Search PubMed⌕ Search

Biomedical subjects

C Barton

Publications and source records attributed to C Barton.

At least 73 records · Page 4Linked to original sources

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↗

Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients.

The possibility that weight loss in cancer patients may be augmented by tumour produced catabolic factors, which stimulate lipid mobilisation, was investigated in a group of cancer patients with total body weight loss ranging from 0 to 50%. The serum and urine lipolytic activity has been determined using freshly isolated murine adipocytes in an in vitro assay. As a control group, we have used patients with Alzheimer's disease, in which some patients may lose a considerable amount of weight, without an obvious cause. The serum lipolytic activity for the Alzheimer's group with weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1 serum) was not significantly different from the group without weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1) or from a healthy control group (0.07 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1), but all three groups were significantly (P less than 0.005) lower than the cancer patient group (0.20 +/- 0.03 mumols glycerol 10(5) adipocytes-1 ml-1), irrespective of weight loss. A similar difference between the cancer and the control group was observed for the urinary lipolytic activity (0.67 +/- 0.03 versus 0.28 +/- 0.03 mumols glycerol released 10(5) adipocytes-1 mg creatinine-1 respectively, P less than 0.01). Weight loss in animals bearing the MAC16 adenocarcinoma was paralleled by a corresponding rise in serum lipolytic activity which peaked when the loss of carcass weight was 16%. A similar decrease in serum lipolytic activity was also observed in cancer patients at high percentages loss in body weight. However, a linear relationship was observed between both the serum and urinary lipolytic activity and weight loss in cancer patients (correlation coefficients 0.79 and 0.70 respectively) when the total body weight loss did not exceed 20%. This suggests that weight loss in cancer patients may be attributed, at least in part, to an, as yet, unidentified lipolytic factor.

Adipose Tissue↗

Alterations in serum lipolytic activity of cancer patients with response to therapy.

The effect of chemotherapy on the serum lipid mobilising activity of a group of cancer patients with or without weight loss has been determined. The pre-treatment level of serum lipolytic activity in all cancer patients, with or without weight loss, was higher than normal controls (0.22 +/- 0.01 versus 0.06 +/- 0.01 mumols glycerol released ml-1 serum respectively). The pre-treatment levels of lipid mobilising activity in the patients serum was proportional to the extent of weight loss (correlation coefficient 0.81), if the extent of weight loss was small (less than 14 kg). Patients who showed a positive response to chemotherapy also showed a decrease in their plasma levels of lipolytic activity, while a patient who showed no response to therapy also showed no change in the serum lipolytic activity. There was no correlation between the serum lipolytic activity and response to megestrol acetate, a synthetic orally active progestogen, which is currently under investigation as an anticachectic agent. Serum from cancer patients showed lipolytic activity which was retained on a DEAE cellulose column and eluted by a salt gradient, in contrast with normal controls. Response to chemotherapy was associated with a decrease of the retained material, although the profile did not return to the normal state. These results need confirmation in a larger group of patients using more specific methods to determine tumour lipolytic activity, but suggest that it may be possible to monitor response to therapy by measurement of the serum lipolytic activity.

Female↗

Improved compliance measures: applications in an ambulatory hypertensive drug trial.

To assess the value of improved monitoring of medication-taking behavior in a drug trial, we employed a modified pill vial with microcircuitry to record the precise times when the vials were opened. After a 3-week placebo washout period, 21 ambulatory subjects with mild hypertension (mean age, 57 years; 67% men; 76% white) randomly received isradipine or enalapril twice daily in a double-blind titration during 10 weeks. Both drugs achieved a 13% reduction in sitting diastolic blood pressure (p less than 0.01) with minimal symptomatic or laboratory toxicity. Although pill counts indicated near-perfect compliance (92% to 99% for both groups), the electronic monitor showed that fewer than half of all openings occurred at the prescribed interval of 12 +/- 2 hours. Modest overdispensing was documented in the 3 days before scheduled visits. The monitor confirmed that pill count misclassified compliance sufficiency in 22% of visits and permitted more discrete attribution for drug-associated adverse reactions and secondary resistance to treatment. We conclude that the electronic monitor reduces ambiguity about medication compliance and helps interpret both the biology and pharmacology of the trial.

Antihypertensive Agents↗

Prediction of outcome of cardiopulmonary resuscitation from end-tidal carbon dioxide concentration.

