Biomedical subjects

A B Johnson

Publications and source records attributed to A B Johnson.

At least 37 records · Page 2Linked to original sources

PubMed1999

Evaluating copper lysine and copper sulfate sources for heifers.

The effects of feeding different sources and quantities of Cu to heifers were evaluated in a 211-d experiment. Forty crossbred predominantly Brahman x Hereford heifers averaging 13.5 mo of age and 301 kg were initially depleted of Cu. The depletion diet was fed for 70 d and consisted of low Cu and high antagonist minerals, Fe, S, and Mo at 1000 mg/kg, 0.5%, and 5 mg/kg (dry basis), respectively. On d 71, heifers continued to receive the antagonistic minerals and were allotted equally to five Cu treatments: 1) control, no additional Cu source; 2) 8 mg of Cu/kg from CuSO4; 3) 16 mg of Cu/kg from CuSO4; 4) 8 mg of Cu/kg from Cu lysine; and 5) 16 mg of Cu/kg from Cu lysine. When no notable change in concentration of Cu in the liver was observed, d 169, a second diet was formulated. The heifers were fed the same Cu treatments, but S and Mo were removed and Fe was lowered to 50 mg/kg. This diet was then fed for the final 42 d of the experiment. In addition to performance, concentrations of Cu, Fe, and Zn in the plasma and liver, plasma ceruloplasmin, hemoglobin, superoxide dismutase (SOD) activity of neutrophils and lymphocytes, and a cell mediated immune response (phytohemagglutinin-P, PHA) were measured. Heifers in this study had increased growth over time, but there were no treatment differences for growth and average daily gain. Liver and plasma Cu concentrations were not greatly influenced by different supplemental Cu sources. However, compared with other treatments, Cu lysine (16 mg/kg) increased liver Cu in cattle that were deficient and tended to increase plasma Cu in animals that were marginally deficient in Cu. Iron concentrations decreased over time in liver and plasma, but there was no difference in Fe and Zn concentrations in liver and plasma among treatments. Differences in ceruloplasmin and hemoglobin concentrations were significant over time but not among treatments. The SOD activity in neutrophils did not change over time, but SOD activity of lymphocytes increased over time. For the PHA immune response test, there was no effect of time or a time by treatment interaction. These data suggest that all Cu sources were available, but Cu at 16 mg/kg from Cu lysine was more beneficial than were other sources and particularly for heifers with low Cu status.

Animal Nutritional Physiological Phenomena↗

PubMed1998

Laparoscopic appendectomy is an acceptable alternative for the treatment of perforated appendicitis.

BACKGROUND: Ever since laparoscopy was first applied to the treatment of appendicitis, a controversy has existed as to whether the acknowledged benefits of a minimally invasive approach warrant its preference over the conventional treatment, which historically has had relatively low morbidity. The purpose of this study was to determine if laparoscopic appendectomy should be performed preferentially in cases where surgeons are not limited by technical constraints. METHODS: A retrospective chart review was performed of 112 patients operated on for suspected appendicitis from June 1995 to July 1996. Forty-eight patients underwent laparoscopic appendectomy, and 64 had conventional open appendectomy. Laparoscopic appendectomy was performed using a three-trocar technique and the endoscopic stapler. RESULTS: The histopathological diagnosis of appendicitis was confirmed in 82.6% of cases. Overall, laparoscopic appendectomy reduced length of hospital stay (1.54 versus 4.09 days; p < 0.0001) compared to conventional open appendectomy, with no significant difference in hospital cost ($6430 versus $6669; p = ns). Although the total OR time was longer in the laparoscopic group (75.8 versus 60.2 min; p < 0.0001), laparoscopy resulted in both a reduction in length of stay (2.17 versus 6.27 days; p < 0.0001) and hospital cost ($7506 versus $10,504; p < 0.02) for cases of perforated appendicitis. Conversion to open appendectomy was performed in 6% of patients, all of whom had perforated appendicitis. CONCLUSIONS: Our data suggest that most cases of acute appendicitis with suspected perforation could be managed laparoscopically. Laparoscopic appendectomy significantly reduces length of stay and hospital costs in patients with perforated appendicitis.

Adolescent↗

PubMed1998

Laparoscopic Collis gastroplasty and Nissen fundoplication. A new technique for the management of esophageal foreshortening.

