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Biomedical subjects

M Hoffman

Publications and source records attributed to M Hoffman.

At least 91 records · Page 5Linked to original sources
PubMed1999

Stability of methacholine chloride in isotonic sodium chloride using a capillary electrophoresis assay.

OBJECTIVE: To investigate the stability of methacholine chloride in 0.9% sodium chloride solutions. METHOD: Methacholine powder was mixed with diluent to a final concentration of 5 and 10 mg/ml. Duplicates of each admixture were divided and stored in glass vials at 25 degrees C, 4 degrees C and -20 degrees C for 12 months. At appropriate times intervals, samples were removed from solutions and analysed. Methacholine concentrations were measured using a high performance capillary electrophoresis assay. RESULTS: No colour or other visual changes were seen in any sample. However, an additional peak was observed in some samples. CONCLUSION: Methacholine chloride solutions 5 mg/ml were stable in isotonic sodium chloride after refrigeration or freezing over a period of one year; methacholine chloride solutions 10 mg/ml were stable for one year after freezing. The solutions stored at ambient temperature were stable for 35 days and for less than 14 days, respectively, for the 5 and the 10 mg/ml solutions.

Bronchoconstrictor Agents↗
PubMed1999

Modifiable risk factors for Type 2 diabetes mellitus in a peri-urban community in South Africa.

AIMS: To investigate the prevalence of Type 2 diabetes mellitus (DM) and its risk factors in a working class peri-urban community in South Africa. METHODS: A cross-sectional descriptive study was conducted in 1996, where all persons aged 15 years and older, who were resident in randomly selected houses in Mamre, 55 km from the centre of Cape Town, were sampled. Subjects underwent a 75-g oral glucose tolerance test. Socio-demographic and anthropometric data were obtained and physical activity was assessed using a 7-day activity recall questionnaire. The 1985 WHO criteria were used to define diabetes. RESULTS: The response rate was 64.5% (n = 974). The participants comprised 56% women, 44% men, mean age 37.6 (range 15-86) years. The crude prevalence of Type 2 DM was 7.1% and impaired glucose tolerance (IGT) 8.0%. The age-adjusted prevalence of Type 2 DM was 10.8% (95% confidence interval (CI) 8.2-13.5%) and IGT 10.2% (95% CI 7.7-12.8%). Regression analysis indicated that age (risk ratio (RR) 7.40, 95% CI 3.45-15.86), waist circumference (RR 4.53, 95% CI 2.04-10.05), low total energy expenditure (RR 1.75, 95% CI 1.07-2.56) and family history of diabetes (RR 2.31, 95% CI 1.42-3.77) were independent risk factors for Type 2 DM, while sex, obesity and regular alcohol consumption were not. CONCLUSIONS: This previously unstudied community has an intermediate prevalence on the international scale of Type 2 DM, which is linked to potentially modifiable risk factors.

Adolescent↗
PubMed1999

Thrombin activates factor XI on activated platelets in the absence of factor XII.

Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides. However, a physiological cofactor for thrombin activation of factor XI has not been identified. We examined this question in a cell-based, tissue factor-initiated model system. In the absence of factor XII, factor XI enhanced thrombin generation in this model. The effect on thrombin generation was reproduced by 2 to 5 pmol/L factor XIa. A specific inhibitor of factor XIIa did not diminish the effect of factor XI. Thus, factor XI can be activated in a model system that does not contain factor XIIa or nonphysiological cofactors. Preincubation of factor XI with activated platelets and thrombin or factor Xa enhanced subsequent thrombin generation in the model system. Preincubation of factor XI with thrombin or factor Xa, but without platelets, did not enhance thrombin generation, suggesting that these proteases might activate factor XI on platelet surfaces. Thrombin and factor Xa were then directly tested for their ability to activate factor XI. In the presence of dextran sulfate, thrombin or factor Xa activated factor XI. Thrombin, but not factor Xa, also cleaved detectable amounts of factor XI in the presence of activated platelets. Thus, thrombin activates enough factor XI to enhance subsequent thrombin generation in a model system. Platelet surfaces might provide the site for thrombin activation of functionally significant amounts of factor XI in vivo.

Anticoagulants↗
PubMed1999

Characteristics of HIV-infected men with low serum testosterone levels.

Low levels of serum testosterone may have negative implications on morbidity in HIV-infected men. The purpose of this study was to determine demographic and clinical characteristics that predict low serum testosterone among men attending our HIV clinic. A cross-sectional study of 587 HIV-positive male patients who presented at the Louisiana State University HIV Outpatient (HOP) Clinic between August 1997 and January 1999 was conducted. Demographic and clinical characteristics were collected and analysed. Of the 587 men studied, 119 (20.3%) had a serum testosterone level below 400 ng/dl. Significantly more men with low serum testosterone levels had a presence of opportunistic infection (especially HIV wasting syndrome, oesophageal candidiasis, or dementia), CD4+ cell counts below 200 cells/mm3, or were taking megestrol acetate. Early detection of low serum testosterone will allow for expedient testosterone supplementation therapy, which could improve morbidity and quality of life for HIV-infected men.

