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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 181 records · Page 10Linked to original sources
PubMed1994

Medicaid policies for HIV-related prescription drugs.

As State Medicaid programs become increasingly important sources of payment for acquired immunodeficiency syndrome (AIDS)-related care, and drug regimens the major weapons available to fight human immunodeficiency virus (HIV)-related illnesses, Medicaid drug policies will have a substantial impact. State Medicaid programs were surveyed to identify policies on a range of prescription drug policies affecting these recipients. All Medicaid programs provide prescription drug benefits to all categorically needy recipients, and about three-fourths of the States provide these benefits to medically needy recipients. However, utilization limits, copayments, and off-label-use and prior-authorization policies in many States weaken the drug benefit available.

Cost Sharing↗
PubMed1994

Results of uncemented porous-coated anatomic total hip replacement.

We reviewed a consecutive series of 241 uncemented, porous-coated anatomic (PCA) hip replacements at an average follow-up of five years (2 to 9). Of these, 32 had failed (13%), 26 at the acetabular component (11%) and six at the femoral component (2%). Acetabular failure was associated with local osteolysis and excessive polyethylene wear in 20 cases: in these histological examination showed giant macrophages incorporating numerous particles of high-density polyethylene. The femoral failures were related to a poor intramedullary fit with subsequent subsidence. Using the recommendation for revision as the end point, the cumulative survival rate for prostheses was 91% at six years (95% CI +/- 6%), 73% (+/- 11%) at seven years, and 57% (+/- 20%) at eight years. The result of uncemented PCA hip replacement is satisfactory up to six years, but then increasing failure of the acetabular component appears to be due to polyethylene wear, leading to osteolysis, loosening and component migration. At first, failure is often asymptomatic; routine follow-up of uncemented hip replacement is essential, especially after five years.

Acetabulum↗
PubMed1994

The role of antibiotics in the treatment of periodontitis. (Part I--Systemic delivery.

Controlled release devices containing tetracyclines or metronidazole are now commercially available for use in periodontal pockets. This review, in two parts, evaluates the evidence for and against using antibiotics in the treatment of periodontitis and considers the role for systemic and local delivery. Guidelines for antibiotic usage and recommended regimes are proposed.

Adult↗
PubMed1993

Triple helix formation at distant sites: hybrid oligonucleotides containing a polymeric linker.

An oligonucleotide hybrid is described which possesses two triple helix forming oligonucleotides which have been connected by a flexible polymeric linker chain. As a prototype, binding of this class of oligonucleotide to duplex DNA has been studied using a segment of the HSV-1 D-glycoprotein promoter, which possesses a pair of 12bp target sites for stable triple helix formation, separated by a duplex spacer region which is one helical turn long. Band shift and footprinting analysis show that such hybrids can bind to both 12bp elements simultaneously, if flexible linkers are included which are longer than 20-25 rotatable bonds. Molecular modeling confirms that a flexible polymeric linker as short as 22 rotatable bonds is enough to link the two distant segments of triple helix, providing that the linker element travels a path which is external to the helix grooves and parallel to the long helix axis.

Base Sequence↗
PubMed1993

Lipopolysaccharide-induced cytokine production and mortality in mice treated with Corynebacterium parvum.

Tumor necrosis factor alpha (TNF-alpha) has been shown to be an important mediator of the lethal effects of endotoxin in several experimental models of septic shock. However, studies with a recombinant human interleukin-1 (IL-1) receptor antagonist protein (IL-1ra) suggest a role for IL-1 as a mediator of septic shock as well. In the present study, we show that mice treated in vivo with Corynebacterium parvum are primed for the production of interferon-gamma (IFN-gamma) and exhibit an enhanced capacity to produce serum IL-1 alpha, TNF-alpha, and IL-6 when challenged intravenously with lipopolysaccharide (LPS). The majority of C. parvum-treated mice die within 24 h of an LPS challenge. Pretreatment with a rat antimouse TNF-alpha monoclonal antibody (mAb) protected 90% of the animals against the lethal endotoxin challenge, while an anti-IFN-gamma mAb gave approximately 75% protection. The anti-IFN-gamma mAb also caused a reduction in LPS-induced serum TNF-alpha and IL-1 alpha. Anti-IL-1 alpha, anti-IL-1 beta, and anti-IL-6 neutralizing mAb did not protect against lethality when administered to mice prior to the LPS challenge. These results indicate that TNF-alpha and IFN-gamma are major mediators of endotoxin shock in C. parvum-treated mice. The results further suggest that the IFN-gamma produced by C. parvum-primed mice in response to an LPS challenge serves as a stimulus for enhanced production of TNF-alpha and IL-1 alpha. These findings are consistent with an increasing body of evidence suggesting a major role for IFN-gamma in lethal endotoxemia.

