Search PubMed⌕ Search

Biomedical subjects

P Wallace

Publications and source records attributed to P Wallace.

At least 109 records · Page 6Linked to original sources
PubMed1990

Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans.

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of whole-body and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (approximately 460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9, 12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-VG] x blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 +/- 17 mumol.kg-1.min-1 and 3656 +/- 931 mumol.min-1.leg-1, respectively. Leg blood flow increased twofold from 6.0 +/- 1.7 to 11.7 +/- 3.1 dl/min (P less than 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P less than 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 +/- 0.12, 2.22 +/- 0.30, 2.92 +/- 0.42, 3.02 +/- 0.41 mM, NS between last 2 values) with a half-maximal effective glucose concentration (EG50) of 5.3 +/- 0.4 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity.

The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (approximately 4.5, approximately 8.3, approximately 13.5, and approximately 23.5 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference x blood flow). With this approach, we found that rates of whole-body and leg glucose uptake were significantly lower in obese than in lean subjects at each glucose plateau. Leg blood flow rates increased from 4.3 +/- 0.4 to 6.5 +/- 0.8 dl/min over the range of glucose in lean subjects (P less than 0.05) but remained unchanged in obese subjects. The apparent maximal capacity (Vmax), based on whole-body and leg glucose uptake, was reduced in obese compared with lean subjects, but the apparent Km was similar in the lean and obese subjects (6-9 mM, NS). To assess the affinity of muscle for glucose extraction independent of changes in muscle plasma flow, we determined the mean half-maximal effective glucose concentration (EG50) and found it was similar in the lean and obese subjects (6.0 +/- 0.3 vs. 6.0 +/- 0.8 mM, NS). We conclude that 1) the kinetics of in vivo insulin-mediated glucose uptake in skeletal muscle in human obesity are characterized by reduced Vmax but normal Km; 2) the EG50 for insulin-mediated glucose extraction in skeletal muscle was 6 mM in both lean and obese subjects, consistent with a Km characteristic of the glucose-transport system; 3) obese subjects were unable to generate increases in blood flow in response to hyperglycemia under hyperinsulinemic conditions, and this contributed significantly to lower rates of leg and whole-body glucose uptake.

Adult↗
PubMed1990

Loglinear models, sexual behavior and HIV: epidemiological implications of heterosexual transmission.

An analysis is presented of sexual behaviour data from a "random" sample (n = 780) of the adult population of England and Wales. Sex stratified frequency distributions of the reported number of sex partners/time were analysed for heterosexuals, demographic characteristics associated with the number of sex partners/time were identified, and epidemiological parameters (the basic reproductive rate of HIV and the doubling time of the epidemic) were calculated. These analyses suggest that the size of the group at risk for acquiring the virus by heterosexual transmission may be large and that the age of first sexual intercourse (for males and females) is decreasing in younger cohorts. Members of the potential heterosexual at-risk group may be identified by demographic variables such as marital status (males and females) and age (females only), but not by socioeconomic class. The epidemiological implications of our results for the heterosexual transmission of HIV are discussed.

Adolescent↗
PubMed1989

Coping with patients' problem drinking.

Confronting patients appropriately is a difficult skill to master. The practitioner must first overcome his own inherent biases and feelings of discomfort before tackling the patient on threatening issues. This problem is compounded by delay when a patient has seen his GP for a number of years before a review of the notes reveals the hitherto unsuspected diagnosis.

Adult↗
PubMed1989

Lipid metabolism in non-insulin-dependent diabetes: effects of long-term treatment with fructose-supplemented mixed meals.

Using fructose in the diabetic diet remains controversial primarily because of the potential for adverse effects on serum lipids. Therefore, lipid metabolism was evaluated in five NIDDM subjects (as inpatients) for 3 mo before and after ingestion of mixed meals containing 13% of calories as fructose. Triglyceride (TG) transport in very-low-density lipoproteins (VLDL) was assessed by multicompartmental analysis of VLDL-TG specific activity after injection of 3H-2-glycerol. There were no deleterious changes in lipid metabolism after fructose supplementation. The fructose diet produced no changes in serial free fatty acids (from 0.39 +/- 0.04 to 0.51 to 0.12 mmol/L), total cholesterol (from 5.43 +/- 0.52 to 5.53 +/- 0.57 mmol/L), high-density lipoproteins (from 0.91 +/- 0.08 to 0.93 +/- 0.08 mmol/L), low-density lipoproteins (from 3.10 +/- 0.52 to 2.92 +/- 0.47 mmol/L), VLDL-TG production (from 2.11 +/- 0.36 to 2.07 +/- 0.30 mmol/h), and fractional catabolic rate (from 0.186 +/- 0.014 to 0.196 +/- 0.03/h). Physiologic amounts of fructose are unlikely to have adverse effects on lipid metabolism when consumed by these diabetic subjects in place of sucrose in mixed meals for a prolonged period.

