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Biomedical subjects

C Barton

Publications and source records attributed to C Barton.

At least 19 recordsLinked to original sources

Microinjection of opioid antagonists into the substantia nigra reduces stress-induced eating in rats.

Stress produced by pinching the tail has been shown to cause satiated animals to eat and to display oral stereotypies. Endogenous opioids and central dopamine systems have been implicated in the mediation of these effects. In order to test the possibility that the substantia nigra (SN) might be involved, the amount of food intake and gnawing produced by mild tail pinch were assessed following bilateral microinjections of opioid antagonists into the SN. Evaluations of nociceptive thresholds were also conducted using tail flick and hot plate tests. Eating induced by tail pinch was reduced by microinjections of the non-selective opioid antagonist naloxone (3, 10, 20 and 30 nmol) and by the mu-selective antagonist Cys2, Tyr3, Orn5, Pen7 Amide (CTOP) (1, 3 and 10 nmol). These effects on eating occurred in the absence of effects on gnawing. kappa- and delta-antagonists (10 nmol) had no effect on eating or gnawing. Naloxone did not alter either tail flick or hot-plate response latencies. The highest dose of CTOP increased response latency on the hot-plate test only. The results are interpreted as suggesting that the SN may be an important central site of action for opioid antagonists in reducing stress-induced eating. The possibility that the SN may be a central site mediating the effects of dopamine on this phenomenon is also discussed.

Animals

The erbB-3 gene in human pancreatic cancer.

Abnormalities of the type 1 growth factor receptor family have been implicated in the pathogenesis of pancreatic cancer. There is evidence for a potential autocrine loop involving overexpression of the epidermal growth factor (EGF) receptor and its ligands, as well as overexpression of the erbB-2 receptor. A third member of this receptor family, erbB-3, has recently been recognized and found to be abnormally expressed in some types of human cancer. In this study we show that overexpression of the erbB-3 protein occurs very frequently in carcinoma of the exocrine pancreas and also in chronic pancreatitis. We found no evidence of amplification or rearrangement of the erbB-3 gene by Southern blot analysis of DNA from pancreatic cancer cells lines.

Amino Acid Sequence

In vitro effects of the nephrotoxins ochratoxin A and citrinin upon biochemical function of porcine kidney.

Ochratoxin A and citrinin are nephrotoxic mycotoxins found in a variety of foods and feeds. Before studying possible interactions between these two toxins, their individual biochemical effects were examined in vitro by using renal cortical explants derived from male swine of the Hormel-Hanford strain. The following measurements were performed: macromolecule biosynthesis (protein, RNA, and DNA), respiration (14CO2 from [14C]glucose), organic ion (tetraethyl ammonium acetate, i.e., TEA) transport, and membrane perturbation (protein leakage into medium). Levels of the toxins ranged from 0.001 to 1 mM. Ochratoxin A inhibited macromolecule biosynthesis at a lower concentration (0.001 mM) than did citrinin. Protein and DNA synthesis were particularly sensitive to ochratoxin A. Syntheses of protein and DNA were inhibited at ochratoxin A concentrations of 0.01 and 0.001 mM, respectively. RNA synthesis was less sensitive to the mycotoxin; it was inhibited only 60% at 1 mM, the highest concentration of ochratoxin A tested. Citrinin levels of 0.01 mM were required for inhibition of RNA, DNA, and protein synthesis. Inhibition by citrinin was approximately equal for all three classes of macromolecules. Citrinin was more effective than ochratoxin A in the inhibition of respiration and TEA transport; the minimum effective levels of citrinin were 1 and 0.01 mM, respectively. Serious membrane damage as evidenced by increased protein leakage was not caused by either toxin. Stimulation of respiration, perhaps reflective of uncoupling of oxidative phosphorylation, was produced by an ochratoxin A concentration of 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Bombesin-induced hypothermia and hypophagia are associated with plasma metabolic fuel alterations in the rat.

Microinfusion of bombesin into the preoptic area (POA) has previously been shown to reduce core body temperature and feeding in rats that are food-deprived or made hypoglycemic with insulin. The present study determined the metabolic fuel state of rats under these experimental conditions. In addition, changes in plasma metabolic fuels following the microinfusion of bombesin (50 ng/0.25 microliters) into the POA were evaluated. Rats (n = 8) were tested under conditions of food satiation, food deprivation (20 h), and insulin pretreatment (10 U/kg). Prior to peptide infusion, food-deprived rats exhibited the expected elevation in free fatty acids coupled with a small decline in plasma glucose. Insulin treatment resulted in hypoglycemia which persisted for at least 120 min. Following bombesin infusion, free fatty acids and corticosterone levels were elevated in food-sated rats. Food-deprived rats exhibited elevation in plasma glucose, free fatty acids, and corticosterone following peptide infusion. In insulin-treated rats, bombesin attenuated the hypoglycemia observed in controls and increased corticosterone levels. These findings suggest that bombesin-like peptides localized within the POA may participate in the regulation of metabolic fuels.

