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Biomedical subjects

J E Hall

Publications and source records attributed to J E Hall.

At least 361 records · Page 20Linked to original sources

The correction of spinal deformity in idiopathic torsional dystonias.

The torsional dystonias constitute a group of motion disorders of unknown etiology with variable onset, progression, and severity that frequently result in spinal curvature. Four patients with this uncommon disorder, with curves averaging 70 degrees (range, 55 to 95 degrees), underwent surgical correction for progressive spinal deformity. All of them had improvement in function postoperatively, but there was a high rate of postoperative complications.

Adolescent↗

Mechanism of the blood pressure and renal hemodynamic effects of captopril.

THis study was designed to investigate the mechanisms of captopril's chronic effect on arterial pressure and renal function. In dogs maintained on high sodium intake (250 mEq/day), 6 days of captopril infusion caused no change in arterial pressure, renal hemodynamics, sodium excretion or plasma aldosterone concentration. Infusion of captopril for 7 days also caused no significant changes in arterial pressure or renal function in dogs made hypertensive by chronic infusion of angiotensin II and high sodium intake, a model of hypertension in which plasma renin activity is undetectable and prostaglandin and bradykinin formation may be elevated. In dogs maintained on low sodium intake, chronic infusion of captopril decreased arterial pressure and plasma aldosterone concentration markedly while increasing effective renal plasma flow. Infusion of aldosterone (200 micrograms/day) for 8 days during captopril infusion restored plasma aldosterone concentration but did not significantly change arterial pressure or renal function, indicating that decreased plasma aldosterone concentration did not play a major role in the hypertensive and renal effects of captopril. However, angiotensin II infusion (10 ng/kg/min) for 8 days during captopril infusion restored arterial pressure, plasma aldosterone concentration and renal function toward control levels. These data suggest that the effects of captopril on arterial pressure, renal hemodynamics and electrolyte excretion are mediated primarily by decreased angiotensin II formation.

Aldosterone↗

Hepatic microsomal alterations during chronic trypanosomiasis in the field vole, Microtus montanus.

The field vole, Microtus montanus, was used as a model system to evaluate the chronic effects of infection by Trypanosoma brucei gambiense on hepatic mixed-function oxidase activity. At day 28 post inoculation there was a 97% increase in liver wet weight per g body weight. A portion of the increase (21%) was accounted for by tissue edema which occurred after day 14 of infection. Total hepatic cytochrome P-450 content and related total tissue mixed-function oxidase activities were decreased to about 60% of control levels at day 28 post inoculation. The decrease in total tissue mixed-function oxidase activity was partly due to a small decrease in microsomal protein per cell, and partly to a large decrease in cytochrome P-450 concentration in the endoplasmic reticulum. Although the decrease in total liver monooxygenase activity in several substrates roughly paralleled the loss in cytochrome P-450 content, several other microsomal enzyme markers not related to cytochrome P-450 monooxygenation were elevated in proportion to total liver microsomal protein content. The results suggest that in M. montanus during trypanosomiasis, there is proliferation of hepatic cells with normal content of endoplasmic reticulum. Furthermore, there appears to be selective toxicity for hepatic cytochrome P-450 and related monooxygenase activities. This may compromise the animals' ability to metabolize and dispose of other drugs to which the animal may be exposed in the course of infection.

Animals↗

Phenylalanine metabolism in Microtus montanus chronically infected with Trypanosoma brucei gambiense.

1. Alterations in phenylalanine metabolism were observed in Microtus montanus infected with Trypanosoma brucei gambiense. 2. Reductions were found in the incorporation of phenylalanine into free amino acid pools and into proteins of the liver and other organs of infected animals. 3. Increased quantities of phenylpyruvate, 4-hydroxyphenylpyruvate and pyruvate were found in the urine of infected Microtus. 4. There appeared to be very limited conversion of phenylalanine to tyrosine in infected animals. This suggested that either phenylalanine transaminase activity was greatly elevated in proportion to phenylalanine hydroxylase activity; or that phenylalanine hydroxylase activity was actually reduced during the infection.