BACKGROUND: The short esophagus increases the difficulty and limits the effectiveness of laparoscopic Nissen fundoplication. In out experience, approximately 20-25% of esophagi judged by preoperative criteria to be foreshortened will, after dissection, be insufficiently long to allow 2 cm of esophagus to reside below the diaphragm without inferior distraction (i.e., tension free). Collis gastroplasty combined with Nissen fundoplication has become the standard approach for the creation of an intraabdominal neoesophagus and fundic wrap. METHODS: After developing methods of performing totally laparoscopic stapled gastroplasty in the cadaver lab in 1994, we started applying the technique clinically in 1966. We performed 220 laparoscopic antireflux procedures between January 1966 and July 1997. Of these 220 patients, 26% were suspected to have esophageal foreshortening based on preoperative barium studies and/or endoscopy. RESULTS: After hiatal dissection, nine patients, or 16% of those suspected to have esophageal foreshortening and 4% of the entire population, required the laparoscopic Collis-Nissen procedure. There was symptomatic improvement in all patients as assessed by patient-initiated symptom scores. CONCLUSIONS: The management of patients with esophageal foreshortening is a complex problem. We believe that our technique of laparoscopic Collis-Nissen provides an effective means of achieving intraabdominal placement of the fundic wrap while maintaining the benefits of minimally invasive approach.

Adult↗

PubMed1998

Leptin and the pituitary-thyroid axis: a comparative study in lean, obese, hypothyroid and hyperthyroid subjects.

OBJECTIVE: To study interactions between leptin and the pituitary-thyroid axis, both in euthyroid and dysthyroid states. SUBJECTS AND MEASUREMENTS: We investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment. RESULTS: Median [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively. CONCLUSIONS: (i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary-thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.

Adult↗

PubMed1998

A comparison of automated fructosamine and HbA1c methods for monitoring diabetes in pregnancy.

Two automated methods for measuring fructosamine (Test Plus and the original fructosamine assay) and glycated haemoglobin (Tina-quant immunoassay) were compared to determine which is the best index of blood glucose control during pregnancy. Thirteen women with type 1 diabetes were studied, with four-weekly measurements of HbA1c and fructosamine Test Plus using a Hitachi 911 analyser and fructosamine measured using an Olympus AU800 analyser. HbA1c correlated better (r = 0.573) with mean blood glucose (MBG) concentration than did fructosamine Test Plus (r = 0.347), even after correction for total protein concentration (r = 0.463), while there was no significant correlation with the original fructosamine method (r = 0.201). HbA1c correlated better with fasting/pre-prandial MBG concentrations, whereas fructosamine Test Plus correlated better with post-prandial MBG concentrations. Fructosamine Test Plus decreased with gestational age, and correlated with albumin and total protein concentrations, whereas HbA1c did not change with gestational age. Thus, HbA1c and fructosamine Test Plus were found to be useful in verifying home blood glucose measurements in diabetic pregnancy, with HbA1c being the best predictor of MBG concentration.

Adult↗

PubMed1998

Alternative methods for management of the complicated gallbladder.

Laparoscopic cholecystectomy is the procedure of choice for symptomatic cholelithiasis. However, in the presence of acute cholecystitis, 10% to 15% of patients face conversion to laparotomy. Alternatives to conventional therapy may therefore help to improve the clinical outcome of patients with complicated gallbladder disease. In selecting patients for alternative therapies, preoperative and intraoperative factors must be considered. Preoperative factors include the severity of biliary disease and preexisting medical risk factors; whereas intraoperative factors include conditions at the time of surgery that make dissection difficult or unsafe. Alternative therapies provide the least invasive management to safely temporize or definitively treat the acute condition. These alternatives include percutaneous cholecystostomy alone or followed by laparoscopic cholecystectomy, laparoscopic cholecystostomy followed by laparoscopic cholecystectomy, laparoscopic subtotal cholecystectomy, endoscopic retrograde cannulation of the gallbladder, and extracorporeal shockwave lithotripsy. By appropriate selection of the initial therapeutic approach, the surgeon may ultimately improve the clinical outcome in these complicated patients.

Catheterization↗

PubMed1997

Preliminary voice and speech analysis following fetal dopamine transplants in 5 individuals with Parkinson disease.

