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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 559 records · Page 31Linked to original sources
PubMed1995

Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer.

The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.

Animals↗
PubMed1995

Indications for Neisseria gonorrhoeae cultures in children with suspected sexual abuse.

OBJECTIVE: To determine the clinical predictors of Neisseria gonorrhoeae infection in children examined for sexual abuse. DESIGN: Retrospective review of a prospective management plan. SETTING: A 240-bed children's hospital with 36,000 emergency department visits per year. INTERVENTION: In 1988, a Pediatric Emergency Medicine Department protocol was introduced for the examination of children who present with complaints suggestive of sexual abuse. RESULTS: From January 1990 through December 1991, the records of all children less than 12 years of age examined for suspected sexual abuse were reviewed. Vaginal/urethral, oral, and rectal cultures for N gonorrhoeae were performed in 316 children. Seven children (2.2%) had a total of 12 positive cultures: seven vaginal/urethral, four rectal, and one oral. Evidence of vaginal/urethral discharge on physical examination was the best predictor of N gonorrhoeae infection (sensitivity, 100%; specificity, 88%; positive predictive value, 16%; and negative predictive value, 100%). Historical and physical evidence of discharge was significantly associated with N gonorrhoeae infection (P < .0006 and P < .000001, respectively). CONCLUSIONS: Children less than 12 years of age examined for sexual abuse who did not have evidence on physical examination of vaginal or urethral discharge were found to have a 100% probability of having negative vaginal/urethral, oral, and rectal N gonorrhoeae cultures. These findings do not support the practice of obtaining cultures for N gonorrhoeae routinely in all children who present for evaluation of possible sexual abuse.

Child↗
PubMed1995

A functional factor X deficiency.

A functional factor X deficiency is described which caused pronounced reduction in the in vitro activation of the extrinsic system while marginally affecting the in vitro activation of the intrinsic pathway. All studies were normal with the exception of a prolonged PT, an elevated factor X antigen, and low factor X activity. Western blot analysis revealed the presence of two factor X species. The abnormal molecule was of higher molecular weight. Interestingly, there was no bleeding associated with this deficiency. The biochemical basis of this defect is currently under investigation.

Adult↗
PubMed1995

Lid opening apraxia is associated with medial frontal hypometabolism.

We used [18F]fluorodeoxyglucose with positron emission tomography to explore the functional basis of lid opening apraxia (LOA). We studied four patients with LOA without associated pyramidal or extrapyramidal motor dysfunction (mean age 65.5 +/- 4.7 years). We compared measures of glucose metabolism with those calculated for 10 age-matched normal volunteers (mean age 60.6 +/- 11.4). All four patients demonstrated significant metabolic reductions (> 2 SD) in the medial frontal lobe: bilaterally in two, unilaterally in two. Significant abnormal unilateral metabolic reductions in the left basal ganglia were evident in two patients. These findings suggest that medial frontal lobe hypometabolism is associated with LOA. Abnormal striatofrontal interactions may be involved in the pathogenesis of this condition.

Aged↗
PubMed1995

Plasmodium falciparum: parasites defective in early stages of gametocytogenesis.

Some molecular characteristics of Plasmodium falciparum lines which do not produce gametocytes are described. Parasites carrying a subtelomerically deleted chromosome 9 cannot form even the earliest forms of gametocytes, detectable with antibodies against the gametocyte-specific antigen Pfg27. In a parasite culture of clone HB3, in which both intact and deleted forms of chromosome 9 are present, full-length chromosome 9 molecules are retained mainly in gametocytes. These data suggest that the subtelomeric portion of chromosome 9 is required at an early stage of gametocytogenesis. Parasite subclones derived from gametocyte producing clone 3D7, which completely lost ability to produce gametocytes, are also described. Unlike the previous gametocyteless lines, these parasites stably maintain a full-length chromosome 9 and the ability to cytoadhere to C32 melanoma cells after prolonged asexual propagation. Their defect in sexual development is therefore genetically and functionally distinct from that of parasites carrying a deleted chromosome 9. Gametocyteless subclones derived from 3D7 do not produce any Pfg27 mRNA, while this gene is anomalously expressed in asexual stage parasites of two lines of a different genetic background, 1776sel8 and C10, one able and the other unable to produce gametocytes.

Animals↗
PubMed1995

Improved Anticoagulation with a Weight-Adjusted Heparin Nomogram in Patients with Acute Coronary Syndromes: A Randomized Trial.

