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Biomedical subjects

D G Smith

Publications and source records attributed to D G Smith.

At least 145 records · Page 8Linked to original sources

Infection of cultured rat enterocytes by Ileal symbiont intracellularis depends on host cell function and actin polymerisation.

The mechanisms of entry of Ileal symbiont intracellularis into IEC-18 rat enterocyte cells and subsequent bacterial proliferation were examined in centrifuge-assisted and static infections. Live, oxygen or neomycin damaged, and formalin killed bacteria, each rapidly entered viable cells. Live or damaged bacteria did not enter cells nor proliferate within cells after static infection of cells cooled to 5 degrees C. Infection of cells was greatly reduced at 20 degrees or 32 degrees compared to infection at 37 degrees C. Centrifuge-assisted infection was also reduced by chilling the cells. Cytochalasin D but not B inhibited the entry process indicating an actin-dependent infection, although other pathways may also be involved in centrifuge-assisted infections. Drugs capable of modifying cell membrane charge, heparin receptors or trypsin-labile proteins were all inactive in preventing or enhancing infection. We therefore conclude that infection of enterocytes by IS intracellularis is dependent on host cell activity and actin polymerization, but is independent of bacterial viability.

Actins↗

Graduate students' health insurance status and preferences.

A survey of graduate and professional students at the University of Michigan revealed that many (12.6%) do not have healthcare coverage. Minority students and students who are financing their education with loans and scholarships are at a particularly high risk of being uninsured. Students are divided in their preferences for changes in policies and systems of coverage. Most of the students' preference is for the university to offer a modestly improved plan and a requirement that students prove insurance coverage. In addition, some students indicated that they would like to have an inexpensive plan as well as the current system of voluntary insurance. After the survey, university officials opted to continue with current offerings and to add an improved policy under a voluntary system.

Adult↗

Prosthetic history, prosthetic charges, and functional outcome of the isolated, traumatic below-knee amputee.

PURPOSE: To review the prosthetic history, prosthetic charges, and functional status of traumatic, isolated, unilateral below-knee amputees at select intervals following amputation. METHODS: This descriptive study was conducted among patients admitted to Harborview Medical Center between 1980 and 1987 who survived initial trauma, and who required an isolated, below-knee amputation. Hospital and prosthetist records were abstracted to calculate the number of prostheses fabricated and the prosthetic charges since initial amputation. Functional outcomes were determined by personal interview and self-administration of the SF-36 Health Status Profile. RESULTS: The average age of patients was 36 with the age range extending from 19 to 59 years. The prosthetic history and prosthetic charges were determined from the medical record and the billing records of the prosthetist. Exact charges were determined for 15 of the 20 patients. During the first 3 years, the mean number of prostheses acquired per patient was 3.4 (range 1-5), with average total prosthetic charges of $10,829 (range $2,558-$15,700). Over the first 5 years the mean number of prostheses acquired per patient was 4.4 (range 2-8), with average total prosthetic charges of $13,945 (range $6,203-$20,070). The SF-36 Health Status Profile scores were significantly decreased from published normal aged-matched scores in the categories of physical function and role limitations because of physical health problems and pain. Scores were not significantly different from published normal aged-matched scores in the other five categories: role limitations due to emotional problems, social functioning, mental health, energy/fatigue, and health perception.

Adult↗

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle.

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 micrograms/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration (Cmax), and areas under the concentration curve (AUC0-infinity) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC0-infinity of 457 +/- 66 ng.day/mL (+/- SD) and a mean Cmax of 27.8 +/- 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC0-infinity of 475 +/- 82 ng.day/mL and a mean Cmax of 33.1 +/- 9.0 ng/mL. Absorption constants (ka) determined by modelling were 0.542 +/- 0.336 day-1 after sc administration and 0.710 +/- 0.357 day-1 after i.m. administration. The 90% confidence limits on the difference between mean AUC0-infinity values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. Cmax was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In(Tmax +1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.

Absorption↗

Tolerance to acid in pH 5.0-grown organisms of potentially pathogenic gram-negative bacteria.

A wide range of potentially pathogenic species of Gram-negative bacteria were far more resistant to extreme acidity (pH 2.0-3.5) when cultured at pH 5.0 (habituated to acid) than after pH 7.0 culture. The differences were particularly great for Citrobacter spp., Enterobacter spp., Klebsiella spp. and for Vibrio parahaemolyticus; substantial habituation was also observed for Proteus mirabilis and Aeromonas formicans but the effect was less marked for Serratia marcescens and Acinetobacter calcoaceticus. Growth at pH 5.0 was substantially poorer than at pH 7.0 for most of the above species and also for Salmonella typhimurium and Salm. enteritidis but phosphate markedly enhanced growth at pH 5.0 for many of these species without affecting growth at pH 7.0.

Buffers↗

Fundraising, government grants and donations to nonprofit hospital charities.