Capnography is a valuable tool in the management of cardiac arrest, since end-tidal CO2 (PetCO2) correlates well with cardiac output and there are no other suitable noninvasive ways to measure this important variable during resuscitation. Animal studies also suggest that PetCO2 correlates well with the likelihood of resuscitation, but this has never been confirmed in humans. We prospectively studied 55 adult, nontraumatic prehospital cardiac arrest patients. PetCO2 was monitored with an in-line sensor on arrival in the ED and throughout the arrest, which was managed by the usual advanced cardiac life-support treatment guidelines. Chest compression was carried out mechanically. Patients were assessed for return of spontaneous pulse as evidence of initial resuscitation; hospital discharge and long-term survival were not examined. Fourteen patients developed spontaneous pulses and were resuscitated, and 41 were not. The length and aggressiveness of treatment and CPR were not different between the two groups, nor were there differences in down time, resuscitation time, or other factors known to affect outcome. Patients who developed a pulse had a mean PetCO2 of 19 +/- 14 (SD) torr at the start of resuscitation, and those who did not had a mean PetCO2 of 5 +/- 4 torr (p less than .0001). This difference was significant both in nonperfusing rhythms (asystole and ventricular fibrillation) and in potentially perfusing rhythms (electromechanical dissociation). An initial PetCO2 of 15 torr correctly predicted eventual return of pulse with a sensitivity of 71%, a specificity of 98%, a positive predictive value of 91%, and a negative predictive value of 91%. A receiver operating curve was generated for sensitivity and specificity of the test at varying PetCO2 thresholds.

Aged↗

Identification and molecular characterization of shrunken-2 cDNA clones of maize.

Mutation at the shrunken-2 (Sh2) locus of maize, a gene described more than 40 years ago, greatly reduces starch levels in the endosperm through its effect on the starch synthetic enzyme ADP-glucose pyrophosphorylase, an enzyme thought to be regulatory in this biosynthetic pathway. Although our previous work has suggested that Sh2 is a structural gene for this enzyme, we have also reported data compatible with Sh2 acting post-transcriptionally. In this study, we took advantage of a transposable element-induced Sh2 allele, its progenitor, and revertants to identify a clone for this locus. Although the cloning and identification were done independently of any knowledge concerning the product of this gene, examination of the deduced amino acid sequence revealed much similarity to known ADP-glucose pyrophosphorylase subunits of plants and bacteria, including regions involved in substrate binding and activator binding. Little sequence similarity, however, was found at the DNA level. These observations provide direct evidence that Sh2 encodes a subunit for endosperm ADP-glucose pyrophosphorylase. Analysis of several phenotypically wild-type alleles arising from a mutable sh2-Ds allele revealed one unexpected case in which DNA sequences of Sh2 were rearranged in comparison with the progenitor Sh2. In contrast to wild type, the Ds-induced sh2 allele conditions at least two transcripts in the endosperm.

Alleles↗

Three-monthly GnRH agonist (buserelin) for prostatic cancer.

A new slow release formulation of buserelin given as a 3-monthly depot injection has been evaluated in 4 patients with advanced prostatic cancer previously maintained on shorter acting depots. Treatment was maintained for a mean period of 21 months. Steady state urinary buserelin concentrations were reached by the beginning of the third treatment week and maintained until the end of the third treatment month. Serum testosterone remained suppressed in the castrate range for the duration of the study. Seven previously untreated patients were entered into treatment. Serum testosterone was suppressed into the castrate range between the seventh and fourteenth days after implantation. This preparation offers an advantage for the patient and clinician over existing methods of GnRH analogue administration and will now enter further clinical trial.

Buserelin↗

Bombesin produces hypothermia in insulin treated rats.

Previous studies have shown that central injection of bombesin produces hypothermia in food-deprived, but not food satiated rats at normal ambient temperatures. The present study evaluated the effects of bombesin on core body temperature (Tb) and feeding behavior in rats pretreated with insulin. Administration of bombesin (0.25, 0.5, and 1.0 microgram) into the lateral cerebral ventricle produced hypothermia in rats injected with insulin (10 U/kg; i.m.). No significant change in core temperature was observed in control rats following bombesin. Insulin treatments significantly stimulated feeding behavior and the highest dose of bombesin significantly reduced feeding behavior. The results demonstrate bombesin-induced hypothermia under metabolic conditions similar to acute starvation. These findings are consistent with the hypothesis that bombesin-induced hypothermia in food-deprived rats is directly related to the fasting state.

Animals↗

Bombesin-induced hypothermia in food-deprived rats.

Three separate experiments were conducted to characterize the effects of bombesin on core body temperature in food-deprived rats and further evaluate the role of food deprivation in this response. Previous research has demonstrated that naloxone reverses bombesin-induced hypothermia in cold-exposed rats. The present study was unable to demonstrate a similar reversal under conditions of food deprivation following naloxone. In a second experiment, cold exposure (11 degrees C) was shown to potentiate bombesin-induced hypothermia in food-deprived rats. Taken together, these data support the notion that bombesin-induced hypothermia in food-deprived and cold-exposed rats represent the activation or disruption of different thermoregulatory mechanism(s). The final experiment evaluated the effects of bombesin microinfusion into the preoptic area of the anterior hypothalamus on core body temperature. Animals were tested under conditions of food satiation, food deprivation, and insulin pretreatment. Bombesin produced hypothermia in food-deprived and insulin-treated rats. No hypothermia was observed in food-satiated rats. Our finding supports the notion that factors associated with the fasting state are important for the production of hypothermia by bombesin in food-deprived rats.

Animals↗

The minimizing of blaming attributions and behaviors in delinquent families.

