Search PubMed⌕ Search

Biomedical subjects

T Butler

Publications and source records attributed to T Butler.

At least 55 records · Page 3Linked to original sources

Osmoregulation of vasopressin and thirst: comparison of 20% mannitol with 5% saline as osmotic stimulants in healthy man.

OBJECTIVE: Osmoregulation is normally studied using a 5% saline infusion. This may be deleterious in fluid overloaded patients. Twenty per cent mannitol is another osmotic stimulant. This study aimed to compare 20% mannitol infusion with 5% saline as an osmotic stimulant to thirst and vasopressin secretion in normal volunteers. DESIGN AND PATIENTS: Eight healthy volunteers studied on 2 occasions in random order. Each study involved a 2-hour infusion period of either hypertonic (5%) saline (0.06 ml/kg/h) or hypertonic (20%) mannitol (0.07 ml/kg/h). MEASUREMENTS: Plasma vasopressin (pVp), plasma sodium, plasma osmolality (pOsm), haematocrit (HCT), blood pressure, thirst, blood glucose and volume drunk at end of infusion. RESULTS: Five per cent saline infusion stimulated significantly higher levels of pOsm, pVp and thirst than 20% mannitol. Plasma sodium rose significantly during 5% saline infusion and fell during 20% mannitol infusion. HCT fell and mean arterial pressure rose in both infusions but the changes were not clinically significant. Piecewise linear regression analysis defined the overall threshold for pVp release for the two solutions as 5% saline, 292 mosm/kg and 20% mannitol, 291 mosm/kg, and the post threshold slope as 5% saline, 0.46 pmol/l pVp per mosm and 20% mannitol, 0.30 pmol/l pVp per mosm. The threshold for thirst onset was 5% saline, 291 mosm/kg and 20% mannitol, 290 mosm/kg, and the post threshold slope, 5% saline, 0.58 cm thirst per mosm and 20% mannitol, 0.28 cm thirst per mosm. The differences between the calculated osmotic thresholds and slopes post threshold for the two infusions were not significant for the pVp versus pOsm relationship. The difference between the cumulative volume drunk following the two infusions did not reach statistical significance. Mannitol caused a significant diuresis. CONCLUSIONS: Twenty per cent mannitol infusion is an effective osmotic stimulant to thirst and vasopressin release in normal individuals, but is less potent than 5% saline infusion.

Adult↗

Soluble plasma antigen in experimental Salmonella typhimurium infection in mice.

To detect and characterize Salmonella antigen in blood, outbred CF-1 female mice were inoculated intraperitoneally with S. typhimurium LT-2 and blood was assayed by ELISA for Salmonella common structural antigen. Plasma antigen was detectable early in the course of infection and increased in quantity later in the course of illness when animals showed high grade bacteremia and high counts of splenic bacteria. Antigen was associated with a cell-free plasma fraction of blood, passed through filters with cut-offs of 0.2 mu and molecular mass of 1000 kDa, and was enhanced in detectability after heating to 100 degrees C for 15 min. Antigen was concentrated by diluting plasma 1:4 in 0.1 M EDTA, heating to 100 degrees C, and concentrating the supernate with an ultrafiltration membrane with a molecular mass cut-off of 15 kDa. By gel filtration, antigen was associated with a peak at about molecular mass 300 kDa in heated plasma and a peak at about 380 kDa in unheated plasma. These results indicate that murine typhoid infection results in circulating soluble plasma antigen, which is heat-stable with a molecular mass of approximately 300 kDa.

Animals↗

Pharmacokinetics of ceftriaxone in patients with typhoid fever.

Ceftriaxone in short courses has emerged as an effective alternative to chloramphenicol for the treatment of typhoid fever. To study the pharmacokinetics of ceftriaxone in acute typhoid fever, 10 febrile Nepalese adolescents and young adults with blood culture-positive illness were treated with 3 g of ceftriaxone (intravenous infusion for 30 min) daily for 3 days. On the 1st and 3rd day of treatment, blood and urine samples were collected at defined intervals for measurements of drug concentrations. Kinetic parameters including concentrations at the end of infusion (Cmax) and 24 h after the end of infusion (Cmin), elimination half-life (t1/2), area under the plasma concentration-time curve (AUC), total plasma clearance, renal clearance, percentage excreted in urine, and volume of distribution were estimated. On day 1, mean values were as follows: Cmax, 291 micrograms/ml; Cmin, 21.7 micrograms/ml; plasma t1/2, 5.2 h; AUC, 1,428 micrograms.h/ml; total plasma clearance, 37 ml/min; renal clearance, 19 ml/min; percentage excreted in urine, 49.7%; and volume of distribution, 16.1 liters. Mean values on day 3 were not significantly different from those on day 1. Compared with published values for healthy volunteers who received the same dose, our mean t1/2s and AUCs were lower and our mean total plasma clearances, renal clearances, and volumes of distribution were higher. The good clinical responses of these patients to therapy and the adequate Cmins support the use of ceftriaxone once daily for the treatment of typhoid fever.