Animals↗
PubMed1993

Cytokine gene expression in mice undergoing chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) can be induced in B6D2F1 mice by injection of parental DBA/2 lymphoid cells. Stimulation of donor T cells by host MHC antigens leads to the stimulation of host B cells. Little is known of the lymphokines produced during such a reaction. This study was designed to directly measure the levels of mRNA for interferon-gamma (IFN-gamma), interleukin 2 (IL-2), IL-4, IL-5, and IL-10, as well as several other genes, using semiquantitative polymerase chain reaction (PCR). Semiquantitative PCR was reproducible and signals generated were dependent on the amount of specific RNA or cDNA in each reaction. Early during the progression of GVHD (2 days after the first injection of parental cells) there was little increase in IL-10 mRNA, a slight increase in IL-4 mRNA, and a dramatic increase in IL-2 mRNA. In addition, IL-2 bioactivity was demonstrated in supernatants from GVH splenocytes cultured in vitro for 24 h. Later in the response (1 week after the second and final injection of parental cells) IL-4 mRNA levels were elevated as they were earlier while IL-10 mRNA levels were dramatically increased. IL-2 mRNA levels were no different in mice undergoing GVHD than in normal mice at this time. IFN-gamma mRNA was detectable both early and late, although at similar levels in normal mice and mice undergoing GVHD. At both times examined, IL-4 was below the limits of detection by bioassay and IFN-gamma, IL-4, IL-5 and IL-10 were below the limits of detection by ELISA. Further studies showed that a majority of the IL-4 and IL-10 mRNA found elevated in GVH mice were produced by Thy1.2+ T cells, with small amounts from B220+ B cells. In addition, the detectable IFN-gamma mRNA found in GVH mice at this later time also was produced by Thy1.2+ T cells, with small amounts from B220+ B cells.

Animals↗
PubMed1993

Correlations between graduates' performances as first-year residents and their performances as medical students.

PURPOSE: To correlate graduates' performances as first-year residents with their performances as medical students, particularly their performances as seniors on a clinical skills examination using standardized patients. METHOD: Residency directors were asked to rate the first-year performances of the 232 graduates from the classes of 1989-1991 of the Brown University School of Medicine. Pearson correlation coefficients were calculated for the relationships between these ratings and the two scores (for data collection and interpersonal skills) that the graduates had received in their senior year on a clinical skills examination using standardized patients. Correlations were also calculated between the residency ratings and the graduates' preclinical and clinical course grades and scores on Parts I and II of the National Board of Medical Examiners (NBME) examination. RESULTS: Ratings were returned and complete data were available for 203 (87.5%) of the graduates. Among all the parameters of medical school performance, the data-collection score on the clinical skills examination correlated best (.273) with performance as a first-year resident. The correlations between the residency ratings and scores on the NBME I and II were practically zero. CONCLUSION: This comparatively strong correlation between the graduates' data-collection scores and their performance ratings as first-year residents suggests that performance-based assessments using standardized patients may be at least as good as--perhaps even better than--traditional methods of evaluating medical students in predicting their performances as first-year residents.

Clinical Competence↗
PubMed1993

Chronic thromboxane synthase inhibition with CGS 12970 in human cyclosporine nephrotoxicity.

CsA nephrotoxicity in rats is associated with an increase in renal thromboxane production. Treatment with selective thromboxane synthase inhibitors or receptor antagonists improves renal function in these animal models. In humans, it is unclear whether intervention aimed at reducing the effects of thromboxane on the kidney will be clinically useful. However, we reported previously that thromboxane metabolite excretion is increased in CsA-treated renal allograft recipients with evidence of CsA toxicity and that 48-hr intravenous infusion of the selective thromboxane synthase inhibitor CGS 13080 improves renal function in such patients. We undertook the present study to determine the effect of more prolonged treatment with an oral thromboxane synthase inhibitor, CGS 12970, in renal transplant recipients taking CsA. We measured glomerular filtration rate and p-aminohippurate clearance before and after 4 weeks of treatment with CGS 12970 in 13 patients with renal allografts who had been treated with CsA for a mean 6.3 months and had mild renal insufficiency. Baseline serum creatinine was 1.8 +/- 0.3. Treatment with CGS 12970 resulted in 83% inhibition of urinary thromboxane B2 (TXB2), 93% inhibition of 2,3-dinor-TXB2, and 89% inhibition of 11-dehydro-TXB2, but no change in the urinary excretion of prostacyclin metabolites. However, suppression of urinary thromboxane metabolites to these levels did not significantly affect renal function. Glomerular filtration rate was 45 +/- 4 ml/min/1.73 m2 at baseline and 43 +/- 4 ml/min/1.73 m2 after 4 weeks of treatment with CGS 12970. Estimated renal plasma flow was 272 +/- 21 ml/min/1.73 m2 at baseline and 251 +/- 38 ml/min/1.73 m2 with thromboxane synthase inhibition. Thus, substantial suppression of thromboxane production with CGS 12970 did not improve renal function in CsA-treated renal allograft recipients.

