Biomedical subjects

D G Smith

Publications and source records attributed to D G Smith.

At least 163 records · Page 9Linked to original sources

PubMed1994

Adherence of Ureaplasma urealyticum to human epithelial cells.

Adherence of Ureaplasma urealyticum cells to eukaryotic cell monolayers was quantified using the Bertholet assay to monitor ammonia produced from urea by ureaplasma urease. Adherence was abolished by pre-treatment of ureaplasmas with HeLa cell extracts and inhibited to varying degrees by pretreatment of the ureaplasmas with N-acetylneuraminic acid, specific antisera and monoclonal antibodies. The data suggest the presence of several ureaplasma adhesins, some of which are species- or serotype-specific and some of which are proteinaceous and antigenic. The serotype-8-specific 96 kDa surface-expressed antigen may be one adhesin. Pre-treatment of HeLa cell monolayers with neuraminidase significantly reduced ureaplasma adherence and, using a novel 'immunoblot adherence assay', ureaplasmas were shown to bind to a number of HeLa cell components, three of which appear to terminate in sialic acid.

Adhesins, Bacterial↗

PubMed1994

Achilles tendon tenodesis to prevent heel pad migration in the Syme's amputation.

In an attempt to prevent migration of the heel pad, 11 patients underwent a combined Syme's amputation and Achilles tendon tenodesis between December 1989 and April 1992. Ten patients healed the Syme's amputation, and one patient failed to heal the surgical wounds and required a below-knee amputation. In all 10 successful Syme's cases, the heel pad has remained stable with no migration, and no skin breakdown at an average follow-up of 18.5 months. Published series of Syme's amputations report that the incidence of heel pad migration is between 7.5% and 45%, and occurs primarily in the post-operative or early rehabilitation stage. We believe that tenodesis of the Achilles tendon is a technically easy addition to the Syme's amputation, that it keeps tension off of the incision during healing, and that it prevents migration of the heel pad.

Achilles Tendon↗

PubMed1994

Factitious gingival ulceration: as presenting sign of Munchausen's syndrome?

This report describes the case of a 21-year-old female who presented with localized gingival ulceration that over a period of 4 weeks became generalized, affecting all the buccal gingiva as well as the lower lip. A detailed medical history suggested that the patient was generating the lesions herself. She was monitored for 6 months, during which time additional lesions developed on the scalp and face. Conventional therapy failed to resolve the lesions and the patient was ultimately referred for a psychiatric consultation in view of the similarity of this case with previously reported cases of factitious disease.

Adult↗

PubMed1994

What do we want and what do we get from not-for-profit hospitals?

The tax exemption for not-for-profit hospitals has been subject to many recent challenges, in part related to concerns over whether these hospitals provide sufficient levels of community benefits to merit tax exemption. Computing the value of community benefits for California hospitals as the sum of uncompensated care, education and research, net income, money-losing services, and price discounts from for-profit hospitals reveals that 20 to 80 percent of hospitals would have met various recommended community benefits standards. There is a clear need for hospitals and their communities to establish dialogues on what levels of community benefits are appropriate.

Accounting↗

PubMed1994

Genetic heterogeneity in five captive specific pathogen-free groups of rhesus macaques.

Gene diversity was used to estimate genetic heterogeneity in the founders of five specific pathogen-free (SPF) colonies of rhesus macaques (Macaca mulatta) and ranged from about 0.20 to 0.32. In the founders of three groups at the California Regional Primate Research Center (CRPRC) that have been minimally managed to maintain genetic heterogeneity, gene diversity was about 0.30, approximately the value for that species, and has declined at the rate of only about 2.5% per generation since 1976. Without intervention, less than half the gene diversity in SPF harem groups will remain after 5 generations whereas gene diversity in multimale SPF groups should decline at less than half that rate. The proportion of gene diversity attributable to average differences among the three groups at the CRPRC, indicating the level of genetic subdivision, was lower than that in the founders of all but one of the SPF colonies and actually declined slightly over a 10-year period. Genetic subdivision in SPF colonies consisting of harem breeding groups was about three times that in colonies consisting of multimale breeding groups. The number of male breeders should be increased and variance in male reproductive success should be reduced in all SPF colonies, especially those containing multimale breeding groups. Genetic heterogeneity can most easily be retained, and genetic subdivision prevented, in each breeding group in all SPF colonies by ensuring gene flow among the breeding groups in each colony. Male breeders who exceed the lowest acceptable level of reproductive success in their colony of origin should also be exchanged among different SPF colonies to maximize the effective population size of the breeding groups in all SPF colonies.