The optimal heparin dosing schedule to achieve rapid and therapeutic anticoagulation has not been established. The objective of this study is to determine whether an intravenous heparin dosing nomogram based on body weight achieves adequate anticoagulation more rapidly than a standard-care nomogram. Sixty-four patients requiring intravenous heparin treatment for acute coronary syndromes, but who did not receive thrombolytic therapy, were randomized to a standard-care nomogram in which heparin was given as a 5000 unit IV bolus followed by 1000 U/hr, or a weight-adjusted nomogram in which heparin was given as an 80 U/kg IV bolus and 18 U/kg/hr. Activated partial thromboplastin time (APTT) values were checked at 6, 12, 18, 24, and 48 hours and adjusted either by 100-200 U/hr (standard-care nomogram) or by 2-4 U/kg/hr (weight-based nomogram). Activated partial thromboplastin times were measured using a widely generalizable laboratory method. The primary goal was to achieve and maintain the APTT between 60 and 90 seconds. The median APTT values were higher in the weight-adjusted group compared with the standard-care group at 6, 12, 18, 24, and 48 hours: 150 versus 83 (p = 0.001), 100 versus 79 (p = 0.09), 66 versus 61 (p = 0.005), 63 versus 56 (p = 0.09), and 64 versus 56 (p = 0.11). At 18 hours only 11% of patients in the weight-adjusted group had an APTT <61 compared with 26% in the standard-care nomogram (p = 0.007). No major bleeding complications were noted in either group. A weight-adjusted heparin nomogram offers improved anticoagulation in the first 24 hours after heparin initiation compared with a standard-care nomogram in patients with acute coronary artery syndromes.

Journal Article↗
PubMed1995

Life-threatening alterations in heart rate after the use of adenosine in atrial flutter.

Adenosine has become the preferred treatment for common types of supraventricular tachycardia because it is extremely effective and rarely associated with with serious side effects. It has also been advocated as an intervention for diagnostic use to assess uncommon types of tachycardia. Evidence is shown in this report that adenosine was associated with dangerous worsening of arrhythmia in patients with atrial flutter. In two patients, adenosine precipitated acceleration of ventricular response, in one case necessitating emergent cardioversion. Both patients had atrial flutter with 2 to 1 atrioventricular block that evolved into 1 to 1 atrioventricular conduction. In three other patients, adenosine was associated with prolonged bradyasystole and hypotension. In each of the five patients, adenosine was given in a standard fashion (6 or 12 mg). In summary, adenosine should be recognized as a potentially dangerous intervention in patients with atrial flutter. If it is used for diagnostic purposes, resuscitative equipment should be readily available.

Adenosine↗
PubMed1995

Increased messenger RNA expression of the 695 and 751 amino acid isoforms of the beta-amyloid protein precursor in the thalamus of 17-year-old cynomolgus (Macaca fascicularis) monkeys.

The levels of expression of messenger RNAs of the 695 and 751 amino acid isoforms of the beta-amyloid protein precursor in the brains of three-year-old and 17-year-old cynomolgus monkeys (Macaca fascicularis) were visualized and quantified by in situ hybridization histochemistry using 35S-labelled oligonucleotide probes. The analysis was carried out on coronal brain sections taken through the hippocampus and thalamus at the level of the geniculate nuclei. High densities of beta-amyloid protein precursor695 and beta-amyloid protein precursor751 messenger RNAs were found in the medial aspects of the mediodorsal, centromedian and parafascicular nuclei of the 17-year-old monkeys. The messenger RNA levels of the 695 and 751 isoforms were about two- and seven-fold, respectively, those found in the same nuclei of the three-year-old animals. The levels of these messenger RNA transcripts in the 17-year-old monkeys were not significantly different from those in the three-year-old animals in other brain areas e.g. the temporal cortex, entorhinal cortex and hippocampus. No Alzheimer's disease-like neuropathology in terms of diffuse or senile beta-amyloid plaques, dystrophic neurites or neurofibrillary tangles were detectable by specific innumohistochemical procedures in the above thalamic nuclei of the 17-year-old animals. In addition no reactive gliosis was seen in the thalamus of these monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Deantigenation of human type B erythrocytes with Glycine max alpha-D-galactosidase.