Blood Glucose↗
PubMed1989

A pilot study of sexual lifestyle in a random sample of the population of Great Britain.

Rates of sexual-partner change and patterns of high-risk behaviour are important determinants of the spread of HIV. We carried out a survey to assess the feasibility of studying sexual lifestyle in a random sample of the British population, aged 16-64 years, in November 1987. Two thousand and seventy-seven households were selected using a multi-stage probability sampling procedure. Seven hundred and eight-five adults participated in a structured interview. The schedule included demographic details, attitudes to AIDS, numbers of sexual partners in different time periods, history of homosexuality and contact with prostitutes. An interview was obtained in 61% of households where contact was made, but the overall response rate was low (48%). There was marked variability between individuals in numbers of sexual partners in given time intervals. Men and women in younger cohorts had experienced first sexual intercourse earlier and had higher numbers of sexual partners than people in older cohorts. Surprisingly few reported high-risk behaviour such as homosexuality and use of prostitution. The methodological problems in trying to obtain unbiased and valid data on sexual behaviour are discussed. Further work is necessary to improve the response rate and questionnaire design.

Adolescent↗
PubMed1989

Effects of aging on insulin secretion.

Aging is associated with hyperinsulinemia, but reports vary on the contributions of altered insulin clearance versus insulin secretion to this phenomenon. To elucidate the role of insulin secretion in the hyperinsulinemia of aging, 10 elderly (age 66 +/- 4 yr, body mass index 25 +/- kg/m2) and 8 young (age 30 +/- 5 yr, body mass index 24 +/- 3 kg/m2) subjects were studied to determine rates of insulin secretion in response to fasting, mixed meals, and intravenous glucose administration. Insulin secretion was determined with a two-compartment model based on individual C-peptide kinetic parameters derived after bolus injection of biosynthetic human C-peptide. Basal insulin secretion rates were increased in elderly subjects (82.5 +/- 9.0 vs. 62.8 +/- 6.1 pmol.min-1.m-2; P less than .05). This was reflected in elevated serum insulin levels in elderly subjects (62.8 +/- 10.1 vs. 41.1 +/- 5.0 pM, P less than .05). During a 24-h mixed-meal profile, elderly subjects had an increase in their glucose response (P less than .01 by analysis of variance [ANOVA]) and total insulin secretion (261 +/- 28 vs. 195 +/- 22 nmol.24 h-1.m-2; P less than .05) compared with young subjects. However, the relative total increases in both glycemia and insulin secretion, calculated as a function of basal levels, were similar between the groups (both NS). To experimentally control for differences in glycemia, both groups underwent a 16.8-mM hyperglycemic clamp and a stepped intravenous glucose infusion to match glycemia. Under these steady-state and dynamic conditions, insulin secretion profiles were nearly identical (NS by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Teenagers' health concerns: implications for primary health care professionals.

Four hundred and eighty five students, aged 13-15 years, at nine comprehensive schools in the London borough of Brent completed a questionnaire about health-related behaviours and health concerns. Among general health concerns, most prominent were weight, acne, nutrition and exercise. There appeared to be a considerable unmet need to discuss sexual development, sexually transmitted diseases and contraception. A substantial proportion (16% of the girls and 3% of the boys) reported sexual abuse, but few wished to discuss this with a doctor or nurse. Although a relatively high percentage of the students smoked and a smaller percentage used alcohol or drugs regularly, there was little concern or interest in discussing these matters with a health professional. Most of the schools did not have a formal health education programme, and in none of them were health professionals available for discussion of the issues under study. There appears to be a need for more comprehensive health education in schools and for primary health care professionals, particularly general practitioners to raise these issues opportunistically with their teenage patients.

Adolescent↗
PubMed1988

Randomised controlled trial of general practitioner intervention in patients with excessive alcohol consumption.