Adolescent↗

E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia.

Three cases of acute lymphoblastic leukemia (ALL) with the rare t(17;19)(q22;p13) translocation were investigated for E2A/HLF fusion genes using reverse transcription coupled with polymerase chain reaction (RT-PCR). The patients had C-ALL, F/17 years (case 1) or pre-B ALL, M/11 years (case 2) and M/13 years (case 3). Case 1 had an event-free survival (EFS) of 42 months. Case 2 was ultimately refractory to treatment. Case 3 presented following EFS of 16 months in morphological remission (1% blasts), but with immunological and cytogenetic evidence of active disease, then relapsed, remitted and relapsed. Type II E2A/HLF fusion cDNA was found at diagnosis (cases 1, 2), at presentation (case 3) and in all samples tested, whether with active disease or in complete remission (CR). Case 3 showed, in addition, type I fusion E2A/HLF cDNA at presentation, through induction therapy when there was evidence of active disease, but not in CR. Cases 1 and 3 had bone marrow transplantation while in CR but with residual disease detectable by RT-PCR. All patients have died of ALL. Two cases (2 and 3) had hypercalcemia with bone lesions. No case had any evidence of disseminated intravascular coagulation. This is the first demonstration of the value of RT-PCR for the detection of minimal residual disease in t(17;19) ALL.

Adolescent↗

Heritabilities of clinical chemical traits in chimpanzees.

Clinical chemical measures are commonly used biomarkers of health status in nonhuman primates and may also serve as important covariates or outcome variables in experimental protocols. There is a considerable range of normal variation in most clinical chemical traits and the determinants of this variation have been relatively unexplored in nonhuman primates used as animal models in biomedical research. This study assesses the evidence for genetic determinants of normal variation in nine clinical chemical traits (blood urea nitrogen, creatinine, potassium, sodium, CO2, glucose, albumin, globulin, and total cholesterol concentrations) in an important animal model, the chimpanzee. We found significant moderate heritabilities for potassium, sodium, albumin, globulin, and total cholesterol. The results provide information useful for addressing issues in both genetic management and experimental research.

Age Factors↗

Treatment of acute bacterial diarrhea: a multicenter international trial comparing placebo with fleroxacin given as a single dose or once daily for 3 days.

This study was designed to test the efficacy of 400 mg fleroxacin given orally as a single dose or once daily for 3 days against acute bacterial diarrhea. A group of 508 adults with acute diarrhea were entered into a randomized, double-blind, placebo-controlled, multicenter trial. Patients were examined and asked about numbers of liquid stools daily for 3 days and at 5 days after start of treatment. Repeat stool samples were obtained for culture on days 3 and 5 after start of treatment. A total of 332 patients showed stool cultures positive for bacterial pathogens sensitive to fleroxacin and completed their treatments. Patients treated with fleroxacin, both single-dose and 3-day regimens, showed faster clinical improvement than did placebo-treated patients, as shown by earlier cessation of diarrhea (p < 0.001) and reduction in mean number of loose stools per day on days 2, 3, and 5 after start of therapy (p < 0.05). Bacteriologic efficacy was demonstrated by negative stool cultures for initial pathogens on days 3 and 5 after start of therapy in 94% of patients treated with single doses of fleroxacin and in 93% of patients treated with three doses of fleroxacin as compared with 57% of patients treated with placebo (p < 0.001). Patients with cholera, shigellosis, and infections due to Vibrio parahaemolyticus showed both clinical and bacteriologic responses to fleroxacin treatment, whereas patients with salmonellosis showed only bacteriologic responses. The good overall clinical and bacteriologic responses of most patients with acute bacterial diarrhea of fleroxacin indicate that this convenient single-dose therapy should be advantageous for empiric treatment of certain diarrheal illnesses.

