PubMed HealthSearch

Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 37 records · Page 2Linked to original sources

Modulation by cytosolic pH of calcium and rubidium fluxes in rat pancreatic islets.

Cytosolic pH (pHi) of pancreatic islet cells was assessed using the fluorescent dye 2'7'-biscarboxyethyl-5'(6')-carboxyfluorescein (BCECF). pHi was rapidly lowered by addition of the sodium salt of a weak acid or by treatment with amiloride. In the latter case, no recovery of pHi occurred. NH4Cl produced a rise in pHi. Stimulation of islet cells with glyceraldehyde produced a sustained fall in pHi, whereas glucose and alpha-ketoisocaproate caused a small, gradual rise in pHi. Intracellular acidification, particularly with amiloride, resulted in an immediate potentiation of glucose-induced insulin secretion from perifused islets. In the case of weak acid treatment, subsequent removal of the weak acid produced a paradoxical stimulation of insulin release which was not observed upon removal of amiloride. NH4Cl produced a transient stimulation followed by a reduction in the rate of glucose-induced insulin secretion. A reduction in pHi, either in response to weak acid or amiloride treatment, was associated with a diminution in the rate of efflux of 86Rb+ and of 45Ca2+. Removal of weak acid produced a marked "rebound" stimulation of 86Rb+ and 45Ca2+ efflux. Treatment of islets with NH4Cl, either in the presence or absence of glucose or Ca2+, resulted in a marked stimulation of efflux of 86Rb+ and 45Ca2+. The stimulatory effect of NH4Cl on 45Ca2+ efflux was markedly impaired in the absence of Na+. It is concluded that pHi can influence the secretory activity of pancreatic islets, possibly via effects on potassium permeability and sodium-calcium exchange across the plasma membrane, resulting in altered mobilisation of calcium in the islet cell. However, it is unlikely that glucose or other nutrient stimuli activate islets solely via an effect on pHi.

Amiloride

Phase I trial and clinical pharmacological evaluation of hexamethylene bisacetamide administration by ten-day continuous intravenous infusion at twenty-eight-day intervals.

We have treated 33 patients with different types of advanced cancer by 10-day continuous i.v. infusion courses of hexamethylene bisacetamide (HMBA), a drug that produces differentiation of a variety of transformed cell lines on prolonged exposure in vitro to drug concentrations of 3 to 5 mM. In this dose-finding and pharmacokinetic study, five dosage levels were explored from 12 to 28 g/m2/day. Patients who had not shown progression of disease were given repeat courses of therapy at 28-day intervals. Seventy-two courses of therapy were administered; 17 patients received one course; eight patients received two; six patients received three; and one patient each received four and 17+ courses, respectively. The maximal tolerated dose was 28 g/m2/day for 10 days; the dose-limiting toxic effects were thrombocytopenia with hemorrhage and central nervous system dysfunction manifesting as disorientation and confusion. Based on these studies the recommended dosage for Phase II studies by the 10-day schedule is 24 g/m2/day. Pharmacokinetic studies demonstrated rapid clearance of HMBA from plasma; the decay phase data fit a one compartment model with a mean plasma half-life of 2.5 h and a range from 0.6 to 5.8 h. Mean plasma steady-state levels in our patients were 0.37, 0.58, 0.86, 0.88, and 1.42 mM, at the 12-, 16-, 20-, 24-, and 28-g/m2/day dosage levels, respectively. The data indicate that plasma HMBA concentrations of 1 mM can be maintained for 10 days with acceptable patient tolerance, but that HMBA concentrations in excess of 1.4 mM for 10 days are associated with substantial hematological and central nervous system toxicity. Objective antitumor effects were observed in five patients; one woman with non-small cell lung cancer, who has received 17+ courses over a period of 28+ mo, achieved a partial remission that continues at 28+ mo on therapy. Transient regression of cutaneous metastases was observed in three patients with breast carcinoma and one patient with colorectal carcinoma.

Acetamides

Limitations on psychiatrists' discretionary civil commitment authority by the Stone and dangerousness criteria.