OBJECTIVE: To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption (35 U or more a week for men, 21 U or more for women). DESIGN: Randomised, controlled double blind trial over 12 months with interim assessment at six months. SETTING: Group practices (n = 47; list size averaging 10,000) recruited from Medical Research Council's general practice research framework, mostly in rural or small urban settings. PATIENTS: Patients recruited after questionnaire survey. Of total of 2571 (61.2%) of 4203 patients invited for interview who attended, 909 (35.4%) stated that in past seven days they had drunk above the limits set for study and had not received advice; they were randomised to control and treatment groups. INTERVENTIONS: Patients in treatment group were interviewed by general practitioner (who had had a training session) and received advice and information about how to reduce consumption and also given a drinking diary. END POINT: Study aimed at detecting a reduction in proportion of men with excessive alcohol consumption of 30% in treatment group and 20% in control group (for women 40% and 20%, respectively) with a power of 90% at 5% level of significance. In addition, corroborative measures such as estimation of gamma-glutamyltransferase activity were included. MEASUREMENTS AND MAIN RESULTS: At one year a mean reduction in consumption of alcohol of 18.2 (SE 1.5) U/week had occurred in treated men compared with a reduction of 8.1 (1.6) U/week in controls (p less than 0.001). The proportion of men with excessive consumption at interview had dropped by 43.7% in the treatment group compared with 25.5% in controls (p less than 0.001). A mean reduction in weekly consumption of 11.5 (1.6) U occurred in treated women compared with 6.3 (2.0) U in controls (p less than 0.05), with proportionate reductions of excessive drinkers in treatment and control groups of 47.7% and 29.2% respectively. Reduction in consumption increased significantly with number of general practitioner interventions. At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men (-2.4 (0.9)IU/l) than in controls (+1.1(1.0)IU/l; t = 2.7, p less than 0.01). Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men. Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups. CONCLUSIONS: If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess. General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities.

Adolescent↗
PubMed1988

Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans.

In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Fasting decreases rates of noninsulin-mediated glucose uptake in man.

Although fasting decreases insulin-mediated glucose uptake (IMGU), its effect on noninsulin-mediated glucose uptake (NIMGU) is not known. To examine this issue we studied seven obese men [mean (+/- SD) age, 36 +/- 5 yr; weight, 91 +/- 13 kg] after an overnight fast (day 0) and 3 days (day 4) and 9 days (day 10) of total fasting and six normal weight men (age, 32 +/- 4 yr; weight, 73 +/- 6 kg) after an overnight and 3 days of fasting. To study NIMGU, somatostatin (0.16 micrograms/kg.min) was infused to create severe insulin deficiency and [3H]3-glucose to measure glucose disappearance (Rd), while serum glucose was sequentially clamped at a level of about 4.7 mmol/L for 180 min and about 11 mmol/L for an additional 100 min. The results from the last 60 min of each glycemic plateau were used for analysis. Under these conditions insulin action is absent and Rd = NIMGU. Since under conditions of euglycemic insulinopenia, NIMGU into noncentral nervous system tissues is negligible, and central nervous system (CNS) glucose uptake saturates at physiological glucose concentrations, it follows that at a glucose level of about 4.7 mmol/L, NIMGU reflects CNS glucose uptake and at about 11 mmol/L, NIMGU reflect CNS plus non-CNS tissues. Thus, non-CNS NIMGU = NIMGU at 11 mmol/L - NIMGU at about 4.7 mmol/L. The obese subjects' mean weight fell to 88 +/- 5 kg on day 4 and 85 +/- 5 kg on day 10 (P less than 0.001 between all values). The mean basal serum glucose level fell from 5.3 +/- 0.1 on day 0 to 4.2 +/- 0.2 and 3.8 +/- 0.2 mmol/L on days 4 and 10, respectively (P less than 0.01 between all values). During insulinopenia plasma FFA and serum beta-hydroxybutyrate levels on day 10 were 3- and 30-fold higher than the basal prefast levels, respectively. Noninsulin-mediated glucose clearance at about 4.7 mmol/L did not change during fasting [0.0016 +/- 0.0001 (day 0) vs. 0.0016 +/- 0.0001 (day 4) and 0.0014 +/- 0.0001 L/kg.min (day 10); P = NS between all values]; at about 11 mmol/L noninsulin-mediated glucose clearance fell from 0.0016 +/- 0.0001 on day 0 to 0.0001 +/- 0.0001 dL/kg.min on day 10 (P less than 0.001). Results in the lean group were similar to those in the obese group after a 3-day fast.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus.

Increased interest in using omega-3 fatty acids led us to examine their metabolic effects in six men with type II (non-insulin-dependent) diabetes mellitus. After 1 month of a diet supplemented with these fatty acids, the patients' fasting glucose rose from 13.1 +/- 1.3 to 15.3 +/- 1.3 mmol/L (P = 0.03) and glucose area during a mixed meal profile rose by 22% (P = 0.04). Basal hepatic glucose output rose from 97 +/- 9 to 122 +/- 8 mg/m2 . min (P = 0.004) but glucose disposal rates measured by euglycemic glucose clamp were unchanged. Fasting insulin levels were similar; peak insulin levels stimulated by meals or intravenous glucagon fell by 30% and 39%, respectively. Plasma and erythrocyte content of omega-3 fatty acid rose significantly. After omega-3 fatty acid withdrawal, fasting glucose returned to baseline. Omega-3 fatty acid treatment in type II diabetes leads to rapid but reversible metabolic deterioration, with elevated basal hepatic glucose output and impaired insulin secretion but unchanged glucose disposal rates. Caution should be used when recommending omega-3 fatty acids in type II diabetic persons.

