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Biomedical subjects

C Robertson

Publications and source records attributed to C Robertson.

At least 181 records · Page 10Linked to original sources
PubMed1994

Long-term prospective study of postpartum thyroid dysfunction in women with insulin dependent diabetes mellitus.

Postpartum thyroid dysfunction (PPTD) is a common autoimmune disorder. Type I diabetes mellitus (IDDM) is an autoimmune disease with a high incidence of concomitant autoimmune thyroid failure. We hypothesized that women with IDDM would have an increased incidence of PPTD. Women with IDDM in New York City, were followed prospectively during the second and third trimester of pregnancy and at 6 weeks, 3 months, 6 months, 9 months, and 1 yr postpartum. A long-term follow-up was performed at 31 months postpartum. Forty-one women with IDDM were recruited at their initial prenatal visit. Two women (4.8%) had thyroid function test abnormalities observed at screening, three (7.3%) had a spontaneous miscarriage, and eight (19.5%) women were noncompliant with follow-up. Twenty-eight women (68.2%) completed the study. Thyroid function tests and thyroid autoantibody determinations were obtained at all visits. PPTD was defined as a TSH greater than 5.0 or less than 0.2 mU/L in the postpartum period with documented normal thyroid function tests during pregnancy. The incidence of PPTD in women with IDDM was 25%. This is a 3-fold increase compared to a similar study by our group in a nondiabetic population. Forty-three percent of the women (3/7) who developed PPTD required treatment in the immediate postpartum period and at long-term follow-up. The remainder of the women with PPTD, as well as all women who did not develop PPTD were euthyroid at 31 months postpartum. Women with IDDM are at high risk for PPTD. We recommend that all women with IDDM be screened for thyroid hormonal abnormalities during pregnancy and at 3 months postpartum for postpartum thyroid dysfunction. Long-term follow-up did not reveal an increased incidence of hypothyroidism in women who did not require treatment in the first postpartum year.

Autoantibodies↗
PubMed1994

Province-based study of neurologic disability among survivors weighing 500 through 1249 grams at birth.

BACKGROUND: As the mortality of children weighing 500 through 1249 g at birth decreases, the published rates of neurologic disability among survivors have caused concern. Outcome information from a province-based study in which perinatal/neonatal regional care is well developed and includes high-risk identification, early referral, organized transport, and outreach education, provides data from a Canadian source for comparison with epidemiologic reports. METHODS: Neurologic disability rates among 2- to 3-year-old survivors weighing 500 through 1249 g at birth is provided based on all live births/neonatal survivors/1-year survivors born in Alberta, Canada to Alberta residents in 1990. RESULTS: Corrected survival to 1-year was 163 of 229 or 71% of live births of the total group weighing 500 through 1249 g. Of 168 live births, 143 or 85% weighing 750 through 1249 g, free from lethal anomalies, survived. Based on 1-year survival, disability rates were: cerebral palsy, 67/1000; vision loss (acuity in the best seeing eye after correction, < 20/60), 12/1000; neurosensory hearing loss (loss of > or = 30 dB binaurally), 12/1000; and trainable/profound mental retardation, 18/1000. No survivor had a convulsive disorder. No vision loss or mental retardation as defined by this study occurred in survivors of > or = 750 g. All children with cerebral palsy were or were projected to become ambulatory. CONCLUSIONS: Neurologic disability among small preterm surviving infants can occur less frequently than suggested by published reports. We believe this provincial study supports the value of well developed regional perinatal programs.

Alberta↗
PubMed1994

Platelets from bleeding Simmental cattle mobilize calcium, phosphorylate myosin light chain and bind normal numbers of fibrinogen molecules but have abnormal cytoskeletal assembly and aggregation in response to ADP.