The dangerousness-oriented commitment criteria of Massachusetts were compared with the paternalistic Stone model of commitment in an emergency setting. In a sample of 1062 patients, the Stone criteria were more restrictive than the dangerousness-oriented criteria; 91 patients were committable by the Stone model compared with 218 under the present statute. A second comparison of only those patients who refused treatment yielded similar findings--52 patients were committable according to the Stone criteria compared with 80 under the Massachusetts statute. The greater restrictiveness of the Stone criteria in each comparison was in large part the result of the requirement that the treatment decisions of the patient be incompetent; in the broader sample, the criterion of major patient distress had a comparable impact. A comparison of patients committable under both standards with those patients currently committable who would be excluded under the Stone standard revealed significant differences. The dually committable patients were more likely to be psychotic, to meet statutory criteria for grave disability, and to be diagnosed as manic. The implications of the findings are discussed.

Adult

The value of the ice water test in the management of the neurogenic bladder.

Ice water tests (IWT) and gas cystometrograms were performed on 30 consecutive spinal cord injury in-patients on an intermittent catheterization program over a 6-month period. The tests were used to determine the presence of bladder reflex activity. A three-step grading system was formulated to clinically determine the degree of detrusor reflex activity on IWT. A 3+ IWT was used to indicate the expulsion of the catheter from the bladder and urethra following instillation of recently thawed ice; a 2+ IWT meant voiding around the catheter after instillation of 90 ml of ice water; and a 1+ IWT indicated voiding around the catheter after instilling a total of 300 ml of ice water into the bladder. The study shows that the ice water test was more sensitive test than CO2 cystometrogram in detecting the presence of detrusor reflex activity.

Adolescent

Posttraumatic syringomyelia associated with heavy weightlifting exercises: case report.

Posttraumatic syringomyelia is a well-recognized late sequel to spinal trauma occurring in 1% to 3.2% of spinal cord injured patients. Its clinical presentation is usually marked by pain, ascending sensory loss, increased muscle weakness, and depressed deep tendon reflexes. The case of a 25-year-old man with C8 complete quadriplegia, who developed a syrinx five years after his initial injury, is presented. This patient kept a log of his daily physical workout which consisted of lifting weights of 50 to 60 pounds with his neck extensors and biceps. The diagnosis was made clinically and confirmed by magnetic resonance imaging. Repeated valsalva maneuvers from daily heavy weightlifting exercises most likely predisposed this patient to the development and extension of his syringomyelia. Dramatic improvement followed surgical placement of a subarachnoid shunt.

Adult

An unusual presentation of gluteal hematoma during anticoagulation therapy for deep venous thrombosis in spinal cord injury.

Soft tissue bleeding can be manifested clinically by swelling, skin discoloration, pain and tenderness. Early recognition can be difficult in the spinal cord-injured population in whom sensation is impaired. We are presenting a case of occult bleeding into the gluteal region during anticoagulation therapy in a paraplegic patient that presented as migrating pain and tenderness in the hip and pelvic area.

Adolescent

Wrist ratio correlation with carpal tunnel syndrome in industry.

Employees from a large midwestern automobile manufacturing plant completed a preemployment evaluation which included a personal and family history, physical examination, and wrist ratio determinations obtained by dividing the anteroposterior diameter by the mediolateral diameter of the wrist. Over a 3-year period, 80 of these employees who developed symptoms compatible with carpal tunnel syndrome within 4-12 months of employment were entered into the study and were evaluated with standard electrodiagnostic techniques. The symptoms included nocturnal hand pain, paresthesia and weak grasp. Thirty-nine of the 80 employees had wrist ratios equal to or greater than 0.70. Twenty-four percent of the employees with wrist ratios less than 0.70 had abnormal electrodiagnostic studies compared with 74% of employees with wrist ratios greater than or equal to 0.70. Regression analysis performed on the data revealed a significant positive correlation between distal median motor latency and wrist ratio (P = 0.001). The study suggests the practical value of wrist ratio determination in job placement.

Adult

Ground reaction forces, center of pressure, and duration of stance with and without an ankle-foot orthosis.

