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Biomedical subjects

D F Gardner

Publications and source records attributed to D F Gardner.

At least 19 recordsLinked to original sources

Successful cyclophosphamide treatment of cryoglobulinemic membranoproliferative glomerulonephritis associated with hepatitis C virus infection.

A 54-year-old man with cryoglobulinemia and chronic hepatitis C infection presented with progressive renal insufficiency caused by membranoproliferative glomerulonephritis. Because of a steady decline in renal function, cyclophosphamide therapy was instituted. Within 1 month of starting therapy, his cryoglobulins disappeared, and in 3 months, his creatinine clearance had improved from 56 mL/min to 89 mL/min. At no point in his course was there clinical evidence of liver disease. After 1 year, cyclophosphamide was successfully stopped. Fourteen months later, his creatinine clearance is 105 mL/min. These results suggest that cyclophosphamide may be useful therapy for patients with cryoglobulinemic membranoproliferative glomerulonephritis and hepatitis C virus infection who have progressive renal insufficiency.

Cryoglobulinemia↗

Cushing's disease in two sisters.

Hereditary Cushing's syndrome is an uncommon clinical entity, and most reported cases have been described in families with nodular adrenocortical dysplasia. Isolated cases of Cushing's disease (pituitary-dependent bilateral adrenal hyperplasia) have been reported in association with the multiple endocrine neoplasia syndrome, Type I (MEN I), but there are no published reports of pedigrees with more than one affected family member. Within a period of 8 months, two sisters presented with clinical findings suggestive of hypercortisolism, and Cushing's disease was confirmed by appropriate diagnostic studies. There was no evidence of any other endocrine excess syndrome in either patient. Transsphenoidal pituitary surgery confirmed the presence of an ACTH-immunostaining pituitary adenoma in each woman. The authors think this is the first report in the English literature of Cushing's disease in first-degree relatives.

Adenoma↗

Primary lymphangioma of the thyroid gland.

A 21-year-old woman presented with a solitary, hypofunctioning right thyroid nodule. Findings of fine-needle aspiration biopsy were consistent with a thyroid cyst, but a subsequent biopsy demonstrated changes suggestive of a papillary neoplasm. Surgery was performed and a well-circumscribed 12-mm nodule was identified within the thyroid parenchyma. Microscopic examination confirmed the presence of a thyroid lymphangioma. To our knowledge, this is the first case of a primary thyroid lymphangioma reported in the English literature.

Adult↗

Effects of low dose oral iodide supplementation on thyroid function in normal men.

Previous studies have demonstrated that short-term oral iodide administration, in doses ranging from 1500 micrograms to 250 mg/day, has an inhibitory effect on thyroid hormone secretion in normal men. As iodide intake in the USA may be as high as 800 micrograms/d, we investigated the effects of very low dose iodide supplementation on thyroid function. Thirty normal men aged 22-40 years were randomly assigned to receive 500, 1500, and 4500 micrograms iodide/day for 2 weeks. Blood was obtained on days 1 and 15 for measurement of serum T4, T3, T3-charcoal uptake, TSH, protein-bound iodide (PBI) and total iodide, and 24 h urine samples were collected on these days for measurement of urinary iodide excretion. TRH tests were performed before and at the end of the period of iodide administration. Serum inorganic iodide was calculated by subtracting the PBI from the serum total iodide. We found significant dose-related increases in serum total and inorganic iodide concentrations, as well as urinary iodide excretion. The mean serum T4 concentration and free T4 index values decreased significantly at the 1500 micrograms/day and 4500 micrograms/day doses. No changes in T3-charcoal uptake or serum T3 concentration occurred at any dose. Administration of 500 micrograms iodide/day resulted in a significant increase (P less than 0.005) in the serum TSH response to TRH, and the two larger iodide doses resulted in increases in both basal and TRH-stimulated serum TSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein) on thyroid function in normal men.