A surgical procedure involving transplantation of fetal dopamine cells into the striatum of persons with advanced Parkinson disease (PD) has recently been performed in an attempt to alleviate Parkinsonian and drug-dose related symptoms (e.g., the "on-off" phenomena). Improvements in limb motor and neurological function, as well as less severe and shorter on-off episodes have been reported following fetal cell transplant (FCT) surgery. Acoustic, electroglottographic, and perceptual measures were analyzed pre- and post-surgery to determine if phonotory and articulatory function were affected by this relatively new form of treatment. In addition, speech and motor exam measures were compared to determine if similar directional changes across motor systems were apparent. Findings suggest that FCT surgery did not systematically influence voice and speech production. Also, it appears that FCT surgery may differentially affect phonatory, articulatory, and limb motor systems. Findings are discussed relative to these differential effects.

Aged↗

PubMed1997

Zinc repletion with organic or inorganic forms of zinc and protein turnover in marginally zinc-deficient calves.

We conducted two experiments using marginally Zn-deficient (-Zn) calves to determine which supplemental chemical form of Zn would most rapidly reverse certain Zn deficiency signs and to determine whether a change in protein turnover had occurred in Zn deficiency. In Exp. 1, 40 crossbred beef heifers were allocated by BW to four groups. The control group received 23 mg Zn/kg diet DM from ZnSO4 supplemented to the -Zn diet (17 mg Zn/kg diet DM). The three other groups received the -Zn diet. After 21 d, based on a decreased (P < .05) feed efficiency, they were deemed -Zn. Cell-mediated immune (CMI) response to phytohemagglutinin (PHA) was reduced (P < .05) but plasma and liver Zn were unaffected in the -Zn calves. Zinc was repleted by feeding iso-Zn amounts (23 mg Zn/kg diet DM) from Zn lysine, Zn methionine, or ZnSO4. At 8 h after injection of PHA, control CMI response values were similar to Zn Methionine, and Zn lysine was lower (P < .05). In Exp. 2, 10 Holstein steers were allocated by BW to two groups. One group received the -Zn diet, and the other received the +Zn diet. Urine collections were obtained from both groups of calves when the -Zn calves showed a decrease (P < .05) in feed efficiency relative to the controls and when they were repleted with 23 mg Zn/kg diet DM from ZnSO4 and their feed efficiency had returned to that of the controls. Urinary 3-methylhistidine indicated that -Zn calves had less (P < .05) daily protein degradation than the controls. Refeeding Zn to the -Zn group did not change BW or daily protein degradation. Results indicated that a marginal Zn deficiency decreased fractional accretion rate, increased (P < .05) urine excretion, and tended to increase (P < .19) Na and decrease (P < .12) K concentrations in the urine.

Animals↗

PubMed1996

Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity and human papilloma virus tumor status.

Specific human papilloma virus (HPV) types appear to be necessary etiological factors for most cervical cancers, yet additional genetic alterations seem to be required for their development and progression. The aim of this study is to determine the likely chromosomes location of tumorigenicity suppressor-like genes, the loss of function of which might be important in the origin or progression of cervical carcinomas. PCR with primers for 75 highly polymorphic microsatellite loci located on the major autosome arms were used to estimate the incidence of loss of heterozygosity (LOH) in 38 tumors. The HPV status of the tumors was also determined. LOH was found to involve 19 chromosome arms in 20-43% of the tumors. Chromosome arms 6p, 3p, and 18q are most frequently involved in LOH in 43, 39, and 35% of the informative carcinomas, respectively. The respective regions involved are 6p21.1-23, 3p13-25.3, and 18q12.2-21.2. LOH is generally limited to specific band segments within these regions. Similar high incidences of LOH of the same 3p segments have been reported in cervical carcinomas from different parts of the world. The same 3p and 6p segments are involved in many types of common cancers, whereas 18q changes are less frequent in other cancers. Chromosome arms 1q, 2q, 3q, 4p, 4q, 5p, 5q, 6q, 7q, 8p, 8q, 11q, 13q, 16p, 18p, and 19p are involved in LOH in 20-33% of the cervical tumors. Chromosome 11 alterations are among the most frequently found in many different types of neoplasias. In this study, 11p was involved in 16% of the tumors, and 11q was involved in 22%. Chromosome 17 alterations are found in more cancers than those of any other chromosome, frequently involving the p53 gene on 17p. LOH of 17p was found in 5 (15%) cervical tumors; 2 of these were HPV negative and expressed mutant p53. In such HPV-negative tumors, direct mutation of the wild-type p53 appears to replace the inactivation of the p53 product by oncogenic HPV types. Tumors with LOH at many loci were, on the average, at more advanced stages, as were tumors with mutant p53. The higher overall incidence of LOH in cervical carcinomas as compared to other cancers, and the diversity of LOH patterns found, suggest that different cervical carcinomas probably arise and/or progress, in part, because of the loss of function of different yet finite sets of tumorigenicity suppressor genes and genes that are involved in tumor progression and metastasis. The findings also indicate that certain chromosome segments that are often altered in cervical carcinomas are also frequently altered in several other types of cancers. It remains to be determined whether the same or different genes located within these segments are involved in the different cancer types.

