Benue State of Nigeria. 471 children were screened and 271 (59%) of these had plasmodium parasites thus showing a high transmission rate at a time of the year with scarce rainfall. Of the 42 children on chloroquine and who were followed up to day 2, 4 or 9.5% of them were parasitologic failures while none of the 45 children on pyrimethamine-sulphadoxine (P-S) failed parasitologically. By day 7, 21 (50%) of the children on chloroquine and 4 or 8.9% of those on P-S. had become parasitologic failures. The total number of parasitologic failures on day 14 were 21 (50%) and 4(8.9%) for chloroquine and P-S groups respectively. Chloroquine improved the clinical state of the patients better than P-S. However, P-S appears superior in clearing the parasites. These results confirm the existence of both chloroquine and pyrimethamine-sulphadoxine resistant strains of P. falciparum in some regions of Nigeria. The routine chloroquine chemoprophylaxis of children under 5 years of age should be discontinued so as not to hasten the intensification of chloroquine resistance and because of its probable marginal efficacy at chemoprophylaxis dosages. There is also need for a national policy on pyrimethamine-sulphadoxine usage in order not to hasten its resistance to P. falciparum.

Shortly after the introduction of sulfa drugs, sulfapyridine was found to have unique therapeutic properties, unrelated to antibacterial activity. Later, sulfones were found to share the same properties. The disorders initially improved were dermatitis herpetiformis, pyoderma gangrenosum, subcorneal pustular dermatosis, acrodermatitis continua, impetigo herpetiformis and ulcerative colitis. They were also sometimes helpful in many other disorders. They are effective in select disorders characterized by edema followed by granulocytic inflammation or edema followed by vesicle or bullae formation. The sulfones work in low doses in leprosy and their mode of action is not fully understood. Several pieces of experimental information are available. It is proposed that these drugs are entering or influencing the protein moiety of glycosaminoglycans and decreasing tissue viscosity. This decreased tissue viscosity prevents edema and dilution of tissue fluid and decreases acute inflammation and vesicle and bullae formation.

This study appreciated the efficiency of uncomplicated malaria second line treatment (P. falciparum) in an area with high level of chemoresistance. No therapeutic failure was found with sulfadoxine-pyrimethamine (Fansidar), and mefloquine-sulfadoxine-pyrimethamine (Fansimef), in contrast with a rate of 8% with quinine. The authors discuss the place of these therapeutic, in the treatment of malaria.