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Biomedical subjects

W M Clark

Publications and source records attributed to W M Clark.

At least 73 records · Page 4Linked to original sources

Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment.

Activated leukocytes appear to be directly involved in ischemic central nervous system injury. A surface glycoprotein (CD18) on the leukocyte is required for endothelial adherence and subsequent function and can be blocked with leukocyte adhesion antibody treatment. We used two animal models to determine the efficacy of anti-CD18 antibody treatment in preserving neurologic function after central nervous system ischemia. We gave a dose of 1 mg/kg anti-CD18 to treatment rabbits 30 minutes before inducing irreversible ischemia in the brain with intraarterial microspheres or in the spinal cord using reversible aortic occlusion. Treatment with anti-CD18 produced a significant reduction in neurologic deficits in the reversible spinal cord model, but not in the irreversible microsphere model. This protective effect supports the active role of leukocytes in central nervous system reperfusion ischemic injury and offers potential for future therapy.

Animals↗

Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule.

Activated leukocytes appear to be directly involved in potentiating ischemic central nervous system (CNS) injury. Adhesion of leukocytes to endothelium is essential for their migration and requires the binding of adhesion receptors of the leukocyte (CD 18) to an intercellular adhesion molecule (ICAM) on endothelium. Monoclonal antibodies to an ICAM can block leukocyte adhesion and transendothelial migration. To determine the efficacy of anti-ICAM antibody treatment in preserving neurological function after CNS ischemia, two animal models were used. A 1-mg/kg dose of anti-ICAM was given to rabbits 30 minutes before induction of ischemia either in the spinal cord using temporary aortic occlusion or in the brain using intra-arterial microspheres. In this study, treatment with anti-ICAM produced a significant reduction in neurological deficits in the reversible spinal cord ischemia model but not in the irreversible brain ischemia model. This protective effect supports the active role of leukocytes in CNS reperfusion ischemic injury and offers potential for future therapy.

Animals↗

Treatment with conotoxin, an 'N-type' calcium channel blocker, in neuronal hypoxic-ischemic injury.

Therapeutic efficacy of calcium channel blockers in stroke remains controversial, but previously used agents bind almost exclusively to L-type calcium channels. The newly-discovered N-type calcium channel is specific to neurons, and therapy involving blockade of this site has not been previously attempted. We assessed the neuroprotective effect of omega-conotoxin GVIA (CgTx), a blocker of N-type calcium channels, using both in vitro hypoxic injury to rat cortical neurons and an in vivo model of reversible spinal cord ischemia in the rabbit. In cell cultures, CgTx inhibited hypoxia-induced 45Ca accumulation and neuronal injury minimally, compared to the NMDA antagonist ketamine. In vivo, the duration of spinal cord ischemia which produced permanent paraplegia in 50% of control animals (ET50) was 24.0 +/- 2.6 min. Animals treated 2 h prior to ischemia with 0.5 nmol CgTx in the subarachnoid space had an ET50 of 26.9 +/- 1.8 min (P = 0.36). Animals treated 24 h prior to ischemia (all had persistent systemic tremor) had a ET50 of 28.9 +/- 1.8 min (P = 0.13). We conclude that pharmacologic modulation of the N-type calcium channel does not provide a significant protective effect against neuronal hypoxic-ischemic injury.

Animals↗

Incidence of cerebral hemorrhage after treatment with tissue plasminogen activator or streptokinase following embolic stroke in rabbits [corrected].

We studied thrombolysis in an animal model of embolic stroke to determine the safety of tissue plasminogen activator and streptokinase. We occluded the middle cerebral arteries of 137 rabbits with radiolabeled blood clots and administered tissue plasminogen activator (n = 49), streptokinase (n = 40), or saline (n = 48) at various times after embolization. We assessed the rate of thrombolysis and cerebral hemorrhage 24 hours later. Both drugs were very effective in producing thrombolysis. Compared with saline, streptokinase caused a significant increase in the rate of cerebral hemorrhage (p less than 0.05), but tissue plasminogen activator did not. We conclude that thrombolytic therapy for acute stroke should be safer with tissue plasminogen activator than with streptokinase.

Animals↗

Impact of variation in carbohydrate intake on mineral utilization by vegetarians.

