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Biomedical subjects

B Maxwell

Publications and source records attributed to B Maxwell.

16 recordsLinked to original sources

Development and evaluation of an inner city mental health team.

The objective of this study was to examine the development and activity of a Community Mental Health Team, originally targeted to meet the needs of African Caribbean, Asian and homeless populations in an inner city area. The study was based on all (n = 1046) client referrals to the Bristol Inner City Community Mental Health Team between 1987 and 1994. Additional qualitative interviews were held with general practitioners (GPs) from each of the nine practices in the area. The setting was the inner city area of Bristol, an area with a population of around 35,000 27% of whom are from ethnic minority communities. This is an area shown in previous research to have a high level of mental health problems. Trends in referral rates, demographic characteristics and seriousness of psychiatric illness amongst those referred to the Inner City Mental Health Team were the main outcome measures used. In the years studied there were significant increases in the number and proportion of overall referrals from GPs and psychiatrists and decreases in referrals from other agencies. In particular, there were reductions in the referral both of clients from the originally identified target groups and of patients with serious mental illness. GPs tended to refer a greater proportion of patients with less serious mental illness. The results of the study showed that a team originally developed to meet the needs of the homeless and those from ethnic minorities has, with the removal of special project funding, shifted its focus away from the client groups for whom it was originally developed to those with less serious mental health problems. These changes are partially attributable both to changes in the remit of the team, making it more acceptable to GPs, and to a growing acceptance of community-based mental health services among GPs and their patients. Changes in the geographic catchment area served by the team has also played a role in the observed trends. Commissioners of mental health services need to bear in mind the needs of high-risk groups when making contracts. It may be that in order to meet effectively the needs of inner city populations with a high prevalence of mental health problems, there is a need for specialist teams with a specific remit.

Adult↗

Assessment of health risks due to hazardous air pollutant emissions from electric utilities.

Hazardous air pollutant (HAP) emissions from electric utilities were evaluated. Cancer risks, as well as noncancer effects, due to inhalation exposure were assessed for 67 HAPs. Also, cancer risks due to multipathway exposure to radionuclide emissions were assessed. In addition, an assessment of the fate of mercury (Hg) through various environmental media was included. Results suggest arsenic, chromium, and nickel are the HAPs that present the highest cancer risk due to inhalation exposure. For noncancer effects due to inhalation exposure, hydrogen chloride appears to present the greatest potential concern. The risks due to multipathway exposure to radionuclides are estimated to be of similar magnitude to the risks posed by inhalation of arsenic and nickel. Mercury is of potential concern for multipathway exposures because it persists in the environmental and bioaccumulates in the aquatic food web. The study suggests there is a plausible link between Hg emissions from utilities and the Hg found in soil, water, and freshwater fish.

Air Pollutants↗

Translational inhibition by 5'-polycytidine tracts in Xenopus embryos and in vitro.

Introduction of in vitro transcribed mRNA into Xenopus laevis embryos is a useful technique for analyzing gene function. In order to optimize expression of cDNA constructs from in vitro transcribed mRNAs, we examined the translational efficiency of reporter genes that simulated cDNAs synthesized by tailing with deoxyguanosine (dG) before second strand cDNA synthesis. When transcribed in vitro, these cDNAs give rise to RNAs containing a 5'-homopolymeric cytidine (poly(C)) stretch. We observed that the presence of a 5'-poly(C) tract depressed translation of a CAT reporter gene at least 100-fold in Xenopus embryos and up to 5-fold in vitro. This effect was not seen when a 5'-polyadenosine tract was tested. Translational depression was dependent on the phage polymerase used for in vitro transcription: RNAs transcribed by T7 polymerase translated far more poorly than those transcribed by SP6 polymerase. These results have general implications for optimizing expression of cDNA constructs.

Animals↗

Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning.

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.

Acoustic Stimulation↗

Beneficial effects of taurolidine in experimental pancreatitis.

Taurolidine has potent antiendotoxin and antimicrobial effects in vitro. This study assessed the effect of taurolidine in a well-described model of acute pancreatitis. Ninety-five male Wistar rats (250 g) were studied. Pancreatitis was induced by intraductal injection of 50 microliters of a 4% sodium taurocholate solution at a pressure of 25 cm water. Animals were randomly allocated to 1 of 10 groups: 4 groups were used to characterize the model and there were 6 treatment groups. Taurolidine (100 mg/kg) or saline was administered intravenously at Time 1, 4 hr, or 4 and 24 hr following induction of pancreatitis. Serum amylase, endotoxin levels, and blood cultures were assessed at 4 and 24 hr. Survival was documented at 1 week. Serum amylase levels were elevated in animals in whom acute pancreatitis was induced; however, there was no difference in serum amylase between animals treated with taurolidine and those treated with saline. Positive blood cultures were more numerous in saline-treated groups. Treatment with taurolidine was associated with significantly (P < 0.01) lower endotoxin levels (14 +/- 8 pg/ml) compared with saline-treated animals (350 +/- 87 pg/ml). Taurolidine administration significantly improved survival compared with controls, when given at 4, 24, and 4/24 hr postinduction of pancreatitis (P < 0.05). Taurolidine was beneficial in this model of acute pancreatitis.

