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Biomedical subjects

D Sherman

Publications and source records attributed to D Sherman.

At least 55 records · Page 3Linked to original sources

A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor.

Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent survival factors for sympathetic, sensory and central nervous system neurons. GDNF mediates its actions through a multicomponent receptor system composed of a ligand-binding glycosyl-phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) and the transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which the NTN signal is transmitted is not well understood. Here we describe the identification and tissue distribution of a GPI-linked protein (designated NTNR-alpha) that is structurally related to GDNFR-alpha. We further demonstrate that NTNR-alpha binds NTN (K[d] approximately 10 pM) but not GDNF with high affinity; that GDNFR-alpha binds to GDNF but not NTN with high affinity; and that cellular responses to NTN require the presence of NTNR-alpha. Finally, we show that NTN, in the presence of NTNR-alpha, induces tyrosine-phosphorylation of Ret, and that NTN, NTNR-alpha and Ret form a physical complex on the cell surface. These findings identify Ret and NTNR-alpha as signalling and ligand-binding components, respectively, of a receptor for NTN and define a novel family of receptors for neurotrophic and differentiation factors composed of a shared transmembrane protein tyrosine kinase and a ligand-specific GPI-linked protein.

Amino Acid Sequence↗

Fetomaternal haemorrhage discovered after trauma and treated by fetal intravascular transfusion.

Fetomaternal haemorrhage can occur spontaneously, or after abdominal trauma. We describe a case of fetomaternal haemorrhage diagnosed at 27 weeks gestation after blunt trauma. The Kleihauer-Betke smear on admission and during the first week was positive, ranging between 3% and 5%. Cordocentesis revealed a fetal haemoglobin of 8.8 gm/dl. An intravascular fetal transfusion was performed. The weeks until delivery and the neonatal period were unremarkable. Fetal anaemia can be a serious complication of fetomaternal haemorrhage, however, intravascular fetal transfusion is an effective treatment when this occurs. The Kleihauer-Betke test should be performed in every patient with a history of abdominal trauma during pregnancy.

Adult↗

Cytomegalovirus gB genotype distribution differs in human immunodeficiency virus-infected patients and immunocompromised allograft recipients.

Cytomegalovirus isolates can be grouped into 4 gB and 2 gH genotypes. gB genotypes were studied in patients infected with human immunodeficiency virus (HIV) and in allograft transplantation recipients. In allograft recipients, the distribution of gB 1, -2, -3, and -4 in leukocytes and urine, respectively, was 36%, 21%, 43%, and 0% and 39%, 30%, 17%, and 13%. However, in leukocytes of HIV-infected patients with <100/microL CD4 cells, gB1 was found significantly less often than in allograft recipients (11% vs. 36%) but gB2 was more frequent (56% vs. 21%; P < .05). The decreased incidence of gBl and increased incidence of gB2 compared with allograft recipients was also seen in urine of HIV-infected patients and reflected the distribution seen in leukocytes. gB4 was found significantly more often (P < .05) in semen than in leukocytes of HIV-infected patients with < 100/microL CD4 cells. gB1-4 genotypes were similar in patients with < 100/microL CD4 cells with or without retinitis.

AIDS-Related Opportunistic Infections↗

Variations in colon and rectal surgical mortality. Comparison of specialties with a state-legislated database.

PURPOSE: This study was designed to examine variations in operative mortality among surgical specialists who perform colorectal surgery. METHODS: Mortality rates were compared between six board-certified colorectal surgeons and 33 other institutional surgeons using comparable colorectal procedure codes and a validated database indicating patient severity of illness. Thirty-five ICD-9-CM procedure codes were used to identify 2,805 patients who underwent colorectal surgery as their principal procedure between July 1986 and April 1994. Atlas, a state-legislated outcome database, was used by the hospital's Quality Assurance Department to rank the Admission Severity Group (ASG) of 1,753 patients from January 1989 to April 1994 (higher ASG, 0 to 4, indicates increasing medical instability). RESULTS: Colorectal surgeons had an eight-year mean in-hospital mortality rate of 1.4 percent compared with 7.3 percent by other institutional surgeons (P = 0.0001). There was a significantly lower mortality rate for colorectal surgeons compared with other institutional surgeons in ASG 2 (0.8 and 3.8 percent, respectively; P = 0.026) and ASG 3 (5.7 and 16.4 percent, respectively; P = 0.001). CONCLUSIONS: Board-certified colorectal surgeons had a lower in-hospital mortality rate than other institutional surgeons as patients' severity of illness increased.