Dietary intakes of two groups of vegetarians (of Asian Indian and of American origin) residing in the United States were compared with intakes of a group of nonvegetarians. Mineral intakes and balances were determined for all three groups for a 7-d period. The vegetarians had a significantly higher percent of energy intake from carbohydrate and significantly higher intakes of crude fiber (CF) and neutral detergent fiber (NDF) than did the nonvegetarians. The American vegetarians had significantly higher intakes of magnesium, iron, and copper than did the other groups. Manganese intakes were significantly higher for the two vegetarian groups than for the nonvegetarians. Calcium, iron, zinc, and copper balances were not significantly different among the groups. Magnesium and manganese balances were significantly more negative for the American vegetarians than for the other two groups. In general, the higher percent of carbohydrate intake or the higher level of fiber intake did not appear to affect mineral utilization by the vegetarians.

Adult↗

Mineral balances of men fed a diet containing fiber in fruits and vegetables and oxalic acid in spinach for six weeks.

In an investigation of the effects of fiber and oxalic acid on weekly mineral balances, 12 men consumed two diets consisting of natural foods for 6 wk each in a crossover design. One diet contained about 25 g neutral detergent fiber (NDF) in fruits and vegetables and included 100 g spinach, which is high in oxalic acid, every other day. The second diet was a low fiber diet that contained about 5 g NDF and the same amount of spinach as the first diet. On the basis of mean values for 6 wk, balances for calcium, magnesium, iron, zinc or manganese were not significantly different due to diet. Copper balances were significantly lower when the low fiber diet was consumed than when the diet containing fiber in fruits and vegetables and consequently a higher level of copper was consumed. Mineral balances were significantly different due to week. When results of both diets were considered together, mean mineral balances decreased at some time after wk 1 and returned to the wk 1 level during wk 6. Balances for wk 1 and 6 were not significantly different for any of the six minerals. These results demonstrate the importance of determining weekly balances for several weeks when conducting a human metabolic study.

Adult↗

Monoclonal antibody-defined correlations in melanoma between levels of GD2 and GD3 antigens and antibody-mediated cytotoxicity.

A monoclonal antibody is described that specifically detects the ganglioside antigens GD2 and GD3, binding preferentially to GD2, in melanoma. Antibody specificity was demonstrated with solid-phase radioimmunoassay and enzyme-linked immunosorbent assay as well as by immunostaining on thin-layer chromatography plates using structurally characterized gangliosides. Binding of both the IgG3 antibody and its IgG2a switch variant were assayed on live cells by cytofluorography and by immunoperoxidase staining on frozen tissue sections. The binding patterns correlated with antitumor activity in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays with human effector cells and complement in an 111In-release assay using cell lines derived from the same individual. The significant level of killing in all tumor cells tested that express GD2, GD3, or both, suggests the importance of multiple specificity towards tumor antigens, i.e., binding of a monoclonal antibody to two or more tumor-associated antigens.

Animals↗

Effects of glycine on hemodynamic responses and visual evoked potentials in the dog.

To study the potential contribution of glycine toxicity in the transurethral resection syndrome, we evaluated hemodynamic and visual evoked potential responses to glycine infusion (1 g/kg) in 22 dogs anesthetized with halothane (1.0-1.2% end tidal. Three dogs received 5% glucose in normal saline without glycine; three received arginine (4 mg/kg) in normal saline without glycine; three received arginine (4 mg/kg) in normal saline without glycine; 10 received glycine (1 g/kg), then arginine (4 mg/kg) 120 min after the completion of glycine infusion; and six received arginine 30 min after the completion of glycine infusion. Arginine was infused to evaluate potential antagonistic effects of glycine toxicity. Blood levels of glycine, ammonia, arginine, urea, and formate were determined after infusions of glycine or arginine. All animals received about 5 ml X kg-1 X hr-1 of normal saline during the 2-4 hr of study. Immediately after glycine infusion, cardiac output increased 57%, whereas systemic vascular resistance and mean arterial pressure decreased 32% and 8%, respectively. Later cardiac output and mean arterial pressure were 41% and 18% less than control levels, whereas systemic vascular resistance returned to control levels. Both amplitude and latency of visual evoked potential waveforms were altered in the animals receiving glycine infusion but not in the control animals. These responses were associated with elevations of blood glycine (149 +/- 5 to 9591 +/- 809 microM/L, mean + SEM) and blood NH3 (10.5 +/- 2.8 to 100.0 +/- 13.6 microM/L), but not with formate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗

Fiber intakes, stool frequency, and stool weights of subjects consuming self-selected diets.

Neutral detergent fiber (NDF) contents of duplicate collections of food consumed by 29 men and women were determined for 7 days four times during the year. The ratio of analyzed NDF to calculated crude fiber intakes was approximately 2. Although mean NDF intake was 7.7 g/day for females and 9.5 g/day for males, the majority of the subjects had NDF intakes of from 4 to 9 g/day. Fiber-containing foods consumed with the greatest frequency were vegetables. NDF intakes were greater in the winter than in the spring and summer. Caloric and total carbohydrate intakes, number of stools, and fecal weights were greater for the males than for the females. Fecal weights were significantly correlated with caloric intake, NDF intake, and number of stools. It is suggested that the insoluble fiber measured by the NDF method is likely to be better correlated with fecal weight than the total dietary fiber which includes soluble fibers.