We analyzed the effects of an ankle-foot orthosis (AFO) on the ground reaction forces, the position of the center of pressure, and the timing of stance phase events during walking in 18 healthy volunteers between the ages of 19 and 38 years. The magnitude and direction of the ground reaction forces and the locus of the center of pressure were recorded every one-sixtieth of a second during free-speed ambulation. The horizontal force components of the ground reaction force were plotted vectorially, and the vertical force component was displayed by its magnitude expressed in percentage body weight. All this information was superimposed on the subject's footprint and statistically analyzed, comparing right to left, narrow to wide, and ipsilateral to contralateral use of an AFO. The results showed a significant reduction in the mean duration of the stance phase of 4.83% (p less than 0.05) with the AFO. This reduction was due primarily to the significant reduction during midstance of 7% (p less than 0.025), which was more pronounced with the use of the wide AFO. Using an AFO also resulted in a mean increase of 20% (p less than 0.05) in the vertical force magnitude at the end of push-off. With the use of an AFO, there was a shift of the point of impact at heel strike to a more posterior location and a shift of the trajectory of the center of pressure to a more lateral position throughout the stance phase. These changes should be kept in mind when prescribing an ankle-foot orthosis.

Adult

Dysphagia in acute stroke.

A prospective study was undertaken to define the incidence, duration, and consequences of dysphagia in an unselected group of 91 consecutive patients who had suffered acute stroke. The site of the present lesion and of any previous stroke was determined clinically and was confirmed by computed tomography of the brain or necropsy in 40 cases. Of 41 patients who had dysphagia on admission, 37 had had a stroke in one cerebral hemisphere. Only seven patients showed evidence of lesions in both hemispheres. Nineteen of 22 patients who survived a stroke in a hemisphere regained their ability to swallow within 14 days. Dysphagia in patients who had had a stroke in a cerebral hemisphere was associated in this study with a higher incidence of chest infections, dehydration, and death.

Acute Disease

Role of immediate versus delayed nephrectomy for failed renal transplants.

The role of timing of transplant nephrectomy after renal transplantation has not been well defined. This report compares the morbidity, mortality, and hospitalization costs of 37 patients undergoing transplant nephrectomy within 14 days after graft failure and return to dialysis, with 31 patients undergoing delayed transplant nephrectomy (less than 14 days after graft failure and return to dialysis). This analysis revealed that there were no significant (P greater than .05) differences in patient morbidity and mortality between these groups. There was, however, a substantial increase (P less than .05) in the cost of hospitalization in the delayed nephrectomy group. For this reason, we recommend early nephrectomy after renal transplant failure in order to minimize the cost of health care for these patients undergoing failed cadaver donor transplant nephrectomy.

Costs and Cost Analysis

Evidence for a direct action of exogenous insulin on the pancreatic islets of diabetic mice: II. Prolonged insulin therapy before islet isolation and perifusion.

24 week old diabetic mice of the C57Bl/Ks (db/db) strain were treated with subcutaneous injections of Ultratard M.C. insulin at a dose of 40 mU/animal rising to 100 mU/animal after 12 weeks. The mean plasma insulin value was 146 +/- 20 microU/ml (n = 6). During this time, the mean body weight of the animals rose significantly (p less than 0.05) and the mean blood glucose concentration fell significantly (p less than 0.005) until a value 2-3 times normal was reached, the insulin dose was then adjusted empirically to maintain hyperglycaemia at this level. Pancreatic islets from these animals, untreated diabetic mice and normal (+/+) mice were isolated by collagenase digest and perifused with a modified Krebs-Ringer medium containing either 3 mmol/L or 15 mmol/L glucose. During glucose challenge, normal islets demonstrated the usual biphasic insulin response, but high glucose levels elicited no response from islets of untreated diabetic mice. Previous treatment of diabetic mice with insulin led to a restoration of the first phase of glucose mediated insulin secretion on perifusion and a significant increase (p less than 0.05) in the second phase. Such an improvement in beta-cell function in the face of prevailing hyperglycaemia, even allowing for the possible mediating effect of a 30% fall in blood glucose, was taken as further evidence for a direct action of exogenous insulin on the islets of diabetic mice.