Adult↗
PubMed1993

Pericardial extramedullary haemopoiesis in chronic myelomonocytic leukaemia.

Chronic myelomonocytic leukaemia (CMML) is a myelodysplastic syndrome with a diverse clinical spectrum. A case of a 60 year old man with CMML who developed cardiac tamponade is reported. Cytological examination of the pericardial effusion fluid showed extramedullary haemopoiesis. Serous effusions are well recognised in association with this disease, but this seems to be the first reported case of extramedullary haemopoiesis resulting in a pericardial effusion in a patient with CMML.

Cardiac Tamponade↗
PubMed1993

The incidence of fatal pulmonary embolism after knee replacement with no prophylactic anticoagulation.

We made a prospective study of the incidence of fatal pulmonary embolism in patients after total knee replacement with no prophylactic anticoagulation. There were 499 consecutive patients having 527 knee replacements. They all wore anti-thromboembolic stockings and were mobilised 48 hours after surgery. No patient was lost to follow-up. One patient died of pulmonary embolism 22 days after operation. There were no other deaths within three months of operation. The incidence of fatal pulmonary embolism was 0.19% (95% confidence interval: 0 to 0.6%). Fatal pulmonary embolism is rare after total knee replacement without prophylactic anticoagulation and the routine anticoagulation of these patients is of doubtful value.

Adolescent↗
PubMed1993

Effect of low-dose aspirin on thromboxane production and the antihypertensive effect of captopril.

Some of the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors occur through nonangiotensin II-mediated mechanisms. One of these is through decreased kinin degradation, leading to enhanced production of vasodilator arachidonic acid metabolites. It was reasoned that if ACE inhibition also leads to an increase in the production of the potent vasoconstrictor thromboxane A2, then maneuvers that selectively inhibit thromboxane production without reducing prostaglandins (PG) E2 + PGI2 might enhance the antihypertensive effect of ACE inhibition. This double-blinded, randomized, crossover study was therefore undertaken to determine: (1) if captopril increases platelet and/or renal thromboxane production; and (2) if low-dose aspirin enhances the antihypertensive effect of captopril. Patients with mild essential hypertension and no other significant medical problems were studied. In a double-blinded, random order, patients took captopril alone (25 mg every 12 h) for 2 wk and captopril plus aspirin (75 mg/day) for another 2 wk. Active treatment periods were preceded by 2 wk of single-blind placebo. Fifteen patients with a mean age of 53 yr and an average mean arterial pressure (MAP) of 114 +/- 8 (+/- SD) mm Hg were studied. Serum thromboxane B2 was higher (P < 0.05) during treatment with captopril/placebo (600 +/- 46 (+/- SE) pg/mL) than during the two washout periods combined (420 +/- 57 and 553 +/- 78) and was lowest (P < 0.0005) during treatment with captopril/aspirin (302 +/- 36). Captopril treatment significantly increased the urinary excretion of PGE2 (P = 0.038). Captopril/placebo significantly lowered MAP (P < 0.05) to 105.0 +/- 3.7 mm Hg compared with the washout period. However, the addition of aspirin to captopril caused no additional lowering of MAP (105.2 +/- 2.8 mm Hg). It was concluded that treatment with captopril does increase platelet thromboxane production. However, lowering platelet thromboxane with low doses of aspirin may not enhance the antihypertensive effect of captopril.

Adult↗
PubMed1993

Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation end-product formation.

This study was undertaken to compare the ability of two guanidine compounds (aminoguanidine and methylguanidine), with different in vitro effects on NO synthase activity and AGE formation, to inhibit diabetic vascular dysfunction developing early after the onset of diabetes. In rats with STZ-induced diabetes of 5-wk duration, regional vascular [125I]albumin permeation was increased about two- to threefold in ocular tissues, sciatic nerve, and aorta; in general, both guanidine compounds normalized albumin permeation in diabetic rats without affecting it in controls. Methylguanidine was only approximately 7% as effective as aminoguanidine as an inhibitor of AGE formation from L-lysine and G6P; both compounds were poor inhibitors of AR. Methylguanidine was approximately 1-5% as potent as aminoguanidine and L-NMMA as an inhibitor of the cytokine- and endotoxin-inducible isoform of NO synthase. In contrast, the potency of methylguanidine as an inhibitor of the constitutive isoform of NO synthase was comparable to that of aminoguanidine, and both guanidine compounds were much less effective than L-NMMA. These observations suggest a role for a relative or absolute increase in NO production in the pathogenesis of early diabetic vascular dysfunction and raise the possibility that inhibition of diabetic vascular functional changes by aminoguanidine may reflect inhibition of NO synthase activity rather than, or in addition to, prevention of AGE formation.

