Multi-drug therapy trials for leprosy in Senegal: first observations relative to liver tolerance of multibacillary patients. Therapeutic consequences

The authors have studied tolerance of multibacillary patients to 4 MDT regimens. These 4 regimens consist of: One supervised part in which RMP-ETH combination in once-monthly administered; furthermore, in 2 of these regimens, is included one "starter phase" with daily doses of that combination for 2 months. One self-administered part during which CLO is associated either to DDS for new cases, or to ETH for relapses. Clinical Supervision: Out to 310 multibacillary patients, 7 cases of hepatitis with or without icterus, but no death due to the treatment. Interruptions of MDT have been temporary and have been observed in 0.9 to 5.6% of the patients according to the therapeutic regimen. Checking SGOT: The SGOT were abnormally high in 16.3% of the patients before treatment. These pre-existing liver damages do not favour the appearance of intolerance disorders. During MDT, abnormal increases in SGOT are observed in 27% of the patients but there is no exact correlation between the absorbed doses of ETH and the frequency in SGOT increases. The clinical or biological evidence of liver damages occur rather early (1st, 2nd month) in regimens with "starter phase", and later (4th-8th month) in those without "starter phase". But introduction of "Starter phase" does not increase the global frequency of such intolerance accidents. ETH combined with RMP, must be used under steady clinical and biological supervision. Recalling the results of a previous survey, the authors consider that a long duration of MDT is not necessary. For the multibacillary leprosy treatment, they propose a diphasic regimen, more easily applicable in the field than the WHO protocols. In this diphasic regimen, the only part which must be supervised is the initial "starter phase" of 2 month. It consists of daily administration of 3 antibacillary drug among which RMP and ETH. The second phase is a relay treatment using 2 drugs, CLO combined with DDS or ETH, self-administered until smear negativity.     

Dopamine in the conscious dog with chronic heart-block

Summary The chronotropic effects of dopamine were studied in the conscious dog with chronic A-V block. Dopamine at 12.5–200 g/kg and 12.5–50 g/kg/min lowered atrial rate independently of dose. After blockade of muscarine receptors or alpha-adrenoceptors, it raised atrial rate. After blockade of dopamine receptors, dopamine still lowered atrial rate, and did so dose-relatedly after blockade of beta-adrenoceptors. It raised ventricular rate, and at high doses also induced ventricular rhythm disorders. Blockade of muscarine receptors enhanced the ventricular cardioaccelerator effect of dopamine (P<0.025) at 100 g/kg, while blockade of alpha-adrenoceptors reduced it (P<0.05). Blockade of dopamine receptors did not modify this effect, but blockade of beta-adrenoceptors reversed it. Dopamine at 25–200 g/kg raised mean blood pressure. This effect was enhanced by blockade of muscarine receptors, reversed by blockade of alpha-adrenoceptors, and was unaffected by blockade of beta-adrenoceptors or dopamine receptors. These results show that the atrial cardiomoderator effect of dopamine is a vagal reflex response to its hypertensive action, and that it is limited by its direct beta-adrenergic stimulating action. They also show that the ventricular cardioaccelerator effect of dopamine is attenuated by a reflex vagal depressor effect consequent to the induced hypertension. No evidence was found for the existence of positive chronotropic dopamine receptors in either atria or ventricles.A preliminary report of these findings was presented at the Symposium on Peripheral Dopaminergic Receptors, July 1978, in Strasbourg, France (Boucher et al. 1979b)     

Modulation of immune response with ornithine A-ketoglutarate in burn injury: an arginine or glutamine dependency?

