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Biomedical subjects

J D Wagner

Publications and source records attributed to J D Wagner.

At least 91 records · Page 5Linked to original sources

The effects of hormonal replacement therapy on insulin sensitivity in surgically postmenopausal cynomolgus monkeys (Macaca fascicularis).

OBJECTIVE: Our purpose was to evaluate the effect of hormone replacement therapy on insulin resistance in postmenopausal cynomolgus monkeys (Macaca fascicularis). STUDY DESIGN: We studied 37 surgically postmenopausal cynomolgus monkeys that were fed a moderately atherogenic diet for 12 weeks with either no treatment (control), conjugated equine estrogens, medroxyprogesterone acetate, combination conjugated equine estrogens and medroxyprogesterone acetate, or tamoxifen. Insulin sensitivity and glucose effectiveness were determined by the frequent-sampling intravenous tolerance test by means of the minimal model analysis. RESULTS: There were no differences in body weight, total plasma cholesterol, or body fat distribution between control and conjugated equine estrogens, medroxyprogesterone acetate, or combination treatment groups. However, compared with control animals (insulin sensitivity = 5.9 +2- 1.2 x 10(-4) min-1 microU-1 ml) or conjugated equine estrogens treatment (6.3 +/- 1.1 x 10(-4) min-1 microU-1 ml) insulin sensitivity was significantly decreased in animals treated with medroxyprogesterone acetate (2.9 +/- 0.4 x 10(-4) min-1 microU-1 ml, p < 0.001) or conjugated equine estrogens and medroxyprogesterone acetate (2.8 +/- 0.6 x 10(-4) min-1 microU-1 ml, p < 0.001). Although insulin sensitivity was shown to be decreased in the tamoxifen-treated animals (insulin sensitivity = 4.6 +/- 0.6 x 10(-4) min-1 microU -1 ml), the difference was not statistically significant compared with the control or conjugated equine estrogens-treated animals. No significant differences were seen for glucose effectiveness comparing control animals (glucose effectiveness = 0.043 +/- 0.006 min-1) to animals treated with medroxyprogesterone acetate (glucose effectiveness = 0.046 +/- 0.009 min-1), conjugated equine estrogens and medroxyprogesterone acetate (0.048 +/- 0.008 min-1) or tamoxifen (0.039 +/- 0.006 min-1). CONCLUSION: These results suggest that progestins alone or in combination with estrogens can induce insulin resistance in postmenopausal monkeys while having no effect on plasma lipid concentrations or glucose effectiveness.

Animals↗

The health of rural homeless women with young children.

More than 30 percent of the homeless are families with children; however, little is known about these families, particularly rural homeless mothers with children. The purpose of this study was to describe the characteristics of rural homeless mothers, their physical and mental health, and their health care practices. A descriptive cross-sectional design was used to study a sample of 76 rural mothers with children younger than age 13. An interview schedule and the SCL-90-R were used to collect data about these families. The majority of the families had been homeless for more than four months, 46 percent were woman-headed, 17 percent of the mothers reported having a physical health problem, and only 3 percent had scores on the SCL-90-R that were indicative of needing additional evaluation for possible mental health problems. The use of drugs was higher than expected, which puts both the mothers and their children at risk for health problems.

Adult↗

Bipedicled axial cross-lip flap for correction of major vermilion deficiency after cleft lip repair.

Vermilion irregularities are common secondary deformities after cleft lip repair. Particularly severe in bilateral clefts, vermilion deficiency attracts considerable attention and detracts from an otherwise excellent lip repair. Minor and moderate vermilion deficits can be corrected with upper lip advancement, rotation flaps, tongue flaps, or grafts. Major defects defy correction with local flaps, because of an absolute shortage of upper-lip tissue. A technique is described for correction of large absolute tissue deficits of the upper-lip vermillion using a bipedicled lower to upper cross-lip visor flap. A lower lip wet vermilion/mucosal flap is based bilaterally near the commissures on the coronary arteries and transferred to a releasing incision at the wet/dry vermilion border of the upper lip. The commissural pedicles are divided and inset at a second stage 10 days later to complete the transfer. The procedure provides ample bulk and lining for major upper-lip vermilion augmentation and tubercle reconstruction without disturbing the obicularis oris muscular oral sphincter. In addition it balances the lips and allows for feeding. The technique is illustrated in two patients with major upper-lip vermilion defects after repair of bilateral cleft lips.