Erythrosine (Er), a tetraiodinated derivative of fluorescein, is a coloring agent widely used in foods, cosmetics, and pharmaceutical products. Because of its high iodine content and previous reports demonstrating an inhibitory effect of erythrosine on hepatic 5'-monodeiodination, we studied the effects of this compound on thyroid function and serum and urinary iodide concentrations in normal subjects. Thirty normal men, equally divided into three treatment groups, each received a 14-day course of oral Er in doses of 20, 60, or 200 mg/day. Serum thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), thyroid stimulating hormone (TSH), protein-bound iodide (PBI), and total iodide concentrations, serum T3-charcoal uptake, and 24-hour urinary iodide excretion were measured on Days 1, 8, and 15. Thyrotropin-releasing hormone (TRH) tests were performed on Days 1 and 15. There were no significant changes in serum T4, T3, rT3, and T3-charcoal uptake values at any dose. In men receiving 200 mg Er/day, the mean basal serum TSH concentration increased significantly from 1.7 +/- 0.1 (SE) on Day 1 to 2.2 +/- 0.1 microU/ml on Day 15 (p less than 0.05), and the mean peak TSH increment after TRH increased from 6.3 +/- 0.5 to 10.5 +/- 1.0 microU/ml (p less than 0.05). There were no significant changes in basal or peak TSH responses in the men receiving 20 or 60 mg Er/day. Significant dose-related increases in serum total iodide and PBI concentrations occurred during all three doses, and significant dose-related increases in urinary iodide excretion occurred during the 60 and 200 mg/day Er doses. These data suggest that the increase in TSH secretion induced by Er was related to the antithyroid effect of increased serum iodide concentrations, rather than a direct effect of Er on thyroid hormone secretion or peripheral metabolism.

Adult↗

Perceptions and beliefs of nursing and medical personnel about needle-handling practices and needlestick injuries.

A survey of 1473 nursing and medical personnel employed in two hospitals in a large metropolitan area was conducted to determine perceptions and beliefs about needle-handling practices and needlestick injuries. Additional questions in the survey focused on responsibility for discarding needles and syringes and the correct practice for disposal of needles and syringes in various situations presented. Analyses were based on 488 responses (33%). Nurses at the 437-bed University Hospital handled more needles and experienced more needlestick injuries than did nurses at the 300-bed Community Hospital. Needle-handling and needlestick injuries among medical personnel at the two hospitals were similar, although University Hospital interns and residents and University Hospital fourth-year medical students handled more needles than did the medical staff at either hospital. A total of 164 (33.6%) respondents reported receiving one or more needlestick injuries during 1983. A large proportion of respondents in each group reported that they did nothing about the needlestick injuries they experienced. Carelessness was perceived by all groups to be the most common reason for needlestick injuries. Most respondents reported some knowledge of proper needle disposal techniques and perceived lack of knowledge as the least important reason for needlestick injuries.

Attitude of Health Personnel↗

Iodine retention and thyroid dysfunction in patients on hemodialysis and continuous ambulatory peritoneal dialysis.

Povidone-iodine is frequently used as an antiseptic in patients on chronic dialysis. In order to determine if the use of povidone-iodine affects thyroid function in these patients, we measured serum iodine and thyroid hormone levels in dialysis patients prior to and following discontinuation of topical povidone-iodine antiseptics. Serum inorganic iodine levels were elevated initially in nearly 90% of the patients (19 on hemodialysis, 12 on continuous ambulatory peritoneal dialysis [CAPD]). Following discontinuation of povidone-iodine, iodine levels over a 3-month period decreased modestly in patients on CAPD (n = 5) and were unchanged in patients on hemodialysis (n = 5). Total and free thyroxine levels were frequently low but did not correlate with protein-bound or inorganic iodine levels and did not change after discontinuation of povidone-iodine. Thyrotropin levels correlated significantly (r = .62, P less than .01) with inorganic iodine levels in patients on hemodialysis, but not for patients on CAPD. We conclude that abnormal thyroid function tests are common in dialysis patients but are not related to iodine retention or to the routine use of topical povidone-iodine-containing antiseptics.