Parents' data were evaluated in three studies of families with a delinquent adolescent. Families were provided with different forms of a positive versus negative interactional (attributional) context. Study 1 demonstrated that the negative context elicited significantly more negative behaviors than did the positive context when parents interacted with each other and with their delinquent adolescent. Study 2 demonstrated that the dispositional attributions of parents were influenced by the manipulation of set, with a dissatisfied set producing negative blaming attributions and a satisfied set producing nonblaming, positive attributions. Study 3 demonstrated that parents' negative sets regarding their adolescent's negative behaviors, once established and discussed by the family for 5 min, were unresponsive to a subsequent positive reattribution regarding those behaviors. Taken together, the data provide some support for reattribution techniques such as relabeling. Yet, the data question the ease with which such techniques can be successful and challenge proponents of such techniques to develop methodologically sound empirical demonstrations of their effectiveness.

Adolescent↗

Bombesin-induced hypothermia in the insulin-treated rat: effect on tail-skin temperature.

Bombesin-like peptides are widely distributed in the mammalian central nervous system and appear to participate in the regulation of a variety of autonomic functions. Bombesin has been shown to alter feeding behavior, locomotor activity, and thermoregulation. Microinfusion of bombesin into the preoptic area of the hypothalamus produces a reduction in core body temperature, but only if the rat has been cold-exposed, food-deprived, or pretreated with insulin. The mechanism for bombesin-induced hypothermia under the latter two conditions is unknown. The present study evaluated the possible contribution of peripheral heat loss mechanisms in bombesin-induced hypothermia. Rats were administered insulin (10U/kg, Regular Iletin I i.m.) or saline followed by an intrahypothalamic injection of bombesin (.05 microgram/.25 microliter) or peptide vehicle. Rectal and tail-skin temperatures were measured continuously for 120 min. Changes in temperature were evaluated at 30, 60, 90, and 120 min., using analysis of variance. As previously demonstrated, bombesin produced hypothermia in rats pretreated with insulin. This reduction in core temperature was not associated with any significant alteration in tail-skin temperature. Results suggest that bombesin-induced hypothermia in rats pretreated with insulin may not be mediated by an increase in peripheral heat loss.

Animals↗

The impact of hydronephrosis on renal function in patients treated with cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors.

We analysed renal function before and after chemotherapy in 130 patients with large (greater than 5 cm in diameter) abdominal masses from malignant non-seminomatous germ cell tumors (NSGCT). The mean glomerular filtration rate assessed by 51Chromium (51Cr) ethylenediamine tetraacetic acid (EDTA) clearance was lower in 46 patients with radiologic evidence of hydronephrosis than in 84 patients with abdominal masses but no hydronephrosis (102 ml/min versus 139 ml/min; P less than 0.01). Patients with hydronephrosis who were treated with cisplatin-based chemotherapy demonstrated a slight early improvement in renal function followed by a fall, in contrast to those treated with carboplatin-based chemotherapy in whom renal function improved. Patients with hydronephrosis who showed no improvement in glomerular filtration rate after the first course of chemotherapy were at an increased risk of renal atrophy and chronic renal damage developing. Long-term renal toxicity may be avoided in these patients either by the use of carboplatin or by the use of drainage procedures such as ureteric stenting or nephrostomy.

Adolescent↗

Childhood leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities in relation to nuclear establishments in the vicinity.

During the years 1972-85, 89 children aged 0-14 were registered with leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities. Two nuclear establishments are located within the health authorities, and a third is situated nearby. Fifty of the 143 electoral wards in the two district health authorities lie wholly within, or have at least half their area lying within, a circle of radius 10 km around the establishments. In those 50 electoral wards 41 children aged 0-14 were registered with leukaemia, 28.6 registrations being expected on the basis of leukaemia registration rates in England and Wales (incidence ratio = 1.4, p less than 0.05). This excess was confined to children aged 0-4, among whom there were 29 registrations of leukaemia, 14.4 being expected (incidence ratio = 2.0, p less than 0.001). In the remaining 93 electoral wards there was a small and non-significant increase in the number of registrations of leukaemia at age 0-14 (48 observed, 40.8 expected; incidence ratio = 1.2). There was no obvious trend in the incidence of childhood leukaemia over the 14 years and the overall occurrence of the malignancy in the 143 electoral wards was consistent with a random distribution. In the surrounding Oxford and Wessex Regional Health Authorities the number of registrations of leukaemia at age 0-14 was virtually identical with that expected on the basis of registration rates in England and Wales (362 observed, 372.5 expected; incidence ratio = 1.0). These data indicate that in the two district health authorities studied there was an excess incidence of childhood leukaemia during 1972-85 in the vicinity of the nuclear establishments. In the West Berkshire and Basingstoke and North Hampshire District Health Authorities an average of 60,000 children aged 0-14 lived within a 10 km radius of a nuclear establishment each year. The normal expectation of leukaemia in these children was two cases a year, whereas the recorded incidence was three cases per year, representing one extra case of leukaemia each year among these 60,000 children.

Adolescent↗