Animals↗

Calcium-induced inactivation of alamethicin in asymmetric lipid bilayers.

This paper discusses a calcium-dependent inactivation of alamethicin-induced conductance in asymmetric lipid bilayers. The bilayers used were formed with one leaflet of phosphatidyl ethanolamine (PE) and one of phosphatidyl serine (PS). Calcium, initially confined to the neutral lipid (PE) side, can pass through the open alamethicin channel to the negative lipid (PS) side, where it can bind to the negative lipid and reduce the surface potential. Under appropriate circumstances, the voltage-dependent alamethicin conductance is thereby inactivated. We have formulated a model for this process based on the diffusion of calcium in the aqueous phases and we show that the model describes the kinetic properties of the alamethicin conductance under various circumstances. EGTA on the PS side of the membrane reduces the effects of calcium dramatically as predicted by the model.

Alamethicin↗

Carbon-13 nuclear-magnetic-resonance studies of glucose catabolism by Trypanosoma brucei gambiense.

13C Nuclear magnetic resonance studies have been performed in vivo on Trypanosoma brucei gambiense. The glycolytic pathway has been observed using specifically labelled 13C-enriched glucose and it has been ascertained that there is, under anaerobic conditions, predominant incorporation of C-1 of glucose into glycerol while there is complete randomisation of C-6 of glucose into glycerol and pyruvate. These observations cannot be reconciled by the Embden-Meyerhof glycolytic pathway, purportedly the mechanism by which glucose is catabolised in these organisms, and an alternative pathway must exist. Comparison of whole-cell and acid-lysate 13C nuclear magnetic resonance spectra concludes that pyruvate may be initially formed bound to a macromolecular species. Also, alanine is found to be a major end product of glucose catabolism.

Glucose↗

Renal hemodynamic responses to increased renal venous pressure: role of angiotensin II.

Studies were performed to quantitate the effects of progressive increases in renal venous pressure (RVP) on renin secretion (RS) and renal hemodynamics. RVP was raised in 10 mmHg increments to 50 mmHg. Renin secretion rate increased modestly as RVP was increased to 30 mmHg and then increased sharply after RVP exceeded 30 mmHg. Glomerular filtration rate (GFR), renal blood flow (RBF), and filtration fraction (FF) did not change significantly when RVP was elevated to 50 mmHg. GFR and RBF were also measured after the renin-angiotension system (RAS) was blocked with the angiotensin converting enzyme inhibitor (CEI) SQ 14225. After a 60-min CEI infusion, RBF was elevated (32%), GFR was unchanged, FF was decreased, and total renal resistance (TRR) was decreased. As RVP was increased to 50 mmHg, GFR and FF decreased to 36.3 and 40.0% of control, respectively, RBF returned to a value not significantly different from control, and TRR decreased to 44.8% of control. The data indicate that the RAS plays an important role in preventing reductions in GFR during increased RVP because blockade of angiotensin II (ANG II) formation by the CEI results in marked decreases in GFR at high RVPs. The decreases in GFR after ANG II blockade and RVP elevation were not due to lack of renal vasodilation, since TRR was maintained below while RBF was maintained either above or at the pre-CEI levels.

Angiotensin II↗

Combined anterior and posterior fusion in seventy-three spinally deformed patients: indications, results and complications.