We have evaluated platelet function in normal Simmental cattle and in those with a congenital, inherited bleeding disorder previously attributed to impaired platelet aggregation. Affected platelets failed to aggregate and secrete in response to ADP and the ionophore A23187, and showed impaired aggregation responses to collagen and ionomycin. Aggregation and secretion of normal and affected platelets was similar in response to thrombin and PMA. Resting cytosolic calcium levels and calcium mobilization in response to ADP and ionomycin were similar in control and four affected animals. Normal and affected bovine platelets phosphorylated myosin light chain and pleckstrin in response to ADP and A23187. Transmission electron microscopy of affected platelets following stimulation with ADP, showed shape change and some degree of centralization of the actomyosin gel. Affected platelets had comparable numbers of GPIIb/IIIa complexes and expressed comparable numbers of fibrinogen receptors as normal platelets in response to ADP. Cytoskeletal assembly in affected platelets was normal in response to PMA but incomplete in response to ADP and A23187. Failure of platelet aggregation in bleeding Simmental cattle is predicted to arise from abnormal cytoskeletal assembly following calcium mobilization and phosphorylation of myosin light chain in response to ADP.

Adenosine Diphosphate↗
PubMed1993

Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system.

Reactive microglia and invading macrophages, which appear in brain damaged by stroke or trauma, secrete neuron-killing factors. This release of cytotoxic substances is a delayed process and is not detected until inflammatory cells reach a peak of reactivity by the second day after injury. Proximity to the site of injury and density of mononuclear phagocytes determine in part the amount of neurotoxic activity released by injured tissues. Moreover, drugs that suppress the accumulation of reactive microglia and macrophages also reduce tissue production of neuron poisons. Neurotoxins released by brain inflammatory cells or extracted directly from inflamed tissues are heat-stable, protease-resistant molecules < 500 daltons with actions blocked by N-methyl-D-aspartate (NMDA) receptor antagonists. These molecules are distinguished from free radical intermediates, bind to cation exchange resins, lack carboxyl moieties, and are separated from excitatory amino acids including glutamate or aspartate and from the NMDA receptor-mediated toxin quinolinic acid by ion exchange and reverse phase chromatography. Our data suggest that an unrecognized class of neuron-killing molecules produced by inflammatory cells mediate the delayed neuronal loss associated with stroke and trauma.

Animals↗
PubMed1993

Vanadate activates platelets by enhancing arachidonic acid release.

Human platelet activation is associated with, and regulated by, the phosphorylation of a number of proteins. Recently, attention has been focused on tyrosine phosphorylation of proteins and their function in platelet activation. Here vanadate, an inhibitor of tyrosine phosphohydrolase, was used to examine the role that tyrosine phosphorylation plays in platelet activation. Vanadate (7.5 to 100 mumol/L) stimulated the dose-dependent aggregation of saponin-permeabilized, but not intact, platelets. Electron-microscopic studies indicated small degranulated aggregates. Vanadate-induced aggregation was inhibited by pretreatment with prostacyclin (1 to 10 nmol/L), genistein (1 to 10 micrograms/mL), aspirin (100 mumol/L), or BW755C (80 mumol/L). Aggregation was associated with the aspirin-sensitive formation of [32P]phosphatidic acid and the phosphorylation of platelet proteins, notably pleckstrin and myosin light chain. Immunoblotting studies indicated that vanadate caused the tyrosine phosphorylation of proteins of approximate molecular weights 26, 29, 32, 40, 42, 80, and 90 Kd. Preincubation with BW755C abolished the phosphorylation of the 26-, 29-, 32-, 40-, and 42-Kd proteins but not the 80- and 90-Kd proteins. Vanadate stimulated the release of [3H]-arachidonic acid that was not affected by pretreatment with BW755C. The subsequent conversion of [3H]-arachidonic acid to [3H]-thromboxane A2 was significantly inhibited. These findings show that vanadate stimulates platelets by promoting arachidonic acid release from phospholipids. Tyrosine phosphorylation, potentially of the 80- or 90-Kd proteins, may regulate a platelet phospholipase A2. The release arachidonic acid was converted to thromboxane A2 that produced secondary effects such as phospholipase C activation, protein phosphorylation, and aggregation, and was associated with the tyrosine phosphorylation of the 26-, 29-, 32-, 40-, and 42-Kd proteins.