Acute Disease↗

Involvement of subdivisions of the medial prefrontal cortex in learned cardiac adjustments in rabbits.

Electrical stimulation of area 24 and area 32 of the medial prefrontal cortex (mPFC) in rabbits elicited increases in respiration rate and decreases in heart rate (HR) and blood pressure. However, stimulation in area 25 elicited pressor responses and a biphasic HR response consisting of an initial HR increase followed by an HR decrease. Administration of an alpha-adrenergic receptor antagonist eliminated the pressor response and bradycardiac response produced by area 25 stimulation but it had no effect on the bradycardia elicited by stimulation of area 24 or area 32. Lesions centered on area 32 of the mPFC greatly attenuated the conditioned bradycardiac response elicited by paired tone and paraorbital shock presentations. Lesions of area 24 produced a decrease in discrimination between a reinforced conditioned stimulus and a nonreinforced conditioned stimulus but had no effect on the magnitude of the conditioned response. Area 25 lesions had no effect on any aspect of conditioned responding.

Animals↗

Phase I/II study of recombinant interferon gamma in advanced renal cell carcinoma.

A phase I and II evaluation of 42 patients with advanced renal cell carcinoma treated with recombinant interferon gamma was done. Patients were treated with either a daily 2-hour infusion or 24-hour infusion for 7 days every 3 weeks for at least 2 cycles. Patients who demonstrated stable disease or improvement on therapy then were continued on a maintenance program of 5 days of recombinant interferon gamma administered every 3 to 4 weeks. The initial starting dose was 10 mcg. per m.2 per day with escalations to 30, 100, 300, 1,000 and 3,000 mcg. per m.2. Dose-limiting toxicity occurred at 1,000 to 3,000 mcg. per m.2, and included leukopenia, chills, fevers, rigors and hepatotoxicity as manifested by elevation in the transaminase and bilirubin levels. Tumor responses were seen initially at the 300 mcg. per m.2 dose level. Over-all, of 41 patients evaluable for therapeutic effectiveness 1 demonstrated a complete response 6 months in duration and 3 demonstrated partial responses 2, 9 and 13 months in duration. However, 6 patients demonstrated organ site responsiveness, including resolution of pulmonary lesions (2 complete and 1 partial responses), lymphadenopathy (1 complete and 1 partial responses), a pleural-based lesion in 1 patient with a partial response and complete resolution of hepatic metastases in 1 patient. We conclude that recombinant interferon gamma at a dose of 1,000 to 3,000 mcg. per m.2 for 7 days and repeated every 2 to 3 weeks had demonstrable anticancer activity in patients with metastatic renal carcinoma.

Adult↗

John Hunter: the first surgical scientist.

John Hunter was a brilliant surgeon and teacher, the father of scientific surgery and surgical pathology and founder of the world-renowned Hunterian museum. This essay attempts to answer the following questions. Who was this man? How did he achieve such a remarkable station? Why was he loved by some yet detested by others? When did the poor student start to become the superb teacher? How did he manage to collect the thousands of specimens he left in his museum? What is it about Hunter that makes him so well remembered today, almost 200 years after his death?

Animals↗

Intravesical doxorubicin for prophylaxis in the management of recurrent superficial bladder carcinoma.

Intermittent intravesical doxorubicin chemotherapy was given to 27 patients with multiple recurrent superficial transitional cell carcinoma of the bladder, including 12 who had become refractory to intravesical thiotepa. The starting dose was 60 mg. doxorubicin diluted in 40 to 50 ml. normal saline solution and doses were increased to 90 mg. The duration of instillation was 60 minutes. Treatments were administered every 3 weeks for a total of 8 doses, then every 6 weeks for 2 doses and then every 12 weeks for 2 doses. Therapy then ended for patients who were rendered free of disease. Cystoscopy and urinary cytology studies were performed every 3 months throughout the study. Of the patients 30 per cent had intermittent episodes of dysuria, 26 per cent had urinary frequency, 41 per cent had hematuria and 15 per cent had bladder spasms. None of these toxicities required discontinuation of the drug. Analysis of plasma samples for doxorubicin and metabolites revealed no systemic absorption and there was no myelosuppression. Of the 27 patients 15 (56 per cent) have maintained complete eradication of bladder cancer without any evidence of residual carcinoma detected endoscopically or with urinary cytology. Recurrent disease developed in 9 patients (33 per cent) while on therapy, including 3 with muscle invasion. Cystoscopy has remained grossly negative in 3 patients who have had positive class 5 cytology studies. The median duration of followup in all patients has been 12 months, with a range of 6 to 24 months. We conclude that intravesical doxorubicin is tolerated well and is effective in the management of multiple recurrent superficial transitional cell carcinoma of the bladder.