Animals↗

PubMed1994

Continuous regional analgesia by intraneural block: effect on postoperative opioid requirements and phantom limb pain following amputation.

The objective of this study was to assess the effectiveness of a previously described technique of regional analgesia (continuous infusion of local anesthetic through a catheter placed at the time of amputation within the exposed sciatic or posterior tibial nerve) on relieving the postoperative pain in a heterogeneous group of patients who underwent lower extremity amputations. A second objective was to determine the effect of such treatment on the incidence and characteristics of phantom limb pain 6 months or more after surgery in the same patients. The study design was retrospective, unblinded, controlled (postoperative pain), and unblinded questionnaire and interview (phantom pain) were utilized. Subjects were inpatients at Harborview Medical Center, University of Washington, Seattle, WA. Nineteen bupivacaine-treated and 40 nonbupivacaine-treated patients who underwent lower extremity amputation subsequent to trauma, infection, long-standing injury (poor or no function), congenital deformity, or burns were evaluated in the postoperative pain management assessment. Nine treated and 12 untreated patients were interviewed in the phantom pain assessment. Bupivacaine 0.5% 2-6 ml/h was infused through a polyamide 20-gauge catheter inserted into the sciatic or posterior tibial nerve sheath under direct vision at the time of surgery. All patients, treated and control, received opioid analgesics systemically during the 72-hour period of study. The postoperative opioid analgesic requirement of treated patients was compared with that of control patients who received opioid analgesics alone. A questionnaire was administered to assess presence, severity, and character of phantom pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Distribution of the 9-bp mitochondrial DNA region V deletion among North American Indians.

The deletion of a 9-bp segment from the intergenic region between the mtDNA cytochrome oxidase II gene and the lysine tRNA gene has been documented mainly in individuals of East Asian ancestry and in individuals from East Asian-derived populations (e.g., Polynesia). Among Native Americans the deletion is absent among Eskimos and northern Na-Dene populations and present among most Amerind populations [sensu Greenberg (1987); i.e., all Native Americans except Eskimo-Aleut and Na-Dene] that have been studied. To better characterize the frequency and distribution of the 9-bp deletion in North America, we surveyed more than 400 individuals from 59 tribes representing a variety of linguistic groups. The absence of the deletion among Eskimo and northern Na-Dene populations is confirmed. Among Amerind groups the deletion is present in all groups represented by more than six individuals. The geographic distribution of the frequencies of the deletion appears to be clinal in North America. The deletion is absent in the Artic and Subartic and reaches its highest frequency in the Southwest. This distribution is consistent with the hypothesis that the ancestors of the Amerinds and Na-Dene arrived in the New World by means of separate migrations. The presence of the 9-bp deletion in high frequencies in all the major linguistic groups in the Southwest suggests that migration among tribes was common.

Base Sequence↗

PubMed1994

Continuous improvement of strategic information systems: concepts and issues.

Health care organizations that want to position themselves for the future must develop and continuously improve strategic information systems (SIS). The authors consider several problem areas on the current frontier of SIS development and propose solutions that for the most part are expedient and pragmatic.

Budgets↗

PubMed1993

cDNA and protein sequence of polymorphic macaque albumins that differ in bilirubin binding.