Adult↗

CT demonstration of hyperdense renal carcinoma.

Sharply demarcated homogeneously hyperdense renal lesions have been found to be benign renal cysts, with hemorrhage or a high protein content the most common etiology of the high density. A similar hyperdense renal lesion is presented that was found to be a renal adenocarcinoma. This lesion showed mild contrast enhancement on CT and was found by ultrasound to be a solid mass. The malignant nature of this lesion suggests that further evaluation, such as ultrasound, fine needle aspiration biopsy, or surgery may be needed.

Adenocarcinoma↗

Ultrasound patterns of disorders affecting the gastrointestinal tract.

A mass associated with the gastrointestinal tract was detected by sonography in 33 patients. Etiologies included primary or metastatic tumor; intussusception; inflammation secondary to bowel infarction, pancreatitis, or irradiation; and a dilated, fluid-filled gut related to retained gastric contents, obstruction, ileus, or an ileal bypass. Mesenteric or omental changes were identified with inflammation and frequently with metastatic disease. The diagnosis was confirmed by repeat sonography, abdominal radiography, barium examination of the small bowel, computed tomography, surgery, or autopsy. Ultrasound patterns are characteristic in tumor, intussusception, and inflammation; specific features allowing differentiation between tumor and inflammation are described. Colonic haustra, valvulae conniventes, or bowel contours and peristalsis on real-time sonography are helpful in identifying fluid-filled bowel loops.

Adult↗

Applications of real-time ultrasound in obstetrics: the linear and dynamically focused phased arrays.

Real-time ultrasound is a dynamic imaging technique that allows in utero orientation to the fetus. It permits rapid and efficient examination of fetal anatomy and provides a dynamic assessment of fetal well-being. The energy dissipation can be comparable to that in conventional ultrasonic B-mode scanning. We have used both linear and dynamically focused phased arrays for fetal examinations in conjunction with conventional gray scale B-mode scanners. The sophisticated phased-array real-time systems have demonstrated higher resolution and an improved gray scale as compared with the linear arrays. Applications of real-time ultrasound in obstetrics are discussed, and appropriate clinical examples are cited that illustrate the value of the technique for study of both normal and abnormal fetal development. We believe that this technique is the most sensitive method of detecting intrauterine fetal demise. The relative advantages and disadvantages of linear and dynamically focused phased arrays in obstetric evaluation are considered.

Abdomen↗

Cervical spine trauma: the common combined conditions.

The two most common groups of combined traumatic conditions of the cervical spine are hyperextension and hyperflexion fracture-dislocations. In a series of 400 patients with fractures and/or dislocations of the cervical spine, 25% had hyperextension and 19% hyperflexion fracture-dislocations. A computer analysis of the cases revealed that there are five distinct types of hyperextension and four types of hyperflexion fracture-dislocations. Each of the types is considered as to incidence, causes, mechanism of injury, and roentgen and differential diagnosis.

Cervical Vertebrae↗

The spectrum of small bowel melanoma.

Twenty-one patients with documented secondary small bowel involvement by malignant melanoma are reviewed. Roentgen mainfestations are discussed and illustrated. A vigorous diagnostic approach emphasizing enteroclysis is described. Clinical awareness and aggressive radiologic investigation are providing these patients with earlier surgical and adjuvant therapy, which appears to be leading to increased length of survival.

Adolescent↗

Principles and applications of a dynamically focused phased array real time ultrasound system.

The physical principles and clinical applications of a high-resolution, dynamically focused phased-array real time ultrasound are described. Advantages of the real time technique include rapid survey capability, efficient selection of an appropriate tomographic plane, identification of pulsating structures, and dynamic studies. The capabilities of a high resolution phased array with extended dynamic focusing to a range of 15-20 cm are demonstrated in vascular, abdominal, and obstetric imaging. Appropriate clinical examples showing normal and pathological anatomy are presented. Comparisons with conventional B scans are illustrated.

Abdomen↗

Chronic oesophageal stricture due to moniliasis.

A case of persistent oesophageal stricture due to moniliasis, which developed while the patient was symptomatic, is reported. The value and therapeutic implications of performing a repeat barium swallow even if the disease appears to be quiescent are discussed.

Adolescent↗