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Biomedical subjects

S McGee

Publications and source records attributed to S McGee.

48 records · Page 3Linked to original sources

Senior surgeons and radiologists should assess emergency patients on presentation: a prospective randomized controlled trial.

The objective of this study was to determine whether abdominal ultrasound and plain film radiography (evaluated by senior radiologists) substantially enhances senior surgical assessment in reducing surgical admissions. A randomized controlled trial was carried out in a teaching hospital; ninety-five emergency referrals to general surgery (mean age 51 years, 37% males), presenting with intrabdominal disturbances not requiring immediate surgery, were selected for study. The major outcome measure was the number of patients not admitted as in-patients. Thirty per cent of the intervention group and 10% of the controls did not need admission (95% confidence interval on this 29% difference, 12-38%). There were no important differences in the mean waiting time in casualty (26 min vs. 25 min), length of admission (4.1-5.9 days), surgical intervention (seven vs. 11 patients), readmission with similar pathology within 3 months (seven vs. three patients), and mortality as an in-patient or within 3 months of discharge. Abdominal ultrasound and plain film radiography, assessed by senior radiologists, enhances senior surgical assessment in reducing unnecessary surgical admissions.

Abdomen↗

Differential use of protein 4.1 translation initiation sites during erythropoiesis: implications for a mutation-induced stage-specific deficiency of protein 4.1 during erythroid development.

Expression of multiple protein 4.1 isoforms in erythroid progenitors and in a variety of nonerythroid tissues results from alternative pre-mRNA splicing. In 4.1 pre-mRNA, several translation initiation sites are present; synthesis of isoforms larger than 80 kD occurs when an upstream 5' AUG is spliced in, whereas the 80-kD mature erythroid isoform is produced when the upstream AUG is spliced out and translation is initiated at the downstream AUG. During erythropoiesis, this splicing switch is developmentally regulated. We studied this developmental switch in hereditary elliptocytosis 4.1Alg, in which a DNA rearrangement involving the exon containing the downstream AUG results in loss of coding capacity for the 80-kD 4.1, leading to mature red blood cells deficient in 4.1 with decreased membrane mechanical stability. Analysis of erythroblast RNA by reverse transcriptase-polymerase chain reaction showed that, although it retained the upstream AUG, its coding region was approximately 2.2 kb, compared with approximately 2.5 kb of normal 4.1 mRNA, because of the deletion of exons, including the one that codes for the downstream AUG. Immunofluorescent microscopy and Western blot analysis documented protein 4.1 expression in HE 4.1Alg erythroblasts. These studies emphasize the crucial role of differentiation-regulated RNA splicing because, within the same erythroid tissue, the HE 4.1Alg phenotype did not appear until after the differentiation-associated splicing event.

Base Sequence↗

Role of fine-needle aspiration cytology and needle-core biopsy in the diagnosis of lobular carcinoma of the breast.

Fine-needle aspiration cytology (FNAC) plays a key role in the preoperative diagnosis of carcinoma of the breast but is less reliable in the diagnosis of infiltrating lobular carcinoma. The method of diagnosis was reviewed in 56 patients with lobular carcinoma who had attended screening and symptomatic clinics. In 29 patients FNAC results demonstrated malignant cells; 15 of these had palpable disease and the mean tumour size was 21 mm. In 27 patients FNAC failed to demonstrate malignant cells; 13 lesions were palpable and the mean tumour size was 23 mm. Ten patients were diagnosed by needle-core biopsy when FNAC was not diagnostic. FNAC may fail to diagnose even large lobular carcinoma and needle-core biopsy is strongly recommended in this situation.

Aged↗

Quantification of evacuation proctography.