Administration, Oral↗

Comparative efficacies of azithromycin and ciprofloxacin against experimental Salmonella typhimurium infection in mice.

Azithromycin was compared with ciprofloxacin for the treatment of established intracellular infection with Salmonella typhimurium LT-2 in CF-1 mice. For studies of mortality, mice received five times the LD50 of organisms intraperitoneally and were given drugs intragastrically once daily for seven days. For studies of in-vivo antibacterial activity, splenic viable counts were measured in mice that had received 0.5 times the intraperitoneal LD50 and had been given drugs for three days. The MICs of azithromycin and ciprofloxacin, respectively, against LT-2 were 4.0 and 0.03 mg/L. The 50% protective doses of the drugs required to prevent mortality were azithromycin 24.7 mg/kg/day, and ciprofloxacin 30.2 mg/kg/day. Treatment with azithromycin and ciprofloxacin in doses of 25 and 100 mg/kg/day resulted in reduction of mean log10 cfu per spleen. Splenic concentrations of azithromycin up to 8 h after treatment exceeded its MIC against the LT-2 strain, whereas serum levels were less than the MIC. These results indicated that azithromycin given orally once daily was as effective as ciprofloxacin against established murine Salmonella infection and that the efficacy of azithromycin correlated with adequate tissue concentrations of antibiotic.

Animals↗

Interleukin-6, gamma interferon, and tumor necrosis factor receptors in typhoid fever related to outcome of antimicrobial therapy.

To study mechanisms of antibiotic effects in typhoid fever, levels of interleukin-6 (IL-6), gamma interferon (IFN-gamma), and cytokine receptors (tumor necrosis factor receptor [TNF-R] p55 and TNF-R p75) were measured in the plasma of 29 adult Nepalese with culture-positive typhoid fever before therapy and on days 4 and 15 after start of therapy with either ceftriaxone at 2 g/day for 3 days or chloramphenicol at 50 mg/kg of body weight per day for 14 days. Bacteriologic cure was defined as blood cultures testing negative on days 4 and 15 after start of therapy; clinical cure was defined as symptomatic improvement within 5 days after start of therapy and absence of relapse. Clinical and bacteriologic cures occurred in 24 patients. There were two clinical failures, two patients who failed to complete therapy because of leukopenia, and one relapse. Mean levels before therapy were elevated compared with those in healthy controls (IL-6, 11.4 pg/ml; IFN-gamma, 1.3 ng/ml; TNF-R p55, 3.8 ng/ml; and TNF-R p75, 6.1 ng/ml) and fell progressively during and after therapy. For six patients (three in each treatment group) who showed prolonged fever (> 5 days) or relapse, mean levels of IL-6 and TNF-R p55 before therapy (29.5 pg/ml and 6.1 ng/ml, respectively) and on day 4 (17.7 pg/ml and 4.0 ng/ml) were significantly greater than corresponding means for 23 patients who showed early defervescence (on admission, 6.7 pg/ml and 3.3 ng/ml, and on day 4, 1.8 pg/ml and 2.7 ng/ml, P < .05). These results indicate that the concentrations of plasma cytokines and their receptors are elevated in typhoid fever and that these concentrations can be useful in predicting outcome.

Adolescent↗

Treatment of typhoid fever with ceftriaxone for 5 days or chloramphenicol for 14 days: a randomized clinical trial.

To compare the therapeutic efficacy of ceftriaxone given once daily for 5 days and chloramphenicol given four times daily for 14 days, a controlled trial was carried out with 59 patients who were culture positive for Salmonella typhi. Ceftriaxone was given to 28 patients in once-daily intravenous doses of 75 mg/kg of body weight to children and 4 g to adults for 5 days; chloramphenicol was given to 31 patients at a dosage of 60 mg/kg/day until defervescence and then at 40 mg/kg/day to complete 14 days of treatment. All Salmonella isolates were susceptible to both antibiotics. Clinical cures (defervescence without complications, no relapse, and no need for further treatment) occurred in 79% of the patients treated with ceftriaxone and 90% of those treated with chloramphenicol (P = 0.37). On the third day of treatment, blood cultures were positive for S. typhi for 60% of the patients in the chloramphenicol group and 0% of the ceftriaxone group (P = 0.001). Defervescence occurred in half the patients in both groups during the first 7 days, but on days 9 to 13 after the start of treatment, nine patients in the ceftriaxone group, compared with six patients in the chloramphenicol group, remained febrile (P = 0.4). The median hematocrit and total leukocyte counts at day 14 were significantly lower for the chloramphenicol group than those for the ceftriaxone group (P = 0.01 and P = 0.02, respectively). These results indicate that the effects of therapy with ceftriaxone for typhoid fever differed from those of chloramphenicol therapy in that blood cultures became negative earlier, prolonged fever persisted in some patients, and bone marrow suppression was reduced. We conclude that a short, 5-day course of ceftriaxone is a useful alternative to conventional 14-day chloramphenicol therapy in the treatment of typhoid fever.

