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Biomedical subjects

S Weisman

Publications and source records attributed to S Weisman.

At least 19 recordsLinked to original sources
PubMed2003

Psoriasis disease severity measures: comparing efficacy of treatments for severe psoriasis.

Measurement of psoriasis disease severity and effectiveness of treatment involves both objective and subjective assessments.1 Comparing the efficacy of different treatments is complicated by the use of different metrics for measuring outcomes.2 Because these measures are not used routinely in clinical practice, interpreting these data, in particular assessing the degree of clinically meaningful improvement, is difficult. The drug approval process and product labeling reflect historical changes in standards of efficacy measurement.3 This paper reviews the metrics used to evaluate psoriasis treatment and compares available information on approved treatments for severe psoriasis. It further attempts to elucidate the value of these metrics and provide some guidance in properly evaluating the relative efficacy of current proven therapy with new treatments. While clinical trials are somewhat artificial, they provide proof that a drug is more effective than placebo. Efficacy in clinical practice, however, may be very different from the clinical trial setting. Comparison of efficacy under the current circumstances of varying evaluative metrics scales is possible with proper knowledge of the functionality of these methods.

Clinical Trials as Topic↗
PubMed2001

Antibody responses to infections with strains of Plasmodium falciparum expressing diverse forms of merozoite surface protein 2.

Individuals living in areas where Plasmodium falciparum is endemic experience numerous episodes of infection. These episodes may or may not be symptomatic, with the outcome depending on a combination of parasite and host factors, several of which are poorly understood. One factor is believed to be the particular alleles of several parasite proteins to which the host is capable of mounting protective immune responses. We report a study examining antibody responses to MSP2 in 15 semi-immune teenagers and adults living in the Khanh-Hoa area of southern-central Vietnam, where P. falciparum is highly endemic; subjects were serially infected with multiple strains of P. falciparum. The MSP2 alleles infecting these subjects were determined by nucleotide sequencing. A total of 62 MSP2 genes belonging to both dimorphic families were identified, of which 33 contained distinct alleles, with 61% of the alleles being detected once. Clear changes in the repertoire occurred between infections. Most infections contained a mixture of parasites expressing MSP2 alleles from both dimorphic families. Two examples of reinfection with a strain expressing a previously encountered allele were detected. Significant changes in antibody levels to various regions of MSP2 were detected over the course of the experiment. There was no clear relation between the infecting form of MSP2 and the ensuing antibody response. This study highlights the complexity of host-parasite relationship for this important human pathogen.

Adolescent↗
PubMed1997

Premedication in the United States: a status report.

We undertook a mailing survey study to assess the current practice of sedative premedication in anesthesia. A total of 5396 questionnaires were mailed to randomly selected physician members of the American Society of Anesthesiologists. Forty-six percent (n = 2421) of those sampled returned the questionnaire after two mailings. The reported rate of sedative premedication in the United States varied widely among age groups and geographical locations. Premedicant sedative drugs were least often used with children younger than age 3 years and most often used with adults less than 65 years of age (25% vs 75%, P = 0.001). Midazolam was the most frequently used premedicant both in adults and children (> 75%). When analyzed based on geographical locations, use of sedative premedicants among adults was least frequent in the Northeast region and most frequent in the Southeast region (50% vs 90%, P = 0.001). When the frequency of premedication was examined against health maintenance organization (HMO) penetration (i.e., HMO enrollment by total population) in the various geographical regions, correlation coefficients (r) ranged from -0.96 to -0.54. Multivariable analysis revealed that HMO penetration is an independent predictor for the use of premedication in adults and children. The marked variation among geographical areas in premedicant usage patterns underscores the lack of consensus among anesthesiologists about the need for premedication. The data suggest that HMO participation may affect delivery of this component of anesthetic care.

Adolescent↗
PubMed1997

Dual diagnosis subtypes in urban substance abuse and mental health clinics.

