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Biomedical subjects

L G Smith

Publications and source records attributed to L G Smith.

At least 55 records · Page 3Linked to original sources

Insulin resistance and development of diabetes mellitus associated with megestrol acetate therapy.

We describe a case of diabetes mellitus induced by megestrol acetate in a patient with the acquired immunodeficiency syndrome. Metabolic studies including an arginine infusion test excluded an insulinopenic state and suggested insulin resistance as the underlying mechanism for hyperglycaemia. Withdrawal of megestrol acetate resulted in rapid correction of all metabolic abnormalities and eliminated the need for exogenous insulin therapy.

Adult↗

The tangled-1 mutation alters cell division orientations throughout maize leaf development without altering leaf shape.

It is often assumed that in plants, where the relative positions of cells are fixed by cell walls, division orientations are critical for the generation of organ shapes. However, an alternative perspective is that the generation of shape may be controlled at a regional level independently from the initial orientations of new cell walls. In support of this latter view, we describe here a recessive mutation of maize, tangled-1 (tan-1), that causes cells to divide in abnormal orientations throughout leaf development without altering overall leaf shape. In normal plants, leaf cells divide either transversely or longitudinally relative to the mother cell axis; transverse division are associated with leaf elongation and longitudinal divisions with leaf widening. In tan-l mutant leaves, cells in all tissue layers at a wide range of developmental stages divide transversely at normal frequencies, but longitudinal divisions are largely substituted by a variety of aberrantly oriented divisions in which the new cell wall is crooked or curved. Mutant leaves grow more slowly than normal, but their overall shapes are normal at all stages of their growth. These observations demonstrate that the generation of maize leaf shape does not depend on the precise spatial control of cell division, and support the general view that mechanisms independent from the control of cell division orientations are involved in the generation of shape during plant development.

Cell Division↗

Combining medical and mechanical methods of cervical ripening. Does it increase the likelihood of successful induction of labor?

OBJECTIVE: To determine if combining two commonly used methods or cervical ripening (intracervical prostaglandin E2 [Pge2] gel and Foley balloon catheter) would result in a higher number of successful inductions and fewer cesarean sections when compared to PGE2 gel alone. STUDY DESIGN: Seventy-eight patients with unfavorable cervixes eligible for induction of labor were prospectively randomized to receive either one dose (0.5 mg) of PGE2 gel followed by insertion of a 24-French Foley catheter (group 1, 41 patients) or two doses of 0.5 mg of intracervical gel (group 2, 37 patients). Outcome parameters included change in Bishop score, number of failed inductions, rate of cesarean section, rate of uterine hyperstimulation and postpartum infection. RESULTS: Patients in group 1 had a significant increase in posttreatment Bishop scores (7.26 +/- 2.0 SD vs. 4.82 +/- 1.8 P = .0001) and fewer failed inductions (0 vs. 6, P = .009) when compared to patients in group 2. Abdominal delivery rates, uterine hyperstimulation and infections complications were not different between the two groups. CONCLUSION: The combination of the Foley balloon and prostaglandin gel significantly improved the Bishop score and led to fewer failed inductions, although it did not increase the vaginal delivery rate.

Adult↗

Overuse of the indwelling urinary tract catheter in hospitalized medical patients.

BACKGROUND: The indwelling urinary tract catheter (IUTC) is an important aspect of medical care. We studied the prevalence of the unjustified use of the IUTC in hospitalized medical patients and identified situations associated with its unjustified use. METHODS: This prospective study involved 202 patients admitted to either the medical intensive care unit (n = 135) or the medical floors (n = 67) of a tertiary care university hospital who were catheterized during the hospital admission. An independent observer assessed the indication of initial catheterization by chart review and interview with the patient and the nurse. The need for continued catheterization was assessed daily by the same observer. The proportion of unjustified IUTC placement was determined using the study guidelines. Complications as a direct consequence of catheter use were recorded. RESULTS: Of the 202 patients who were studied, the initial indication for the placement of an IUTC was found to be unjustified in 21% (95% confidence interval [CI], 15% to 27%). Continued catheterization was unjustified in 47% (95% CI, 42% to 57%) of 912 patient-days with IUTC studied. In the medical intensive care unit, 64% (95% CI, 58% to 70%) of the total unjustified patient-days with IUTC resulted from its excessively prolonged use for monitoring urine output. Urinary incontinence was found to be the major cause of unjustified initial ([52%] 95% CI, 32% to 74%) and continued ([56%] 95% CI, 50% to 62%) use of IUTC in the noncritical care areas. Catheter-related urinary tract infection requiring intravenous antibiotics or continuous bladder irrigation with amphotericin B was observed in 5% of the patients. CONCLUSIONS: The IUTCs are significantly overused in hospitalized medical patients and careful attention to this aspect of medical care may reduce catheter-related complications by primary prevention.

Catheters, Indwelling↗

Beta-lactamase inhibitor combinations.

The beta-lactamase inhibitor combinations present a novel approach to the problem of beta-lactamase-induced resistance to antibiotics. These agents are derived from the generally safe beta-lactam class of antibiotics. They are all principally excreted through the kidneys and require dosage adjustment in the face of significant renal insufficiency. They show significantly increased activity against methicillin-sensitive S. aureus, H. influenzae, B. catarrhalis, and B. fragilis. The activity against Enterococcus, Pseudomonas, and most gram-negative bacilli, however, remains limited to that of the respective antibiotic component. Although shown to be clinically useful in a variety of clinical situations, they appear to be most useful for skin and soft tissue infections and lower respiratory tract infections as well as intra-abdominal and gynecologic infections caused by susceptible pathogens.