Seventy-three patients with complex spinal deformities undergoing combined staged anterior and posterior fusion were analyzed. The indications for the combined approach were (1) severe kyphosis with or without neural compromise; (2) major thoracolumbar or lumbar curves with trunk imbalance or marked pelvic obliquity; (3) severe congenital scoliotic curves associated with hemivertebrae or anterior unsegmented bars; (4) absent posterior elements, e.g., myelodysplasia, post laminectomy; and (5) failed anterior fusion. In 35 patients with kyphosis, the deformity was reduced on the average from 78 degrees to 48 degrees. In 20 patients with marked trunk decompensation and/or pelvic obliquity due to a major thoracolumbar or lumbar curve, the scoliotic deformity was reduced from an average 85 degrees to 33 degrees. In 18 scoliotic patients with marked vertebral body deformation (hemivertebrae, anterior bars, lateral subluxation), the scoliotic curves were reduced from an average 60 degrees to 46 degrees. Postoperative morbidity was not significantly increased because of the combined procedure. The overall complication rate was high (32/73 patients). In view of this high rate of postoperative morbidity, the combined approach should not be undertaken by the occasional spinal surgeon. In selected far advanced or complex spinal deformities, combined anterior and posterior fusion may be indicated to attain optimal correction of the deformity as well as a solid pain-free fusion.

Adolescent↗

Chondrosarcoma in children and adolescents.

Chondrosarcoma is rare in children. Only 12 patients with a diagnosis of chondrosarcoma were treated at Children's Hospital Medical Center in Boston during the period from 1957 to 1980. Pediatric chondrosarcoma has a relatively rapid onset, manifested by pain, a palpable mass and neurological symptoms with the lesion localized in the spinal column. The pelvis was the most frequent location. Ten patients had primary and two patients had secondary chondrosarcoma. Of the latter two, one developed chondrosarcoma in a preexisting osteochondroma and the other had irradiation for neuroblastoma. The poorest outcomes were in patients who had involvement of the pelvic girdle and spinal column. Grade 2 and 3 lesions had the worst prognoses with metastases occurring within 12 months. Eight patients died at the time of study, and the longest survival time was 80 months. If surgically feasible, the treatment is radical excision. Radiation therapy and chemotherapy should be reserved for recurrences or distant metastasis.

Adolescent↗

Osteotomy of the fusion mass in scoliosis.

The value of an osteotomy of the fusion mass in attaining realignment of the spine when a lateral shift of the trunk over the pelvis has developed in the frontal plane was studied in fifty-five patients. All had had a previously fused but progressive spinal deformity. The indications for osteotomy were progression of the curve, imbalance of the trunk, pain, deteriorating cardiopulmonary function, or pseudarthrosis, or a combination of these conditions. Twenty-one patients had idiopathic scoliosis; fourteen, congenital scoliosis; ten, paralytic scoliosis; four, myelodysplastic scoliosis; and six had scoliosis secondary to miscellaneous conditions. A total of 154 osteotomies of the fusion mass, or 2.8 osteotomies per patient, were performed. Nine patients underwent an anterior spinal osteotomy or wedge resection as well. Most had a two-stage procedure which consisted of a posterior osteotomy, halo-femoral traction, and a posterior re-fusion with Harrington instrumentation two weeks later. At an average follow-up of thirty-two months, it was found that osteotomy of the fusion mass enabled the surgeon to realign the trunk over the pelvis and to correct pelvis obliquity, but correction of the angular deformity was only secondary. Although the rate of complications was high (51 per cent, including one postoperative death), osteotomy of the fusion mass and re-fusion may be indicated in a patient with a previously fused but progressively unbalanced, painful deformity of the spine.

Adolescent↗

Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation.

Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control.

Animals↗

Hepatic mixed-function oxidase activity in mice infected with Trypanosoma brucei gambiense or treated with trypanocides.

Three days after mice were inoculated with Trypanosoma brucei gambiense, total hepatic cytochrome P-450 levels were decreased 14% from control values, while the specific mixed-function oxidase activity (per nmole of cytochrome P-450) was inhibited almost 40% in infected animals. Furthermore, drugs used to treat trypanosomiasis (Suramin and Melarsoprol B) are themselves potent in vitro inhibitors of hepatic mixed-function oxidase activity. These two trypanocides also produced a decrease in mixed-function oxidations and an increase in pentobarbital sleeping time when administered intraperitoneally in vivo. These results demonstrate that mice with trypanosomiasis or undergoing trypanosome chemotherapy have a significantly impaired capacity to metabolize foreign compounds.

