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Biomedical subjects

D Turner

Publications and source records attributed to D Turner.

At least 109 records · Page 6Linked to original sources

Using mitotic recombinant mutant clonal lymphocytes for physical mapping of polymorphic loci on the short arm of human chromosome 6.

Immunoselection has been used to identify human lymphocytes that have undergone spontaneous mutation resulting in the loss of expression of one of the codominant HLA-A alleles. Approximately 35% of such mutations are the consequence of mitotic recombination events. Mitotic recombination is the result of nonsister chromatid exchange that leaves the mutated cell homozygous for all loci distal to the crossover point. The location of the crossover has been regionalized for 99 independently derived mutant lymphocyte clones by identification of their loss or retention of heterozygosity at seven reference polymorphic loci on chromosome 6. If a polymorphic locus of unknown map position is studied in clones from this ordered set of mitotic recombinants, and clones that display loss of heterozygosity and retention of heterozygosity of the locus are observed, then the map position of the locus is between the appropriate reference loci of the ordered set. The newly mapped locus becomes a reference locus in turn. In this way the mitotic recombinant mutant clones can be used to generate an ordered set of crossover points with a theoretical resolution limited only by the number of mutants generated. In this paper such a set of mutants is used to refine or confirm the map position of eight polymorphic loci on chromosome 6.

Chromosome Mapping↗

Ovarian transposition in cervical cancer.

One hundred four premenopausal women, 42 years of age or less, with early stage carcinoma of the cervix had surgical management with ovarian retention. Eighty-two had ovarian transposition performed at the time of exploration for radical hysterectomy or staging lymphadenectomy because of known or possible need for radiation therapy. Twenty-two had radical hysterectomy and retained ovaries without transposition. Three patients, all in the transposed group, were lost to follow-up. Sixteen patients died of disease; all but 1 were in the transposed group. Twenty-four transposed patients received postoperative radiation therapy; 12 of these died of disease and all became climacteric prior to death. Only 4 (17%) transposed and radiated patients have continued ovarian function. Of the 58 patients with transposition who received no radiation, 9 of 51 survivors (17.6%) had subsequent oophorectomy for management of painful ovarian cysts at from 25 to 103 months (mean 46.8 months) after treatment. Sixty-seven percent still have ovarian pain and cysts requiring medical therapy. Therefore, only 53% retained ovarian function with no problems. Of the 22 patients whose ovaries were retained but not transposed 10% became climacteric at a mean of 84 months after treatment, and 21% have continued ovary-related pain or cysts at a mean of 32 months. Thus, 71% retained ovarian function and had no problems. The difference in ovarian survival between the transposed and radiated and the nontransposed nonradiated groups was significant (P < 0.001). Only 1 patient developed metastatic disease in the ovary at 17 months and 1 had a benign cystic teratoma at 62 months after treatment. We conclude that transposition is not successful in preserving ovarian function in patients who are likely to need radiation therapy and is, therefore, not indicated. Long-term follow-up is necessary to determine rates of continued ovarian function after surgery. The rate of subsequent malignancy is low.

Adult↗

Implantable programmable insulin pumps for the treatment of diabetes.

Implantable programmable pump systems for insulin delivery to the peritoneal cavity or for intravenous insulin delivery have been recently developed. Thirty-one pumps were implanted in 25 patients between 1987 and 1991. At this writing, 76% of patients had functioning pumps. Ninety-two percent of pumps were functioning at 1 year; 89% at 2 years; and 50% at 3 years. No life-threatening complications, either surgical or metabolic, developed. However, 18 patients required 23 outpatient procedures for maintenance of pump function or for pump removal. Metabolic improvement was evidenced by mean and standard deviation of blood glucose levels and by glycosylated hemoglobin levels.

Abdominal Muscles↗

The myoD gene family: nodal point during specification of the muscle cell lineage.

The myoD gene converts many differentiated cell types into muscle. MyoD is a member of the basic-helix-loop-helix family of proteins; this 68-amino acid domain in MyoD is necessary and sufficient for myogenesis. MyoD binds cooperatively to muscle-specific enhancers and activates transcription. The helix-loop-helix motif is responsible for dimerization, and, depending on its dimerization partner, MyoD activity can be controlled. MyoD senses and integrates many facets of cell state. MyoD is expressed only in skeletal muscle and its precursors; in nonmuscle cells myoD is repressed by specific genes. MyoD activates its own transcription; this may stabilize commitment to myogenesis.

