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Biomedical subjects

J B Chambers

Publications and source records attributed to J B Chambers.

At least 91 records · Page 5Linked to original sources
PubMed1984

Migration of retained pacemaker electrodes.

Two cases of migration of retained pacemaker electrodes are described. The first presented as an unusual cause of deep vein thrombosis while the second was asymptomatic and detected by routine chest x-ray. Both made a good recovery, the first with surgery and the second with the fragment left in situ. A review of the world literature revealed only 13 other such cases. Of the total of 15 cases four are known to have died. In these patients no relationship was found between morbidity and the site of migration or associated infection and/or thrombosis. However surgical treatment appeared to be associated with a better prognosis.

Aged↗
PubMed1982

Comparison of peripheral thyroid hormone metabolism in normal rats and in rats receiving prolonged glucagon infusion.

An elevated plasma glucagon concentration and reduced T3 production from T4 have both been observed in several clinical disorders, including hepatic cirrhosis, uremia, diabetes mellitus, and starvation. The question of whether glucagon has a direct effect on T3 production was studied in normal rats infused iv with [125I]T4 of [125I]T3 and 3 micrograms T4/day, using implanted minipumps. The blood [125I]T4 and [125I]T3 levels maintained a plateau between the fifth and ninth days of infusion. Each animal also received a second minipump, implanted ip, that infused either a diluant solution or 30 micrograms glucagon/100 g BW . day. After 7 days of continuous infusion, the glucagon-treated animals showed a 20% increase in plasma glucose and a 4-fold increase in plasma glucagon from baseline. However, the levels of insulin, T4, and T3 remained unchanged. The MCRs and the disposal rates of T4 and T3, calculated by the constant infusion method, showed T4 and T3 MCRs to be 0.99 +/- 0.18 and 11.25 +/- 2.52 ml/h . 100 g, respectively, and T4 and T3 disposal rates to be 68 +/- 10 and 9 +/- 2 ng/h . 100 g; there was no difference between the control animals and the glucagon-infused animals. T3 production was also determined in vitro from T4 added to a liver homogenate. Compared to control animals, the liver homogenate prepared from glucagon-infused animals showed a modestly higher T3 production rate throughout the 60-min incubation period (P = 0.025--0.05). However, the concentration of nonprotein-bound sulfhydryls was similar in the liver, kidney, brain, muscle, and heart of the two animal groups. In conclusion, glucagon does not have an important regulating role on the peripheral metabolism of thyroid hormone and T3 production in rats.

Animals↗
PubMed1980

The nondeiodinative pathways of thyroxine metabolism: 3,5,3',5-tetraiodothyroacetic acid turnover in normal and fasting human subjects.

Complete turnover studies of T4, T3, rT3, and 3,5,3',5-tetriodothyroacetic acid (TA4) were carried out in normal subjects given T4 (0.2 mg, by mouth daily) by the integration method. When compared to the five fed controls, the four fasting subjects showed a decrease of mean T3 disposal from 41 to 18 micrograms/day, an increase of mean rT3 disposal from 49 to 61 micrograms/day. The mean serum TA4 concentration rose from 53 to 112 ng/dl, while the TA4 metabolic clearance remained unchanged. The fraction of T4 metabolized by deiodination changed from 79.0% to 77.5% in the fasting subjects as the fraction of T4 metabolized by deamination changed from 1.1% to 2.2%. Therefore, fasting induces a significant shunting of T4 away from T3 production into rT3 and TA4 production. However, oxidative deamination remains a minor metabolic pathway of T4 in man during both normal and fasting conditions. Given its low disposal rate and low biological potency, the increased TA4 production during fasting is probably not the inhibitory factor of TSH response to the lowered T3 production during fasting.

Adult↗
PubMed1975

Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis.