Animals↗

Voltage-dependent lipid flip-flop induced by alamethicin.

Alamethicin appears to allow voltage-dependent lipid exchange ("flip-flop") between leaflets of a planar bilayer. In membranes with one leaflet of phosphatidyl serine and one of phosphatidyl ethanolamine, the shape of the nonactin current-voltage curve accurately reports the difference in surface potential between the two sides of the membrane. The surface potential is itself a good measure of membrane asymmetry. Alamethicin added to the bathing solutions of an asymmetric membrane does not per se reduce the membrane asymmetry, but turning on the alamethicin conductance by application of a voltage pulse does. Immediately after application of a voltage pulse, large enough to turn on the alamethicin conductance, the asymmetry of the nonactin-K+ current voltage curve decreases, in some cases, nearly to zero. During the pulse, the alamethicin conductance activates if a decrease in surface potential favors turn-on of the alamethicin conductance or inactivates if a decrease in surface potential favors turn-off of the alamethicin conductance. After the pulse, the nonactin-K+ asymmetry returns to its original value if the alamethicin conductance is not turned on. The time-course of this return allows an estimate of the diffusion constant of lipid in the planar bilayer. The value obtained is 5.1 x 10(-8) cm2/s.

Alamethicin↗

A behavioural and biochemical study in rats of 5-hydroxytryptamine receptor agonists and antagonists, with observations on structure-activity requirements for the agonists.

1 The effect of the putative 5-hydroxytryptamine (5-HT) receptor antagonists, methysergide, methergoline, mianserin, cyproheptadine, cinanserin (all at 10 mg/kg), methiothepin (5 mg/kg) and (-)-propranolol (20 mg/kg) on the behavioural responses to tranylcypromine (10 mg/kg) followed 30 min later by L-tryptophan (100 mg/kg) was examined.2 Methysergide, methergoline, methiothepin and (-)-propranolol inhibited head weaving, forepaw treading and hind-limb abduction. Methysergide and methergoline increased reactivity. In contrast, cypropheptadine, cinanserin and mianserin had no effects on the behaviour.3 Similar findings were obtained when the behaviours were elicited by administration of tranylcypromine (10 mg/kg) followed by the putative 5-HT receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (2 mg/kg).4 When the behaviours were elicited by the putative 5-HT receptor agonist, quipazine (50 mg/kg), all the drugs effectively inhibited head weaving and forepaw treading.5 When the dose of cypropheptadine was doubled to 20 mg/kg an inhibition of the tranylcypromine/L-tryptophan induced behaviours was seen.6 Methiothepin produced a marked inhibition of apomorphine-induced locomotor activity whilst all the others enhanced this response, suggesting that only methiothepin inhibits the 5-HT behaviours by dopamine antagonism and that the increased reactivity seen following tranylcypromine/L-tryptophan after pretreatment with methysergide or methergoline might be due to enhanced dopamine function.7 Pretreatment with p-chlorophenylalanine resulted in enhanced behavioural responses to both 5-MeODMT and quipazine.8 Both methergoline and methiothepin decreased the rate of 5-HT synthesis in whole brain but not spinal cord and methergoline decreased spinal cord 5-HIAA concentration. None of the other drugs had any significant effects on the concentration of 5-HT, 5-HIAA or 5-HT synthesis rate in brain or spinal cord.9 Experiments with compounds structurally related to quipazine and with molecular models suggested that quipazine produces behavioural changes probably by stimulating the 5-HT receptor in a similar way to 5-HT but that it would bind weakly, in agreement with ligand-receptor binding studies.10 It is suggested, therefore, that cyproheptadine, cinanserin and mianserin fail to inhibit 5-HT and 5-MeODMT-induced behaviours because they are weak antagonists whilst they are able to inhibit the same behaviours induced by quipazine because it is a weak agonist.11 These data indicate that extreme care should be taken in accepting or rejecting 5-HT as a mediator of behaviours or of other responses unless several antagonists or agonists have been examined.

Animals↗