Colon↗

A duodenal mucosal abnormality in the reduction of Fe(III) in patients with genetic haemochromatosis.

BACKGROUND: Previous in vitro studies have shown that the uptake of Fe(III) by freshly isolated duodenal mucosal biopsy specimens is increased in patients with genetic haemochromatosis. Moreover, in the mouse it has recently been found that reduction of Fe(III) to Fe(II) is a prerequisite for iron uptake by the proximal intestine. AIMS/METHODS: This study used the in vitro technique to investigate the rates of reduction and uptake of 59Fe(III) by duodenal mucosal biopsy specimens obtained at endoscopy from treated and untreated patients with genetic haemochromatosis. RESULTS: The rate of reduction of iron in the medium was proportional to the incubation time and was not caused by the release of reducing factors from the tissue fragments. Ferrozine, a specific Fe(II) chelator and ferricyanide, a non-permeable oxidising agent, inhibited uptake of 59Fe showing that reduction of Fe(III) precedes uptake. The rates (all values given as pmol/mg/min) of reduction (152 (49) v 92 (23)) and uptake (8.3 (4.0) v 3.6 (1.3), mean (SD)), were significantly increased in biopsy specimens from the untreated group (n = 6) compared with those from 10 control subjects (p < 0.04). Furthermore, the reduction and uptake rates were still increased in five patients in whom iron stores were normal after venesection treatment. CONCLUSIONS: These results show that there is a persistent abnormality in the reduction and uptake of iron by the intestine in genetic haemochromatosis.

Analysis of Variance↗

Social support and patterns of adjustment to breast cancer.

The effect of marital support and support from other adults on the emotional and physical adjustment of 128 women with breast cancer was examined. Role function and satisfaction with health care also were evaluated as predictors of adjustment. Intact data series were obtained at 7-10 days, at 1, 2, 3, and 6 months, and 1 year postsurgery. Emotional adjustment could be predicted by satisfaction with a spouse's response to interactional and emotional needs and by support from other adults. The relationships were significant at concurrent times, across contiguous times, and predicting from the 7-10 day postsurgical period to both the 6-month and 1-year end points. Physical adjustment was not predicted by support but satisfaction with health care was predictive of perceived overall health status. Functional status in vocational, domestic, and social roles was significantly related to emotional and physical adjustment at all phases with few exceptions.

Adaptation, Psychological↗

Differential effects of flumazenil in alcoholic and nonalcoholic cirrhotic patients.

Ligands to the benzodiazepine receptor (BZR) accumulate in hepatic encephalopathy; the benzodiazepine antagonist flumazenil can reverse some manifestations of this condition. This study was designed to explore the effects of flumazenil on cognitive function and anxiety levels in cirrhotic patients without hepatic encephalopathy. Twenty such patients--ten alcoholic, ten nonalcoholics--and ten normal volunteers matched for age and sex were randomly allocated to treatment order (flumazenil or placebo first) in a double-blind cross-over trial. Cognitive function was evaluated with a battery of psychological tests shown previously to be sensitive to the impairment induced by liver disease. Cirrhotic patients performed worse than controls on several tests: digit cancellation, digit symbol substitution, key tapping and Reitan's trail B test. Flumazenil did not reverse these cognitive impairments but it did induce anxiety in nonalcoholic cirrhotics. On one index of memory--delayed word recall--alcoholics performed worse than nonalcoholic cirrhotics. Flumazenil reversed this memory impairment in the alcoholic cirrhotic group. These results suggest that alcohol consumption induces changes at the BZR that are different from changes induced solely by liver impairment.

Adult↗

No association between the c2 allele at the cytochrome P450IIE1 gene and alcohol induced liver disease, alcohol Korsakoff's syndrome or alcohol dependence syndrome.

Cytochrome P450IIE1 metabolises, and is induced by ethanol. The 5' regulatory sequence of the gene is polymorphic; that identified by the c2 allele has been shown by transfection studies to confer an increased rate of transcription. A recent report indicating an association between this allele and alcohol induced cirrhosis suggests that it may contribute to the genetic vulnerability to this disease. We have examined this polymorphism in patients of western European origin with alcohol induced cirrhosis, alcohol Korsakoff's syndrome and alcohol dependence syndrome. We were unable to detect any association between this allele and any of these diseases.