OBJECTIVES: This study sought to determine rates of dual disorders (psychiatric and substance use disorders) in a population of low-income inner-city outpatients, to compare the rates in outpatient mental health and substance abuse treatment settings, and to examine the clinical usefulness of classifying patients with dual disorders into three subtypes. METHODS: A total of 57 low-income urban residents receiving mental health treatment and 73 receiving substance abuse treatment were given semistructured clinical interviews to ascertain lifetime and concurrent DSM-III-R axis I disorders. Patients with dual disorders were classified into subtypes depending on whether their psychiatric or substance use disorder was caused by the comorbid disorder or whether both disorders existed independently. RESULTS: Eighty-three patients had a lifetime history of dual disorders: 34 patients (60 percent) in the mental health settings and 49 (67 percent) in substance abuse treatment. Among the 83 with dual disorders, more than half had experienced symptoms of both disorders within the past year. Each of the disorders was considered primary (that is, no indication was found that one was caused by the other) for 24 patients in the mental health settings (71 percent) and 31 in the substance abuse treatment settings (63 percent). CONCLUSIONS: In each type of treatment setting, nearly two-thirds of the patients met criteria for a lifetime diagnosis of a dual disorder. This high rate of comorbidity did not appear to be attributable to substance use causing psychiatric symptoms, or vice versa. The high rate suggests the need for greater integration of mental health and substance abuse treatment, regardless of setting.

Adult↗
PubMed1995

The glycoprotein Ib-IX complex-specific monoclonal antibody SZ1 binds to a conformation-sensitive epitope on glycoprotein IX: implications for the target antigen of quinine/quinidine-dependent autoantibodies.

The monoclonal antibody SZ1 is of interest for two reasons: it was used to define complex formation between glycoprotein (GP) Ib and GP IX, and its epitope is likely to be identical to that recognized by most quinine- and quinidine-dependent autoantibodies that cause thrombocytopenia. To determine the location of the epitope for SZ1 within the GP Ib-IX complex (which consists of three subunits: GP Ib alpha, GP Ib beta, and GP IX), we tested the ability of the antibody to bind transfected cells that expressed different combinations of complex subunits, and compared this binding to the binding of antibodies of known specificity. SZ1 bound to cells that expressed the entire GP Ib-IX complex in the same pattern as did AN51 (an antibody specific for GP Ib alpha). However, unlike AN51, SZ1 did not bind alpha beta cells (ie, cells that express GP Ib alpha and GP Ib beta, but not GP IX), but did bind to beta IX and alpha IX cells. We then compared the binding patterns of SZ1 and FMC25, an antibody specific for GP IX. Both bound virtually identically to cell lines that expressed every combination of two of the three GP Ib-IX complex subunits. However, the epitopes of the two antibodies were not identical, because fixation with 4% paraformaldehyde of cells that expressed GP IX destroyed the SZ1 epitope while maintaining the FMC25 epitope. Because of the ability of SZ1 to block the binding of many quinine- and quinidine-dependent antibodies, these data strongly suggest that GP IX is the component of the GP Ib-IX complex recognized by those antibodies.

Animals↗
PubMed1994

Glycoprotein (GP) Ib beta is the critical subunit linking GP Ib alpha and GP IX in the GP Ib-IX complex. Analysis of partial complexes.

The glycoprotein (GP) Ib-IX complex is the receptor on platelet surfaces that mediates their adhesion to subendothelium. It comprises three polypeptides (GP Ib alpha, GP Ib beta, GP IX), each of which belongs to a superfamily of proteins containing conserved leucine-rich motifs. In this study, we used Chinese hamster ovary (CHO) cells expressing every combination of two GP Ib-IX complex subunits to demonstrate that GP Ib beta plays an essential role in the synthesis of the heterotrimer by associating with both of the other two subunits. Confocal microscopy demonstrated that GP Ib beta was present in the same cellular locations as GP Ib alpha in CHO alpha beta cells (cells expressing only GP Ib alpha and GP Ib beta) and as GP IX in CHO beta IX cells. The two polypeptides expressed in CHO alpha IX cells did not co-localize. Association between GP Ib alpha and GP Ib beta was demonstrated biochemically on immunoblots of detergent lysates of CHO alpha beta cells; electrophoresis under nonreducing conditions revealed the two subunits to be covalently linked through a disulfide bond. Association of GP Ib alpha and GP Ib beta was further demonstrated by the finding that immunoprecipitations with antibodies against either polypeptide precipitated both. Similarly, immunoprecipitations of lysates of CHO beta IX cells with antibodies against GP Ib beta or GP IX precipitated both polypeptides. In contrast, co-immunoprecipitation of the two polypeptides expressed in CHO alpha IX cells could not be demonstrated. Transient expression in CHO cells of GP Ib beta with GP IX yielded higher GP IX levels on the cell membrane than did expression of GP IX alone; supertransfection of CHO alpha IX cells with GP Ib beta also increased GP IX levels on the cell surface.