Arachidonic Acid↗
PubMed1993

Flow cytometric DNA analysis of interleukin-2 responsive renal cell carcinoma.

Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p2 = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population.

Carcinoma, Renal Cell↗
PubMed1993

Desaturation episodes after severe head injury: influence on outcome.

The relationship of jugular venous desaturation and neurological outcome was examined in 116 patients with severe head injury. Seventy-six episodes of jugular venous desaturation were prospectively identified in 46 (40%) of the patients. The etiology of the desaturations varied, including both systemic and cerebral causes. A poor neurological outcome was strongly associated with the occurrence of jugular venous desaturation.

Adolescent↗
PubMed1993

Measurements of cerebral blood flow and metabolism in severe head injury using the Kety-Schmidt technique.

Global cerebral blood flow (CBF) was measured serially for up to 10 days after severe head injury, and related to outcome. Twenty-five of the patients had a reduced CBF, 47 had a normal CBF, and 30 had an elevated CBF. Patients with a reduced CBF had a poorer outcome than patients with a normal or elevated CBF. There were no differences in the type of injury, initial GCS, severity of intracranial hypertension in each CBF group. Systemic factors did not significantly contribute to the differences in CBF among the 3 groups. A logistic regression model of the effect of CBF on neurological outcome was developed. When adjusted of variables which were found to be significant confounders, including age, initial Glasgow Coma Score, hemoglobin, cerebral perfusion pressure, and cerebral oxygen consumption, a reduced CBF remained significantly associated with an unfavorable neurological outcome.

Adult↗
PubMed1993

Glutathione depletion increases the cytotoxicity of melphalan to PC-3, an androgen-insensitive prostate cancer cell line.

Prostate cancer that is androgen-insensitive is unresponsive to a wide spectrum of cytotoxic agents, including all of the alkylating agents. Since a major pathway for the detoxification of the alkylating agents is conjugation with glutathione (GSH), GSH depletion has proved to be effective as a technique to restore melphalan sensitivity in melphalan-resistant cancer cell lines. However, the effect of GSH depletion has not been widely studied in tumor cell lines that have not developed resistance due to previous exposure to alkylating agents. Thus, we decided to investigate GSH depletion as a technique to increase melphalan cytotoxicity to PC-3 cells, an androgen-insensitive prostate cancer line. After 2 and 6 h incubation with 0.25-5 microM melphalan, virtually no effect was observed on either clonogenic lethality or MTT viability until 5 microM exposures. A 24-h incubation of the cells with 100 microM buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, reduced the GSH content by 70%-75%. Following GSH depletion, an increase in clonogenic lethality and a decrease in MTT viability occurred after exposure to concentrations as low as 0.25 microM. The dose modification factor ranged from 2.9 after 2 h incubation to 4.5 at 6 h. These results provide support for additional studies in prostate cancer for further investigation of GSH depletion as a technique to induce sensitivity to alkylating agents in this chemotherapy-resistant tumor.

Buthionine Sulfoximine↗
PubMed1993

The effect of differing radiotherapeutic schedules on the response of glottic carcinoma of the larynx.

Laryngeal tumours, especially T1N0M0 and T2N0M0 lesions, are readily controlled by radiotherapy. Studies have shown that control varies with the dose of radiotherapy delivered to the tumour. Other factors, including the dose per fraction and the time over which the treatment schedule is delivered are also important. The varying biological effectiveness of a number of different dose fraction time schedules used in the management of laryngeal tumours of different stages are considered, the end points being tumour control and associated morbidity. Special attention has been given to the length of time over which the schedule is delivered. Of the schedules examined the results would suggest that a dose of 60 Gy given in 25 fractions over a period of 35 days is the best of the six schedules studied for T1, T2, T3 and T4 lesions with minimal associated morbidity. It is possible, however, that the poor results shown on the Kaplan-Meier curves for patients treated with the schedule of 60 Gy in 30 fractions over a period of 42 days could be due to geographical misses of the tumours as 56% were treated without a beam directed shell. The poor result obtained when patients were treated with the schedule of 60 Gy given in 30 fractions over 49+ days may be due to tumour repopulation occurring during the rest period though the possibility of geographical misses may contribute to the poor tumour control results. Mathematical modelling using linear quadratic analysis suggests that the shorter the period of time over which the treatment is given the better chance of achieving tumour control irrespective of the stage of the disease. These models were developed for patients treated with a beam directed shell thus excluding those patients who are most likely to be at risk from a geographic miss of the tumour. Linear quadratic analysis of the treatment data suggests that the ratio alpha/beta for tumour cells is estimated in the region of 13 Gy. For T1 lesions the tumour doubling time is in the order of 6 days, with longer doubling times for the more advanced stages. The analysis provides some support for investigative use of accelerated treatment schedules. This analysis also shows the importance of using beam directed shells when treating small fields especially in the head and neck region.