Blood Glucose↗
PubMed1987

The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus.

We compared the glucose-lowering effect of proinsulin, the precursor molecule of insulin, with that of insulin itself. In patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom proinsulin (0.2 U per kilogram of body weight) was subcutaneously injected at 9 a.m., fasting glucose levels (247 +/- 22 mg per deciliter [+/- SEM]) became normal within six hours and elevated rates of hepatic glucose output were lowered. The response to regular insulin (0.2 U per kilogram) was of similar magnitude but faster. Glucose clearance was stimulated less by proinsulin, reflecting its preferential action in suppressing glucose output. Hypoglycemia occurred in five of nine insulin-treated patients, but in only one of nine proinsulin-treated patients. After proinsulin injection at bedtime (30.5 +/- 4 U), serum proinsulin concentrations reached a peak by five hours and declined gradually thereafter. Fasting hepatic glucose output became normal, and euglycemia was sustained without overnight hypoglycemia. Proinsulin reduced plasma glucose more effectively than an equal unit dosage of NPH insulin, but since higher doses of NPH insulin were not used, no conclusions could be drawn about the relative desirability of these preparations for clinical use. We conclude that subcutaneously injected proinsulin has prolonged pharmacokinetics in plasma and can normalize plasma glucose in NIDDM characterized by severe hyperglycemia; as compared with the hypoglycemic effects of regular insulin, those of proinsulin are mostly due to suppression of hepatic glucose output, with little stimulation of glucose disposal and less hypoglycemia; and proinsulin may have a role in the treatment of NIDDM.

Blood Glucose↗
PubMed1987

Evaluation of splenectomy in large granular lymphocyte leukaemia.

We performed splenectomy in four patients with severe neutropenia (less than 0.5 X 10(9)/l), recurrent infections, and splenomegaly associated with large granular lymphocyte leukaemia. Prior to splenectomy, elevated levels of neutrophil-reactive IgG were detected in sera of all three patients tested. In all patients, enlargement of the spleen was due to a characteristic lymphoid infiltration of red pulp cords. Splenectomy resulted in an increased neutrophil count greater than 0.5 X 10(9)/l in all patients; this response was sustained in two patients who benefited clinically by a dramatic reduction in frequency of infections. Poor clinical response was associated with elevated levels of antineutrophil antibody post-splenectomy. All four patients had an increase in number of circulating large granular lymphocytes post-splenectomy; one patient who had attained a sustained neutrophil response died of an accelerated lymphoproliferative disorder 19 months post-splenectomy. We conclude that splenectomy may be of value in correcting severe neutropenia and reducing infections in some patients with large granular lymphocyte leukaemia. However, splenectomy appeared to be of no value in treatment of the underlying lymphoproliferative disorder.

Evaluation Studies as Topic↗
PubMed1987

In vivo regulation of non-insulin-mediated and insulin-mediated glucose uptake by epinephrine.

In vivo glucose uptake (Rd) occurs via two mechanisms: 1) insulin-mediated glucose uptake (IMGU), which occurs in insulin-sensitive tissues, and 2) noninsulin-mediated glucose uptake (NIMGU), which occurs in both insulin-sensitive and insulin-insensitive tissues. Thus, in the postabsorptive (basal) state Rd = IMGU + NIMGU. To determine whether these two pathways for in vivo glucose disposal are regulated independently, we studied the effect of stress levels of epinephrine (EPI) on IMGU and NIMGU in seven normal men after an overnight fast. To study NIMGU, somatostatin (600 micrograms/hr) was infused to suppress endogenous insulin secretion, and glucose turnover was measured isotopically while the serum glucose level was clamped at about 200 mg/dL for 240 min. Separate studies were done during the infusion of saline or EPI (0.2 microgram/kg X min). The final 120 min of each study were used for data analysis. Under these conditions insulin action is absent and Rd = NIMGU. NIMGU was 210 +/- 15 (+/- SEM) and 200 +/- 17 mg/min during saline and EPI treatment, respectively (P = NS). Therefore, EPI has no ability to modulate NIMGU. To measure the effect of EPI on Rd, hyperglycemic (200 mg/dL) hyperinsulinemic clamp (30 mU/M2 X min) studies were performed during the infusion of saline and EPI. EPI decreased Rd by 46 +/- 6% (751 +/- 85 to 405 +/- 43 mg/min; P less than 0.01). When the effect of EPI on IMGU (Rd - NIMGU) was considered separately, the inhibitory effect of EPI was more potent, as indicated by a 61 +/- 12% decrease in IMGU. In conclusion, 1) EPI inhibits IMGU, but has no effect on NIMGU; 2) when NIMGU is taken into account, EPI has a more potent ability to inhibit IMGU than previously found; and 3) the systems responsible for NIMGU and IMGU are independently regulated.

Adult↗