Adolescent↗

The effect of dietary protein supplementation on insulin-like growth factors (IGFs) and IGF-binding proteins in children with shigellosis.

Nutrient deficiency causes growth failure and decreases serum insulin-like growth factor-I (IGF-I) concentrations. Because IGFBPs modulate the concentrations and availability of IGFs in serum, IGF-binding proteins (IGFBPs) were measured along with IGF-I and IGF-II before and after 21 days of refeeding in 22 undernourished Bangladeshi children (2-4 yr of age) with shigellosis. The effects of a 150 Cal/kg.day diet with a normal protein (6%; n = 10) or high protein (15%; n = 12) content were studied. The results were compared with those of 25 age-matched healthy American children (controls). Body weight gain was better in patients receiving the high protein diet than in those receiving the normal protein diet. In both groups, initial IGF-I (32 +/- 6 and 24 +/- 7 ng/mL; mean +/- SD) and IGF-II (177 +/- 15, 174 +/- 45 ng/mL) concentrations were low compared to controls (100 +/- 12 and 542 +/- 29 ng/mL, respectively; P < 0.007). After refeeding, IGF-I increased to 160 +/- 26 ng/mL on the normal protein diet and to 322 +/- 41 ng/mL on the high protein diet, exceeding values in controls (P < 0.007). IGF-II increased more than 2-fold on each diet (P < 0.007), reaching control values. IGFBP-2 concentrations before refeeding were twice those in controls (750 +/- 200 vs. 317 +/- 33 ng/mL; P < 0.007) and normalized after refeeding in the high protein group (288 +/- 32 ng/mL; P = NS), but remained elevated in the normal protein group (526 +/- 77 ng/mL; P < 0.007). IGFBP-3 levels before refeeding were low and returned to normal on each diet. IGFBP-3 proteolytic activity in serum was initially increased and declined on the high protein diet. In conclusion, protein content in the refeeding diet differentially affects IGFs and IGFBPs in young undernourished children with infection. IGF-I and IGFBP-2 seem to be particularly sensitive to dietary protein alterations. We speculate that an increase in IGF-I concentrations, normalization of IGFBP levels, and a decrease in IGFBP-3 proteolytic activity in serum may all be involved in the improved recovery and catch-up growth observed with the high protein diet.

Carrier Proteins↗

A comparison of cefpodoxime proxetil and cefaclor in the treatment of acute exacerbation of COPD in adults.

In this multicenter, observer-blinded study, 301 patients with signs and symptoms of acute bacterial exacerbation of COPD were randomized (2:1) to receive either cefpodoxime proxetil (200 mg, bid) or cefaclor (250 mg, tid) for 10 days. Clinical and microbiologic evaluations were performed before treatment, during therapy (study days 3 to 5), at the end of therapy (3 to 7 days posttreatment), and at long-term follow-up (4 weeks posttreatment). The most common pretreatment isolates were Haemophilus influenzae, Haemophilus parainfluenzae, and Streptococcus pneumoniae. Significantly (p < 0.001) more bacterial isolates were susceptible in vitro to cefpodoxime (233 of 256, 91 percent) than to cefaclor (215 of 255, 84 percent). There were no statistically significant differences between the two drug regimens in eradication of the initial pathogen (cefpodoxime, 116 of 128, 91 percent; cefaclor, 59 of 64, 92 percent) or end-of-therapy clinical response (cure + proved; cefpodoxime, 99 of 100, 99 percent; cefaclor, 45 of 49, 92 percent) rates for evaluable patients. Both drug treatments were well-tolerated, with a similar incidence of drug-related adverse events (cefpodoxime 11 percent, cefaclor 12 percent). Cefpodoxime (bid) was as safe and effective as cefaclor (tid) in the treatment of acute exacerbation of COPD. The less frequent dosing regimen of cefpodoxime may improve patient compliance compared to those antibiotics that require three or four daily doses.