Animals

Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the treatment of advanced breast cancer: a randomised clinical trial.

Patients with advanced breast cancer were randomised to 3M (mitozantrone 6.5 mg/m2q 21 days, methotrexate 30 mg/m2q 21 days, mitomycin C 6.5 mg/m2q 42 days) or 2M (as 3M but without mitomycin C). The objective response rates of 30% in 51 evaluable patients receiving 3M and 26% of 54 patients receiving 2M were not significantly different. 4/16 patients not responding to 2M responded to 3M on crossover. Both regimes were well tolerated but there was significantly less haematological toxicity and fewer dose reductions and delays with 2M. We conclude that patients should initially be treated with 2M and that non-responding patients should be crossed to 3M.

Antineoplastic Combined Chemotherapy Protocols

Sequential interleukin-2 and alpha interferon for renal cell carcinoma and melanoma.

There is a theoretical basis for the synergy of interleukin-2 (IL-2) with other cytokines. We have investigated sequential treatment with IL-2 and alpha interferon. 1 of 22 patients with metastatic renal cell carcinoma had a partial response and one a minimal response to continuous infusion IL-2 but none of the 9 patients with melanoma responded. 16 of 17 patients with renal cell cancer, and 8 with melanoma, were then treated with alpha interferon. 2 patients with renal cell cancer responded to alpha interferon with sustained remissions of 30 and 40 months; both had responded to IL-2. The investigation of combination therapy with other cytokines is suggested, by these unusually long responses to alpha interferon.

Adolescent

The 1989 Loma Prieta earthquake: impact on hospital patient care.

STUDY OBJECTIVE: To provide an overview of the Loma Prieta earthquake regarding patient care in affected hospitals. DESIGN: A retrospective review of medical records using International Classification of Disease, ninth revision (ICD-9) codes and a personal interview questionnaire. SETTING: Fifty-one hospitals in the six-county area most affected by the earthquake. TYPE OF PARTICIPANTS: Patients seeking care in emergency departments of study hospitals and supervising emergency physicians and ED nurses at the time of the earthquake. MEASUREMENTS: ED census data, complaint and diagnosis, disposition, and operative procedures for patients seen during the study period. MAIN RESULTS: Affected hospitals experienced a 15% increase in ED census during the study period. Minor trauma was the most common patient complaint. Open wound (870-897), contusion (920-924), and fracture (800-829) were the most common ICD-9 diagnostic categories. The percentage of patients presenting to EDs during the study period who were hospitalized increased slightly compared with baseline. Seventy-five percent of operative procedures were earthquake related; 63.7% of these were for fracture reduction. Physicians and nurses had somewhat conflicting opinions on adequacy of ED staffing. A small number of emergency physicians had difficulty in obtaining diagnostic tests on the night of the earthquake. Physicians noted no differences in diagnosis or treatment resulting from the earthquake. CONCLUSION: The Loma Prieta earthquake resulted in minimal negative impact on patient care in hospitals in the study area. The use of the ICD-9 classification deserves further consideration and study to improve the predictive value of disaster illness and injury reporting. The event has provided the stimulus for Bay Area hospitals to further improve plans for patient care during a disaster.

California

Effect of epinephrine on the ability of end-tidal carbon dioxide readings to predict initial resuscitation from cardiac arrest.

OBJECTIVE: To determine if the administration of epinephrine changes the partial pressure of end-tidal CO2 during cardiac arrest, as previously reported. Such a change could diminish the demonstrated ability of end-tidal CO2 measurements to predict resuscitation from cardiac arrest. DESIGN: The partial pressures of end-tidal CO2 of adult cardiac arrest patients who received i.v. epinephrine in doses from 1 to 15 mg were monitored throughout arrest. SETTING: Emergency department of a university hospital. PATIENTS: Adults (n = 64) in cardiac arrest with a mean age of 70 +/- 12 yrs, of whom 35 were males and 15 had a mean time of return of spontaneous circulation of 6.5 +/- 11 hrs. INTERVENTIONS: End-tidal CO2 (in torr) was analyzed on arrival, before the first dose of epinephrine, and 4 mins after epinephrine was administered in varying doses chosen by the supervising physician. MEASUREMENTS AND RESULTS: The end-tidal CO2 decreased an average of 0.3 torr (0.04 kPa) after epinephrine was administered. Patients with a return of pulse had a decrease of -2 torr (-0.3 kPa) vs. an increase of 0.3 torr (0.04 kPa) for those patients with no return of pulse (p = .07). In 33% of patients, there was no change; in 28%, the partial pressure of end-tidal CO2 increased, and in 39%, it decreased. There was no correlation between the change in end-tidal CO2 after epinephrine and whether or not patients regained a pulse (r2 = .08, p = .07), although a decrease in end-tidal CO2 was most often associated with return of pulse. At a threshold of 10 torr (1.3 kPa), the first end-tidal CO2 had a positive predictive value for return of pulse of 50% and a negative predictive value of 82%. Just before epinephrine administration, the positive predictive value was 71% and the negative predictive value was 83%; 4 mins after epinephrine administration, the positive predictive value was 64% and the negative predictive value was 86%. A decrease in end-tidal CO2 after epinephrine had a positive predictive value of 53% and a negative predictive value of 92%. End-tidal CO2 readings predicted resuscitation most accurately when taken after initial stabilization and before administration of epinephrine. CONCLUSIONS: Although epinephrine administration may decrease end-tidal CO2 tensions in cardiac arrest, it does so unpredictably in individual patients, and it does not eliminate the predictive value of this measurement.