Adult↗

Baroreflex control of plasma norepinephrine and heart period in healthy subjects and diabetic patients.

Resting diabetic patients may have excessively rapid heart rates, reduced heart rate variability, and subnormal plasma catecholamine levels. Although all of these abnormalities may relate in some way to baroreceptor reflex function, there have been surprisingly few attempts to evaluate systematically baroreflex mechanisms in diabetic patients. Accordingly, we studied autonomic responses over a range of pharmacologically induced arterial pressure changes in 10 unselected young adult insulin-dependent diabetic patients who had no symptoms of autonomic neuropathy, and 12 age-matched nondiabetic subjects. Sympathetic responses were estimated from antecubital vein plasma norepinephrine levels, and parasympathetic responses were estimated from electrocardiographic R-R intervals and their variability (standard deviation). Both were correlated with other noninvasive indexes of peripheral and central nervous system function. Multiple derangements of baroreflex function were found in the diabetic patients studied. Sympathetic abnormalities included subnormal baseline norepinephrine levels, virtual absence of changes of norepinephrine levels during changes of arterial pressure, and supranormal pressor responses to phenylephrine infusions. Parasympathetic abnormalities included subnormal baseline standard deviations of R-R intervals, and R-R interval prolongations during elevations of arterial pressure which were unmistakably present, but subnormal. Our data suggest that in diabetic patients, subnormal baseline plasma norepinephrine levels may signify profound, possibly structural defects of sympathetic pathways. Subnormal resting levels of respiratory sinus arrhythmia may have different implications, however, since vagal, unlike sympathetic reflex abnormalities, can be reversed partly by arterial pressure elevations.

Adult↗

Pharmacology of propylthiouracil (PTU) in pregnant hyperthyroid women: correlation of maternal PTU concentrations with cord serum thyroid function tests.

Previous studies have characterized the pharmacology of propylthiouracil (PTU) in normal and hyperthyroid subjects, but there is little information available regarding PTU pharmacokinetics in pregnant hyperthyroid women. We investigated the serum PTU response to an oral dose of PTU in six hyperthyroid pregnant women both ante- and postpartum. The serum PTU profile during the third trimester of pregnancy was qualitatively similar to that in nonpregnant subjects, but serum PTU concentrations were consistently lower in the late third trimester compared with postpartum values. Cord serum PTU concentrations were consistently higher than simultaneously obtained maternal serum PTU concentrations, suggesting slower PTU clearance in the fetus. There was a significant inverse correlation (r = -0.92; P = 0.026) between the maternal serum PTU area under the curve in the third trimester and the cord serum free T4 index.

Adult↗

Prolonged action of regular insulin in diabetic patients: lack of relationship to circulating insulin antibodies.

We previously reported that in insulin-treated diabetic subjects the time course of action of regular insulin injected sc is different from that reported in standard textbooks. The present studies evaluated the role of insulin antibodies (Abs) in the altered pharmacokinetics of regular insulin by comparing the time course of insulin action in 10 patients receiving chronic insulin therapy and having insulin Abs with that in 15 previously untreated patients without detectable Abs. After an overnight fast, the patients were given an infusion of 5% dextrose in water at 100 ml/h. Regular insulin (15 U) was then injected sc in the deltoid region of the arm. The onset of action of sc insulin, as indicated by a 10% fall in serum glucose, was similar in both patient groups [1.9 +/- 0.1 (+/- SEM) hour in Ab-negative and 1.8 +/- 0.1 h in Ab-positive patients]. The peak effect of insulin action, as determined by the nadir of serum glucose, was 4.6 +/- 0.2 h in the previously untreated patients, not significantly different from the value in the diabetic patients with insulin Abs (5.2 +/- 0.4 h). The duration of action of insulin was also similar in both groups (14.7 +/- 0.7 vs. 14.4 +/- 1.0 h). No significant correlations were found between insulin Ab levels and any of these 3 parameters of insulin action. However, the peak effect and total duration of insulin action were significantly correlated with the baseline serum glucose levels. A possible role of insulin Abs was evaluated in these patients by repeating the studies over a 2-year period. During this time, the previously untreated patients were treated with highly purified pork insulin, to which they developed low titers of insulin Abs. The diabetic patients who had been chronically treated with insulin were changed from less purified insulin to highly purified pork insulin, and all had a significant reduction in their Ab titers. No changes in insulin pharmacokinetics were found in either group. These studies demonstrate that the prolonged action of sc injected regular insulin in diabetic patients is not related to the effect of circulating insulin Abs.