Animals↗

Duodenitis: a reliable radiologic diagnosis?

The authors performed a retrospective study of 50 patients with endoscopically diagnosed duodenitis who had undergone double-contrast upper gastrointestinal (GI) examinations. Duodenitis was diagnosed on the original radiographic reports in six of 37 patients (16%) with mild-to-moderate duodenitis, five of 13 patients (38%) with severe duodenitis, and 11 of 50 patients (22%) with all grades of duodenitis on endoscopy. Subsequent analysis of the films revealed one or more radiologic signs of duodenitis (including folds more than 4 mm in thickness, mucosal nodularity, bulbar deformity, and erosions) in 18 of 37 patients (49%) with mild-to-moderate duodenitis, eight of 13 patients (62%) with severe duodenitis, and 26 of 50 patients (52%) with all grades of duodenitis on endoscopy. In a separate part of the study, the authors identified another 20 patients with radiographically diagnosed duodenitis who had undergone endoscopic examinations. Nine of those 20 patients (45%) had duodenitis on endoscopy. Subsequent analysis of the films revealed one or more signs of duodenitis in 17 patients from this group. Nine of the latter patients (53%) had duodenitis on endoscopy. Using established radiologic criteria for duodenitis, our rate of false-positive and false-negative radiologic diagnoses still was about 50%. Thus, the double-contrast upper GI examination is a relatively unreliable technique for diagnosing duodenitis.

Adult↗

Endometrial carcinoma: transvaginal ultrasonography prediction of depth of myometrial invasion.

Myometrial invasion greater than 33% negatively affects the prognosis of endometrial carcinoma. Since the endometrium is readily differentiated from myometrium via high-resolution transvaginal sonography (TVS), this prospective study was undertaken to evaluate the efficacy of TVS in determining the depth of myometrial invasion in women with endometrial adenocarcinoma. Eighteen subjects underwent TVS utilizing 5.0- and 7.5-MHz probes by a single examiner blinded to stage and grade of adenocarcinoma. Predicted TVS ratios were categorized as less than 33% or greater than or equal to 33% and compared to actual histologic invasion. Ultrasound predicted that TVS ratios greater than or equal to 33% are significantly associated with deep (greater than 33%) histologic invasion (P less than 0.01, Fisher's test). When histologic invasion was greater than or equal to 33%, TVS was 100% accurate with no false negatives. The two cases in which TVS ratios erroneously indicated invasion greater than or equal to 33% contained adenomyosis and leiomyomas. TVS is a highly accurate and convenient method for preoperatively evaluating myometrial invasion. Potentially this evaluation could influence the selection of therapy for poor-surgical-risk candidates or direct appropriate referral of patients with deeper invasion to a gynecologic oncologist.

Adenocarcinoma↗

Use of the infectious disease laboratory in emergency medicine.

Until relatively recent advances in the identification of infectious agents, the emergency physician found only limited usefulness of the infectious disease laboratory. There are some tests that can provide information rapidly enough for the Emergency Department setting and new technologies that hold even greater promise for the future. The tests described in this article are currently available in most moderately sized Emergency Departments.

Bacterial Infections↗

Antibody responses to protein A in patients with Staphylococcus aureus bacteremia and endocarditis.

To assess the significance of antibody to Staphylococcus aureus protein A (SpA) in human sera, we developed a modified enzyme-linked immunosorbent assay (ELISA). SpA antibody levels in 23 patients with S. aureus endocarditis (IE), 21 patients with non-IE S. aureus bacteremia, and 33 controls were measured. Geometric mean levels of antibody to SpA were significantly higher in S. aureus IE patients (134 ELISA units [EU]) than in uninfected controls (52 EU; P less than 0.01). Also, a significantly greater proportion of S. aureus IE patients (12 of 23) and S. aureus non-IE bacteremia patients (11 of 21) had antibody levels greater than an arbitrary threshold of 100 EU compared with uninfected controls (0 of 23; P less than or equal to 0.001). However, no significant differences in geometric mean SpA antibody levels between the bacteremic patients with and without IE were noted. The sensitivity and specificity of this ELISA to distinguish patients with S. aureus IE from those with non-IE bacteremia were low (52 and 48%, respectively). There was a significant association between SpA antibody levels and either immunoglobulin G or immunoglobulin M teichoic acid antibody levels (r = 0.406, P less than 0.05; r = 0.571, P = 0.002, respectively). For patients from whom multiple sera were available (13 IE and 5 non-IE patients), SpA antibody levels were measured over time and showed a wide temporal variation of immune responses. We conclude that antibody responses to SpA can be measured in many patients with invasive S. aureus disease but that the levels are of insufficient sensitivity or specificity to be of clinical use as a diagnostic or prognostic test.