Using 1982-1987 tax return data from California hospital charities, this paper investigates the relationship between fundraising expenditures, government grants and donations, during a time in which significant changes were being made in the system of hospital reimbursement. Empirical results suggest that while donations have been declining, charities have been efficient in their solicitation of donations. Results also suggest that government grants worked to reduce charitable contributions in the period before the institution of Medicare's Prospective Payment System. In more recent years, government grants have been associated with increases in donations to hospital charities.

California↗

Paradoxical transcutaneous oxygen response to cutaneous warming on the plantar foot surface: a caution for interpretation of plantar foot TcPO2 measurements.

We examined the effect of cutaneous warming on the transcutaneous oxygen measurement (TcPO2) at standard locations below the knee, on the dorsal foot, on the plantar right great toe, and on the plantar surface under the second metatarsal head of 656 diabetic and 16 nondiabetic subjects. All subjects underwent a directed medical history, physical examination, and neurovascular lower extremity evaluation and assessment of autonomic neuropathy. Associations between autonomic neuropathy and TcPO2 were tested using two-way analysis of variance and multiple linear regression. An unexpected, statistically significant fall in TcPO2 occurred with cutaneous warming from 37 degrees C to 44 degrees C on the plantar great toe surface that did not differ by presence of autonomic neuropathy, or the presence of diabetes (mean change: -8.82 mmHG, 95% confidence interval [CI]: -7.70 to -9.93). The TcPO2 measured at the plantar metatarsal head site also fell with cutaneous warming from 37 degrees C to 44 degrees C (mean change: -9.67 mmHG, 95% CI: -7.75 to -11.59). As expected, the TcPO2 increased with cutaneous warming from 37 degrees C to 44 degrees C on the dorsal foot site (mean rise:= 35.61 mmHg, 95% CI: 34.18 to 37.04). The mean TcPO2 at any site did not differ by presence of autonomic neuropathy at either 37 degrees C or 44 degrees C. We conclude that cutaneous warming leads to a paradoxical fall in TcPO2 on the plantar foot surface that does not depend on the presence of autonomic neuropathy or diabetes. Caution in interpretation of ambient versus warmed plantar TcPO2 values is recommended.

Adult↗

The independent contributions of diabetic neuropathy and vasculopathy in foot ulceration. How great are the risks?

OBJECTIVE: To describe the relative contributions of neurological and vascular abnormalities to the overall risk of diabetic foot ulceration. RESEARCH DESIGN AND METHODS: A case-control study of diabetic veterans from the Seattle Veterans Affairs Medical Center was conducted using data collected from 46 patients with diabetic foot ulcers and 322 control subjects. Neuropathy was determined by vibratory, monofilament, and tendon reflex testing. Macrovascular disease was measured by ankle-arm blood pressure index, and cutaneous perfusion was measured by transcutaneous oxygen tension (TcPO2) on the dorsal foot. A multivariate logistic regression model was used to adjust for confounding variables and to calculate the odds ratios (ORs) for each independent risk factor. RESULTS: Three variables were significant independent predictors of foot ulceration: absence of Achilles tendon reflexes (adjusted OR 6.48, 95% confidence interval [CI] 2.37-18.06), insensate to the 5.07 monofilament (adjusted OR 18.42, 95% CI 3.83-88.47), and TcPO2 < 30 mmHg (adjusted OR 57.87, 95% CI 5.08-658.96). Absent vibratory sensation and low ankle-arm blood pressure index were not significant independent risk factors. CONCLUSIONS: Both neuropathy and vasculopathy are strong independent risk factors for the development of diabetic foot ulcers. In our model, the strongest risk factor is impaired cutaneous oxygenation. However, in the clinical setting, sensory examination with a 5.07 monofilament probably remains the single most practical measure of risk assessment.

Age Factors↗

High dose interferon alpha-2b therapy for chronic hepatitis C: an open label study of the response and predictors of response.

OBJECTIVES: The current recommended dose of interferon (IFN) for chronic hepatitis C is 3 million units (m.u.) 3 times a wk for 6 months, although the optimal dose is uncertain. In an open label cohort format, we evaluated the response rate at 6 months, the relapse rate at 12 months, the predictors of response, and adverse effects in 34 patients (mean age 42.4 +/- 2.4 yr) with chronic hepatitis C who were treated with 5 m.u. IFN 3 times a wk for 6 months. RESULTS: Twenty-nine patients (85%) responded either totally (TR) or partially (PR), and five (15%) showed no response (NR). Of 18 TR, eight (45%) showed a sustained response (SR), and nine (50%) patients relapsed at 12 months of follow-up with an overall SR rate of 24%. Despite the high frequency of side effects (17-70%), all patients completed the treatment. Of interest, two of three PR treated for an additional 3-6 months with 7.5 m.u. of IFN became TR at 12 months. Univariate and multivariate analysis demonstrated that the known duration of hepatitis and/or abnormal ALT elevation was longer in responders (43.5 +/- 9.1 months) compared with NR (8.2 +/- 1.4 months) (p = 0.018). Age, alcohol abuse, mode of acquisition, transaminase levels, and liver histology did not differ significantly between responders and NR. HCV-RNA in serum by RT-PCR assay was performed in six TR and four PR pretreatment, immediately posttreatment, and 3-6 months later. Five TR showed disappearance of viral RNA posttreatment with reappearance at low concentrations in two patients who relapsed. In four PR, viral RNA was detectable at low concentrations posttreatment. CONCLUSIONS: 1) Higher dose IFN therapy yields higher response rates at 6 months than the dose currently recommended with acceptable toxicity, but does not improve the sustained response rate; 2) the only predictor of a favorable response in this study was a longer known duration of hepatitis/abnormal ALT elevations; 3) serum HCV-RNA levels often disappear with a total response and may be used to monitor the response to treatment and relapse.

