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Biomedical subjects

J R Hamilton

Publications and source records attributed to J R Hamilton.

At least 91 records · Page 5Linked to original sources

Diminished brush border membrane Na-dependent L-alanine transport in acute viral enteritis in piglets.

We studied sodium-dependent uptake of L-alanine into small intestinal brush border membrane vesicles (BBMV) isolated from piglets 40 h after infection with transmissible gastroenteritis (TGE) virus. Vesicles from TGE-infected pigs and uninfected litter-mate controls showed comparable degrees of enrichment and purity. In BBMV prepared by conventional techniques, [3H]L-alanine "overshoot" (peak uptake/equilibrium uptake) in the presence of a Na gradient was preserved in TGE BBMV, unlike [3H]D-glucose "overshoot," which was reduced. When these experiments were repeated using vesicles of greater purity, initial rates of Na-dependent L-alanine influx were reduced in BBMV from infected piglets under voltage clamped conditions with valinomycin. These studies demonstrate a specific amino acid transport defect in the small intestinal epithelium during acute viral diarrhea. They demonstrate too that brush border L-alanine-Na co-transport, although reduced, is present after viral damage, confirming previous studies that showed additive effects of amino acid and glucose on jejunal epithelial Na+ transport in transmissible gastroenteritis. Our findings support the concept that, in viral enteritis, oral rehydration solutions containing amino acid and glucose have a theoretical advantage over glucose electrolyte solutions because they facilitate brush border Na+ entry by two carrier mechanisms.

Acute Disease↗

Itraconazole therapy for cryptococcal meningitis and cryptococcosis.

We studied the efficacy of itraconazole, a new oral triazole, in 33 patients (32 were immunocompromised) with cryptococcosis. Diagnoses included cryptococcal meningitis (24 patients), cryptococcemia (19 patients), cryptococcuria (4 patients), osteomyelitis (1 patient), pulmonary cryptococcosis (1 patient), and soft-tissue cryptococcosis (2 patients). Twenty-six patients had the acquired immunodeficiency syndrome, and 4 were transplant recipients. Therapy (200 mg two times per day) was monitored by clinical response, culture, and cryptococcal antigen testing. Cryptococcemia was abolished in 10 (100%) of 10 assessable patients; clinical abnormalities also cleared. Thirteen (65%) of 20 assessable patients with cryptococcal meningitis had complete responses (clinical resolution and negative cultures), 5 (25%) had partial responses, and therapy failed in 2 (10%). Ten (71%) of 14 patients with the acquired immunodeficiency syndrome who had meningitis and were treated with itraconazole as their sole therapy had complete responses, 3 (21%) had partial responses, and therapy failed in 1 (7%). Partial responses or failures were all associated with the failure of previous therapy, severe disease, low serum itraconazole concentrations, or a resistant organism. Noncompliance was associated with relapse (4 patients). Meningitis recrudesced in 3 (20%) of 15 patients who responded to therapy. All 4 patients with pulmonary cryptococcosis, soft-tissue cryptococcosis, or osteomyelitis responded to therapy (100%). Cryptococcuria was abolished in 3 (60%) of 5 assessable patients. The median survival of the 20 patients with the acquired immunodeficiency syndrome who had meningitis exceeded 10.5 months at this writing. Overall results compare favorably with amphotericin B therapy with or without flucytosine. Forty of 44 isolates of Cryptococcus neoformans were susceptible in vitro to itraconazole (minimum inhibitory concentration less than or equal to 3.13 mg/L), 3 were borderline (minimum inhibitory concentration, 6.25 mg/L), and 1 was resistant (minimum inhibitory concentration, 12.5 mg/L). As itraconazole does not penetrate cerebrospinal fluid, the meningitis results are noteworthy and suggest that meningeal and parenchymal penetration is critical. Itraconazole is promising for the treatment of cryptococcosis in patients with and without the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Viral enteritis.

Rotavirus has emerged as the major enteric pathogen causing acute diarrhea in young children throughout the world. Other viral pathogens have been recognized and additional candidate agents are suspected but none approaches rotavirus in its global impact. A strong appropriate emphasis has been placed on preventive therapy. Although vaccines are not yet available, it is clear that improved hygienic practices, particularly in pediatric institutions, and breast feeding can do much to prevent serious illness during the early months when babies are so vulnerable. During the past decade, from clinical studies and animal models, much has been learned about the pathogenesis of rotavirus diarrhea. These findings provide a sound basis for the use of rational oral fluid therapy, early feeding, and avoidance of drugs during active management. Among the many challenges that remain are the elucidation of the full spectrum of enteric viral pathogens, their impact on man, and their prevention and active therapy.

Child↗

Comparison of Meritec-Strep with Streptex for direct colony grouping of beta-hemolytic streptococci from primary isolation and subculture plates.