Adult↗

PubMed1996

Interaction of different organic and inorganic zinc and copper sources fed to rats.

A study was conducted to compare bioavailability, interactions and retention of different sources of Zn and Cu fed to rats. Sixty-three male CD rats were fed individually a purified diet and deionized water ad libitum. The nine treatments included were all combinations of three Zn (ZnMet, ZnLys, ZnSO4) and three Cu (CuLys, CuSO4, CuO) sources added to the basal diet at 30 mg/kg of Zn and 6 mg/kg of Cu forming a 3' 3 factorial experiment. After the four-week supplementation phase, four randomly selected rats from each treatment were sacrificed (Phase 1). The remaining rats were fed the purified, unsupplemented diet for an additional week (Phase 2) and then sacrificed. Mineral (Zn and Cu) concentrations were determined in plasma, liver, kidney, bone and muscle, and metallothionein (MT) content was determined in liver and kidney. Plasma Cu concentrations were lower (p < 0.05) for CuO-than CuSO4- and CuLys-supplemented rats. Bone Zn concentrations were higher (p < 0.05) for CuLys-than for CuO-supplemented rats. In all tissues where Cu was measured, CuO was the lowest (p < 0.05) available source of Cu. Furthermore, in muscle, CuSO4-supplemented rats had higher (p < 0.05) Cu concentrations than CuLys-supplemented rats. Kidney MT concentrations followed the same pattern as Cu concentrations, with CuO-fed rats having the lowest (p < 0.05) MT concentrations. Plasma Cu concentrations of depleted rats were lower (p < 0.05) for CuO-than CuLys-supplemented rats. Kidney Zn concentrations were lower (p < 0.05) for CuSO4-than for CuO-supplemented rats after depletion. In liver, CuO supplemented rats had the lowest (p < 0.05) Cu concentration. Copper oxide was less available than CuLys and CuSO4 when added in adequate dietary levels. However, organic (ZnMet and ZnLys) and inorganic (ZnSO4) sources of Zn were similar.

Animals↗

PubMed1996

Relative bioavailability of zinc methionine and two inorganic zinc sources fed to cattle.

A 12-week experiment was conducted to compare supplemental ZnMet, ZnSO4, and ZnO on Zn, Cu and metallothionein (MT) concentrations in various fluids and tissues of 32 yearling cattle. Supplemental Zn (360 mg per day) was fed for four weeks, withdrawn for four weeks, and then resumed for another four weeks. Mineral (Zn and Cu) concentrations were determined in serum, liver, pancreas, kidney, bone, bone marrow (metacarpus), hair, hoof and neck muscle (sterno mandibularis), and Zn only in erythrocytes, skin and cornea. Metallothionein levels were determined in liver, pancreas and kidney. There were no treatment differences (p > 0.05) in serum or erythrocyte Zn content for all days of collection. Serum Cu concentrations tended to decrease with all treatments. There were no treatment differences (p > 0.05) in Zn and Cu tissue concentrations and liver, kidney and pancreas MT concentrations. Tissue Cu concentrations did not drop in the supplemented treatments when compared to controls. At adequate levels of dietary Zn, bioavailability of supplemental Zn sources may be less important than under conditions of limited dietary Zn or if very high levels of supplemental Zn are fed.

Animal Feed↗

PubMed1996

Does suppression of postprandial blood glucose excursions by the alpha-glucosidase inhibitor miglitol improve insulin sensitivity in diet-treated type II diabetic patients?