Aldehyde Reductase↗
PubMed1993

In vitro and in vivo immunopharmacological profile of Sch 40120.

Sch 40120 (10-(3-chlorophenyl) - 6,8,9,10- tetrahydrobenzo [b] [1,8] naphthyridin-5 (7H)-one) is a leukotriene inhibitor that is also a potent inhibitor of acute inflammatory responses in rodent systems. In the present study, we have evaluated the effects of this drug on immune function as well as its activity in models of immune mediated chronic inflammatory disease. Sch 40120 was particularly effective in suppressing T cell proliferative responses in vitro. Antigen-specific and poly-clonally-induced in vitro antibody responses were also inhibited by the drug. However, the in vivo potency of Sch 40120 in suppressing immune responses and in inhibiting the pathological changes seen in rodent models of autoimmune disease (EAE and adjuvant arthritis) was somewhat less than that previously observed in models of acute inflammation. Nevertheless, the spectrum of activities exhibited by Sch 40120 suggests that it will be particularly useful in the treatment of psoriasis where T lymphocytes have been implicated in the development of disease and leukotrienes appear to have a role in the persistence of psoriatic plaques.

Animals↗
PubMed1993

Growth factor effects on cells of the vascular wall: a survey.

Acidic and basic fibroblast growth factors (aFGF, bFGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming growth factor type beta (TGF-beta) are well-characterized growth regulators. Though there are reports of the effects of some of these factors on vascular cells, variability in the purity of growth factor preparations and differing cell culture conditions make comparison among the results difficult. Thus, a study employing homogeneous preparations of recombinant growth factors on well-characterized cell populations was conducted. Each of the factors was tested for its effect on the proliferation of cells derived from large and small blood vessels: aortic and capillary endothelial cells (EC), smooth muscle cells (SMC) and pericytes. Of the five growth factors only bFGF stimulated the proliferation of both large vessel and microvessel EC; aFGF was mitogenic for microvessel but not large vessel EC. Neither PDGF (AA, BB or AB) nor EGF had any effect on EC growth. TGF-beta was a potent inhibitor of both aortic and capillary EC proliferation with half maximal inhibition at concentrations as low as 0.05 and 0.25 ng/ml for microvessel and aortic EC, respectively. The FGFs were potent mitogens for the mural cells, SMC and pericytes. Likewise, PDGF was stimulatory for SMC and pericytes. The BB homodimer yielded the greatest degree of growth stimulation for both pericytes and SMC. In the case of SMC the AA homodimer stimulated small but significant growth and the effect of AB was intermediate to that of the homodimeric forms. On the other hand, neither the AA homodimer nor the heterodimer stimulated any significant increase in pericyte number. EGF was moderately mitogenic for both types of mural cells, reaching maximum stimulation at 100 pg/ml of EGF. TGF-beta was inhibitory for SMC but not for pericyte proliferation. These data indicate both quantitative and qualitative differences between the responses of large and small vessel EC to the various growth factors and distinct differences in the responsiveness of SMC and pericytes to PDGF and TGF-beta.

Adrenal Cortex↗
PubMed1993

Radiographic assessment of component orientation in elbow arthroplasty. A technical description.

We describe an alternative method of taking standardized radiographs of the elbow in patients with rheumatoid arthritis, taking into account fixed deformities. The technique enables assessment of the orientation of joint replacement components, including their axial rotational alignment. The accuracy of the method for calculating axial rotational alignment has been evaluated using a skeleton model. Within the 20 degrees limits of arm position the accuracy was found to be on average 1.4 degrees for the humerus and 2.2 degrees for the ulna.

Arthritis, Rheumatoid↗
PubMed1993

Pharmacist clinical intervention program.

Our efforts have helped us demonstrate the positive impact of pharmaceutical care for patients. Our experience with the Clinical Notes section of our computer system leads us to recommend that such capabilities be sought in all pharmacy computer systems. A significant advantage to avoiding paper-based systems for documenting and collecting information relevant to clinical interventions, ADRs, DUE data, and patient outcomes has been proven in our institution. Various ways to categorize intervention data have been reported in the literature. We recommend clinical intervention categories be based on the eight categories of drug misadventuring so that data from different hospitals can be tabulated or compared. The success of our system is that it is one system rather than many systems. The importance of pharmacist documentation demands that it be simple, efficient, and painless, or it will be nonexistent.

Adverse Drug Reaction Reporting Systems↗