PURPOSE: This study was designed to determine if evacuation proctography provides a clinically acceptable estimate of the time and completeness of rectal evacuation. METHODS: Rectodynamics, using a weight transducer and chart recorder to quantify the weight and rate of contrast expelled, was combined with evacuation proctography to assess agreement between the evacuation times recorded and the weight of contrast expelled compared with the lateral area change on proctography. RESULTS: Mean difference of evacuation times measured by the techniques was 0.1 seconds and the standard deviation of the differences was 1.9 seconds with 95 percent agreement limits of +/- 3.9 seconds. The mean difference between the percentage of contrast evacuated by weight and the change in rectal area on proctography was 4.3 percent. The standard deviation of the differences was 11.9 percent with 95 percent agreement limits of -19.5 percent and +28.1 percent. CONCLUSION: Evacuation proctography provides a valid estimation of the time and completeness of rectal evacuation.

Barium Sulfate↗

Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit.

BACKGROUND: We hypothesized that: (1) endogenous adenosine released during ischemia/reperfusion reduces infarct size and preserves postischemic myocardial blood flow by receptor-mediated mechanisms and (2) this cardioprotection is exerted predominantly during reperfusion. METHODS AND RESULTS: Sixty-one anesthetized open-chest rabbits subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion were randomized to six groups: group 1, saline (Vehicle) (n = 10) to allow receptor interaction of endogenous adenosine (Ado) during ischemia/reperfusion; group 2, Ado-receptor blockade during both ischemia and reperfusion with intravenous 8-p-sulfophenyltheophyl-line (10 mg/kg) (SPTIR, n = 10); group 3, Ado-receptor blockade in multiple doses during both ischemia and reperfusion (MSPTIR, n = 11); group 4, blockade during reperfusion (SPTR, n = 10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n = 10); and group 6, blockade after 30 minutes of reperfusion (SPT30R, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at risk (Ar) (15-microns radiolabeled microspheres) was reduced by 96.7% in all groups, from 137.9 +/- 15.5 to 4.5 +/- 1.4 mL.min-1 x 100 g-1 (P < .001). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144 +/- 18, 141 +/- 22, and 144 +/- 20 mL.min-1 x 100 g-1, respectively) compared with Vehicle (257 +/- 40 mL.min-1 x 100 g-1, P < .05). This attenuation was more pronounced in the necrotic zone than in the nonnecrotic zone. Reactive hyperemia at 15 minutes of reperfusion in SPT30R group was comparable to the Vehicle group. At 120 minutes of reperfusion, blood flow in Ar was significantly less in MSPTIR (77 +/- 10), SPTIR (82 +/- 9), and SPTR (80 +/- 11) compared with Vehicle (140 +/- 12) and SPT30R (105 +/- 24 mL.min-1 x 100 g-1). Infarct size (by triphenyltetrazolium chloride), expressed as a percent of Ar, was largest in the multiple-dose group with blockade during both ischemia and reperfusion (MSPTIR, 51.9 +/- 2.3%) and was significantly increased also in single-dose SPTIR (39.1 +/- 2.2%) compared with 25.7 +/- 1.7% in the Vehicle group (P < .05). Ado-receptor blockade only during reperfusion was associated with 14% smaller infarct size in the SPTR group than the MSPTIR group (P < .05). In contrast, Ado-receptor blockade after 30 minutes of reperfusion (SPT30R) did not increase infarct size (27.9 +/- 2.2%), which was comparable to infarct size in the Vehicle group. CONCLUSIONS: We conclude that: (1) endogenous adenosine released from the myocardium during ischemia/reperfusion reduces infarct size by receptor-mediated mechanisms and (2) Ado-mediated cardioprotection is most pronounced during the early phase of reperfusion.

Adenosine↗

Differentiation-associated switches in protein 4.1 expression. Synthesis of multiple structural isoforms during normal human erythropoiesis.