Meritec-Strep (Meridian Diagnostics, Inc., Cincinnati, Ohio) a coagglutination method, was compared with Streptex (Wellcome Diagnostics, Research Triangle Park, N.C.), a latex agglutination method, for the identification of beta-hemolytic streptococcal groups A, B, C, F, and G by the direct colony method. A total of 124 beta-hemolytic streptococcal isolates were tested, which included 77 from group A, 15 from group B, 10 from group C, 1 from group F, and 21 from group G. All were tested from subculture, and 74 (60%) were also tested from primary isolation plates. For Meritec-Strep, usually one colony was directly applied to the reaction card for testing each grouping reagent, while for Streptex, five colonies were tested after a 1-h extraction process. Complete agreement was obtained for all isolates tested from subculture with the kits. From primary isolation plates, Meritec-Strep correctly identified 97.3% of the isolates compared with 94.6% correctly identified for Streptex. Meritec-Strep produced a false-negative for one group A isolate and positive reactions for group A and F reagents with another group A isolate. A diphtheroid contaminant caused the positive group F reaction. Streptex produced false-negative results for one group A and three group C isolates. Most positive reactions were strong and rapid (less than 30 s) for both kits. The negative test control provided in the individual group A and B kits was nonreactive for all isolates. Meritec-Strep accurately identified isolated colonies of beta-hemolytic streptococci on primary isolation and subculture plates. It provided faster results than Streptex by eliminating the time and manipulation of antigen extraction and needed fewer colonies when individual group A or B reagents were used.

Agglutination Tests↗

Failure of ornithine decarboxylase inhibition to alter small intestinal epithelial repair after transient segmental ischaemia.

To evaluate the roles of ornithine decarboxylase (ODC) and polyamines in the regulation of epithelial repair, rabbit mid-small intestine after transient ischaemic villus injury in the presence and absence of DL-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC was studied. Rabbits received 2% (w/v) DFMO in drinking water for two days before undergoing a sham laparotomy, or a 90 minute mesenteric vascular occlusion of 20 cm of mid-intestine. DFMO fed and control rabbits were studied four, 24, 72, or 120 hours after this ischaemic intestinal injury. In controls, ischaemic injury caused shortened villi at four hours (p less than 0.01), diminished mucosal sucrase and alkaline phosphatase activities at 24 hours (p less than 0.05), but raised ODC (p less than 0.001) and thymidine kinase (p less than 0.01) activities at four hours with recovery by 72 hours. DFMO treatment significantly reduced ODC activity at all stages of the experiment and significantly inhibited the rise in activity observed after injury (p less than 0.01). Mucosal concentrations of the polyamines, spermidine and spermine, were similar in the sham operated groups; four hours and 24 hours after ischaemia, they increased in the DFMO animals (p less than 0.01) but fell (p less than 0.05) in those that did not receive DFMO. After ischaemic injury, DFMO treatment inhibited ODC but failed to influence recovery of villus structure or enzyme activities in the small intestine. We conclude that ODC and the polyamines, spermidine and spermine, are not key regulators of small intestinal repair after transient ischaemia.

Animals↗

Effect of glucocorticoid on piglet jejunal mucosa during acute viral enteritis.

We measured the effect of pharmacological doses of glucocorticoid on piglet jejunal structure and function during acute viral diarrhea. Weaned piglets, infected experimentally with transmissible gastroenteritis virus, a coronavirus that induces a diarrheal illness similar to human rotavirus infection, received methylprednisolone (30 mg/kg) or saline intramuscularly at 48 and 72 h after infection; noninfected littermate controls were similarly injected with methylprednisolone. Animals were killed at 96 h, at the height of diarrhea, and jejunal epithelium was studied in vitro. Transmissible gastroenteritis, as expected, induced structural, enzyme, and Na transport abnormalities. Methylprednisolone did not affect small intestinal structure or function of noninfected control piglets. In transmissible gastroenteritis-infected piglets, jejunal villi were longer and glucose-facilitated Na absorption was greater after methylprednisolone than after saline treatment. Increased glucose stimulation of Na flux in vitro in the methylprednisolone-treated infected group was not attributable to enhanced Na+-K+-ATPase activity and occurred despite persistence of the virus within mucosal cells, shown by immunofluorescence microscopy. In this piglet model of viral diarrhea, early regeneration of absorptive surface that precedes recovery of disaccharidase function is accelerated by glucocorticoid therapy.

Acute Disease↗

Surgical management of thoracic malignancy in childhood: eight years' experience in Leeds.

