Biomedical subjects
Publications and source records attributed to T F Gallagher.
We report a 34-yr-old patient with multiple endocrine neoplasia 2B and achalasia of the cardia who was successfully treated with pneumatic dilation. The various gastrointestinal manifestations of this syndrome are discussed.
Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas-kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6% patient survival (1 cardiovascular death), 97.1% kidney graft survival, and 94.2% pancreas graft survival. Thirty-three evaluated patients (24.1%) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n = 12) and pancreas graft survival after PTA is 83.3 and 50%, respectively. Our conclusion is that a multidisciplinary approach was used for recipient selection for PT based on degree of nephropathy, cardiovascular risk, and presence of diabetic complications. Nearly 75% of diabetic patients evaluated were acceptable candidates for PT. Only 4 (3.8%) of these selected patients died while awaiting or undergoing PT, thus optimizing the use of scarce allograft resources and providing evidence for appropriate patient selection.
We performed fasting and postprandial recordings of antroduodenal manometry in 21 normal volunteers, 13 patients with insulin-dependent diabetes mellitus and gastrointestinal symptoms, and 11 patients with the irritable bowel syndrome. None of the patients or volunteers had previously undergone an intestinal intubation study. Recordings could not be obtained from four of the diabetic patients due to failure to intubate the pylorus. Catheter migration led to incomplete antral data in a further 21% of all recordings. Due to the wide variations demonstrated by the normal volunteers, parameters of either the migrating motor complex (MMC) or the fed response could not differentiate between either of the patient groups and/or the controls. Similarly, while abnormal patterns of either fasting or postprandial motility were common in the diabetic patients, manometry had a sensitivity of only 67% in comparison to the less invasive radionuclide gastric emptying study. Furthermore, manometry failed to identify any diagnostic abnormality in irritable bowel patients; in particular, the incidence of "clustered" contractions was similar in all three groups. We conclude that short duration antroduodenal manometry is of limited diagnostic usefulness due to the difficulties in pyloric intubation in the presence of a dilated stomach and the intrinsic variability in normal motor patterns, perhaps excerbated by the stressful effects of the procedure itself in tube-naive subjects.
UNLABELLED: In the last 2 years, we have performed combined pancreas-kidney transplantation in 38 Type I diabetics with nephropathy. The mean age of the recipient group was 35 years (range 24-51) with a mean duration of diabetes of 22 years (range 13-41). All patients received quadruple immunosuppression with OKT3 induction. All patients are normoglycemic and insulin independent with a mean glycosylated hemoglobin level of 5.2 +/- 1.1% and a mean serum creatinine of 1.9 +/- 0.5 mg/dl. Metabolic effects of pancreas transplantation included fasting hyperinsulinemia and hyperglucagonemia with exaggerated insulin and glucagon responses to glucose and arginine, respectively, that improved slightly with time. Patient and kidney graft survival are 100% and pancreas graft survival is 94.7% after a mean follow-up interval of 15 months. CONCLUSION: Combined pancreas-kidney transplantation is the treatment of choice for selected Type I diabetics with nephropathy and results in euglycemia despite immunosuppression.
Dr. Ruth Harrell and her colleagues conducted a study in 1981 in which the administration of high dosages of vitamins were determined to dramatically improve the intellectual functioning of mentally retarded children. This paper documents the efforts of its authors to replicate the Harrell et al. research and, although no significant differences were found between active treatment groups and control groups at study's end, a thorough comparison is made between the two research efforts.
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Subcutaneous oxygen tension (tissue PO2) was measured by a polarographic method in the legs of insulin-dependent diabetics (IDDM) and controls. Current flow was measured continuously using a five-stage protocol: baseline; 4 min of complete arterial occlusion; during recovery from ischemia; baseline approximately re-established; induction of hyperemia by local application of heat. Eleven patients with IDDM of 4-32 years of duration, without peripheral arterial disease, were studied and compared with 10 controls. The mean baseline subcutaneous PO2 in diabetics was less than controls; however, the difference was not statistically significant. At the end of arterial occlusion the mean decrease in tissue PO2 was less (P less than 0.025) in diabetics (4.7 +/- 0.9 mm Hg, SEM) compared to controls (10.2 +/- 1.6 mm Hg). With induction of hyperemia the increase in tissue PO2 was lower (P less than 0.001) in diabetics (7.4 +/- 0.4 mm Hg) than in controls (18.6 +/- 1.7 mm Hg). The observed differences provide for the first time direct evidence of altered tissue PO2 responses in diabetes.
Chloroplast development in higher plants is light dependent, and is accompanied by the synthesis of chlorophyll and the accumulation of many chloroplast polypeptides. There is a 100-fold greater content of the photosynthetic enzyme, ribulose-1,5-bisphosphate carboxylase-oxygenase, in light-grown seedlings of Pisum sativum than in dark-grown seedlings. Following the illumination of dark-grown seedlings, there is a parallel increase in the content of both the mRNA and the polypeptide of the small subunit of the carboxylase; this subunit is a product of the nuclear genome. The increases in the mRNA and the polypeptide of the large subunit, which is a product of the chloroplast genome, show less synchronicity. Studies with isolated leaf nuclei show that the increase in small subunit mRNA is mediated primarily at the level of transcription. Three distinct effects of light on transcription of small subunit genes have been found; a rapid (approximately 1 h) burst, followed by a decline, when etiolated plants are first exposed to light; a slow (approximately 36 h) development of the competence to transcribe rapidly after the initial burst; rapid (approximately 20 min) switches in both directions when fully greened plants are exposed to light-dark transitions.
