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Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 145 records · Page 8Linked to original sources

The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications.

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Adult↗

Membrane transport of sodium ions in erythrocytes of the American black bear, Ursus americanus.

1. Membrane transport of Na ions was investigated in red blood cells of bears by methods of measurement of unidirectional isotopic fluxes. 2. Like red blood cells of dogs, bear red cells contain a high Na concentration and low concentrations of K and ATP. 3. As in dog red cells, Na efflux from bear cells was not inhibited by ouabain but was activated by the presence of Ca in the medium, possibly indicating the presence of a Na-Ca exchange mechanism. 4. ATP depletion of cells was accelerated by Ca in the medium, consistent with the presence of a strong ATP-dependent Ca pump. 5. As in other carnivore red cells, Na influx into bear cells was strongly activated by shrinkage and inhibited by swelling. Shrinkage-activated influx was blocked by amiloride. 6. Amiloride-sensitive influx was activated by cytoplasmic Ca and also correlated with the presence of a Na-dependent, amiloride-sensitive H loss. 7. Amiloride-sensitive Na influx exhibited a strong seasonal cycle with a minimum in the middle of the hibernation period, suggesting a possible avenue of cellular energy conservation.

Animals↗

Vestibulo-ocular reflex as a parameter of seasickness susceptibility.

The vestibulo-ocular reflex (VOR) is known to be modulated in response to changing vestibular and optokinetic stimuli. The purpose of this study was to investigate possible relationships between VOR and future susceptibility and habituation to seasickness. Thirty candidates for future maritime service were exposed to a series of yaw axis smooth harmonic accelerations before and after 6 months of regular sailing, and their VOR gain and phase responses were recorded. Seasickness severity was estimated after 1 and 6 months of service by a questionnaire. We conclude that VOR gain at 0.01 Hz may serve as a physiologic correlate helping to predict seasickness susceptibility, and that the increase in phase lead at 0.02 Hz may mark the habituation process to sea conditions.

Acceleration↗

Hyperbaric oxygenation for necrotizing (malignant) otitis externa.

Two patients with extensive necrotizing otitis externa have been treated by hyperbaric oxygenation. One patient had facial nerve palsy and the other suffered from skull base involvement. Due to severe side effects, the preferred combined intravenous antibiotic therapy was changed to monotherapy in one case and completely withdrawn in the second. This was done before the commencement of hyperbaric oxygenation, while the necrotizing infection was still active. Hyperbaric oxygenation therapy was followed by complete resolution of the necrotizing otitis externa, which did not recur. The pathogenesis of the disease and mechanisms by which hyperbaric oxygenation might be of benefit are described. We conclude that hyperbaric oxygenation should be considered as adjuvant therapy for necrotizing otitis externa whenever a therapeutic pressure chamber is available.

Aged↗

Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice.

We studied the effects of recombinant murine tumor necrosis factor-alpha (TNF-alpha) on autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Treatment with TNF-alpha, begun after the onset of clinical disease, improved survival relative to control mice: at age 10 months, 92% of mice treated with TNF-alpha were alive compared with 42% of control mice (P less than 0.05). Administration of TNF-alpha delayed the progression of renal disease, but sustained therapy did not prevent the eventual development of severe nephritis. Despite the improvement in survival, treatment with TNF-alpha did not inhibit anti-dsDNA antibody production. However, it accelerated T lymphocytopenia and abolished natural killer cell activity. These observations suggest that TNF-alpha may retard murine lupus in B/W mice through effects on cellular rather than humoral mechanisms. Our findings also indicate that the beneficial effects of TNF-alpha cannot be sustained indefinitely by chronic therapy.

Animals↗

Does residual insulin secretion (assessed by C-peptide concentration) affect lipid and lipoprotein levels in insulin-dependent diabetes mellitus?

1. Residual endogenous insulin secretion can be assessed by the circulating C-peptide concentration and is present in up to 15% of subjects with established insulin-dependent diabetes mellitus (IDDM). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM. 2. Lipid and lipoprotein levels and glycaemic control did not differ significantly between patients with undetectable, low or high C-peptide responses. 3. High density lipoprotein (HDL) cholesterol and its subfractions were inversely related to concentrations of serum triacylglycerols (P less than 0.01-0.001), but not to C-peptide or glycated haemoglobin (HbA1) levels. Levels of HbA1 and triacylglycerols were correlated with one another (P less than 0.01). Analysis of variance revealed that differences in gender and triacylglycerol concentrations were the most important determinants of HDL and HDL2 cholesterol levels. C-peptide only exerted a weak effect on HDL2 cholesterol levels and no significant predictors of HDL3 cholesterol were found. 4. It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.

Adolescent↗

Detection of crystals in synovial fluids by light microscopy: sensitivity and reliability.

Polarised light microscopy of synovial fluid is an established diagnostic technique widely regarded as reliable for the detection of crystals. The threshold concentration of crystals which can be detected has been investigated and the sensitivity and specificity of six observers compared. Various concentrations of laboratory manufactured crystals of monosodium urate monohydrate (MSUM), calcium pyrophosphate dihydrate (CPPD), and basic calcium phosphates (BCP) were added to the synovial fluid. The threshold for reliable identification of MSUM and CPPD was in the range of 10-100 micrograms/ml. False positives were frequent. The mean sensitivity of the six observers for MSUM was 69% and for CPPD was 82%. The mean specificity for MSUM was 97% and for CPPD was 78%. There was much discrepancy in the results of the slides stained with alizarin red S. Thus the value of alizarin red S as a screening test for BCP is questioned. In view of the variable sensitivity and specificity of different observers for MSUM and CPPD and the concentration threshold for reliable crystal identification, greater caution in the interpretation of synovial fluid analysis is advised, and recommendations for increased quality control are supported.

Anthraquinones↗

The process of recovering from anorexia nervosa.

The authors describe the process of recovering from anorexia nervosa as it is revealed by 13 women who have recovered from the illness. Emphasizing the patient's perspective, the paper reviews the perceived causes of the disorder, helpful and harmful therapy-related and life experiences, features hardest to change, the defensive function of anorexia nervosa and residual traits. Generally, the movement toward health entails forming a therapeutic relationship in which the anorexic can identify and express feelings, experience the empathic, nonjudgmental understanding of another person, separate from a pathological family system, resolve hostile dependent attachment to parents, assuage primitive guilt, and engage in the trials of adolescent psychosexual development to enter adulthood with the beginnings of a firm, cohesive sense of self.

Adult↗

The parents' relationship and the child's illness in anorexia nervosa.

The authors examine the impact on the preanorexic child of the parents' relationship with one another, particularly the models they present of mature male/female relationships. The authors suggest that patterns of maternal perfectionism and self-sacrifice combined with paternal entitlement makes sexual maturity particularly threatening for female children in these families, and may partially explain the greater incidence of anorexia nervosa in women, and its explosive incidence in adolescence.

Anorexia Nervosa↗

Prevalence of mitral valve prolapse in primary fibromyalgia: a pilot investigation.

Fifty patients with primary fibromyalgia and a negative cardiovascular symptom history underwent echocardiography to determine the prevalence of mitral valve prolapse (MVP). The mean age of the population was 40 +/- 13 years (14 men, 36 women). Mitral valve prolapse was detected in 75%; 33% with myxomatous mitral valve leaflets. The prevalence of MVP in this population is significantly higher (p less than 0.0001) than in the general population. Primary fibromyalgia and MVP may be part of a more generalized connective tissue abnormality characterized by distinct genetically determined variants.

Adult↗

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↗