Antibodies, Bacterial↗

A placebo-controlled study of enciprazine in the treatment of generalized anxiety disorder: a preliminary report.

Enciprazine is a propanolamine derivative with a preclinical profile similar to buspirone but with less affinity for the postsynaptic dopamine receptor (Linden et al. 1988). We report on the outcome, using intent-to-treat data, of a 5-week, double-blind trial comparing three dose strengths of enciprazine (5 mg t.i.d., 10 mg t.i.d., and 20 mg t.i.d.) to placebo. A dose escalation was permitted after 2 weeks of active drug treatment, which 61 percent of patients overall took advantage of. A "last observation carried forward" (LOCF) analysis found a mean improvement in Hamilton Anxiety Scale (HAM-A) scores by Week 5 of -11.0 for the combined enciprazine treatment groups, and -4.4 for the placebo group (p less than .05). Fifty-two percent of enciprazine patients were judged to be "much" or "very much" improved, whereas none of the placebo patients were judged to have comparable improvement. Enciprazine was well-tolerated, with low levels of sedative and asthenic side effects reported. The compound appears to have promise as an anxiolytic agent.

Adult↗

A preliminary trial of the programmable implantable medication system for insulin delivery.

We undertook a trial to determine whether an implanted insulin-delivery system, the programmable implantable medication system (PIMS), could be used to treat patients with insulin-dependent diabetes. PIMS is a pulsatile, programmable pump with a battery life expectancy of five years. The reservoir is refilled transcutaneously every two months with a surfactant-stabilized human insulin preparation containing 400 U of insulin per milliliter. Eighteen patients received PIMS-delivered insulin for 4 to 25 months (mean, 18). The total PIMS-implantation experience comprised 28 patient-years. Good glycemic control was established and sustained during treatment (mean plasma glucose level, 7.3 mmol per liter; mean glycohemoglobin level, 8 percent [upper limit of normal, 7.5 percent]), with significantly reduced glycemic fluctuations. The total mean daily insulin dose did not change. Insulin solutions withdrawn from the pump reservoirs contained 92 percent native insulin and preserved biologic activity. There were no surgical or skin complications, severe hypoglycemic episodes, or instances of diabetic ketoacidosis. One pump was replaced because of a manufacturing defect, and four patients had catheter blockages due to omental-tissue encapsulation; two withdrew from the study and two had devices that were repaired successfully. The actuarial rate of survival of catheter function was 78 percent at 1.5 years. We conclude from this pilot study that insulin treatment with an implanted, variable-rate, programmable pump is feasible for periods up to two years.

Adult↗

Comparison of intraperitoneal and subcutaneous insulin administration on lipids, apolipoproteins, fuel metabolites, and hormones in type I diabetes mellitus.

The relative biologic efficacy of intraperitoneal (IP) insulin administration over peripheral routes of insulin infusion for artificial delivery devices is still poorly documented. Thus, the effects of IP insulin administration have been compared with the effects of subcutaneous (SC) insulin administration upon circulating fuel metabolites, hormones and lipoproteins. In a longitudinal study, seven type I diabetic patients, aged 33 +/- 3 years, duration 16 +/- 4 years, were studied. SC intensive insulin therapy was used for 3 months, then insulin was infused IP via an implantable pump for 6 months with a similar good blood glucose control. Lipids including high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol, apolipoproteins A-I, A-II, and B were measured every 3 months. Although all values remained in the normal range, significant changes occurred in plasma triglycerides (63 +/- 9 SC v 88 +/- 12 mg/dL IP, P less than .05) and HDL-cholesterol (57 +/- 4 SC v 42 +/- 4 mg/dL IP, P less than .05) without concomitant changes in apolipoprotein levels. In another cross-sectional study, six of the patients consumed a standardized 400 kcal breakfast after 0.15 U/kg insulin. Eight SC insulin infused age-, glucose control- and weight-matched diabetic patients also underwent the same test using SC insulin. Six normal subjects consumed the same breakfast and served as controls. Plasma glucose, B-hydroxybutyrate, lactate, alanine, free fatty acids, free insulin and glucagon were measured for five hours after the meal. All measured parameters were comparable in both groups except free insulin and lactate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Classification behavior and measures of intelligence: dimensional identity versus overall similarity.