The role of liver in the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) was studied in normal subjects and patients with alcoholic liver disease by measurement of thyrotrophin (TSH) and total and free T4 and T3 in randomand serial serum samples. Also, T4 to T3 conversion rates and T3 disposal rates were compared by noncompartmental analysis. While the mean total serum T4 values were similar for the two groups, 8.6 and 8.1 mug/kl, the mean free T4 value was significantly higher in the cirrhotic patients (3.3 ng/dl) than in the normal subjects (2.1 ng/dl, P less than 0.001). The mean serum T3 value, 85 ng/dl, was significantly reduced in the hepatic patients as compared to a mean serum T3 value of 126 ng/dl in the normal subjects (P less than 0.001), while the free T3 value was 0.28 ng/dl in both groups. The reduction of the serum total and free T3 values were closely correlated with the degree of liver damage, as indicated by elevation of serum bilirubin (r equal -0.547) and reduction of serum albumin (r equal 0.471). The mean serum TSH level was 3.1 muU/ml in the normals and 7.1 muU/ml in the cirrhotic aptients ( less than 0.001). 15% of the hepatic patients had serum TSH values above 10 muU/ml, which, however, did not correlate with any of the four liver function tests studied. Serial blood sampling from two convalescing patients with alcoholic hepatitis showed a gradual normalization of serum TSH and T3 levels as the liver function improved. After oral T4 administration, 0.25 mg/day for 10 days, three of four cirrhotic patients studied failed to raise their serum T3 values. The mean T4 to T3 conversion rate of seven normal subjects was 35.7%. The mean T4 to T3 conversion rate of four cirrhotic patients studied was significantly reduced to 15.6% (P less than 0.001). The mean disposal rates of T4 and T3 of the normal subjects were 114 and 34 mug/day, respectively. The ratio of T4 disposal to T3 disposal was 3.5. In contrast, the mean T4 disposal rate, 82 mug/day, and the mean T3 disposal rate, 10 mug/day, were both reduced in the cirrhotic patients. Their ratio of T4 disposal to T3 disposal was 7.9. These findings suggest that impairment of T4 conversion in patients with advanced hepatic cirrhosis may lead to reduced T3 production and lowered serum T3 level. Therefore, the liver is one of the major sites of T4 conversion to T3.

Adult↗
PubMed1972

Urinary metabolites of 14 C-labeled thyroxine in man.

Studies were carried out to determine the chemical structures of thyroxine metabolites after total deiodination. Normal subjects were given thyroxine labeled with (14)C on the nonphenolic ring and the alanine side chain, 8-11 mug/day for 10 days. By paper chromatography of fresh urine, six or more (14)C-labeled compounds were separated. The (14)C-labeled metabolites were concentrated by passing the urine through a nonionic polymeric adsorbent. Two major thyroxine metabolites were identified. The identification was made by three different methods: (a) chromatography, (b) synthesis of derivatives, and (c) recrystallization to constant specific activity. One (14)C-labeled metabolite was identified as thyroacetic acid or 4-phenoxy-(4'-hydroxy) phenyl-acetic acid. Another one was identified as thyronine. Of the total urinary (14)C radioactivity, 43.7% was recovered as thyroacetic acid and 19.8% was recovered as thyronine. Approximately one-fifth of each of these metabolites was present in the urine in bound form which released the free metabolites during acid hydrolysis. The average daily excretion of thyroacetic acid was 13.7% of the renal disposal rate of thyroxine, or approximately 7.5 mug/day. The average daily excretion of thyronine was 6.5% of the renal disposal rate of thyroxine or approximately 3.9 mug/day while the urinary iodide made up 64.7% of the renal disposal rate of thyroxine. Our findings provide the needed proof that the major metabolic pathways of thyroxine remove the iodine atoms by substituting hydrogen for iodine and leave the diphenyl ether nucleus intact.

Carbon Isotopes↗
PubMed1971

The extrathyroidal conversion rate of thyroxine to triiodothyronine in normal man.