Amidohydrolases↗
PubMed1994

Technetium 99m-MDP scintigraphy of patients undergoing implant prosthetic procedures: a follow-up study.

The clinical evaluation of peri-implant tissue is mainly based on x-rays. In recent years, radioisotope scintigraphy using Tc-99m-MDP (technetium-99m-methylene diphosphonate) proved to be a useful and reliable clinical method for measuring increased metabolic activity at specific sites of the skeletal tissue. Twenty-six (26) patients (26 to 75 years) who were diagnosed for implant prosthetic treatment modality were randomly chosen to participate in this study. Each patient was injected with 20 mCi of Tc-99m-MDP was scanned 2 hours later by gamma-camera for isotope uptake levels in the jaws. Each patient was scanned 1 to 4 times, starting 2 weeks after implant surgery and up to the 40th week postsurgery. Blade and screw type implants using the non-submerged, one-stage technique were placed. Therefore, the prosthetic reconstruction was initiated 2 weeks after implant surgery. In order to compare the different scans we formulated a relative "bone scan index" (BSI). The results of 62 scans were plotted as BSI against time after implant surgery. A mathematical regression analysis of the BSI was also performed. At the initial stage of 2 to 3 weeks after surgery the BSI is high and then gradually declines. While BSI of the implants in the mandible reaches baseline levels after 12 weeks, the BSI in the maxilla reaches baseline only after 20 weeks. On the other hand, there was no difference in BSI with regard to blade or screw type implant. Here we were able to demonstrate that the process is independent of implant modality and depends on the specific metabolic properties of the jaw.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Association of GP Ib with actin-binding protein does not require GP IX.

GP IX is necessary for optimal expression of the GP Ib-IX complex on the surface of transfected cells, and presumably also on the surface of the platelet. The authors investigated whether increasing complex association with the cytoskeleton is one mechanism by which GP IX exerts its effect. CHO and L cell lines that express high levels of GP Ib were used to determine whether GP Ib (GPIb alpha and GPIb beta) associated with the cytoskeleton. GP Ib in these cells was found in the insoluble cytoskeletal fraction from Triton X-100 lysates in a proportion similar to that found in cells expressing the full complex. As in platelets and cells expressing the full complex, the association of GP Ib with the cytoskeleton was shown to be mediated by actin-binding protein (ABP). This was demonstrated by the observation that a monoclonal antibody against GPIb alpha precipitated ABP from GP Ib-expressing cells, and polyclonal anti-ABP antibodies specifically coprecipitated GP Ib. In addition, colocalization of the two components in intact cells was demonstrated by confocal microscopy. These data indicate that the association of GP Ib with the cytoskeleton is independent of GP IX, which therefore must increase surface expression of the complex by another mechanism.

Animals↗
PubMed1993

Biopharmaceutical characterisation of a low-dose (75 mg) controlled-release aspirin formulation.

The release of aspirin from a 75 mg controlled-release formulation, designed to inhibit maximally thromboxane A2 production while sparing stimulated prostacyclin biosynthesis, was characterised in healthy subjects. The calculated in vivo release rate of aspirin matched the design goal of approximately 10 mg h(-1). The C(max) of aspirin associated with the controlled-release formulation was lowered 15-fold relative to a solution formulation of the same dose. The bioavailability of aspirin (based on salicylate concentrations) from the controlled-release formulation was approximately 90% relative to the solution, and drug release was not affected by co-administration of a standard breakfast.

Adolescent↗
PubMed1991

The decision to execute a durable power of attorney for health care and preferences regarding the utilization of life-sustaining treatments in nursing home residents.