Aged

Bladder cancer: inter-relationships between chemotherapy and radiotherapy.

There has been increasing interest in the role of chemotherapy as primary treatments for patients with urothelial cancer and because of the poor prognosis of locally advanced tumours with conventional treatment, trials have been initiated comparing radiotherapy with chemotherapy as primary therapies. In this context it is important to assess the relationship between the responses to chemotherapy and radiotherapy, and this we have examined in 64 patients treated with MVMJ (methotrexate, vinblastine, mitozantrone and carboplatin). Either a complete or a partial response was found in 29 of the 64 patients, 15 had stable disease and 13 had progression of disease. Seven patients died within the first treatment month. The survival of the responding patients ranged from 114 to 1184 days. Six of 15 patients who had had pelvic irradiation prior to chemotherapy responded to MVMJ, the maximum duration of response being more than 3 years. Twenty-two patients had radiotherapy following their chemotherapy. One of 13 patients not responding to MVMJ had a transient response to radical radiotherapy. Only 1 of 9 patients responding to chemotherapy and then relapsing responded to subsequent radical radiotherapy. Patients with metastatic disease or with recurrent disease after radiotherapy have a worthwhile chance of responding to chemotherapy and achieve durable remissions. In contrast, radiotherapy appears relatively ineffective in patients whose disease progresses or relapses after chemotherapy given as primary treatment with curative intent.

Adult

Issues in patient compliance: the search for therapeutic sufficiency.

Distinguishing among biological, pharmacological, and behavioural variability is essential for proper interpretation of the therapeutic experiment at each return visit. Within the behavioural component, partial compliance refers to all suboptimal levels of concordance between the patient's behaviour and the clinical prescription. However, the assessment of compliance is limited largely by imperfect measures of medication taking which are frequently distant in time and space from the medication-taking event itself. Most studies indicate compliance levels of only 50-70% with antihypertensive regimens as well as considerable variance from day to day and person to person. Therapeutic outcome may be a misleading method to assess the sufficiency of a regimen because of the high prevalence of suboptimal medication-taking behaviour. In selected situations, prolongation of pharmacological effect may compensate for imperfect medication-taking behaviour, confirmed by electronic medication monitors. Such pharmacodynamic prolongation exemplifies therapeutic sufficiency, a new paradigm for therapeutics in the 1990s.

Antihypertensive Agents

High-dose epinephrine improves the return of spontaneous circulation rates in human victims of cardiac arrest.

STUDY OBJECTIVES: To evaluate the return of spontaneous circulation (RSC) rates in human victims of cardiac arrest treated with standard doses of epinephrine (SDE) or high-dose epinephrine (HDE). DESIGN: Prospective case series. SETTING: A university hospital emergency department during 1987 through 1989. PARTICIPANTS: Forty-nine adult victims of nontraumatic cardiac arrest. INTERVENTIONS: At the discretion of the treating physician, patients received epinephrine in bolus doses ranging from 1 to 15 mg. HDE was defined as a dose of at least 0.2 mg/kg; smaller doses were defined as SDE. Patients were grouped as +RSC if they developed a sustained spontaneous palpable pulse or blood pressure and as -RSC if they did not develop a pulse or blood pressure. MEASUREMENTS: Patients were grouped as +RSC if they developed a sustained spontaneous palpable pulse or blood pressure and as -RSC if they did not develop a pulse or blood pressure. Patients were also grouped by their presenting rhythm. Potentially perfusing rhythm was electromechanical dissociation or ventricular tachycardia. Nonperfusing rhythm was asystole or ventricular fibrillation. Rates were analyzed using the Fisher exact test and the two-tailed unpaired t test. HDE improved the rate of initial resuscitation (P = .008). The effect was greatest in patients with nonperfusing rhythms (P = .014) and disappeared when evaluating patients with potentially perfusing rhythms. No patient survived to hospital discharge. CONCLUSION: High-dose epinephrine improves initial resuscitation rates in human victims of cardiac arrest. Its greatest effect is in patients with a nonperfusing rhythm.