Animals

Superior mesenteric artery syndrome after resection of an arteriovenous malformation in the cervical cord.

Any disease process decreasing the angle between the superior mesenteric artery and the abdominal aorta can result in the external compression of the duodenum and subsequent intestinal obstruction. This unusual type of intestinal obstruction known as superior mesenteric artery syndrome is a well-recognized clinical entity. It is diagnosed radiologically by an abrupt, vertical cutoff of barium flow in the third portion of the duodenum. The management is primarily medical but occasionally surgical correction is required. Herein, the diagnosis of superior mesenteric artery syndrome was made in an incomplete quadriplegic woman who had recently undergone surgical resection of an arteriovenous malformation in the cervical cord. This case was managed successfully with gastrointestinal decompression, proper positioning in the side-lying position, and adequate nutrition.

Adult

Electrodiagnostic characteristics of acute carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) exemplifies a cumulative trauma disorder which may occur in industrial settings. Occasionally, industrial workers develop CTS acutely over the course of a few days to a few weeks. We recently performed electrodiagnostic studies on 22 workers at a midwestern automobile manufacturing plant who developed symptoms compatible with CTS. All tests were within eight weeks of symptom onset; 70% were within four weeks. The acute syndrome was manifested by a conduction block of sensory, motor, or both fiber types beneath the carpal ligament. All patients received sensory studies; nine had motor studies as well. Sensory nerve latencies were not prolonged in proportion to the symptoms, which were short in comparison to the low amplitude sensory nerve action potential evoked proximal to the carpal ligament. Sensory nerve action potential amplitude at midpalm averaged 200% of the value obtained proximally. Because of short distance and residual latency, comparison of motor latencies proximal and distal to the carpal ligament was less helpful than the difference in amplitude of the evoked potentials. Amplitude of the distal response increased an average of 32%. Prompt identification of acute CTS was followed by a recommendation for job change which, along with conservative therapy, led to resolution of symptoms in 77% of patients. The diagnosis of acute CTS leading to avoidance of inciting activities is beneficial in the industrial setting.

Action Potentials

Efficacy of transdermal scopolamine against seasickness: a 3-day study at sea.

Transdermal scopolamine has been reported to provide protection against motion sickness, both while sailing at sea (7-8 h) and under experimental conditions. In this study, we tested the efficacy of transdermal scopolamine and evaluated its side effects during a 72-h cruise at sea. We tested 38 male volunteers, 20-25 years old, who were located on a 3000-ton vessel. The presence of seasickness, defined by Graybiel's diagnostic criteria, was used to calculate percent protection. When sickness was considered as malaise II or more, the drug provided 74, 73, and 39% protection during the three sailing days, respectively. There were no significant differences in the magnitude of the side effects reported by experimental and placebo groups. We conclude that transdermal scopolamine's efficacy against seasickness during a 3-day cruise was not associated with significant side effects and, therefore, we find the drug suitable for long-term use by sailing crews.

Administration, Cutaneous

The purification of mouse monoclonal antibodies from ascitic fluid.

A method is described for the purification of monoclonal antibody from mouse ascitic fluid. The fluid is clarified and the lipid removed using silicon dioxide powder, before the immunoglobulin is precipitated using polyethylene glycol. The method provides IgM antibody in high yield and good purity. In the case of IgG antibodies the purity is 30-40% after PEG precipitation and the yield is high. The enriched IgG is adequate for many purposes and is suitable for further purification on an ion exchange column.

Animals

Yeast DNA replication.

We have explored various strategies for exploiting the yeast genetic and biochemical system for understanding DNA replication. Because of the long time that has intervened between the isolation of random replication mutants of yeast and the identification of the gene products affected, an alternative approach to elucidating the molecular basis of replication has been needed. One such alternative involves purifying replication proteins, isolating the genes encoding them, and constructing the appropriate mutant from the cloned gene. We have applied this "reverse genetics" strategy to three different replication activities: DNA polymerases, single-stranded DNA binding proteins, and proteins that bind to autonomously replicating sequence (ARS) elements.

DNA Polymerase I