Adult↗

The pharmacokinetics of subcutaneous regular insulin in type I diabetic patients: assessment using a glucose clamp technique.

We recently reported that the peak effect and duration of action of regular insulin injected sc were prolonged in diabetic patients and were not related to the presence of insulin antibodies. The results suggested that the ambient level of plasma glucose might be an important factor in determining the pharmacokinetics of regular insulin. In the present study we used a glucose clamp technique, which minimizes interference by counterregulatory phenomena, to study the pharmacokinetics of regular insulin injected sc at 2 different blood glucose concentrations [276 +/- 7 (+/- SEM) and 130 +/- 5 mg/dl] in 10 insulin-dependent diabetic patients. The patient's blood glucose concentration was maintained constant by means of a variable rate iv infusion of 20% dextrose in water after sc injection of regular insulin (0.2 U/kg) in the deltoid region of the arm. The onset of insulin action occurred at similar times at both glucose concentrations (0.6 +/- 0.1 h at 276 mg/dl vs. 0.5 +/- 0.1 h at 130 mg/dl; P greater than 0.05). Peak insulin action (determined from the time of the maximal glucose infusion rate) was delayed in the studies done at 276 mg/dl (4.7 +/- 0.2 h) compared to that in studies done at mean glucose concentrations of 130 mg/dl (4.3 +/- 0.2 h; P less than 0.05). The duration of insulin action was also significantly prolonged in the studies done at the higher glucose concentrations (9.1 +/- 0.3 h at 276 mg/dl vs. 7.7 +/- 0.2 h at 130 mg/dl; P less than 0.01). These results confirm previous reports of prolonged insulin action in diabetic patients, especially in the presence of hyperglycemia.

Adult↗

Preferential binding of vasoactive intestinal peptide to hepatic nonparenchymal cells.

The binding of 125I-vasoactive intestinal peptide (125I-VIP) and 125I-insulin has been examined in highly enriched populations of rat hepatocytes and hepatic nonparenchymal cells. 125I-VIP bound to high-affinity sites (Ka = 1.7 X 10(9) M-1) in nonparenchymal cells. Specific binding in these cells was nearly fivefold greater than in hepatocytes (15.0 +/- 0.6% vs. 3.6 +/- 0.7% radioactivity bound per 4 X 10(5) cells). In contrast, 125I-insulin binding was similar in both cell populations (18.2 +/- 2.4% per 4 X 10(5) cells in hepatocytes vs. 17.1 +/- 1.0% in nonparenchymal cells). Glucagon and insulin had no effect on 125I-VIP binding in nonparenchymal cells. Secretin inhibited 125I-VIP binding but was only about 1% as potent as unlabeled VIP. VIP had no apparent effect on cAMP levels in either cell population, whereas glucagon increased cAMP levels in both cell types. Our findings suggest that VIP binds preferentially to hepatic nonparenchymal cells and that these cells are primarily responsible for the clearance of VIP from the portal circulation.

Animals↗

Auditory and somatosensory far-field evoked potentials in diabetes mellitus.

The effects of insulin dependent diabetes mellitus (IDDM) on brainstem auditory evoked potentials and early components of somatosensory evoked potentials were evaluated in 10 young IDDM patients and 10 control subjects. The IDDM group showed significantly longer intervals between major components of both types of evoked potentials. The results indicated that IDDM patients are at risk for central as well as peripheral neuropathy.

Adult↗

Effect of psychosocial factors on success in a program of self-glucose monitoring.