Adolescent↗

Metopic synostosis: evaluation of aesthetic results.

Analysis of intermediate- and long-term results of surgical treatment of metopic synostosis is lacking. We therefore retrospectively studied 23 patients with metopic synostosis (14 males, 9 females) who have been followed from 3 months to 8.1 years (mean 42.5 months) after operation. Age at first operation ranged from 2 to 56 months (mean 8.2 months), with 15 patients operated on before 6 months and 8 after 7 months. Fronto-orbital remodeling and calvarial vault reshaping with floating forehead techniques were carried out in all patients. Stabilization of bony segments was accomplished with microplates and screws in 7 patients (30 percent), wires in 15 (65 percent), and absorbable sutures in 1. Complications included minor wound dehiscence (n = 1), seizures (n = 1), and increased intracranial pressure (n = 1). Postoperative photographic documentation of surgical results was available in 17 of the 23 patients. Aesthetic outcome in these 17 patients was graded (I = none or minor contour irregularities; II = moderate; and III = severe) by one of the authors (Cohen) and by a lay panel (n = 3) according to the degree of residual cranio-orbital deformity. Judged by the surgeon, grade I results were present in 53 percent, grade II in 35 percent, and grade III in 12 percent. To date, total reoperation (reoperative fronto-orbital remodeling and calvarial vault reshaping) was necessary in 2 patients (9 percent), one of whom had signs of increased intracranial pressure 3 years after the original craniofacial procedure, while partial reoperation (temporal cranioplasty) was carried out (n = 2) or recommended (n = 3) in another 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

The pharmacokinetics of acetazolamide during CAPD.

Acetazolamide is a carbonic anhydrase inhibitor commonly used to reduce intraocular pressure (IOP). We report the first pharmacokinetic study of acetazolamide in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD). The patient was a Type I diabetic with end-stage renal disease (ESRD) undergoing CAPD who received acetazolamide for elevated IOP after surgery for a detached retina. Serum acetazolamide concentrations were measured prior to a 250 mg oral dose and 12 additional times during a 24-h dosing interval. All dialysate effluent was collected and assayed for acetazolamide. Serum concentrations at the beginning and end of the dosing interval were 18 and 17 mcg/mL, respectively, with a maximum concentration of 27 mcg/mL at 6.5 h (therapeutic range = 5-10 mcg/mL). The elimination half-life was prolonged, 28.5 h, compared to that seen in subjects with normal renal function (5-10 h). CAPD did not remove a clinically significant amount of drug (17.1 mg, or 6.8% of dose recovered in dialysate). The patient was very lethargic during therapy, a possible manifestation of acetazolamide toxicity. Marked reduction in acetazolamide dosage (in this case, 125 mg/day) would be required to prevent drug accumulation and toxicity.

Acetazolamide↗

Mineralocorticoid therapy lowers serum potassium in patients with end-stage renal disease.