Erythroid differentiation is accompanied by dramatic alterations in morphology and membrane mechanical properties resulting, in large part, from reorganization of the membrane skeletal protein network. The 80-kD protein 4.1 is an important organizational component of this membrane skeleton. Recently, it has been recognized that multiple structural isoforms of 4.1 are encoded by a single gene via alternative pre-mRNA splicing, and that an upstream ATG can be spliced in and used for translation of high molecular weight 4.1. We are exploring the hypothesis that differentiation-associated switches in protein 4.1 structure play an important role in membrane reorganization. To study changes in 4.1 gene expression during normal human differentiation, we analyzed 4.1 protein and mRNA structure at various developmental stages. Using immunofluorescence microscopy, we observed high molecular weight 4.1 isoforms in preproerythroblasts producing punctate, predominantly cytoplasmic staining with a perinuclear area of intense fluorescence, while mature red cells expressed very little high molecular weight 4.1. Isoforms containing an alternatively expressed 102-nucleotide exon near the COOH terminus were abundant in both preproerythroblasts and mature cells but produced a punctate distribution of fluorescence over the entire preproerythroblast and intense membrane-associated fluorescence in the erythrocyte. Characterization of RNA by polymerase chain reaction and nuclease protection assays revealed a differentiation-associated switch in pre-mRNA splicing in the spectrin-actin binding domain. Since this domain plays a critical role in regulating membrane material properties, we speculate that this switch may be crucial to reorganization of the skeletal network during erythropoiesis. We conclude that 4.1 isoforms are differentially expressed and differentially localized during erythropoiesis, and that this isoform family is likely to have diverse functions during terminal differentiation.

Alternative Splicing↗

Hydrostatic balloon dilatation of benign colonic anastomotic strictures.

From 1985 to 1990, 25 patients with benign colorectal anastomotic strictures were treated. The majority of the patients presented with decreasing stool caliber and abdominal cramps. Most of the strictures were secondary to anastomosis utilizing the EEA stapling device (United States Surgical Corp., Norwalk, CT) for malignant neoplasm. Under IV sedation, strictures were dilated endoscopically with the TTS balloon (Microvasive). No complications were encountered in this series. Hydrostatic balloon dilatation is a safe and effective modality for treatment of anastomotic strictures.

Aged↗

Myocardial protective effects of adenosine. Infarct size reduction with pretreatment and continued receptor stimulation during ischemia.

BACKGROUND: We hypothesized that 1) endogenous adenosine released during ischemia conferred an inherent cardioprotection, and 2) a pretreatment dose of adenosine before ischemia would provide additional protection independent of hemodynamic effects. METHODS AND RESULTS: Thirty-six anesthetized New Zealand White rabbits underwent 30 minutes of regional ischemia produced by coronary occlusion followed by 2 hours of reperfusion. The adenosine group (ADO, n = 9) received a 5-minute pretreatment infusion of 140 micrograms/kg/min of adenosine before ischemia. A control group (SAL, n = 9) received saline before ischemia. To separate the effects of adenosine used as a pretreatment versus the effects during ischemia, a third group (ADO+SPT, n = 9) received adenosine as pretreatment followed by 10 mg/kg 8-p-sulfophenyl theophylline (8-SPT), an A1/A2-receptor antagonist given before ischemia, thus allowing pretreatment with adenosine but antagonizing its effects during ischemia. To preclude any protection from endogenous adenosine released during ischemia, the fourth group (SAL+SPT, n = 9) received saline as pretreatment and 8-SPT before ischemia. Area of necrosis within the area at risk (infarct size) was determined with tetrazolium and Evans blue stains, and transmural blood flow was measured using radioactive microspheres. Collateral blood flow in the area at risk was similar in all groups, as was the size of the area at risk. Infarct size was reduced by adenosine pretreatment (ADO, 8.4 +/- 7.2%) in contrast to saline vehicle (SAL, 27.8 +/- 6.3%; p less than 0.05 versus ADO). alpha 1/alpha 2-Receptor blockade after adenosine pretreatment abolished the ischemic protection provided by pretreatment adenosine (ADO+SPT, 42.7 +/- 8.3%; p less than 0.05 versus ADO). Finally, receptor blockade of endogenously released adenosine without adenosine pretreatment increased infarct size by 24% over the nonpretreated saline group (SAL+SPT, 51.5 +/- 9.0%; p less than 0.05 versus SAL). CONCLUSIONS: We conclude that 1) endogenous adenosine building up during ischemia is cardioprotective, and 2) pretreatment with adenosine confers cardioprotection independent of hemodynamic effects. Whether pretreatment effects of adenosine subsequently modulate the effects of endogenous adenosine (through alterations in receptor population or sensitivity) or endogenous and exogenous adenosine represent additive compartments is unclear.