Eight normal subjects were administered tracer amounts of a (14)C-labeled thyroxine, L-[tyrosyl-(14)C] T(4), by multiple injections. Then serial blood samples were collected for isolation of the thyroxine, triiodothyronine, and tetraiodothyroacetic acid fractions by a combination of column and paper chromatographies. The chromatographic artifacts were corrected by adding to the sera a purified (3)H-labeled thyroxine, D,L-[alpha,beta-(3)H] T(4) immediately after the separation of sera from blood. 1-2% of the serum (14)C radioactivity was observed in the triiodothyronine fraction and 2-4% of the serum (14)C radioactivity was observed in the tetraiodothyroacetic acid fraction. Complete kinetic studies of thyroxine and triiodothyronine were compared in the same individual in four of the subjects. The extrathyroidal conversion rates of thyroxine to triiodothyronine were calculated from data obtained during both the injection and the postinjection periods as functions of the (14)C-labeled thyroxine and triiodothyronine remaining in the body at time t and their fractional turnover rates. The average daily rate of the extrathyroidal conversion of thyroxine to triiodothyronine was 4% of the extrathyroidal thyroxine pool or 33% of the total thyroxine production. The amount of triiodothyronine generated by this pathway (22 mug/day) was found to contribute 31% of the extrathyroidal triiodothyronine pool or 41% of the daily triiodothyronine production. This pathway is a major source of triiodothyronine production. The extrathyroidal conversions of thyroxine to triiodothyronine and tetraiodothyroacetic acid are major metabolic pathways of thyroxine in normal man.

Adult↗
PubMed1970

The integrity of the ether linkage during thyroxine metabolism in man.

The structures of thyroxine metabolites after total deiodination bear on the mode of thyroxine (T(4)) action in vivo. The present study was undertaken to determine the integrity of the ether linkage during thyroxine metabolism in man. Normal volunteers were given simultaneous intravenous injections of two thyroxines labeled with either (14)C or (3)H on the opposite sides of the ether linkage, D,L-[alpha,beta-(3)H]T(4) and D,L-[phenolic ring-(14)C]T(4). The ratio of alanine side chain to phenolic ring which was measured as (3)H:(14)C ratio was found to remain constant in the serum, urine, and feces during the subsequent 3 wk. The disappearance rates of the (3)H and (14)C radioactivity from blood were similar. The values of half-life were in the ranges of 4.2-6.7 days. 51-63% of the (3)H and 50-57% of the (14)C doses were recovered from urine and 13-20% of the (3)H and 15-20% of the (14)C doses were recovered from feces. Chromatography of the urinary metabolites confirmed that the phenolic ring and the nonphenolic ring including at least part of the side chain remained linked together.

Adult↗
PubMedDate not supplied

The effects of propranolol on thyroxine metabolism and triiodothyronines production in man.

The effects of propranolol on the turnover of thyroxine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) were determined by a noncompartmental analysis in seven normal men. Fourteen normal subjects were treated with 0.2 mg T4 daily, and half of this group (seven) received in addition 80 mg propranolol daily. Fifteen days of propranolol treatment did not alter serum T4 concentration or T4 turnover. However, it lowered serum T3 concentration from 173 to 102 ng/dl (P = 0.001); T3 clearance was unchanged. Propranolol treatment elevated serum rT3 concentration from 54 to 69 ng/dl (P = 0.05); rT3 metabolic clearance rate fell from 105 to 90 liters/day but the difference did not reach statistical significance. The rT3 disposal rate was unchanged by propranolol. The fractional T4 disposal which was degraded via the deiodinative pathways was reduced from 82.0 per cent in the control subjects to 65.5 per cent in the propranolol treated subjects. Therefore, propranolol appears to be a potent inhibitor of 5'-deiodination. The interpretation of serum T3 measurements in patients treated with propranolol requires caution.

Adult↗
PubMedDate not supplied

Retrospective review of osteoarticular infections in a pediatric sickle cell age group.