Administration, Topical↗

Intestinal secretion of mucin in chronically reserpine-treated rats.

Intestinal glycoprotein synthesis and secretion were measured in vivo and in vitro in rats treated for 7 days with reserpine. Goblet cell mucin was measured by radioimmunoassay. Reserpine-treated rats contained 1.4 times more mucin in intestinal tissue than control rats (P less than 0.05) and incorporated [1-14C]glucosamine in vivo at 1.52 times the rate of controls (P less than 0.01). Intestinal slices incubated for 90 min in vivo incorporated 1.4 times more [14C]glucosamine (P less than 0.001) and 3.0 times more [3H]threonine (P less than 0.01) into protein of reserpine-treated tissue than controls. The extra 14C was localized to mucin and to smaller components that had affinity for Concanavalin-A-Sepharose, did not bind to mucin antibody, and were therefore nonmucin glycopeptides. In vitro secretion of mucin was three times greater for reserpine-treated tissue than for control tissue (P less than 0.0001). There was an impairment in the mucin secretory response of reserpine-treated tissue to the addition of cholera toxin. Thus, chronic reserpine treatment results primarily in a generalized increase in the rate of intestinal glycoprotein synthesis, subsequent accumulation in tissues, and an increased (but not fully proportional) secretion of mucin. We speculate that in cystic fibrosis a similar sequence of glycoprotein abnormalities may be responsible for the gradual obliteration of exocrine gland ducts with viscous mucus.

Animals↗

Multiple- and single-unit activity in area 32 (prelimbic region) of the medial prefrontal cortex during Pavlovian heart rate conditioning in rabbits.

Data from both brain lesion and brain stimulation experiments suggest that area 32 of the medial prefrontal cortex (prelimbic area) participates in the acquisition and/or expression of conditioned bradycardia. This report describes experiments designed to determine whether cells in this area of the brain exhibit changes in neural activity during classical conditioning that can be related to these learned heart rate changes. Thus, multiple- and single-unit activity was recorded from area 32 in rabbits during Pavlovian heart rate (HR) conditioning. In the first experiment, neuronal discharge recorded from chronically implanted multiple-unit electrodes in the superficial and deep layers of area 32 increased systematically in response to the presentation of tone conditioned stimuli (CS) paired with paraorbital electric shock as the unconditioned stimulus (US). This tone-evoked increase in multiple-unit activity (MUA) closely paralleled the acquisition of the decelerative HR conditioned response in animals that received paired CS/US presentations, but was of smaller amplitude in animals given unpaired CS/US presentations. Tone-evoked increases in MUA also occurred during tone-alone presentations prior to training, but this activity declined over trials. During extinction, CS-evoked MUA increases also declined over trials. These findings suggest that the CS-evoked increase in neuronal activity in area 32 was associatively produced. A second experiment examined the CS-evoked response of single units (n = 98) in area 32 during differential Pavlovian conditioning, in which one tone (CS+) was consistently followed by the paraorbital shock US and a second tone (CS-) was not. Four types of cells were found: (1) 32% of the cells studied showed no change in response to either CS+ or CS- presentation, (2) 48% showed CS-evoked increases to either CS+ or CS-, (3) 14% showed CS-evoked decreases to CS+ or CS-, and (4) 7% showed a biphasic response, in which an increase was followed by a decrease in activity. These cell types are similar to those previously found in the more dorsal anterior cingulate cortex (area 24) and frontal eyefields (area 8). However, a major difference between the present findings and those of our previous studies of areas 8 and 24 is that in several instances changes in CS-evoked activity in area 32 were significantly greater in response to the CS- than to the CS+, suggesting that some cells in the prelimbic region may code the absence of aversive stimulation, that is, a period of relative "safety."

Acoustic Stimulation↗

Clinical interpretations of the measurement of folic acid and vitamin B12 in neuromuscular disease.

56 patients were studied in an attempt to define neurologic complications associated with folic acid and vitamin B12 deficiency. 2 patients had abnormal levels of vitamin B12. 1 of these showed decreased vibRATORY SENSE IN THE LEGS. 10 of 15 patients with serum folate less than 4.0 ng per ml and 16 of 23 patients with serum folate less than 6.0 ng per ml by radioassay had neurologic abnormalities. The control group demonstrated 17/31 with neurologic abnormalities, a figure not significantly different from the deficient group. It is suggested that more patients with "pure folate deficiency" must be analyzed to eliminate the possible role of toxic effects of alcohol and other diseases of the nervous system in patients with low serum folate and neurologic problems.

Adolescent↗