Alcohol Amnestic Disorder↗

Noninvasive monitoring of cardiac output by Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage.

OBJECTIVE: To assess the validity and potential clinical utility of cardiac output monitoring using Doppler echocardiography in patients treated with volume expansion after subarachnoid hemorrhage. DESIGN: Observational study of patients in a randomized, clinical trial. SETTING: Neurologic intensive care unit. PATIENTS: Simultaneous, blinded measurements of cardiac output by thermodilution and Doppler echocardiography were performed in 48 patients 1 or 2 days after aneurysmal clipping. Follow-up Doppler echocardiography was performed an average of 3.9 days later (range 3 to 6) in 15 patients assigned to normovolemia and 24 patients assigned to hypervolemia. INTERVENTION: Patients received supplemental 5% albumin in order to maintain increased (hypervolemia) or normal (normovolemia) cardiac filling pressures. MEASUREMENTS AND MAIN RESULTS: The overall degree of correlation between the two measures was moderate (r = .67, r2 = .45, p < .0001). Bias and precision calculations (-0.75 +/- 1.34 L/min) showed a tendency for Doppler echocardiography to underestimate thermodilution, particularly when cardiac output was very high. Although hypervolemia patients received more 5% albumin than normovolemia patients, mean percent change in Doppler echocardiography cardiac output did not differ between the two groups. Multiple regression analysis showed that the percent change in Doppler echocardiography cardiac output correlated strongly with changes in heart rate (p < .0001), but not with daily net fluid balance or 5% albumin administration. CONCLUSIONS: Agreement was poor between Doppler echocardiography and thermodilution measurements of cardiac output, and trends reflected variations in heart rate rather than fluid status. Monitoring of cardiac output by this technique cannot be recommended in patients treated with volume expansion after subarachnoid hemorrhage.

Adult↗

Acute, reversible left ventricular dysfunction in status asthmaticus.

Three cases of rapidly reversible severe myocardial depression are described in patients with status asthmaticus. Initial echocardiograms obtained within 1 day of hospital admission revealed global left ventricular hypokinesis with ejection fractions of 11 to 34%. Follow-up echocardiograms obtained only 3 to 8 days later revealed marked improvement of left ventricular function. Possible mechanisms responsible for the observed rapidly reversible myocardial depression and the clinical implications of this finding are discussed.

Adult↗

Electrocardiographic markers of abnormal left ventricular wall motion in acute subarachnoid hemorrhage.

A reversible and presumably neurogenic form of myocardial dysfunction may occur following subarachnoid hemorrhage (SAH), but the relationship of this finding to electrocardiographic abnormalities remains unclear. To clarify this issue, serial electrocardiograms (ECGs, mean 6.2 per patient) and echocardiograms (mean 3.4 days after SAH) were obtained in 57 SAH patients without preexisting cardiac disease. The goal was to determine which specific electrocardiographic changes, if any, reflect abnormal left ventricular wall motion in acute SAH. Wall motion abnormalities were identified in five (8%) of 57 patients. Four of these affected patients experienced hypotension (systolic blood pressure < 100 mm Hg) and three exhibited pulmonary edema within 6 hours of SAH, compared to none of the 52 patients with normal wall motion (p < 0.0001). Patients with abnormal wall motion were more likely than patients with normal echocardiograms to have symmetrical T wave inversion (five of five vs. seven of 52, p < 0.001) and severe (> or = 500 msec) QTc segment prolongation (five of five vs. three of 52, p < 0.001) on serial ECGs. These associations maintained their significance with analysis limited to single ECGs performed on or near the day of echocardiography. Abnormal wall motion was also associated with borderline (2% to 5%) creatine kinase MB elevation (five of five vs. three of 52, p < 0.001) and poor neurological grade (p < 0.0001). Although no combination of findings on a single ECG resulted in 100% sensitivity for abnormal wall motion, the presence of either inverted T waves or severe QTc segment prolongation on serial ECGs was associated with 100% sensitivity and 81% specificity. These results demonstrate an association between reduced left ventricular systolic function, mild creatine kinase MB elevation, and electrocardiographic repolarization abnormalities in acute SAH. Symmetrical T wave inversion and severe QTc segment prolongation best identified patients at risk for myocardial dysfunction and may serve as useful criteria for echocardiographic screening following SAH.

Acute Disease↗