Hyperkalemia is a commonly encountered problem in dialysis patients with end-stage renal disease. In this study we evaluated the effect of mineralocorticoid therapy (MCT; fludrocortisone 0.1-0.3 mg per os daily) on serum potassium of hyperkalemic end-stage renal disease patients. Consecutive monthly clinical and biochemical profiles 3-6 months before and after MCT were compared. Twenty-one patients with a mean age (+/- SE) of 54 +/- 4 years (11 male and 10 female) were studied. Two patients were dropped from this study because they required a change in prescription of dialysis after starting MCT. Mean serum potassium levels significantly fell (p < 0.001) during the post-MCT period (4.9 +/- 0.1 mEq/l) compared with potassium levels during the pre-MCT (5.6 +/- 0.1 mEq/l) period. All patients except 1 showed a reduction in serum potassium levels after MCT. Pre- and post-MCT values were not different for body weight, mean blood pressure, blood urea nitrogen, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase, sodium, chloride, bicarbonate, creatinine and albumin. Since the majority of the patients were anuric (n = 15), a decrease in serum potassium values in the post-MCT period was not due to loss of potassium in the urine. MCT appears to decrease serum potassium values in patients with end-stage renal disease by extrarenal mechanisms. We conclude that MCT can be used safely to lower serum potassium in patients with end-stage renal disease.

Female↗

Oral contraceptives decrease hepatic cholesterol independent of the LDL receptor in nonhuman primates.

Pharmacological doses of estrogens have been reported to increase hepatic catabolism of low-density lipoprotein (LDL) by the LDL receptor (LDL-R) pathway and to increase the concentration of mRNA for the LDL receptor. The induction of LDL-Rs by large doses of estrogen may not be relevant to the role of estrogens under physiological conditions. Furthermore, the mechanisms by which oral contraceptives, a combination of synthetic estrogen and progestin, may modulate LDL metabolism remain largely unexplored. Adult female cynomolgus monkeys were given combination ethinyl estradiol/norgestrel preparations (n = 16) for 16 weeks and were compared with a control group that did not receive exogenous sex hormones (n = 7). All animals consumed a diet containing 0.25 mg cholesterol/kcal with 40% of calories from saturated fats. After 16 weeks of treatment there was no significant difference in LDL cholesterol (LDL-C) and hepatic LDL-R mRNA concentration between oral contraceptive-treated animals (LDL-C, 242 +/- 113 mg/dL; LDL-R mRNA, 0.60 +/- 0.31 pg/microgram RNA) and control animals (LDL-C, 277 +/- 100 mg/dL; LDL-R mRNA, 0.51 +/- 0.21 pg/microgram RNA). In contrast, the hepatic cholesteryl ester concentration was significantly lower in the oral contraceptive-treated animals (7.28 +/- 3.59 mg/g liver) compared with the control animals (16.07 +/- 11.86 mg/g liver; P = .01) with no significant difference in hepatic free cholesterol concentration between the groups. Thus, oral contraceptives decrease hepatic cholesterol concentration independent of LDL-R expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oral contraceptive treatment decreases arterial low density lipoprotein degradation in female cynomolgus monkeys.

The effect of oral contraceptive therapy on early events in atherogenesis was studied in female cynomolgus monkeys. After a 1-month dietary challenge, monkeys were randomized into three groups stratified by total plasma cholesterol and high density lipoprotein cholesterol concentrations. The monkeys were then fed a cholesterol-containing diet for 16 weeks. This relatively short period ensured that studies were done before any treatment-induced differences in arterial morphology occurred. Monkeys were treated with either diet alone (control group), with the addition of a monophasic oral contraceptive (equivalent to a human dose of 50 micrograms ethinyl estradiol and 500 micrograms norgestrel per day), or with a triphasic oral contraceptive (equivalent to a human dose of 30-40 micrograms ethinyl estradiol and 50-125 micrograms levonorgestrel per day). Twenty-four hours before necropsy, low density lipoproteins (LDLs) labeled with 131I and LDLs labeled with the residualizing label 125I-tyramine cellobiose were injected into the animals. The arterial LDL degradation rate, amount of undegraded LDLs, and total LDL accumulation were then determined. Although there were regional differences in LDL metabolism, both treatments decreased the rate of LDL degradation and LDL accumulation in the coronary arteries and other arterial sites. Treatment also resulted in significantly lower LDL molecular weights. Despite a trend toward a more atherogenic lipid profile (decreased high density lipoprotein cholesterol and increased total plasma/high density lipoprotein cholesterol ratio), oral contraceptive treatment may inhibit atherogenesis by decreasing arterial LDL degradation.