Enterally administered ornithine alpha-ketoglutarate (OKG) is an efficient complement of nutritional support in trauma situations, especially after burn injury. A typical feature observed in this intense catabolic state is insufficient production of glutamine (Gln) and arginine (Arg), two amino acids (AAs) involved in the immune response. As OKG in vivo metabolism generates these two AAs, we investigated, in burned rats, the action of OKG with regard to modulation of immunity. Male Wistar rats were randomly allocated to four groups. On day 0, 12 rats were burned with boiling water (20% body surface area). After a 24-h fast, they were enterally refed for 48 h using Osmolite, as a low-calorie low-nitrogen regimen, supplemented with either 5 g OKG x kg(-1) x d(-1) (n = 6) or an equivalent amount of nitrogen in the form of glycine (n = 6). Non-burned pair-fed controls treated with glycine (n = 6) and healthy rats fed ad libitum (n = 6) were also studied. Nitrogen balance was assessed from daily measurement of total nitrogen excretion. On day 3, thymus, Anterior tibialis muscle and proximal jejunum weights were recorded. Muscle and intestinal AA concentrations were also quantified. OKG counteracted (P<0.01) the thymic involution that occurs with burn injury, and increased the concentrations of Gln and Arg in both the muscle (P<0.01 and P<0.05, respectively) and the jejunum (P<0.01 for Gln). When all groups were taken together, a positive correlation was found between thymus weight, and Gln and Arg muscle concentrations (r = 0.71, P<0.001 and r = 0.58, P<0.01, respectively). Furthermore, as expected, OKG improved nitrogen balance. As it is known that total number of thymocytes parallels thymic weight, and as Gln and Arg are essential nutrients for activated immune cells, our results suggest that Gln and Arg derived from OKG are responsible for the immunomodulating properties of this molecule in burn injury.     

Testing various methods of introducing health charts into medical records in family medicine units.

OBJECTIVE: To test three methods of introducing health charts into the medical records of six family medicine units. DESIGN: Quasi-experiment. PARTICIPANTS: The staff physicians and family medicine residents in all six units and the nurses in two units. INTERVENTIONS: Group 1 (minimal intervention): health charts, a user's guide and one training session. Group 2 (intermediate intervention): same intervention as for group 1 plus two feedback sessions at 3 and 6 months. Group 3 (maximum intervention): same intervention as for group 2 plus promotion of the team concept (nurses were included). The intervention phase lasted from September 1987 to August 1988. OUTCOME MEASURES: The frequency with which the health charts were used, the item scores of each preventive care activity and the overall unit scores. Data were gathered through chart audits at baseline and at the end of the intervention phase. RESULTS: The frequency with which the health charts were used varied from 3.9% to 26.9%. The greatest increases in item scores were observed in the use of mammography (20.0%), counselling on lifestyle (19.4%) and breast examination (17.2%). Although the overall improvement in the unit scores was statistically significant (p less than 0.05) the hypothesis of an increasing gradient of effect across the three intervention groups could not be tested because of the variation in scores across the units. CONCLUSION: Health charts and other similar tools are useful; however, they are not sufficient to change practice behaviours. The support of a "champion" on the health care team might well be a determining factor of success for the delivery of preventive services in primary care practice.     

Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients

Azathioprine (AZA) is metabolized via the cytosolic enzyme thiopurine S-methyltransferase (TPMT). TPMT activity exhibits genetic polymorphism with four prevalent (75%) mutant alleles TPMT*2 (G238C) and TPMT*3 (A719G and/or G460A) and a wild-type allele TPMT*1. To test the hypothesis that presence of these mutations is associated with greater toxicity of AZA in heart transplant recipients, 30 consecutive patients treated with AZA were followed up for the first month after heart transplant. Mutation of TPMT gene (mutation-specific polymerase chain reaction-based methods) was observed in four patients (A719G: n = 2; A719G plus G460: n = 2). Agranulocytosis did not occur in patients with the wild genotype. It occurred in the two patients with mutation A719G and there was a 40% drop in neutrophils in the two other patients. Discontinuation of AZA in the four mutant patients corrected for the drop. Presence of TPMT mutations is associated with a greater likelihood of agranulocytosis. Determination of these mutations could reduce the risk for hematological side-effects.