The rhesus monkey, Macaca mulatta, exhibits a geographically restricted polymorphism of serum albumins Mac A and Mac B that is recognized by electrophoresis and is associated with a difference in bilirubin-binding parameters. To identify the basis of the polymorphism, the cDNA and protein sequences of serum albumin from M. mulatta were determined. Screening of a lambda gt11 rhesus liver cDNA library yielded a 1988-bp cDNA sequence that encodes the complete amino acid sequence of mature albumin, the entire propeptide, and part of the prepropeptide. Isoelectric focusing and amino-terminal protein sequencing of CNBr fragments of albumin from A/A and B/B homozygotes were performed, and the structural difference was localized to a CNBr fragment (MCB3) spanning residues 124-264. Sequence analysis of lysyl endopeptidase peptides of MCB3 established that Mac A albumin has a glutamine residue at position 188 while the Mac B albumin has a glutamic residue at the same position. PCR amplification, subcloning, and DNA sequence analysis of clones from A/A and B/B homozygotes confirmed the protein sequence data and the codon difference of CAA versus GAA, respectively. Comparison of macaque and human serum albumin shows a 93.5% identity at the amino acid level. In human serum albumin, Glu188 is located close to the IIA binding pocket for ligands, probably including bilirubin. Derivatives of coumarin compete more efficiently with bilirubin for binding sites on the Mac A albumin than on the Mac B albumin. In regions where coumarin-containing plants are important food resources, Mac B albumin may confer a selective advantage because bilirubin is less readily displaced from it.

Amino Acid Sequence↗

PubMed1993

Chronic fatigue: electromyographic and neuropathological evaluation.

Single fibre electromyography of extensor digitorum communis muscle (EDC) was performed on 35 patients with chronic fatigue, the majority of whom also had creatine kinase estimation and biopsy of EDC. The subjects were categorised as having an acute-onset post-viral fatigue syndrome, a non-specific chronic fatigue or possible muscle disease in view of pronounced myalgia. Of 11 subjects who had myalgia as a significant symptom, abnormalities in fibre density were found in 6, and 5 of these had some non-specific abnormalities on muscle biopsy, with creatine kinase levels being normal in all cases. Fibre density estimation may be a useful way of identifying a subgroup of chronic fatigue sufferers with a possible primary muscle disorder.

Adolescent↗

PubMed1993

Targeting vector configuration and method of gene transfer influence targeted correction of the APRT gene in Chinese hamster ovary cells.

A 21-bp deletion in the third exon of the APRT gene in Chinese hamster ovary (CHO) cells was corrected by transfection with a plasmid containing hamster APRT sequences. Targeted correction frequencies in the range of 0.3-3.0 x 10(-6) were obtained with a vector containing 3.2 kb of APRT sequence homology. To examine the influence of vector configuration on targeted gene correction, a double-strand break was introduced at one of two positions in the vector prior to transfection by calcium phosphate-DNA coprecipitation or electroporation. A double-strand break in the region of APRT homology contained in the vector produced an insertion-type vector, while placement of the break just outside the region of homology produced a replacement-type vector. Gene targeting with both linear vector configurations yielded equivalent ratios of targeted recombinants to nontargeted vector integrants; however, targeting with the two different vector configurations resulted in different distributions of targeted recombination products. Analysis of 66 independent APRT+ recombinant clones by Southern hybridization showed that targeting with the vector in a replacement-type configuration yielded fewer targeted integrants and more target gene convertants than did the integration vector configuration. Targeted recombination was about fivefold more efficient with electroporation than with calcium phosphate-DNA coprecipitation; however, both gene transfer methods produced similar distributions of targeted recombinants, which depended only on targeting vector configuration. Our results demonstrate that insertion-type and replacement-type gene targeting vectors produce similar overall targeting frequencies in gene correction experiments, but that vector configuration can significantly influence the yield of particular recombinant types.

Adenine Phosphoribosyltransferase↗

PubMed1993

Effect of formulation on the pharmacokinetics and efficacy of doramectin.

The pharmacokinetics of doramectin, a novel avermectin, were evaluated following parenteral administration in a range of oil-based formulations in an attempt to optimise the formulation. Therapeutic and persistent efficacies against Cooperia oncophora were also evaluated. This approach led to the identification of formulations based upon sesame oil and ethyl oleate which gave more prolonged doramectin plasma concentrations with no loss in therapeutic efficacy and improved persistent efficacy following subcutaneous administration to cattle at a dosage of 200 micrograms kg-1. The importance of using both pharmacokinetic and efficacy end points to distinguish between formulations is discussed. All formulations were well tolerated as evidenced by the absence of any reaction to injection either in the form of behavioural responses, injection site swelling or postmortem lesions. Sesame oil with ethyl oleate was the best parenteral vehicle tested for doramectin, allowing the expression of a high level of therapeutic and persistent efficacy and offering the benefit of excellent injection site toleration.