Animals↗

Role of glycated proteins in detecting and monitoring diabetes in cynomolgus monkeys.

The use of glycated serum protein testing, as measured by serum fructosamine, to detect and monitor the diabetic state in 363 cynomolgus monkeys (Macaca fascicularis) consuming either standard diet or atherogenic diet was evaluated. Reference ranges were also established in 142 rhesus monkeys (M. mulatta) and 55 stumptail monkeys (M. arctoides). Values for serum fructosamine in all species ranged from approximately 0.5 to 2 mMol/liter. After determining the colony mean for each species and diet group, four cynomolgus monkeys were found to have serum fructosamine levels more than two standard deviations above the mean, whereas all values were normal in the rhesus and stumptail monkey colonies. These four animals were determined to be diabetic by repeated fasting glucose determinations and intravenous glucose tolerance testing. Serum fructosamine values correlated significantly with glycated hemoglobin (r = 0.61, P < 0.001) and fasting blood glucose (r = 0.70, P < 0.001) determinations in all diabetic and nondiabetic monkeys. The usefulness of serum fructosamine testing to monitor longitudinal glycemic control was also evaluated. Fasting blood glucose and fructosamine values for five previously diagnosed diabetic and five nondiabetic monkeys determined at 2-week intervals over a 20-week period correlated significantly (r = 0.75, P < 0.001). In conclusion, serum fructosamine may provide an objective parameter of antecedent glycemic control in nonhuman primates.

Animals↗

Keeping abreast of the medical/dental literature: a simplified approach.

Surveys report journal reading to be the most important continuing education activity in terms of practitioner preference. Clinical reading can be increased by perfecting the skills and habits that will permit selection of the most useful articles. In this article, an algorithm and basic methods are presented to enhance the practitioner's skill in reviewing the literature.

Algorithms↗

Clinical utility of open lung biopsy for undiagnosed pulmonary infiltrates.

Open lung biopsy (OLB) is often performed as the definitive diagnostic procedure in patients with undiagnosed pulmonary infiltrates, but controversy exists as to the clinical utility of this practice. A retrospective review of 50 consecutive patients who underwent OLB for undiagnosed pulmonary infiltrates was done to assess the diagnostic value as well as the frequency with which these results affected therapy and mortality. Histologic tissue diagnoses were obtained in all patients. Specific pathologic diagnoses were obtained in 56% of patients, nonspecific in 44%. Lobar or lateralized infiltrates were more likely to yield a specific diagnosis (87%) than diffuse, bilateral infiltrates (42%). Thirty-four patients (68%) had previously had a nondiagnostic transbronchial biopsy; 58% of these patients had a specific diagnosis established by OLB. Twelve patients (24%) were in acute respiratory failure at the time of OLB; this group had a 50% mortality rate as compared with only 2.6% for patients not in acute respiratory failure (p less than 0.01). Therapy was altered (new specific or nonspecific treatment initiated or therapy withdrawn) in 78% of patients undergoing OLB. Thirty-day in-hospital survival was significantly higher in patients for whom either specific or nonspecific therapy was indicated and initiated versus those in whom no therapy was initiated or all therapy was withdrawn (mortality: 5.5% versus 35.7%; p = 0.01). Mortality was not related to the presence of immunosuppression or to the finding of a specific diagnosis. The overall mortality rate of 14% in this series compares favorably with mortality rates found in similar series, reflecting differences in patient populations and possibly the timing of intervention. OLB remains a clinically valuable diagnostic tool in selected patients.

Adult↗

Case management of homeless families.

