Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine

Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Delayed traumatic aorto-pulmonary artery fistula

Delayed aorto-pulmonary artery fistula represents an uncommon delayed sequelae of penetrating cardiac trauma. A case is presented that demonstrates the need for a high index of suspicion, follow-up, and a complete evaluation of the patient who survives a penetrating heart injury. The mechanisms of delayed presentation, diagnosis, and management of the fistula are discussed.     

The role of complex formation in the neurotoxicity of crotoxin components A and B

Human adipose tissue was transplanted to the mouse mutant nude (nu/nu). All the grafts were accepted and contained fat cells easily distinguishable from those of the mouse. No detectable relation between the histological pictures before and after grafting was found. In some transplants nerve tissue, and in others macrophages containing fat droplets, were found. The fat tissue graft might be useful for investigation of the influence of various hormones on human fat cells.     

Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.     

Surface markers of human eosinophils

Peripheral blood eosinophils from patients with eosinophilia and from healthy subjects were studied for surface immunoglobulins, receptors for the Fc region of IgG, complement receptors, and spontaneous rosette formation with sheep and mouse erythrocytes. Eosinophils were found to have receptors for complement and for aggregated IgG, and to have the same two types of complement receptors as do lymphocytes and monocytes. Immune adherence type receptors were specific for C4 or C3b, while C3d receptors were specific for C3d but unreactive with C4. Eosinophils differed from fully mature neutrophils in that the former had C3d receptors and relatively weak immune adherence (C4 or C3b) receptors, while the later did not have the C3d receptors and had strong immune adherence receptors. Eosinophil phagocytosis of complement-receptor bound erythrocytes was dependent on the presence of IgG in the antibody coating the red blood cells; this requirement for IgG resembled that found in neutrophil phagocytosis. No surface Ig or spontaneous erythrocyte rosette formation was observed with eosinophils.     

Experimental meningococcal septicemia. Effect of heparin therapy

The pathogenesis of experimental meningococcal septicemia and the efficacy of heparin sodium therapy were evaluated by inoculating rabbits intraperitoneally with type B meningococci in mucin. Half the rabbits died, and the respiratory distress and circulatory failure that occurred during the terminal phase of the disease were associated with diffuse pulmonary capillary and venular thrombosis and with renal glomerular fibrin deposition. Platelet and leukocyte counts and plasma fibrinogen levels decreased in all rabbits, and prothrombin and partial thromboplastin times were prolonged. Pretreatment with heparin sodium diminished intravascular fibrin deposition but failed to prevent the pulmonary microthrombi and did not either reduce the mortality or improve the survival time. We conclude that death in meningococcal septicemia is due to widespread thrombosis of the pulmonary microcirculation. The disease is complicated by diffuse intravascular coagulation, which can be controlled with heparin sodium but which is not immediately life-threatening.     

Indications for conjunctival transplantation

Long-term follow-up (two to five years) of 12 unilateral chemical burn patients treated by conjunctival transplantation shows permanent stabilization of the ocular surface. The procedure was used in another group of five patients with unilateral recalcitrant epithelial defects. Regardless of the etiology of the epithelial defect, prompt healing of the surface occurs after conjunctival transplantation with no further stromal loss and long-term stabilization of the surface. Such results suggest that epithelial replacement may be a valuable therapeutic approach to a variety of ocular surface disorders.     