One hundred three nursing home residents were interviewed regarding their preferences for the choice of an agent for health-care decision making while being offered the opportunity to execute a Durable Power of Attorney for health care. They also completed a questionnaire that tapped their preferences regarding the use of four types of life-support treatment under three hypothetical levels of future cognitive functioning. Factors that might influence these preferences, such as previous experiences with life-sustaining treatments, religious beliefs, and personal values, were also examined. Participants tended to choose their son or daughter as their agent for future health-care decision making. They had clear and consistent patterns of preferences regarding the utilization of life-sustaining treatment. Generally, participants opted not to be treated, although there was variability among participants. They were even less inclined to opt for treatment as their perceived level of future cognitive functioning declined, or when the life-sustaining treatment involved permanent rather than temporary procedures.

Aged↗
PubMed1989

Characterization of nonmotile neutrophil subpopulations in neonates and adults.

Previous studies have demonstrated that polymorphonuclear leukocytes (PMN) are not a homogeneous population of cells but differ significantly in their structure and function. PMN move at varying rates, and a fraction estimated from 20 to 70% do not move at all in response to chemotactic stimuli. To characterize this PMN subpopulation better, we studied PMN motility in neonates and adults using a polycarbonate micropore filter chemotactic assay and the 31D8 MAb. Most PMN strongly bind 31D8 MAb (31D8 "bright"), but a minority (31D8 "dull") weakly bind the antibody and in this respect are similar to immature PMN precursors. The 31D8 "dull" PMN have impaired function compared with 31D8 "bright" PMN. In the present study, a PMN subpopulation that failed to migrate using the micropore filter assay accounted for 58 +/- 7% of adult PMN and was similar to the migrating subpopulation in regard to viability and phagocytic function. The nonmotile subpopulation had a higher percentage of bands (5 +/- 3% versus 1 +/- 2%, p less than 0.01) and decreased binding of 31D8 MAb compared with the motile subpopulation. Neonates had a larger nonmigrating PMN subpopulation and 31D8 "dull" PMN subpopulation than those of adults (76 +/- 3% versus 58 +/- 7%, p = 0.04 and 26 +/- 11% versus 8 +/- 2%, p less than 0.01, respectively). These data indicate that although PMN appear morphologically as a homogeneous population of cells, there exists a viable, nonmotile PMN subpopulation that may be less mature than the motile PMN subpopulation. They also indicate that impaired neonatal PMN motility may be attributable in part to an increased size of the nonmotile PMN subpopulation.

Adult↗
PubMed1987

Aminocaproic acid reduces the risk of secondary hemorrhage in patients with traumatic hyphema.

In a prospective, randomized, double-masked study, 34 patients (34 eyes) with nonperforating ocular injury and traumatic hyphema were treated with either aminocaproic acid (Amicar), 100 mg/kg every four hours, up to a maximum of 30 g/d, or placebo for five days. None of 21 patients who were treated with aminocaproic acid rebled, while three (23%) of 13 patients who were treated with placebo rebled. This difference was statistically significant. Of the three patients who rebled, two required surgical intervention, with one patient requiring four surgical procedures. Although complications following aminocaproic acid therapy included light-headedness, nausea and vomiting, and systemic hypotension, only one patient was withdrawn from the study because of drug-related adverse reactions. This study strongly confirms that aminocaproic acid therapy significantly reduces the incidence of secondary hemorrhage following traumatic hyphema.

Aminocaproates↗
PubMed1987

The effect of the thromboxane A2 synthesis inhibitor OKY-046 on renal function in rabbits following release of unilateral ureteral obstruction.

A marked decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) was found after 24, 48 and 72 hours of total unilateral ureteral obstruction (UUO) in the rabbit. Contralateral GFR showed a modest increase consistent with compensatory hypertrophy. The urinary excretion of thromboxane B2 (TxB2), the stable metabolite of the vasoconstrictor prostaglandin, thromboxane A2 (TxA2) was significantly elevated in the urine obtained following release of the obstructed ureter when compared to the TxB2 level in the urine from the contralateral kidney. Continuous infusion of OKY-046 at 100 micrograms./kg./min. over 24 hours during UUO decreased TxB2 excretion by greater than 80 per cent. However there was no significant preservation of RBF or GFR of the obstructed kidney following ureteral release despite the selective inhibition of TxA2. Moreover the increase in contralateral GFR was also abolished. Taken together with other studies these results strongly suggest that the potent vasoconstrictor TxA2 is not responsible for the rise in renal resistance that follows acute UUO.

Acrylates↗