Acute renal failure in sickle cell anemia

We performed a case-control study of acute renal failure (ARF) in patients hospitalized with sickle cell anemia (SCA). Twelve of the 116 patients (10.3%) whose records were suitable for analysis were diagnosed as having ARF based on a minimum of doubling of their serum creatinine levels (mean rise was 205 +/- 49%). ARF patients were more likely to have been admitted with infection and had a lower mean hemoglobin level than the control group. Volume depletion was the most common identifiable cause for ARF. Two of 3 patients with severe ARF received dialytic support. Ten of 12 ARF patients survived and subsequently had recovery of renal function.     

Additive Effects of Hypothermia and Phenobarbitol upon Cerebral Oxygen Consumption in the Rat

The quantitative effects of a combination of hypothermia and phenobarbital on cerebral oxygen uptake (CMRo2) was studied in rats, curarized and artificially ventilated with 70% nitrous oxide in oxygen. Cerebral blood flow (CBF) was measured with a modification of the KETY & SCHMIDT (1948) technique, using 133xenon as a tracer. Arteriovenous difference in oxygen content over the brain was measured and CMRo2 was calculated. Four groups were studied. Group 1 was a control group. The three experimental groups were injected with phenobarbital intraperitoneally: Group 2 with 50 mg/kg body weight; Group 3 with 150 mg/kg; and Group 4 with 50 mg/kg of phenobarbital, and, in addition, body temperature was lowered to 32 degrees C in this group. CMRo2 in groups 2, 3 and 4 was reduced by 22, 37 and 43%, respectively, compared to Group 1. The changes in CBF were of the same magnitude. In a previous study we have found that CMRo2 decreases by 5% per 1 degree C decrease in body temperature. The value for CMRo2 in Group 4 is close to the value obtained if the effect of 50 mg/kg body weight of phenobarbital on CMRo2 is added to the effect of a temperature reduction of 5 degrees C. It is concluded that the effects of barbiturates and hypothermia on CMRo2 are additive.     

Striatal dopaminergic pathways as a target for the insecticides permethrin and chlorpyrifos

Because insecticide exposure has been linked to both Parkinsons disease and Gulf War illness, the neurotoxic actions of pyrethroid and organophosphate insecticides on behavior and striatal dopaminergic pathways were investigated in C57BL/6 mice treated with permethrin (three i.p. doses at 0.2-200 mg/kg) or chlorpyrifos (three s.c. doses at 25-100 mg/kg) over a 2-week period. Permethrin altered maximal [3H]dopamine uptake in striatal synaptosomes from treated mice, with changes in Vmax displaying a bell-shaped curve. Uptake was increased to 134% of control at a dose of 1.5 mg/kg. At higher doses of PM (25 mg/kg), dopamine uptake declined to a level significantly below that of control (50% of control at 200 mg/kg, P < 0.01). We also observed a small, but statistically significant decrease in [3H]dopamine uptake by chlorpyrifos, when given at a dose of 100 mg/kg. There was no significant effect on the Km for dopamine transport. Evidence of cell stress was observed in measures of mitochondrialfunction, which were reduced in mice given high-end doses of chlorpyrifos and permethrin. Although cytotoxicity was not reflected in decreased levels of striatal dopamine in either 200 mg/kg PM or 100 mg/kg CPF treatment groups, an increase in dopamine turnover at 100 mg/kg CPF was indicated by a significant increase in titers of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid. Both permethrin and chlorpyrifos caused a decrease in open field behavior at the highest doses tested. Although frank Parkinsonism was not observed, these findings confirm that dopaminergic neurotransmission is affected by exposure to pyrethroid and organophosphorus insecticides, and may contribute to the overall spectrum of neurotoxicity caused by these compounds.     

(1)N,(12)N]Bis(Ethyl)-cis-6,7-dehydrospermine: a new drug for treatment and prevention of Cryptosporidium parvum infection of mice deficient in T-cell receptor alpha

Cryptosporidium parvum infection of T-cell receptor alpha (TCR-alpha)-deficient mice results in a persistent infection. In this study, treatment with a polyamine analogue (SL-11047) prevented C. parvum infection in suckling TCR-alpha-deficient mice and cleared an existing infection in older mice. Treatment with putrescine, while capable of preventing infection, did not clear C. parvum from previously infected mice. These findings provide further evidence that polyamine metabolic pathways are targets for new anticryptosporidial chemotherapeutic agents.     

Nocturnal urinary protein excretion rates in patients with sleep apnea

We observed nocturnal urinary protein excretion to be 16.2 +/- 5.5 micrograms/min (mean +/- SE) in 9 healthy control subjects (group I), 29.3 +/- 9.5 micrograms/min in 12 obese patients suspected to have obstructive sleep apnea syndrome (OSAS) but with negative polysomnographic studies (group II), and 94.0 +/- 31.8 micrograms/min in 14 patients with documented OSAS (group III) (II vs. I, NS; III vs. I, p less than 0.05; III vs. II, p less than 0.05). The frequency of abnormal proteinuria, defined as protein excretion greater than the highest rate observed in group I (46 micrograms/min), was 14% in group II and 64% in group III (p less than 0.05). There were no significant differences in age, body weight, body surface area, blood pressure, or indices of sleep apnea between OSAS patients with and without proteinuria. Although the mechanism is unclear, this study shows that nocturnal protein excretion rates are commonly elevated in patients with OSAS.     

Left ventricular volume determination using single-photon emission computed tomography

A new method for measuring left ventricular (LV) volume based on gated single-photon emission computed tomography (SPECT) is described. Preliminary phantom studies showed an excellent correlation between SPECT and observed volumes (r = 0.99, standard error of the estimate [SEE] = 4.9 ml). SPECT was performed 24 hours after biplane contrast LV angiography in 36 patients. Transaxial blood pool tomograms were reconstructed by filtered back projection and reoriented to views orthogonal to the cardiac axes. Volume was calculated from serial short-axis tomograms by determining the base, apex and lateral borders of the LV blood pool, ascertaining the number of pixels in this volume and multiplying by the known volume of a pixel. Gated SPECT volumes were compared with contrast angiographic volumes. At end-systole, r = 0.96 and SEE = 12 ml; at end-diastole, r = 0.81 and SEE = 27 ml. For ejection fraction, r = 0.85 and SEE = 0.06. To test interobserver variation in processing, count data from 5 patients were processed twice (r = 0.98, SEE = 8.3 ml). There is an excellent correlation between SPECT and contrast angiographic volumes at end-systole; at end-diastole the relation is good. SPECT requires no arbitrary background correction, allows systematic isolation of the left ventricle from other overlapping cardiac chambers and requires no geometric assumptions for volume determination. It has promise as a direct method for measuring LV volume in a minimally invasive manner.