Homeless families are the fastest growing subgroup of the homeless population. They have multiple health care needs that can be best met by the community clinical nurse specialist. Nursing actions must be planned based on an assessment of this group's unique service needs. Interventions require the use of individualized delivery strategies such as case management, which necessitates that the clinical nurse specialist develop specialized skills in both service stimulation and system advocacy.

Adult↗

Regional differences in arterial low density lipoprotein metabolism in surgically postmenopausal cynomolgus monkeys. Effects of estrogen and progesterone replacement therapy.

To determine if arterial lipoprotein metabolism may be involved in mediating well-known anatomic regional differences in susceptibility to atherosclerosis, arterial low density lipoprotein (LDL) metabolism and extent of atherosclerosis were studied in 17 ovariectomized female cynomolgus monkeys. The animals were fed an atherogenic diet for 18 weeks, during which time one group received 17 beta-estradiol and cyclic progesterone treatment (n = 9) and the controls received no hormone replacement therapy (n = 8). As reported previously, hormone replacement markedly reduced the accumulation of LDL in coronary arteries without affecting plasma lipoprotein patterns. We report here that LDL metabolism differed among arterial sites. LDL accumulation, LDL degradation rate, and the concentration of undegraded LDL were greatest in the coronary arteries and carotid bifurcations compared with the aorta, iliac arteries, and cerebral arteries. Although hormone replacement decreased indexes of LDL metabolism, there was no effect on intimal thickness or indexes of endothelial injury, such as leukocyte adhesion and endothelial cell turnover rate. There were, however, regional differences in these morphological parameters. The intima was thickest in the aorta, and leukocyte adhesion and endothelial cell turnover rates were greatest in the carotid bifurcation and thoracic aorta. The decreased accumulation and metabolism of LDL caused by hormone replacement therapy was specific to the arterial system and did not occur in the liver or other peripheral tissues.

Animals↗

Preoperative laboratory testing for the oral and maxillofacial surgery patient.

Studies estimate that approximately 60% of preoperative testing could be eliminated without adversely affecting patient care. Unnecessary testing tends to cause extra risk to the patient, inefficient operating room schedules, and unnecessary costs. These extra tests may be hazardous to patients because of the pursuit and treatment of borderline positive or false-positive results. Furthermore, extra testing may also increase medicolegal risk, because the abnormalities that are discovered are usually not noted on the chart. A reliable and effective method for ordering laboratory tests to assess patients preoperatively and reduce morbidity and cost is presented.

Clinical Laboratory Techniques↗

Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys.

The effect of estrogen and progesterone replacement therapy on the initiating events in atherogenesis was studied in surgically postmenopausal cynomolgus monkeys. Monkeys were ovariectomized and divided randomly into two groups, one receiving 17 beta-estradiol and cyclic progesterone treatment (n = 9) and ovariectomized controls receiving no hormone replacement therapy (n = 8). The monkeys were fed a moderately atherogenic diet for 18 wk to accelerate the early pathogenic processes but not to be of sufficient duration to produce grossly visible atherosclerotic lesions. Sex hormone replacement therapy decreased the accumulation of LDL and products of LDL degradation in the coronary arteries by greater than 70% while having no significant effect on plasma lipid, lipoprotein, or apoprotein concentrations. Arterial intimal lesions were small with no difference between groups. The reduction in arterial LDL metabolism occurred very early in the pathogenesis of atherosclerosis and was independent of indices of endothelial cell injury, such as enhanced endothelial cell turnover or leukocyte adhesion to the endothelium. Results of this study suggest that one mechanism by which sex hormone treatment inhibits the initiation of atherosclerosis is a direct effect at the level of the arterial wall by suppressing the uptake and/or degradation of LDL.

Animals↗

Assessment of Proplast-Teflon disc replacements.

This retrospective study reports the findings in the follow-up of 31 temporomandibular joints in which Proplast-Teflon (Vitek Inc, Houston, TX) replacements were used. Among the problems noted were pain, malocclusion, restricted opening, and degenerative changes in the condyle and fossa.

Adult↗