Acute Disease↗

Genetic analysis of hematological traits in chimpanzees (Pan troglodytes).

Hematological traits are commonly assessed markers of health status that have been used in a large number of anthropological studies, especially those focusing on high-altitude adaptation. Despite the wealth of literature on environment-associated variation in these traits, relatively few studies have dealt with the underlying genetic components of hematological measures. The purpose of this study is to estimate heritabilities for eight hematological traits using data obtained from a large pedigreed chimpanzee colony. Seven of the eight hematological traits exhibited significant heritabilities, ranging from h2 = 0.308 for mean cell volume to h2 = 0.834 for red blood cell count. The use of multiple measures per individual proved to be essential for the accurate estimation of heritabilities. We conclude that the underlying genetic variation in hematological traits should be considered when these measures are used in study protocols.

Animals↗

Nutritional intake, height and weight of 11-12-year-old Northumbrian children in 1990 compared with information obtained in 1980.

There is little age-specific information on changes in dietary intake over time in this country, yet this is valuable in assessing the effectiveness of health education programmes particularly in vulnerable groups such as adolescents. In 1990, 379 children aged 12 years completed two 3 d dietary records. They were interviewed by one dietitian on the day after completion of each diary to verify and enlarge on the information provided and, with the aid of food models, obtain a quantitative record of food intake. Nutrient intake was calculated using computerized food tables. These children attended the same seven Middle schools in Northumberland as 405 children of the same age who recorded their diet using the same method, 10 years previously. Heights and weights were also recorded in both studies in the same manner. Comparing the nutrient intakes in 1990 with 1980, energy intake fell in the boys (to 8.6 MJ) but not in the girls (8.3 MJ). The contribution of fat to energy intake was unchanged at about 40% (about 90 g/d). Likewise, intake of sugars was unchanged at about 22% of energy (about 118 g/d). Calcium intake remained the same in the girls (763 mg/d in 1990) but fell in the boys (786 mg/d in 1990). Iron, vitamin C and unavailable carbohydrate intakes increased in both sexes, and the nutrient density of the diet improved in all sex and social-class groups. However, a social trend evident in 1980 still existed in 1990 with low social groups having the poorest-quality diet. It is concluded that there is little evidence of substantial progress towards improving the diet of adolescents in this country.

Body Height↗

Risk factors for the development of persistent diarrhoea and malnutrition in Burmese children.

To identify socioeconomic and behavioural risk factors for development of persistent diarrhoea and malnutrition in children, a case-control study was carried out in Burma. Cases were 67 children 1-59 months old hospitalized for diarrhoea lasting > 14 days and complicated by severe malnutrition; for each case, a healthy control child was selected who was age- and sex-matched from the same neighbourhood. Homes of cases and controls were visited for interviews and for direct observation of household child-care practices. Risk factors were catalogued and calculations made for relative risk and etiologic fractions. Risk factors that were associated with persistent diarrhoea and malnutrition included low family income, low education of mothers, unhygienic latrines, flies in the house and on the child, dirty appearance of child and mother, mother not using soap and water when washing child's hands, defaecation of child on floor, breastfeeding on demand, child eating food from floor, not feeding recommended weaning foods, and lack of knowledge by mother about causes of diarrhoea and about foods that prevent malnutrition. These results indicated that persistent diarrhoea and malnutrition in Burma is caused by a complex of several interrelated socioeconomic factors, unsanitary behaviour pertaining to personal hygiene, the practice of demand breastfeeding and lack of certain weaning foods, and low education of mothers who showed less knowledge about causes of diarrhoea and prevention of malnutrition.

Case-Control Studies↗

Patterns of alcohol consumption in white collar-workers--a cross-sectional and longitudinal study.

A 6-year follow-up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to data on sickness absence, promotion and labour turnover, revealed that even moderate alcohol and consumption in this population was associated with social costs for the employer and the employee, particularly in terms of sickness absence. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on promotion prospects and labour turnover.

Adult↗

A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol.

Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover.

Absenteeism↗