Patients with sickle cell disease have been documented to be particularly susceptible to osteoarticular infections. Controversy exists concerning the bacteriology, etiology, and clinical presentation in differentiating osteoarticular infections from bone infarct. We retrospectively reviewed all cases from our institution over the past 22 years of osteoarticular infections in children who carry the diagnosis of sickle cell disease. Two thousand consecutive patient charts of children enrolled in the Pediatric Sickle Cell Clinic of our institution between 1973 and 1995 were evaluated. There were 14 cases of bone or joint infections (10 osteomyelitis, four septic arthritis). There was one case of multicentric osteomyelitis and one case of meningitis complicating the septic arthritis. There were nine male and five female patients with ages ranging from 6 months to 17 years (mean, 8.0). All patients were noted to have hemoglobin SS. The predominant presenting symptoms were pain (79% of cases) and swelling (71% of cases). The most frequent physical findings were fever >38.2 degrees C (71% of cases) and tenderness (86% of cases). Ninety-three percent of the children had a white blood count exceeding 15,000/mm3 (range, 7,900-32,300). Westergren sedimentation rates ranged from 14 to 89 mm/h with 93% of the children exceeding the normal value in our hospital. Cultures were positive in 75% of tissue biopsies, 58% of the blood cultures, and 70% of the bone or joint aspirates. The most common offending organism found in osteomyelitis was Salmonella (eight of 10 cases); however, no predominant organism found was identified in cases of septic arthritis. Radiographs and bone scans were of limited value in the differential diagnosis between osteoarticular infections and bone infarction. Early diagnosis and treatment of osteoarticular infections is key to satisfactory outcome. This study suggests that an ill-appearing patient with a fever >38.2 degrees C, pain, and swelling should prompt the physician to aspirate or biopsy the area and not rely on diagnostic studies that we found to be unreliable.

Adolescent↗
PubMedDate not supplied

Regression of left ventricular hypertrophy with 1 year of antihypertensive treatment in type 1 diabetic patients with early nephropathy.

M-mode echocardiograms were recorded in 22 Type 1 diabetic patients with microalbuminuria (n = 10) or early persistent proteinuria (n = 12). Eight (36%) had both an increased left ventricular mass (males greater than 131 g m-2; females greater than 100 g m-2) and a systolic blood pressure above the 75th centile of the normal blood pressure distribution. These eight patients were treated with antihypertensive drugs, predominantly enalapril, for 1 year. Echocardiograms were repeated after 3 and 12 months. Systolic blood pressure at recruitment was 155 +/- 14 (+/- SD) mmHg, and was significantly lower after 3 months (146 +/- 12 mmHg; p less than 0.05) and 12 months (139 +/- 8 mmHg; p less than 0.005). Diastolic blood pressure did not change significantly. Both intraventricular septal width and left ventricular posterior wall thickness fell progressively and were significantly lower after 12 months treatment (15.0 +/- 2.7 vs 13.0 +/- 2.6 mm, and 10.3 +/- 1.9 vs 8.8 +/- 1.3 mm; both p less than 0.05). Left ventricular mass index was 148 +/- 29 g m-2 at recruitment, but lower after 3 months (131 +/- 25 g m-2; p less than 0.05) and 12 months (132 +/- 26 g m-2; p less than 0.005) antihypertensive therapy.

Adult↗
PubMedDate not supplied

Coronary bypass grafting in South Thames: the correlation between clinical scores and waiting times.

To determine waiting times before surgery and their correlation with clinical need, we examined the files of 1049 patients on the waiting list for coronary bypass grafting in 1996. The total waiting time to bypass grafting was 279 (SD 209) days (range 1-1579 days). Waiting time to specialist consultation was 36 (SD 43) days, and time on the waiting list for coronary angiography was 85 (SD 89) days. The mean time on the surgical waiting list was 133 (SD 134) days. Patients with a Birmingham clinical score below 10 waited between 27 and 879 days, and patients with scores above 35 waited between 3 and 282 days. Total waiting time was weakly associated with the priority score (Pearson correlation = -0.51). We conclude that waiting times were long with wide variation at every stage between referral and coronary bypass grafting. There was little correlation between clinical scores and waiting times.

Adult↗