Adenosine↗

Functional chiral asymmetry in descending thoracic aorta.

To determine whether rotational blood flow or chiral asymmetry exists in the human descending thoracic aorta, we established the ability of color Doppler ultrasound to detect rotational flow in a tornado tube model of a vortex descending fluid column. In a model of the human aortic arch with a pulse duplicator, color Doppler was then used to demonstrate that rotational flow occurs first in the transverse arch and then in the proximal descending thoracic aorta. With the use of color Doppler esophageal echocardiography, 53 patients (age range, 25-78 years; mean age, 56.4 years) were prospectively examined for rotational flow in the descending thoracic aorta. At 10 cm superior to retro-left ventricular position, 22 of 38 patients (58%) revealed rotational flow with obvious diastolic counterclockwise rotation but less obvious systolic clockwise rotation. At 5 cm superior to retro-left ventricular position, 29 of 46 patients (63%) revealed rotational flow with a tendency toward systolic clockwise and diastolic counterclockwise rotation. At the retro-left ventricular position, 47 of 53 patients (89%) revealed rotational flow, usually of a clockwise direction, occurring in systole. Our data suggest that aortic flow is not purely pulsatile and axial but has a rotational component. Rotational flow begins in the aortic arch and is carried through to the descending thoracic aorta, where flow is chirally asymmetric with systolic clockwise and diastolic counterclockwise components. These data demonstrate an aortic rotational flow component that may have physiological implications for organ perfusion.

Adult↗

Immune complex disease. VII. Experimental mesangiopathic glomerulonephritis produced by chronic immunization with thyroglobulin.

Immunohistologic and electron microscipic studies were performed on the kidneys of rabbits given daily intravenous injections of porcine thyroglobulin in amounts adjusted to the immune response of the individual rabbits. Glomerular lesions were restricted to the mesangium, were characterized by varying degrees of proliferation of mesangial cells and increase of mesangial matrix, and were accompanied by accumulations of rabbit immunoglobulins, C3, and porcine thyroglobulin. Electron-dense deposits were localized to the mesangium and the adjacent subendothelial space. Less than 10 per cent of the animals with mesangila lesions developed obvious impairment of glomerular function. Thyroglobulin-containing immune complexes were found to be rapidly removed from the mesangium, so that overloading of the mesangium and consequent accumulation of complexes in the adjacent capillary loops could not occur. Thus, the results provide further evidence that when immune complex deposition is restricted to the mesangium, relatively little interference with glomerular function results. This situation is paralleled in man by the lesions of subclinical lupus nephritis, chance proteinuria and hematuria, and the early lesions of Berger's disease.

Animals↗

Antibasement membrane disease. II. Mechanism of glomerular injury in an accelerated model of Masugi nephritis.

Rabbits were given injections of preformed complexes of purified goat antirabbit glomerular basement membrane antibody and rabbit antigoat immunoglobulin. When the animals were killed 24 hours later, examination of their kidneys revealed diffuse glomerulonephritis with widespread areas of localized loop necrosis, associated with extensive accumulations of polymorphonuclear leukocytes. By electron microscopy, accumulations of polymorphonuclear leukocytes in various degrees of disintegration were associated with areas of the basement membrane that appeared to be losing their structural integrity, suggesting that the damage to the membrane was brought about by the action of lysosomal enzymes. Reduction of the number of circulating polymorphonuclear leukocytes by pretreatment of the animals with nitrogen mustard completely prevented the lesions. Reduction of circulating complement levels by pretreatment of the animals with cobra venom factor prevented the occurrence of localized necrosis but allowed the development of the diffuse lesion.

Animals↗