Adult↗

Nonradioactive detection of hypervariable simple sequence repeats in short polyacrylamide gels.

A method for resolving and visualizing genotypes for simple sequence repeat loci on short (20 cm) polyacrylamide gels is described. This method makes use of a modified vertical electrophoresis cell to allow rapid electrophoresis without variation in migration rates due to uneven gel heating. Gels are stained with SYBR Green to visualize and photograph bands on an ultraviolet transilluminator, thereby eliminating the need for traditional radioisotope labeling of PCR products for autoradiography.

Animals↗

Philanthropy and hospital financing.

OBJECTIVE: This study explores the relationships among donations to not-for-profit hospitals, the returns provided by these hospitals, and fund-raising efforts. It tests a model of hospital behavior and addresses an earlier debate regarding the supply price of donations. DATA SOURCES: The main data source is the California Office of Statewide Health Planning data tapes of hospital financial disclosure reports for fiscal years 1980/1981 through 1986/1987. Complete data were available for 160 hospitals. STUDY DESIGN: Three structural equations (donations, returns, and fund-raising) are estimated as a system using a fixed-effects, pooled cross-section, time-series least squares regression. PRINCIPAL FINDINGS: Estimation results reveal the expected positive relation between donations and returns. The reverse relation between returns and donations is insignificant. The estimated effect of fund-raising on donations is insignificantly different from zero, and the effect of donations on fund-raising is negative. Fund-raising and returns are negatively associated with one another. CONCLUSION: The empirical results presented here suggest a positive donations-returns relations and are consistent with a positive supply price for donations. Hospitals appear to view a trade-off between providing returns and soliciting donations, but donors do not respond equally to these two activities. Attempts to increase free cash flow through expansion of community returns or fund-raising activity, at least in the short run, are not likely to be highly successful financing strategies for many hospitals.

California↗

Capitation contracts: why take the risk?

There is no such thing as a simple acceptance of a capitation contract. There are at least four crucial considerations a physician should make before entering into such a contract. This article reviews those considerations and other pertinent issues.

Capitation Fee↗

Inhibition of cyclic nucleotide phosphodiesterase by derivatives of 1,3-bis(cyclopropylmethyl)xanthine.

Alkylation of the selective type IV phosphodiesterase inhibitor, 8-amino-1,3-bis(cyclopropylmethyl)-xanthine (1, BRL 61063), led exclusively to the N-7 substituted derivatives 2-9, which showed varying selectivities for the PDE type IV isoenzyme relative to PDE Va. The 4-methoxybenzyl derivative 6 in particular was a highly potent PDE Va inhibitor (IC50 0.14 microM) and showed a 24-fold selectivity for this isoenzyme relative to PDE IV. Sulfonation of 1 was more complex, with the product profile being highly dependent on the reaction conditions. As with alkylation, sulfonation at N-7 generally increased potency against PDE Va, especially in the aryl-containing moieties lacking strongly electron-withdrawing substituents (12, 15-17, 19). Bis-arylsulfonation at the exocyclic amino group generally reduced inhibitory potency against both PDE IV and Va. An 8-amidino compound 33, formed by the unusual reaction of 1 with N-methylpyrrolidinone in the presence of benzenesulfonyl chloride, had an IC50 value of 0.05 microM against PDE Va and is believed to be the most potent inhibitor of this isoenzyme reported. No correlation of PDE IV inhibition with displacement of [3H]rolipram from its high-affinity binding site was demonstrated. This suggests that either the catalytic site and the rolipram binding site are not the same or that PDE IV can exist in two conformations, only one of which binds to rolipram with high affinity, and that the compounds described vary in their selectivity for this isoform.

Adenosine↗

Beyond the uninsured: problems in access to care.

This paper investigates the difficulties that people encounter in their attempt to obtain needed health services, other than their third-party coverage or lack of it. These problems can be temporal, geographic, attitudinal, or financial (even with insurance). A state-wide sample survey conducted in 1989 revealed that about 17% of Michigan's population experienced one or more of these kinds of difficulties in their attempts to receive medical care. Those at greater risk included persons with public insurance coverage (mostly Medicaid), persons with low incomes, persons in poor health, women, and members of some ethnic minority groups. The findings suggest that addressing the problem of access to care through an exclusive focus on the uninsured, especially through public programs, could leave significant residual problems for several segments in American society.

Adolescent↗