During the period 1978 to 1986, 13 children aged 2-15 years underwent surgical resection of malignant thoracic tumours. Five children with neuroblastomas presented with chest pain and infections, pleural effusions, dysphagia, lymphadenopathy and paraplegia. Chemo- and radiotherapy were given preoperatively to previously diagnosed cases and postoperatively to all survivors. At operation, complete tumour clearance was possible in only two cases. Two children remain alive with no sign of recurrence at 6 and 7 1/2 years. Eight children with pulmonary metastases had undergone resection of the primary tumour and systemic chemotherapy. All were asymptomatic and were detected by chest radiographs. Wedge resection or lobectomy was performed. Two required contralateral resections at 4 months. Two children remain alive with no evidence of recurrence at 2 and 6 1/2 years. We conclude that aggressive surgical resection of childhood thoracic malignancy is worthwhile, but cooperation with a paediatric oncology team is essential.

Adolescent↗

Right lower lobe consolidation: an unusual complication of the modified Blalock-Taussig operation.

Persistent right lower lobe consolidation in a 5-year-old girl is described. In infancy she had been diagnosed to have tricuspid atresia and pulmonary stenosis, and she had undergone a modified Blalock-Taussig shunt using a polytetrafluoroethylene tube graft at the age of 1 year. The shunt had parasitized and then occluded the right main bronchus. At bronchoscopy, the shunt was removed. The pneumonia resolved, and the child remains well 10 months later. This complication of the modified Blalock-Taussig shunt, which does not appear to have been reported previously, demonstrates the need for bronchoscopy in unresolving pneumonia in childhood.

Arteriovenous Shunt, Surgical↗

Radionuclide angiography and surgery for familial bilateral chemodectomas.

Carotid body tumours, or chemodectomas, can occur on both sides of the neck (5%), and this bilaterality increases sixfold (30%) where a familial pattern is evident. The known pathological behaviour of chemodectomas makes early recognition and management desirable, especially when an inherited predisposition can be anticipated. Difficulties in clinical diagnosis and the hazards of blind exploration have imposed a reliance on contrast angiography, which is a potentially dangerous procedure. The family tree of a patient with bilateral chemodectomas was traced and 28 individuals were studied using radionuclide angiography (99mTechnetium gluconate), a quick, safe technique with a high yield. Bilateral chemodectomas were observed in five siblings, establishing conclusively the existence of a dominant hereditary trait. Excision of newly discovered tumours was accomplished without complication. The techniques which permitted such a favourable surgical outcome are discussed, emphasising the view that these tumours are best dealt with by vascular surgeons.

Carotid Body Tumor↗

Absence of a cAMP-mediated antiabsorptive effect in an undifferentiated jejunal epithelium.

In the relatively undifferentiated jejunal mucosa occurring in piglet viral enteritis, we measured the response of transepithelial Na+ and Cl- fluxes in vitro to raised intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. At the acute 40-h stage of transmissible gastroenteritis (TGE), luminal membrane markers, sucrase and lactase, and a basolateral jejunal epithelial membrane marker Na+-K+-ATPase, were significantly decreased in activity, while a proliferative marker, thymidine kinase, was significantly enriched; these enzyme characteristics are typical of enterocytes isolated from crypts of other species. As expected, control piglet jejunum in short-circuited Ussing chambers after theophylline (10 mM) developed significant net secretory Na and Cl fluxes primarily due to significant antiabsorptive effects (delta JNa m----s = 3.48 +/- 0.52, delta JCl m----s = 2.59 +/- 0.28). Furosemide (10(-4) M), an inhibitor of electroneutral NaCl cotransport, produced antiabsorptive effects (delta JNa m----s = 2.53 +/- 0.31, delta JCl m----s = 2.58 +/- 0.28) in control jejunum that were not significantly different from those seen in response to theophylline. TGE jejunum, however, responded to theophylline not by an antiabsorptive effect but by significant electrogenic Cl- secretion (delta JCl s----m = 1.59 +/- 0.48); furosemide had no effect on ion fluxes in TGE tissue. Control and TGE jejunal mucosal homogenates did not differ in their basal or theophylline-stimulated levels of cAMP. We conclude that the relatively undifferentiated small intestine occurring in acute TGE does not generate either a cAMP-mediated antiabsorptive effect or a furosemide-mediated antiabsorptive effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The management of psychopathic offenders.

The concept of psychopathic disorders has persisted in mental health legislation despite doubts as to its validity as a diagnosis and its treatability. There is a need for careful selection of those psychopathic offenders most likely to respond to medical treatment in hospital and to admit them under the appropriate section of the Mental Health Act.

Antisocial Personality Disorder↗

Henoch-Schönlein purpura: problems in surgical diagnosis and management.

The clinico-pathological features of 133 consecutive cases of Henoch-Schönlein purpura are presented, with emphasis on the gastrointestinal manifestations. The potential pitfalls of contrast radiography are underlined with respect to management of intussusception and a plea is made to re-establish clinical assessment of the abdomen as the prime indicator in deciding to undertake laparotomy.

Abdomen↗