Individuals tend to adopt either analytic or holistic modes of categorizing objects. In two studies, we examined the relation between these categorization tendencies and cognitive abilities as measured by standard psychometric instruments. The participants in both studies were pretested with a restricted classification task in which it was possible for them to classify simple stimuli by dimensional identity or overall similarity. Those making a large number of either type of categorization were then tested with subtests of the WAIS-R and with the Raven's progressive matrices. Across both studies, the analytic individuals (many dimensional identity classifications) scored higher than the holistic individuals (many overall similarity classifications) on some but not all of the subtests. The results are consistent with the idea that holistic modes of categorization may be more "primitive" than analytic modes. The findings are discussed in terms of the association between categorization mode and either general or specific cognitive abilities.

Adult↗

Comparison of the safety and effectiveness of human and bovine long-acting insulins.

Since ultralente insulin pharmacokinetics suggest faster absorption by human insulin when compared with bovine insulin using the subcutaneous route, the safety and efficacy of human ultralente in the outpatient setting was evaluated. Twenty type I patients participated in a randomized study using a crossover design of four six-week phases: (a) one daily injection of human ultralente; (b) two daily injections of human ultralente; (c) one daily injection of bovine ultralente and (d) two daily injections of bovine ultralente. Pre-meal human regular insulin was used with ultralente insulins and comprised 39 +/- 2% of the total daily insulin dose. Total and ultralente daily insulin doses were lower with human ultralente insulin (51.3 +/- 3.0 total and 30.9 +/- 3.4 ultra lente u/day) when compared to bovine ultralente insulin (57.8 +/- 4.4 and 36.1 +/- 4.4 u/day, p less than 0.01), yet the metabolic control achieved was virtually identical during both phases: (hemoglobin Alc 8.6 +/- 0.2% human vs. 8.4 +/- 0.4 bovine, p = NS). The frequency of mild hypoglycemia was 3.0 +/- 0.5 events per week vs 2.0 +/- 0.3 (p = NS). No severe hypoglycemia occurred. There were no differences between blood glucose daily profiles, insulin doses, hemoglobin Alc (8.6 +/- 0.4% BID vs. 8.4 +/- 0.3% QD injections) and occurrence of hypoglycemia between the single and two-dose long-acting regimens. These data indicate that long-acting semi-synthetic human insulin (a) can be effectively used as a once daily injection, (b) may be more biologically active than bovine, and (c) can be associated with safe and effective diabetes control.

Adult↗

The prevalence of plasma heparin neutralizing activity and the effect of treatment on it in women with a gynecologic malignancy.

Plasma samples from some women with a variety of advanced gynecologic malignancies have been shown to neutralize exogenous heparin. The purposes of this investigation were to determine the prevalence of neutralizing activity in a referral population of women with a gynecologic malignancy and to determine whether the level of neutralizing activity is related either to histology or stage or whether it is affected by treatment. One hundred thirty-eight patients were studied over a 1-year interval; 121 had a documented malignancy, 16 were healthy, and one had a benign ovarian neoplasm. The mean heparin neutralizing activity in the healthy patients was 4.5% +/- 7% and it was 46.2% +/- 26% in the group with malignancy (p less than 0.0000, two-tailed). Seventy-five percent of all patients with malignancy had neutralizing activity greater than 25%. The percent of staged, untreated patients with neutralizing activity increased significantly with advancing stage (from 59% with stage I to 85% with stages III and IV disease). There was no significant relationship between neutralizing activity and histology, site of origin, or patient weight. In 10 patients in whom the disease outcome was clear, the change in neutralizing activity reflected (or predicted) the response to therapy. We conclude that heparin neutralizing activity is a generalized phenomenon in women with one of the malignancies studied, and it may potentially be useful in the evaluation of the patient's response to therapy.

Adenocarcinoma↗