Analysis of Variance↗

PubMed1993

Persistent efficacy of doramectin against experimental nematode infections in calves.

Three studies were conducted involving cattle exposed to experimental nematode infections. These studies were designed to investigate the prophylactic activity of a single subcutaneous treatment of doramectin at 200 micrograms kg-1 body weight against infections of Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus. For each study, parasite-naive calves were randomly allocated to either a treated or a matched control group. One group received doramectin and the other received doramectin and the other received either no treatment or an injection of saline at 1 ml per 50 kg body weight by the subcutaneous route. Thereafter, all calves received a daily oral challenge of infective larvae of the particular parasite species on test in each study. Challenge of each pair of treatment/control groups continued for periods of 14, 21 or 28 days. An interval of 14-21 days was then allowed to permit the parasites which had established to mature, after which all animals were slaughtered and their worm burdens determined using standard techniques. Geometric mean worm burdens were calculated from the log worm counts and used to estimate percentage efficacy. Accumulated burdens of C. oncophora in doramectin-treated cattle resulting from a daily challenge infection for 14 or 21 days were reduced by 99.2% and 90.7% respectively, in comparison with those of non-treated control animals. For D. viviparus, burdens were reduced by 100% and 99.9% after a 21 or 28 day challenge, respectively. The corresponding figures for O. ostertagi were 99.9% after a 21 day challenge and 93.7% after a 28 day challenge.

Analysis of Variance↗

PubMed1993

Efficacy of doramectin in the prevention of gastrointestinal nematode infections in grazing cattle.

Two studies were performed to investigate the efficacy of doramectin in the prevention of infection with Ostertagia ostertagi and Cooperia oncophora in grazing calves. In each study, 24 parasite-naive calves were randomly allotted to two equal groups and treated with either doramectin at 200 micrograms kg-1 or saline prior to mid-season turnout (Day 0) onto contaminated pasture. Faecal egg counts were carried out twice weekly from 15 to 64 days after turnout and the cumulative faecal egg count was calculated for each group of calves. In the doramectin-treated animals, eggs first appeared in the faeces 19 days and 22 days later than in controls for Studies 1 and 2, respectively. Mean cumulative faecal egg counts over the 64 days were reduced in the doramectin-treated groups by 71% and 87% for Studies 1 and 2, respectively (P < 0.01). The potential utility of injectable doramectin in the seasonal control of gastrointestinal nematode infestations in relation to these findings is discussed.

Analysis of Variance↗

PubMed1993

Efficacy of doramectin against warble fly larvae (Hypoderma bovis).

The efficacy of doramectin in the treatment of cattle harbouring naturally acquired infestations of first, second and third instar larvae of Hypoderma bovis was determined in two studies carried out in the Burgundy region of France. In the first study, cattle on six farms with a history of H. bovis infestations were treated during October 1989 with either doramectin at a dose of 200 micrograms kg-1 liveweight (186 animals) or with an equivalent volume of saline (157 animals). During the following March and April, all animals were examined for the presence of warbles. In the second study, cattle on four farms with warbles present in their backs were treated during March 1990, with either doramectin or saline (as before). The viability of larvae within each warble on all the animals was then assessed every 2 days for 14 days. In Study 1, no warbles were present in any of the doramectin-treated cattle at any time, whereas warbles were found in 135 saline-treated animals. In Study 2, all larvae in warbles on the backs of the doramectin-treated cattle were dead by Day 14 after treatment, whereas viable larvae were still present in warbles in the backs of all saline-treated cattle. No adverse reaction to doramectin treatment was observed in any animal at any time. It was concluded that doramectin is both safe and 100% efficacious in the treatment of first, second and third instar H. bovis infections of cattle.