Anti-Bacterial Agents↗

Twin autonomous bipartite nuclear localization signals direct nuclear import of GT-2.

GT-2 is a DNA-binding protein with high target-sequence specificity toward functionally defined, positively acting cis elements in the rice phytochrome A gene promoter. Using immunocytochemical procedures, it is shown here that GT-2 is localized to the nucleus, consistent with a function in transcriptional regulation. Immunoblot and immunocytochemical analyses show that rice shoots contain higher levels of GT-2 protein than roots, and that no photo-induced changes in GT-2 abundance or spatial distribution are detectable in these tissues, a result consistent with the proposed constitutive activity of GT-2. In both shoots and roots, GT-2 protein is undetectable in meristematic tissue but becomes expressed at later stages of cellular development, consistent with a role in contributing to the pattern of phytochrome A gene expression. By transfecting protoplasts with a series of constructs containing deletion derivatives of GT-2 fused to beta-glucuronidase (GUS), followed by in situ localization of GUS activity, two independent, functionally active nuclear localization sequences (NLSs) have been identified in GT-2. One NLS resides within each of a pair of previously identified, spatially separate, trihelix motifs in the protein. Sequence inversion and alanine-scanning mutagenesis has identified residues within these NLSs necessary for nuclear localization. Each NLS contains two basic domains separated by 10 amino acids, conforming to the bipartite class of NLS involved in the targeting of numerous other nuclear localized proteins.

Amino Acid Sequence↗

Hematologic malignancies during pregnancy.

Most hematologic malignancies are rare during the childbearing years with the exception of Hodgkin's lymphoma. However, the continued spread of retroviruses, such as human immunodeficiency virus, in the heterosexual population may result in a substantial rise in viral-induced non-Hodgkin's lymphomas. Although pregnancy does not affect the natural course of these illnesses, adequate staging and therapy can be a difficult task. The obstetrician and the consultant hematologist/oncologist must weigh the benefit of immediate treatment while minimizing toxicity to the fetus.

Decision Trees↗

Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer.

The human DNA mismatch repair gene homologue hMSH2, on chromosome 2p is involved in hereditary non-polyposis colon cancer (HNPCC). On the basis of linkage data, a second HNPCC locus was assigned to chromosome 3p21-23 (ref. 3). Here we report that a human gene encoding a protein, hMLH1 (human MutL homologue), homologous to the bacterial DNA mismatch repair protein MutL, is located on human chromosome 3p21.3-23. We propose that hMLH1 is the HNPCC gene located on 3p because of the similarity of the hMLH1 gene product to the yeast DNA mismatch repair protein, MLH1, the coincident location of the hMLH1 gene and the HNPCC locus on chromosome 3, and hMLH1 missense mutations in affected individuals from a chromosome 3-linked HNPCC family.

Adaptor Proteins, Signal Transducing↗

Postmenopausal uterine bleeding due to estrogen production by gonadotropin-secreting lung tumors.

Two postmenopausal women are described who had uterine bleeding due to hormone production by lung tumors--a large cell carcinoma in one case and a choriocarcinoma in the other. Both tumors stained positively for one or more placental peptides (human chorionic gonadotropin [hCG], placental lactogen, or pregnancy-specific beta-1 glycoprotein) and both patients had extremely elevated serum levels of hCG, suggesting the tumors had some placental-like endocrine function. Clinical and hormonal data supported the concept that the uterine bleeding resulted from estrogen excess due to steroid bio-transformation by the tumors.

Biopsy↗

Calcium homeostasis in pregnant women receiving long-term magnesium sulfate therapy for preterm labor.

OBJECTIVES: The hypothesis of this study is that calcium homeostasis and bone mineralization are altered in pregnant women receiving long-term therapy with magnesium sulfate as compared with similar women not receiving magnesium sulfate to control preterm labor. STUDY DESIGN: Thirty-nine women between 24 and 32 weeks' gestation, matched for age, race, and duration of bed rest, were enrolled. Indices of calcium homeostasis in serum and urine were measured serially, and bone mineralization of the distal radius was measured at 1 and 11 weeks post partum. RESULTS: Magnesium therapy was administered for a mean duration of 26 +/- 14 days and a cumulative dose of 1405 +/- 963 gm. Serum concentrations of magnesium, phosphorus, and parathyroid hormone increased and those of calcium decreased from baseline values in the magnesium sulfate group and remained uniform throughout the 3-week investigation. The serum magnesium, phosphorus, parathyroid hormone, and calcium concentrations in the control group were unchanged during the study and differed significantly from those in the magnesium sulfate group (p < 0.001). Urinary output of magnesium, calcium, and copper was significantly greater in the magnesium sulfate group than in the control group throughout the study. Urinary losses of calcium in the magnesium sulfate group, approximately 800 to 900 mg/day, were substantial. Although radius bone density 1 week post partum did not differ between groups, the change in bone density from 1 to 11 weeks post partum was significantly lower in the magnesium sulfate group than in controls. CONCLUSIONS: These data suggest that calcium homeostasis is altered during and after long-term magnesium sulfate therapy. The marked, prolonged urinary calcium losses may affect maternal bone mineralization.

Calcification, Physiologic↗