Amniotic fluid and maternal plasma volumes were estimated in high-risk obstetric patients suspected of being hypovolemic. Excluding cases of intrinsic maternal or fetal disease, there were good (P less than 0.001) correlations between maternal plasma volume expansion and amniotic fluid volume. In the presence of oligohydramnios, there is usually maternal hypovolemia, and vice versa. Oligohydramnios may often be corrected by vigorous maternal plasma volume expansion, which is sometimes indicated in the treatment of cases of fetal distress. It is presumed that only when maternal plasma volume expansion is normal, is uterine perfusion sufficient to provide amniotic fluid formation in normal amounts. The varying amounts of amniotic fluid seen in normal pregnancies at term probably reflect the varying fetal activities of swallowing and voiding.
Nuclei isolated from both light-grown and dark-grown leaves of Pisum sativum by Percoll density gradient centrifugation incorporate labelled UTP into RNA when supplemented with the other three nucleoside triphosphates. The RNA is heterodisperse, with transcripts up to at least 25S in size. Among these transcripts are sequences hybridizing to cloned DNA probes for wheat rRNA and two abundant chloroplast polypeptides of Pisum, viz. the small subunit of ribulose bisphosphate carboxylase and a polypeptide of the light-harvesting chlorophyll a/b binding complex. Transcription of small subunit and light-harvesting complex sequences is greater (18-fold and 9-fold, respectively) in nuclei from light-grown leaves than in nuclei from dark-grown leaves. Transcription of ribosomal genes, by contrast, is only doubled by growth in the light. Small subunit and light-harvesting complex sequences transcribed in dark-grown nuclei are not degraded in a 120 min chase. These results suggest that the stimulation of accumulation of small subunit and light-harvesting complex mRNAs by exposure of Pisum seedlings to light is mediated by an increase in transcription rather than by a decrease in RNA degradation.
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Eight patients are presented in whom obesity developed in association with documented hypothalamic lesions. These lesions included trauma, inflammatory disease, an aneurysm of the internal carotid artery, and five cases of tumor. Detailed metabolic studies were performed in four patients with hypothalamic obesity and in five age- and weight-matched patients with essential obesity(i.e., obesity with no definable etiology). Fasting insulin concentrations were significantly higher in the patients with hypothalamic obesity. During a seven-day fast the insulin levels in patients with essential obesity decreased by 24 to 48 hours, whereas patients with hypothalamic obesity showed a variety of changes; In three out of four of these patients with hypothalamic obesity there was no evidence for hyperplasia of the fat cells. Basal oxygen consumption, body composition, and metabolism of adipose tissue did not differ between the patients with essential obesity and those with hypothalamic obesity. There was no difference in activity of the enzymes in the glycerophosphate cycle. Our data on eight patients with hypothalamic obesity were compared with data on patients in literature. Most cases of hypothalamic obesity occur with space-occupying tumors arising at the base of the hypothalamus. However, trauma, inflammatory diseases, and leukemia are also associated with hypothalamic obesity. Patients with hypothalamic obesity rarely weigh more than 140 kg.
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Patients with the genetic liver disease, acute intermittent porphyria (AIP), have a defect in the reductive transformation of steroid hormones that is manifest by the disproportionate generation of 5beta-steroid metabolites from precursor hormones. 5beta-steroid metabolites were earlier shown to be potent inducers experimentally of delta-aminolevulinate synthetase (ALAS), the mitochondrial enzyme that is rate-limiting in porphyrin synthesis, and that is found at high levels of activity in the livers of AIP patients. In this report, the basis for the defective steroid metabolism in AIP has been shown, through studies with the (14)C-labeled adrenal hormone 11beta-hydroxy-Delta(4)-androstenedione, to reside in a substantial deficiency of hepatic steroid Delta(4)-5alpha-reductase activity. This enzymic deficiency was found in all seven AIP patients studied, and ranged from 34% to as much as 70% below the mean enzyme activity characterizing normal subjects. The functional consequence of the low levels of 5alpha-reductase activity in AIP is to divert the reductive transformation of certain natural hormones from the 5alpha- to the 5beta-pathway; the latter is the metabolic route through which endogenous steroids having the potential for inducing hepatic ALAS are generated. It is not presently known whether the 5alpha-reductase deficiency in AIP is acquired in some fashion or whether it has partial genetic determinants. It seems probable, however, that this enzymatic abnormality, coupled with the dramatic increase in hormone synthesis that occurs at puberty, may be of major importance in determining clinical expression of the latent gene defect for AIP in many individuals. The 5alpha-reductases for steroid hormones are known to be localized in the endoplasmic reticulum of hepatic cells and the present findings in AIP thus represent the first demonstration that an enzymic component of these membranous structures is functionally abnormal in this hereditary liver disease.
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