Conversion of erythrocyte membrane B antigen to H antigen produces blood type O which is universally transfusable. If efficient large-scale production of enzymatically converted red blood cells is to be achieved, then optimal conditions for deantigenation must be determined. Cell suspension assays were used to study the blood group B activity of Glycine max (soybean) alpha-D-galactosidase on native human erythrocytes. The enzyme readily hydrolyzed the terminal alpha-D-galactosyl residue of the B antigen, converting it to H antigen. Optimal conditions for the enzymatic conversion of red cells with the Glycine enzyme are described. Normal cell morphology and function were maintained under optimal conditions.

ABO Blood-Group System↗
PubMed1995

Failure of intrathymic inoculation of donor-specific splenocytes to prolong cardiac or renal allograft survival in dogs.

The intrathymic inoculation (ITI) of donor splenocytes into potential organ transplant recipients has been demonstrated to result in donor-specific unresponsiveness and greatly prolonged survival of subsequent organ allografts in rodents without the need for long-term pharmacological immunosuppressive therapy. We have studied the effect of the ITI of saline (controls) (groups 1 (n = 6) and 3 (n = 6)) or donor splenocytes (groups 2 (n = 10) and 4 (n = 8)) in dogs that received either pharmacological immunosuppression (with cyclosporine and prednisone, +/- azathioprine/cyclophosphamide) (groups 1 and 2) or rabbit anti-dog antithymocyte globulin (groups 3 and 4) at the time of ITI. Kidney or heart allografting (from the donor of the splenocytes) was carried out 16-74 days after ITI; all but four transplants were performed within 16-22 days after ITI. Mean kidney allograft survival was 6, 10, 9, and 9 days, respectively, in groups 1-4. Mean cardiac allograft survival was 7, 14, 8, and 7 days, respectively. There was no statistical difference in allograft survival between those dogs that received ITI of saline and those that received donor splenocytes. These results would suggest that the protocols developed to date using ITI in rodent species may not be successful in dogs.

Animals↗
PubMed1995

In vitro selection of RNA-based irreversible inhibitors of human neutrophil elastase.

INTRODUCTION: We describe a new approach to drug discovery which joins the technologies of medicinal and combinatorial chemistry, allowing selection of the most active variant of a lead compound from a large (> 10(12)) pool. A small-molecule covalent inhibitor of elastase was coupled to a randomized pool of RNA, and this assembly was iteratively selected for oligonucleotide sequences that promote the covalent reaction of the inhibitor with the human neutrophil elastase (hNE) active site. RESULTS: Incorporation of the covalent inhibitor into the randomized pool increases the second-order rate of inactivation of hNE by approximately 15-fold; sequences selected from this pool show an additional approximately 20-fold increase in activity. The relative rate of cross-reaction with another serine protease, cathepsin G, was reduced > 100-fold. Low doses of the inhibitor were found to prevent lung damage inflicted by human neutrophils in an isolated rat lung model of acute respiratory distress syndrome (ARDS). CONCLUSIONS: This result supports the hypothesis that neutrophil elastase is a significant effector of inflammatory disease. More generally, our findings demonstrate that blending small molecules into combinatorial libraries is a feasible method of drug discovery.

Animals↗
PubMed1995

Clearance of chronic hepatitis B virus infection in young children after alpha interferon treatment.

Nine children aged 18 months to 17 years (mean 5.7 years) with chronic hepatitis b virus infection and chronic active hepatitis were treated with 5 to 6 million units/m2 of body surface area of interferon -alpha 2b administered subcutaneously three times per week for 4 months (n = 1) or 6 months (n = 8). At 12 months after the start of therapy, six children less than 3 years of age responded to the treatment (three completely and three partially), whereas only one of three children older than 7 years of age responded. We conclude that IFN treatment may be effective in children with chronic HBV infection, especially when administered while they are young.

Adolescent↗
PubMed1995

The efficacy of audiotapes in promoting psychological well-being in cancer patients: a randomised, controlled trial.

Open or uncontrolled studies have suggested that providing cancer patients with audiotapes of their clinical interviews can improve information recall and reduce psychological distress. We tested these hypotheses in a 'clinician-blind', prospective, randomised controlled trial. A total of 117 patients newly referred to a medical oncology clinic who were to be given 'bad news' had their consultations audiotaped. Blind to the clinician, patients were randomly allocated to receive a copy of the tape to play at home or not (control group). At 6 months follow-up, tape group patients reported positive attitudes to the audiotape and were shown to recall significantly more information about their illness than did controls. Overall improvement in psychological distress at 1 and 6 months follow-up, as measured with the 30-item General Health Questionnaire and the Hospital Anxiety and Depression Scale was no different in the two groups. However, a second-order interaction suggested that poor-prognosis patients were disadvantaged specifically by access to the audiotape, with less improvement in psychological distress at 6 months follow-up than non-tape controls. Patient access to audiotapes of clinical interviews promotes factual retention but does not reliably reduce psychological distress and may be actively unhelpful in some subgroups of patients.