Adult↗
PubMed1993

An investigation into the effect of cimetidine pre-treatment on raft formation of an anti-reflux agent.

It is now becoming common practice to co-administer H2-receptor antagonists and anti-reflux agents in the treatment of reflux oesophagitis. The mechanism by which anti-reflux agents achieve flotation requires a small amount of gastric acid to be present in the stomach. This study investigated whether an anti-reflux agent would remain effective after the decrease in acid secretion produced by a typical clinical dosage regimen of cimetidine (400 mg q.d.s., 7 days). Gastric distribution and residence of a meal and an anti-reflux agent were assessed in 12 normal subjects using gamma scintigraphy. The area under the gastric and fundal emptying curves demonstrated that Liquid Gaviscon (sodium alginate compound) had a significantly greater gastric residence than the meal, both during the control period and after cimetidine pretreatment, and that the majority of the Gaviscon was located in the fundus. The distribution of Gaviscon into the fundus was not affected by cimetidine pretreatment. Cimetidine pre-treatment slightly, but not significantly, increased the time for half the meal and the Gaviscon to empty from the stomach. The results suggest that the mechanism of action of Liquid Gaviscon is not compromised by concurrent H2-antagonist therapy.

Alginates↗
PubMed1993

Antibody responses to a 33 kDa cysteine protease of Trypanosoma congolense: relationship to 'trypanotolerance' in cattle.

A cysteine protease of Trypanosoma congolense (congopain) elicited IgG1 antibodies in those cattle which exhibited a degree of resistance to disease during experimental infections (Authié et al. 1992, 1993). The aim of the present study was to investigate further the association between anti-congopain antibodies and resistance to trypanosomiasis, and to provide a lead into the mechanisms responsible for the differential responses to congopain in cattle. Isotype characteristics and kinetics of the antibody response to congopain were studied in three N'Dama (trypanoresistant) and three Boran (susceptible) cattle during primary infection with T. congolense ILNat 3.1. In both groups an IgM response to congopain was elicited, thus demonstrating that congopain is antigenic in both types of cattle. Most of the IgM appeared to be incorporated into immune complexes. IgG was detected as free antibody; IgG1 but not IgG2 was detected. All three N'Dama, but none of the three Boran cattle, mounted a significant IgG response to congopain. Sera from 70 primary-infected cattle belonging to five breeds of differing susceptibility were tested for their reactivity to congopain. High levels of IgG to congopain were observed in the two trypanotolerant breeds, whereas the three susceptible breeds had lower levels of these antibodies. Crosses between N'Dama and Boran cattle, which exhibit an intermediate susceptibility, had intermediate levels of antibodies. Thus, the results from experimental infections confirmed our initial observations. However, under natural tsetse challenge, repeated infections and trypanocidal treatments in Zebu cattle stimulated as high anti-congopain antibody levels as in non-treated trypanotolerant taurine cattle.

Analysis of Variance↗
PubMed1993

Prospective audit of the pattern, severity and circumstances of injury sustained by vehicle occupants as a result of road traffic accidents.