Aged

Arthritic presentation of childhood leukaemia.

Three cases of childhood acute lymphatic leukaemia masquerading as juvenile chronic arthritis are presented. All had symptoms and signs for at least 4 months before leukaemia was diagnosed and in two the full blood count was normal at presentation. The importance of a high index of suspicion is emphasized, particularly if the white cell count is low.

Adolescent

A phase II study of ifosfamide in endometrial cancer.

Around 32% of all patients with endometrial carcinoma relapse after primary therapy. The outlook for these patients is poor. Ifosfamide (IFX) has activity in a number of gynaecological malignancies and was selected for evaluation in this disease. The aims of this study were to assess the activity and toxicity of IFX in recurrent endometrial carcinoma no longer amenable to radical local treatment. In all, 16 evaluable patients with symptomatic advanced metastatic or recurrent disease entered a phase II study of this drug. Patients received IFX (5 g/m2) as a 24-h infusion, with mesna (8 g/m2) given during and for 12 h following IFX to prevent urothelial toxicity. Treatment was repeated every 21 days. Two patients showed evidence of response [one complete response (CR) of 3 months and one partial response (PR) lasting 5 months]. Most patients experienced nausea and vomiting, and WHO grade 3/4 alopecia invariably occurred after two or more cycles. Four patients developed severe (grade 3/4) IFX/mesna CNS toxicity, and four other patients had mild (grade 1/2) CNS toxicity. Significant myelosuppression was seen in 3/41 cycles. Haematuria was uncommon and invariably mild. There were two toxic deaths (one due to grade 4 CNS toxicity and one due to septicaemia). IFX has activity in endometrial carcinoma, but responses are of limited duration and toxicity is considerable.

Adenocarcinoma

Microinfusion of bombesin into the hypothalamic paraventricular nucleus produces hypothermia in the insulin-pretreated rat.

Bombesin-like peptides are widely distributed in the mammalian central nervous system and participate in the regulation of a variety of autonomic functions. Central injection of bombesin produces hypothermia at normal ambient temperatures, but only if the rat has been food-deprived or made hypoglycemic with insulin. Two experiments were conducted to reevaluate the impact of bombesin microinfusion into the hypothalamic paraventricular nucleus (PVN) on core body temperature and feeding behavior. In Experiment 1, bombesin (0.05 and 0.1 microgram/1.0 microliter) produced hypothermia, but not hypophagia, in rats (n = 5) pretreated with insulin (10 U/kg; IM). Since a similar response was observed in rats with injection sites adjacent to the PVN, a smaller injection volume was evaluated in Experiment 2. Hypothermia, but not hypophagia, was observed in rats (n = 5) pretreated with insulin following bombesin (0.025 and 0.05 micrograms/0.5 microliter). Bombesin did not produce hypothermia in rats with injection sites outside of the PVN. These findings suggest that the PVN is a sensitive site for bombesin-induced hypothermia.

Animals

Effects of chemotherapy on fertility.

Over recent years radical improvements in the treatment of malignant disease have resulted in the cure of patients in or approaching reproductive age, and with that cure, the effects on gonadal function have become apparent. Gonadal failure is particularly important in Hodgkin's disease, germ cell tumours, choriocarcinoma, and leukaemia, diseases of young people which are largely curable. Premature ovarian and testicular failure are easily missed by doctors concerned primarily with the erradication or arrest of a life-threatening disease, but for the patient the hormonal, psychological and social sequelae of treatment may be devastating. In this article we review the effects of chemotherapy on gonadal function and discuss the management of gonadal failure.

Antineoplastic Agents

Refeeding attenuates bombesin-induced hypothermia in the rat.

The tetradecapeptide bombesin is a potent agent in producing hypothermia when injected centrally. Bombesin-induced hypothermia at normal ambient temperature occurs under conditions of food deprivation or insulin-induced hypoglycemia. This experiment examined the effect of refeeding on the duration of bombesin-induced hypothermia. Rats (n = 7) received microinfusions of bombesin (0.1 microgram/1.0 microliter) into the preoptic area under separate conditions of food deprivation (18 h) and insulin pretreatment (10 U/kg, IM). Core body temperature was evaluated over a period of 4 h with or without food available during testing. Hypothermia was observed under all conditions during the first 2 h. Food-deprived and insulin-pretreated rats not permitted access to food remained hypothermic until at least 4 h following bombesin. These results are discussed in terms of the possible role of glucose availability in the production and duration of bombesin-induced hypothermia.

Animals