Analysis of Variance↗

PubMed1993

Informed consent for blood transfusion: a regional hospital survey.

Ninety-two hospitals in a three-state mid-Atlantic region were surveyed to determine their policy toward obtaining written informed consent for transfusion and to examine the content of written consent documents and the process by which consent is obtained. Of 81 hospitals responding, 50 (62%) required written informed consent. Hospitals with fewer than 200 beds were more likely to require written informed consent. The attending physicians had responsibility for obtaining consent in 28 (57%) of 49 institutions, most often on the day or evening before surgery. Twenty-seven of 48 forms mentioned complications: hepatitis in 80 percent, human immunodeficiency virus infection in 46 percent, nonhemolytic reactions in 32 percent, and hemolysis in 25 percent. Alternatives to allogeneic transfusion were mentioned infrequently; eight hospital forms listed autologous transfusion options and only two mentioned designated donation. The reading level required to comprehend 34 consent forms submitted was grade 14.6, which has been attained by only 23 percent of the adult United States population. Although the majority of respondent institutions require written informed consent, those forms, per se, do not document that the fundamental tenets of informed choice have been applied to the decision to transfuse blood.

Blood Banks↗

PubMed1993

Hydrolysis of urea by Ureaplasma urealyticum generates a transmembrane potential with resultant ATP synthesis.

When urea is added to Ureaplasma urealyticum, it is hydrolysed internally by a cytosolic urease. Under our measuring conditions, and at an external pH of 6.0, urea hydrolysis caused an ammonia chemical potential equivalent to almost 80 mV and, simultaneously, an increase in proton electrochemical potential (delta p) of about 24 mV with resultant de novo ATP synthesis. Inhibition of the urease with the potent inhibitor flurofamide abolished both the chemical potential and the increase of delta p such that ATP synthesis was reduced to approximately 5% of normally obtained levels. Uncouplers of electrochemical gradients had little or no effect on these systems. The electrochemical parameters and ATP synthesis were measured similarly at three other external pH values. Any change in delta p was primarily via membrane potential (delta psi), and the level of de novo ATP synthesis was related to the increase in delta p generated upon addition of urea and more closely to the ammonia chemical potential. Although the organisms lack an effective mechanism for internal pH homeostasis, they maintained a constant delta pH. The data reported are consistent with, and give evidence for, the direct involvement of a chemiosmotic mechanism in the generation of around 95% of the ATP by this organism. Furthermore, the data suggest that the ATP-generating system is coupled to urea hydrolysis by the cytosolic urease via an ammonia chemical potential.

Adenosine Triphosphate↗

PubMed1993

Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome.

AIMS: To investigate in detail various biochemical and pathophysiological indices of muscle pathology in acute onset post-viral fatigue syndrome (PVFS). METHODS: Twenty three patients with PVFS (of mean duration 4.6 years) were subjected to needle biopsy for histomorphometry and total RNA contents. Plasma analysis included serology and creatine kinase activities. Indices of whole body mass were also measured--namely, whole body potassium content and plasma carnosinase activities. RESULTS: About 80% of the patients had serology indicative of persistent enteroviral infection as determined by VP1 antigen assay. Only about 10% of that same group of patients had serological indications of current enterovirus infection by IgM assay; a separate subset of 10% showed antibody changes suggestive of reactivation of Epstein-Barr virus. Quantitative morphometric analysis of skeletal muscle fibres indicated that the quadriceps muscle was normal or displayed only minor abnormalities in 22 patients. The Quetelet's Index (body mass index) and whole-body potassium values (index of lean body mass) were not affected in PVFS. The mean plasma carnosinase and creatinine kinase activities were also generally normal in these patients. The mean muscle RNA composition--mg RNA/mg DNA: was significantly reduced in acute onset PVFS by about 15%. The protein:DNA ratio was not significantly affected. CONCLUSIONS: Patients with acute onset PVFS, therefore, lose muscle protein synthetic potential, but not muscle bulk. Histopathology is consistent with these observations. These perturbations may contribute to the apparent feature of perceived muscle weakness associated with the persistent viral infection in the muscle themselves.

Adolescent↗