OBJECTIVE: Insulin sensitivity is impaired in patients with type II diabetes and is exacerbated by high mean blood glucose (BG). Potentially, large postprandial swings in BG could result in further decrements of insulin sensitivity. Because alpha-glucosidase inhibitors cause a marked reduction in the amplitude of BG changes, the aim of this study was to determine if such a BG-smoothing effect improves insulin sensitivity in well-controlled type II diabetic subjects treated with diet alone. RESEARCH DESIGN AND METHODS: Patients received either miglitol (BAY m 1099) (50 mg three times daily) or placebo for 8 weeks in a randomized double-blind parallel study. The miglitol (9 men, 2 women) and placebo (7 men, 3 women) groups were well matched (mean +/- SD) for age, weight, and blood glucose control (fasting BG, 6.4 +/- 1.0 vs. 6.9 +/- 1.6 mmol/l; HbA1, 7.7 +/- 1.0 vs. 7.9 +/- 0.4%; fructosamine, 0.99 +/- 0.08 vs. 1.07 +/- 0.17 mmol/l). The glucose metabolic clearance rate was calculated during the last 30 min of a 150 min glucose/insulin sensitivity test (glucose, 6 mg . kg-1 . min-1; insulin, 0.5 U . kg-1 . min-1). RESULTS: There was no significant improvement in metabolic clearance rate (0.21 +/- 0.27 vs. 0.16 +/- 0.35 l . kg-1 . min-1) for the miglitol- and placebo-treated groups, respectively. There were no statistically significant differences between miglitol and placebo for changes from baseline in BG (0.1 +/- 0.1 vs. -0.1 +/- 0.2 mmol/l), HbA1 (0.1 +/- 0.1 vs. 0.3 +/- 0.1%), and fructosamine (-0.06 +/- 0.02 vs. -0.03 +/- 0.02 mmol/l). CONCLUSIONS: Alpha-glucosidase-induced improvement in postprandial hyperglycemia does not result in increased insulin sensitivity.

1-Deoxynojirimycin↗

PubMed1996

Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease.

Canavan disease is inherited as an autosomal recessive trait that is caused by the deficiency of aspartoacylase (ASPA). The majority of patients with Canavan disease are from an Ashkenazi Jewish background. Mutations in ASPA that lead to loss of enzymatic activity have been identified, and E285A and Y231X are the two predominant mutations that account for 97% of the mutant chromosomes in Ashkenazi Jewish patients. The current study was aimed at finding the molecular basis of Canavan disease in 25 independent patients of non-Jewish background. Eight novel and three previously characterized mutations accounted for 80% (40/50) of mutant chromosomes. The A305E missense mutation accounted for 48% (24/50) of mutant chromosomes in patients of western European descent, while the two predominant Jewish mutations each accounted for a single mutant chromosome. The eight novel mutations identified included 1- and 4-bp deletions (32 deltaT and 876 deltaAGAA, respectively) and I16T, G27R, D114E, G123E, C152Y, and R168C missense mutations. The homozygous 32 deltaT deletion was identified in the only known patient of African-American origin with Canavan disease. The heterozygosity for 876 deltaAGAA mutation was identified in three independent patients from England. Six single-base changes leading to missense mutations were identified in patients from Turkey (D114E, R168C), The Netherlands (I16T), Germany (G27R), Ireland (C152Y), and Canada (G123E). A PCR-based protocol is described that was used to introduce mutations in wild-type cDNA. In vitro expression of mutant cDNA clones demonstrated that all of these mutations led to a deficiency of ASPA and should therefore result in Canavan disease.

Amidohydrolases↗

PubMed1995

Phonatory and articulatory changes associated with increased vocal intensity in Parkinson disease: a case study.

This study examined changes in voice and speech production in a patient with Parkinson disease as he increased vocal intensity following 1 month of intensive voice treatment. Phonatory function and articulatory acoustic measures were made before and after treatment as well as 6 and 12 months later. Pre- to post-treatment increases were documented in sound pressure level in sustained phonation, syllable repetition, reading, and monologue. Consistent with mechanisms of intensity change reported in normal speakers, corresponding improvements were measured in estimated subglottal pressure, maximum flow declination rate, laryngeal airway resistance, open quotient, EGGW-25, harmonic-spectral slope, and maximum vowel duration. Measures of phonatory stability in sustained phonation and semitone standard deviation in reading and speaking showed changes accompanying increased vocal intensity. In addition, changes were measured in articulatory acoustic parameters (vowel and whole word duration, transition duration, extent and rate, and frication duration and rise time) in single-word productions. These findings indicate that this patient increased his vocal intensity using phonatory mechanisms that have been associated with the nondisordered larynx. In addition, the increased vocal intensity led to changes in articulation that were not targeted in treatment.