Membrane microviscosity and human platelet function

An increased sensitivity to epinephrine-induced aggregation has been observed both in platelets obtained from patients with type IIa hyperlipoproteinemia and in normal platelets following incubation with cholesterol-rich lecithin dispersions. We have reported previously that the membrane fraction of platelets is enriched with cholesterol relative to phospholipid under each of these conditions. To further explore the effect of cholesterol on platelet membranes, we have examined the fluidity (microviscosity) of whole platelets and platelet subcellular fractions using a hydrophobic fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH), under conditions in which the cholesterol-to-phospholipid mole ratio (C/PL) of platelets was varied by incubation with various cholesterol-lecithin sonicated dispersions. The C/PL of platelets directly influenced the rotational diffusion of DPH, as indicated by changes in fluorescence polarization. This was reflected in an increase in microviscosity at 37 degrees C (ETA37) from 2.84 P in normal platelets to 4.06 P in platelets with a 118% increase in C/PL. Conversely, platelets with a 43% decrease in C/PL had a 13% decrease in eta37. A strong correlation (r = 0.94) existed between C/PL and eta37 throughout this entire range. However, C/PL had no effect on the excited-state fluorescence lifetime of DPH. Both C/PL and eta37 were lower in isolated platelet membranes than in the platelet granule fraction. When platelets were incubated for 20 h with cholesterol-rich dispersions, there was an increase in C/PL and eta37 in both the membrane and granule fractions. However, this occurred more rapidly in membranes so that, at 5 h (a time when an increased sensitivity of whole platelets to epinephrine is evident), membrane C/PL had increased 55% and eta37 had increased 42%, whereas granule C/PL and eta37 had changed minimally. Cholesterol-rich platelets and subcellular fractions had a lower fusion (or flow) activation energy for viscosity (deltaE), reflecting a higher degree of order, and the converse was true in cholesterol-poor platelets. Moreover, a strong negative correlation existed between the percent change in deltaE and the percent change in eta37 induced either by cholesterol incorporation or depletion. These data demonstrate that cholesterol influences the fluidity and the degree of order within the hydrophobic core of platelet membranes. Changes induced in these physical properties by an excess of cholesterol relative to phospholipid may underlie the abnormal reception or transmission of the aggregation stimulus in cholesterol-rich platelets.     

Effects of continuous light and darkness on the eyes of the troglobitic salamander Typhlotriton spelaeus

Larval Typhlotriton spelaeus collected from five caves in Pulaski Co., Missouri, were kept as larvae or induced to transform in darkness or continuous fluorescent illumination. Larvae maintained in darkness for 215 and 279 days had smaller eyes, smaller rod inner and outer segments, and fewer metaphase figures in the germinative zone of the neural retina than comparable larvae maintained in light (258 lux). Except for visual cell size, differences were small and for each characteristic exceptions were observed. One larva kept in light showed early retinal degeneration comparable to that in transformed adults to T. spelaeus. All larvae exhibited optomotor behavior both before and after the experiment. Among animals induced to transform by L-thyroxin and maintained in darkness 111 to 366 days, visual cell and pigment epithelium degeneration was more extensive and more frequent than in animals kept for the same length of time in light (237-298 lux). In darkness the frequency of animals with retinal degeneration increased between 111 and 366 days. In light some animals exhibited pigment epithelium reduction with normal visual cells, and others had free, pigmented cells in the subretinal space. These effects were not comparable to degeneration in darkness. Eyelids covered the eyes of only a few animals in both light and dark treatments. The extent of eyelid encroachment over the eye greater in darkness than in light. Most animals exhibited optomotor responses after experiments, but responses of animals kept in darkness were impaired in comparison to those of animals kept in light.     

Certain quantitative indicators of the cells of human epidermis

Three age- and sex-matched groups of 10 patients were treated intravenously with imipramine, chlorimipramine, and imipramine-N-oxide respectively, in increasing doses from 25 mg to 150-175 mg given as single daily infusions during 1 hour. No systemic changes of heart frequency and blood pressure were found during the infusions in spite of the high dosage of tricyclic antidepressants given such a short period as 1 hour. The patients were examined regarding orthostatic reactions as well as ECG changes before, after 4-5 infusions and after 8-10 infusions. There were more orthostatic abnormalities and ECG changes in the patients treated with imipramine than in those treated with imipramine-N-oxide and there were practically no changes in the chlorimipramine group. However, no statistically significant orthostatic changes were found.