The pattern and severity of injuries sustained by 174 vehicle occupants consecutively admitted to the Accident and Emergency Department of the Edinburgh Royal Infirmary were prospectively documented. Drivers (DR) accounted for 66% of the patients, 20% were front seat passengers (FSP) and 14% were rear seat passengers (RSP). Injured patients were more likely to be male, young, intoxicated and not wearing a seat-belt. The position of the patient within the vehicle at the time of the accident and point of impact significantly affected the pattern of injury sustained. The majority of injuries were sustained by the upper body and the pattern of injury is discussed. Most accidents occurred at low speeds and higher speeds were associated with an increased severity of injury. Seat-belts reduced the overall severity of injuries, in particular those to the face and chest, but may increase the risk of neck injury. Head-rests do not appear to influence the incidence of neck injury. Clinically apparent alcohol intoxication was associated with a markedly increased risk of severe injury.

Accidents, Traffic↗
PubMed1993

Improvement in sodium cromoglycate delivery from a spacer device by use of an antistatic lining, immediate inhalation, and avoiding multiple actuations of drug.

BACKGROUND: Aerosols generated from metered dose inhalers may be highly charged. The aim of this study was to determine whether lining the walls of a polycarbonate spacer device with an antistatic agent would result in an increase in drug output. The effects of multiple actuations of drug into the spacer device and increasing residence time of drug within the spacer were also determined. METHODS: The amount of sodium cromoglycate contained in particles of various size available for inhalation (per 5 mg actuation) from a 750 ml polycarbonate spacer was determined by impinger measurement and spectrophotometric assay. RESULTS: Lining the spacer with an antistatic agent increased the mean (SD) amount of sodium cromoglycate in particles < 5 microns available for inhalation (per 5 mg actuation) by 244% from (0.59 (0.03) to 1.44 (0.2) mg). When there was a 20 second interval between actuation into the spacer device and inhalation, sodium cromoglycate available for inhalation in particles < 5 micrograms decreased by 67% (from 0.59 (0.03) mg to 0.2 (0.01) mg). Use of the spacer device increased sodium cromoglycate available for inhalation in respirable particles (< 5 microns) by 18% compared with direct delivery by metered dose inhaler. Multiple actuations into the spacer decreased the amount of sodium cromoglycate available for inhalation in particles < 5 microns by 31% after two actuations and 56% after three acutations. CONCLUSIONS: Multiple actuations of sodium cromoglycate into a spacer device before inhalation should be avoided, and inhalation from spacer devices should take place immediately after actuation to ensure maximum dose. Lining of a standard spacer device with an antistatic agent significantly increased output of sodium cromoglycate. This may have implications for improved therapeutic response and drug cost.

Administration, Inhalation↗
PubMed1993

Wide distribution of granulophysin epitopes in granules of human tissues.

BACKGROUND: The identification and characterization of granule membrane proteins are becoming increasingly important in understanding the packaging and secretory function of granules and characterizing diseases involving granules. A granule membrane protein, granulophysin, has recently been identified in the membranes of platelet dense granules, organelles that contain stored ADP, ATP, serotonin, and calcium. Antibodies that recognize granulophysin also stain granules of monocytes, neutrophils, and lymphokine activated killer cells. EXPERIMENTAL DESIGN: In the present study, the distribution of epitopes recognized by antigranulophysin monoclonal antibodies in human tissues was investigated using immunohistochemistry on paraffin sections. Quantitation of the protein was also performed by enzyme-linked immunosorbent assay. The protein was also analyzed in various tissues using Western blotting. RESULTS: Granulophysin was localized to the granules of skin melanocytes, neurons, endocrine gland cells, exocrine glands (except mucin producing cells), and surface lining cells. Analysis by Western blots revealed a typical staining pattern for granulophysin in lung, adrenal gland, liver, brain, prostate, and pituitary. Atypical bands were present in the pancreas head (47 kDa) and skeletal muscle (34 kDa). A clear distinction was demonstrated between granulophysin and synaptophysin through both immunochemistry and blotting, despite the known cross-reactivity of these two proteins. CONCLUSIONS: The findings demonstrate that granulophysin is a widely distributed protein that is frequently associated with granules. We speculate that it may be critical in granule function.

Antibodies, Monoclonal↗