Articulation Disorders↗

PubMed1995

Cardiovascular and metabolic responses to adrenaline infusion in patients with short-term hypothyroidism.

OBJECTIVE: The relation between the clinical manifestations of thyroid disease (both hypo and hyper-thyroidism) and tissue sensitivity to catecholamines remains uncertain. It has been suggested that tissue adrenergic responsiveness is decreased in hypothyroidism, but the reports have been conflicting and have invariably focused on a single physiological response. Therefore the aim of the present study was to determine in patients with moderate, short-term, symptomatic hypothyroidism the responses of heart rate, systolic and diastolic blood pressure, forearm blood flow and metabolic rate to adrenaline infused at a rate known to achieve plasma concentrations in the middle of the physiological range. PATIENTS: Ten subjects (5M, age 43 +/- 3 years, mean +/- SEM) were studied. All were on thyroxine replacement for hypothyroidism following either thyroidectomy or radioactive iodine and had been biochemically euthyroid for at least 6 months. DESIGN: Studies were performed in random order. One study was undertaken on full replacement therapy and the other after 50 micrograms thyroxine daily for 2 weeks. After basal, supine measurements adrenaline was infused at 25 ng/kg/min for 30 minutes. MEASUREMENTS: Heart rate, blood pressure, blood glucose, metabolic rate and forearm blood flow were measured at rest and at 10-minute intervals throughout the adrenaline infusion. RESULTS: Free T4 (10.6 +/- 1.3 vs 17.6 +/- 2.0 pmol/l, P < 0.001) and free T3 (3.6 +/- 0.2 vs 4.6 +/- 0.3 pmol/l, P < 0.01) concentrations were significantly lower on 50 micrograms thyroxine than full replacement therapy. Fasting blood glucose concentrations (4.7 +/- 0.2 vs 4.7 +/- 0.1 mmol/l) were similar. The resting adrenaline concentrations were comparable, 0.29 +/- 0.18 and 0.24 +/- 0.14 nmol/l on 50 micrograms thyroxine and full replacement therapy respectively, and increased to a similar level (2.36 +/- 0.39 and 2.36 +/- 0.35 nmol/l) throughout the adrenaline infusion. The resting heart rate and metabolic rate were significantly lower on 50 micrograms thyroxine than full replacement therapy (68 +/- 2 vs 72 +/- 3 beats/min, P < 0.01; and 4.48 +/- 0.35 vs 4.88 +/- 0.39 kJ/min, P < 0.01) respectively, but the increase in heart rate (7 +/- 2 vs 8 +/- 2 beats/min) and metabolic rate (0.43 +/- 0.09 vs 0.43 +/- 0.06 kJ/min) did not differ on the two study days. Resting systolic blood pressure, diastolic blood pressure and forearm blood flow were comparable on 50 micrograms thyroxine and full replacement therapy as were the changes in systolic blood pressure (1 +/- 1 vs 1 +/- 1 mmHg), diastolic blood pressure (-7 +/- 2 vs -7 +/- 1 mmHg), forearm blood flow (1.4 +/- 0.1 vs 1.7 +/- 0.2 ml/min/100ml forearm) and blood glucose concentration (0.7 +/- 0.1 vs 0.7 +/- 0.1 mmol/l). CONCLUSIONS: Patients with short-term hypothyroidism appear to have a normal response to adrenaline infusion despite reduced baseline heart rate and metabolic rate. Thus, under physiological and mild pathophysiological conditions there appears to be no evidence of any synergy between thyroid status and sensitivity to catecholamines.

Adult↗

PubMed1995

Relative bioavailability of two organic and two inorganic zinc sources fed to sheep.