We examined prospectively the relationship of psychosocial factors to glycemic control in a program of self-glucose monitoring (SGM). Measured intelligence (IQ), educational level, and socioeconomic status (assessed by the Two-Factor Index of Social Position) were determined in 25 patients who were followed during 6 months of self-glucose monitoring. Personality categories, reflecting degrees of psychological disturbance, were assigned using the Minnesota Multiphasic Personality Inventory (MMPI). None of the measured psychosocial variables correlated significantly with initial Hgb A1 values. In contrast, after 6 months of SGM, Hgb A1 levels correlated significantly with both socioeconomic status (r = 0.42, p less than 0.05) and educational levels (r = -0.42, p less than 0.05). Hemoglobin A1 levels also correlated significantly with the recorded frequency of SGM (r = -0.65, p less than 0.01), a measure of patient compliance. No significant correlation between IQ and Hgb A1 levels was seen, either initially or during follow-up. High A1 values differed significantly among groups classified by MMPI testing. Patients with severe psychological abnormalities had higher (p less than 0.05) mean Hgb A1 levels. We conclude that psychosocial factors, but not measured intelligence, have an important bearing on patient success in a program of SGM.

Adult↗

Albright's syndrome with reactivation of fibrous dysplasia secondary to pituitary adenoma and further complicated by osteogenic sarcoma. Report of a case.

To our knowledge, this is the only reported case of Albright's syndrome with reactivation of the fibrous dysplasia in adulthood, a marked elevation of growth hormone secondary to a pituitary adenoma, and development of osteosarcoma within the reactivated fibrous dysplasia. In addition, this patient also had hyperthyroidism with normal TSH levels, indicating the presence of two separate endocrinopathies. Reactivation of the fibrous dysplasia after years of arrested growth in this patient is good evidence that fibrous dysplasia does not "burn out" after adolescence but that growth ceases only when growth hormone declines to adult levels.

Adenoma↗

Effect of glycemic control on serum insulin-like growth factors in diabetes mellitus.

We investigated the effect of improving glycemic control on serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II). In 22 adults followed during an intensive home glucose monitoring program for 6 mo, no effect of improving control was seen on either IGF-I or IGF-II. Similar results were obtained in young diabetic children less than 10 yr of age and in diabetic adolescents with detectable puberty before entering the study. In older diabetic children without evidence of puberty before treatment (Tanner prepubertal stage 1), initial IGF-I concentrations were low, but increased during establishment of glycemic control. Puberty developed during therapy in this latter group. Our data do not support a "global" effect of glycemic control on serum IGF-I in diabetic patients. Increases of IGF-I with better glycemic control appear most likely to occur when the metabolic consequences of diabetes have suppressed normal pubertal increases of IGF-I. IGF-II concentrations were unaffected by glycemic control in all subjects.

Adolescent↗

Enteric release of vasoactive intestinal peptide after a peptone meal in the dog.

Vasoactive intestinal peptide (VIP) concentrations were measured by radioimmunoassay in plasma from portal and peripheral venous blood obtained from six alert, non-anesthetized dogs before and after gastric infusion of a 10% peptone meal. Mean basal portal and cephalic vein plasma VIP concentrations were 42 +/- 11.7 and 42 +/- 8.0 (S.E.M.) pg/ml, respectively. No significant changes in peripheral venous plasma VIP concentrations were noted after the peptone meal throughout the duration of the collection period. In contrast, however, the mean VIP concentration in portal plasma increased promptly after the peptone meal with a peak of 79 +/- 8.2 pg/ml (P less than 0.02) occurring 8 min after infusion of the meal. This was followed by a gradual decline in portal plasma VIP levels, with a return to prefeeding concentrations at 60 min (44 +/- 6.3 pg/ml). Results of these studies demonstrate that following gastric infusion of a peptone meal in the dog, portal, but not peripheral, plasma VIP concentrations increase significantly. Failure to detect augmentation of peripheral vein VIP levels after the meal is probably due to hepatic clearance of VIP.

Animals↗