Adult↗
PubMed1995

Should patients with human immunodeficiency virus infection or chronic hepatitis donate blood for autologous use?

BACKGROUND: The purpose of this project is to formally evaluate the benefits and the risks of allowing patients with human immunodeficiency virus (HIV) infection or hepatitis to donate blood for autologous use. STUDY DESIGN AND METHODS: With data on the incidence of transfusion-transmitted hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV; administrative error; and health-care worker exposure, decision analysis was used to quantitate the benefits and risks of autologous blood transfusions versus those of transfusions of blood from allogeneic donors. RESULTS: Assuming the highest documented probability of transfusion-related infection, the days of life saved by allowing the transfusion of autologous blood to a 30-year-old noninfected or HBV-, HCV-, or HIV-infected patient are 92.52, 70.60, 0.95, and 5.69, respectively. Assuming the lowest documented probability of transfusion-related infection, the days of life saved decrease to 2.96, 2.26, 0.15, and 0.18, respectively. Avoidance of HCV accounts for over 90 percent of the days gained. The days of life lost by other noninfected patients through administrative error average 0.11 in the case of HIV and those lost by health care workers average 0.04, 0.18, and 0.07 in the case of HBV, HCV, and HIV, respectively. CONCLUSION: The benefit of autologous transfusions in patients infected with HBV, HCV, and HIV is significantly less than that in noninfected patients. The risks of this infected blood to other noninfected patients are significant only in the case of HIV-infected blood transfusions; however, there is a measurable risk to health-care workers should all infected blood be allowed into the blood supply.

Adult↗
PubMed1995

Moderate folate deficiency does not cause global hypomethylation of hepatic and colonic DNA or c-myc-specific hypomethylation of colonic DNA in rats.

Global and gene-specific DNA hypomethylation is considered to be an important early epigenetic event in several human neoplasms. A growing body of evidence has suggested that DNA methylation can be altered by dietary manipulation of methyl group donors. This study investigated whether moderate depletion of folate, a dietary component needed for the synthesis of methyl groups, would cause decreased hepatic and colonic S-adenosylmethionine concentrations, and thereby lead to global and/or protooncogene-specific DNA hypomethylation. Weanling rats were fed an amino acid-defined diet containing either 0 or 8 mg folate/kg diet for 15 or 24 wk. Significantly lower systemic, hepatic and colonic folate concentrations were observed in the moderately folate-depleted rats than in controls at both 15 and 24 wk (P < 0.005). Although hepatic S-adenosylmethionine was significantly lower in the moderately folate-depleted rats than in controls at the two time points (P < 0.03), colonic S-adenosylmethionine concentrations were not significantly different between the two groups at either time point. No significant differences between the folate-depleted and control animals could be detected with regard to global DNA methylation in the liver or colonic mucosa. Furthermore, c-myc protooncogene-specific DNA methylation in the colonic mucosa was not significantly different between these two groups of animals. These results indicate that moderate folate depletion does not cause a significant reduction in global DNA methylation in liver or colonic mucosa or in c-myc-specific colonic mucosal DNA methylation in this rat model.

Animals↗
PubMed1995

Treatment options for vulvovaginal candidiasis, 1993.

Vulvovaginal candidiasis (VVC), the second most common form of vaginitis, particularly affects women of childbearing age. Since the 1970s, several new agents have become available for the treatment of VVC. This review focuses on options for the treatment of this condition, critically evaluating the relevant published studies. For the treatment of acute episodes of VVC in nonpregnant women, several topical and oral antifungal agents are clinically and mycologically effective. Topical agents should be considered the first line of therapy; however, oral agents are sometimes associated with better compliance among patients. For acute episodes in pregnant women, a topical agent is the treatment of choice. Until data become available on the treatment of VVC in women infected with human immunodeficiency virus (HIV), the same approach as that used for women without HIV infection should be considered as previously written. For recurrent VVC, the optimal maintenance therapy has not yet been established; however, administration of low-dose oral ketoconazole (100 mg/d) has proven effective. Well-designed studies of the best therapy for VVC in women with HIV infection and for recurrent VVC are urgently needed.

Acute Disease↗