A study was conducted to compare supplemental Zn lysine (ZnLys), Zn methionine (ZnMet), ZnSO4, and ZnO on Zn, Cu, and metallothionein (MT) concentrations in various fluids and tissues of 40 wether lambs. Supplemental Zn (360 mg/kg) was fed for 3 wk, withdrawn for 4 wk, and then resumed for another week. Mineral (Zn and Cu) concentrations were determined in serum, liver, pancreas, kidney, bone, bone marrow, hoof, and leg muscle, and only Zn was determined in skin and cornea. Metallothionein concentration was determined in liver, pancreas, and kidney. By d 49 serum Zn had increased less (P < .05) for controls than for all lambs except those fed ZnMet, and on d 55 it had increased more (P < .05) for ZnLys than for all but ZnSO4. There were no treatment effects in serum Cu concentration, but overall Cu concentration fell slightly for all treatments from d 0. The ZnLys-treated lambs had the highest (P < .05) Zn accumulation (581, 389, and 340 mg/kg) in kidney, liver, and pancreas, respectively. Both ZnSO4- and ZnMet-treated lambs had higher (P < .05) liver Zn concentrations (195 and 198 mg/kg, respectively) than the control lambs (127 mg/kg). Mean Zn concentration of bone, bone marrow, cornea, skin, hoof, and muscle was not different (P > .05) for lambs among treatments. The ZnLys-treated lambs had the highest (P < .05) MT concentrations (79, 167, and 68 micrograms MT/g for liver, kidney, and pancreas, respectively). Mean muscle Cu concentration was highest (P < .05) for controls (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

PubMed1993

The impact of metformin therapy on hepatic glucose production and skeletal muscle glycogen synthase activity in overweight type II diabetic patients.

The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients (five males, three females). Patients were treated for 12 weeks with either metformin (850 mg x 3) or matching placebo using a double-blind crossover study design; patients were studied at presentation and at the end of each treatment period. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) before and during a 4-hour hyperinsulinemic euglycemic clamp (100 mU.kg-1 x h-1). Metformin therapy was associated with a significant decrease in fasting blood glucose (6.8 +/- 0.6 v 8.3 +/- 0.9 mmol.L-1, P < .01) and glycosylated hemoglobin ([HbA1] 7.7% +/- 0.4% v 8.5% +/- 0.5%, P < .01) levels. Fasting hepatic glucose production (HGP) was also significantly decreased following metformin therapy (1.98 +/- 0.13 v 2.41 +/- 0.20 mg.kg-1 x min-1, P < .02), whereas fasting insulin and C-peptide concentrations remained unaltered. The decrease in basal HGP correlated closely with the decrease in fasting blood glucose concentration (r = .92, P < .001). Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin (3.8 +/- 0.6 v 3.1 +/- 0.7 mg.kg-1 x min-1, P < .05). This was primarily the result of increased nonoxidative glucose metabolism (1.1 +/- 0.6 v 0.4 +/- 0.6 mg.kg-1 x min-1, P < .05); oxidative glucose metabolism did not change. Metformin had no measurable effect on insulin activation of skeletal muscle GS, the rate-limiting enzyme controlling muscle glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Abnormal activation of glycogen synthesis in fibroblasts from NIDDM subjects. Evidence for an abnormality specific to glucose metabolism.

To determine whether the tendency for NIDDM to run in families could relate to genetically determined defects in insulin stimulation of glycogen synthesis, skin fibroblasts from subjects with a strong family history of NIDDM were studied. Fibroblasts from nondiabetic subjects without any family history of NIDDM were studied as control subjects. The cells were studied after 7-16 passages in culture. Rates of glycogen synthesis were lower in fibroblasts from NIDDM subjects both basally and with maximal insulin stimulation (0.77 +/- 0.11 vs. 0.46 +/- 0.04 pmol.well-1 x h-1 [P < 0.02] and 1.49 +/- 0.26 vs. 0.69 +/- 0.05 pmol.well-1 x h-1 +adP < 0.01]). Rates of glycogen synthesis were stimulated 1.9 +/- 0.2-fold above basal in the control cells and 1.5 +/- 0.1-fold above basal in the NIDDM cells (P < 0.02). Rates of [3H]thymidine uptake were similar in control and NIDDM fibroblasts (basal, 28.3 +/- 2.8 vs. 39.2 +/- 8.0; maximum, 50.9 +/- 7.2 vs. 69.3 +/- 16.9 dpm x 10(-3), respectively). Rates of uptake increased similarly in control and NIDDM cells by 1.8 +/- 0.1- and 1.7 +/- 0.1-fold above basal. Maximum specific fibroblast insulin binding was similar for control and NIDDM subjects (194.0 +/- 29.2 vs. 176.1 +/- 24.9 fmol 125I-labeled insulin bound/mg protein respectively). The tyrosine kinase activity of insulin receptors isolated from the control and NIDDM fibroblasts was similar (basal, 135 +/- 30 vs. 149 +/- 33; submaximal, 153 +/- 28 vs. 155 +/- 30; and maximal insulin, 191 +/- 45 vs. 213 +/- 48 dpm.mg protein-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