AIDS Dementia Complex↗
PubMed1999

Cytotoxicity of 2-chlorodeoxadenosine (cladribine, 2-cdA) in combination with other chemotherapy drugs against two lymphoma cell lines.

Cladribine is a purine analog with impressive activity in patients with low-grade lymphoproliferative disorders. We studied the combination of cladribine with other antineoplastic drugs against two human-derived B-cell lymphoma cell lines in vitro. Cladribine was combined with cisplatin, daunorubicin, chlorambucil, paclitaxel or etoposide. Under the experimental conditions studied, only the combination of cladribine and cisplatin showed significantly increased cytotoxicity compared to the effect of either drug alone.

Antineoplastic Agents↗
PubMed1999

[Inhibitory and bactericidal activity and selection capacity of mutants resistant and tolerant to vancomycin in Staphylococcus aureus strains].

BACKGROUND: The aim of the present was to study the inhibitory and bactericide activity and risk of selection of mutants resistant or tolerant to vancomycin in strains of Staphylococcus aureus resistant to methicillin from out patient and hospitalary patients. MATERIALS AND METHODS: The minimum inhibitory concentration was obtained by the macrodilution method in liquid medium and by the Etest system. The minimum bactericide concentration was obtained by the macrodilution method in liquid medium. The selection of resistant or tolerant mutants was performed inoculating more than 5 x 10(6) UFC/ml in brain-heart agar plates and in tripteinsoya brought with different concentrations of vancomycin. RESULTS: Vancomycin showed greater inhibitory and bactericide activity in strains sensitive to methicillin of out patient and hospitalary origin with respect to strains resistant to methicillin with a minimum inhibitory concentration > 1 mg/l in 23.3, 20.0 and 70.0%, respectively and a minimum bactericide concentration of 90%, 8.16 and 64 mg/l. The incidence of tolerance was greater in the strains resistant to methicillin in comparison with the out patient and hospitalary strains sensitive to methicillin, since a minimum bactericide/inhibitory concentration greater than 4 was obtained in 63.3 in comparison with 20.0%. Only mutants with diminished sensitivity (minimum inhibitory concentration of 3 and 6 mg/l) or tolerant in strains resistant to methicillin could be selected. The increases in the minimum inhibitory concentrations were not stable, while the tolerant mutants preserved this characteristic after 20 subcultures. CONCLUSIONS: The in vitro selection of mutants with decreased sensitivity or tolerant was only obtained in strains resistant to methicillin. The changes in the minimum inhibitory concentrations were not stable in contrast to the increase in the minimum bactericide concentrations which remained unchanged. The differences in the selection of mutants with diminished sensitivity or tolerant among strains resistant and sensitive to methicillin found in this study were correlated with the differences in minimum inhibitory and bactericide concentrations and the relation between both in the clinical isolates.

Drug Resistance, Microbial↗
PubMed1999

An investigation of postural control in postoperative anterior cruciate ligament reconstruction patients.

OBJECTIVE: To investigate quadriceps strength and static and dynamic balance in the anterior cruciate ligament (ACL)-reconstructed patient and to compare these findings with an age-matched, injury-free control group. DESIGN AND SETTING: A 2 x 2 mixed-design analysis of variance (group x leg) was applied to the static posture, dynamic balance, and strength data. In addition, Pearson product-moment correlations were calculated to determine the strength of the relationships among the dependent measures. All data were collected in the Motor Control Laboratory at Indiana University. SUBJECTS: The experimental group was composed of 20 individuals who had undergone ACL reconstruction with a patellar tendon autograft. The control group comprised 20 participants with no history of significant orthopaedic injuries to the lower extremities. MEASUREMENTS: The dependent variables were sway path linear mean for the static condition, dynamic-phase recovery time after perturbation for the dynamic measure, and quadriceps peak torque for strength. RESULTS: We found significant differences between the ACL and control groups on the measures of dynamic-phase duration and peak torque. The static sway variable did not show a significant difference. CONCLUSIONS: Evaluation of the postural control system under 2 conditions, static and dynamic, showed differences between the ACL and control groups for the dynamic condition only. These results suggest the presence of independent control mechanisms for the control of static and more dynamic postures. In addition, because there were no differences between the injured and noninjured legs of the ACL group, the theory of a central postural control scheme is supported.

Journal Article↗
PubMed1998

Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.

Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that has potent biological effects. Its actions are mediated by G protein-coupled thromboxane-prostanoid (TP) receptors. TP receptors have been implicated in the pathogenesis of cardiovascular diseases. To investigate the physiological functions of TP receptors, we generated TP receptor-deficient mice by gene targeting. Tp-/- animals reproduce and survive in expected numbers, and their major organ systems are normal. Thromboxane agonist binding cannot be detected in tissues from Tp-/- mice. Bleeding times are prolonged in Tp-/- mice and their platelets do not aggregate after exposure to TXA2 agonists. Aggregation responses after collagen stimulation are also delayed, although ADP-stimulated aggregation is normal. Infusion of the TP receptor agonist U-46619 causes transient increases in blood pressure followed by cardiovascular collapse in wild-type mice, but U-46619 caused no hemodynamic effect in Tp-/- mice. Tp-/- mice are also resistant to arachidonic acid-induced shock, although arachidonic acid signifi-cantly reduced blood pressure in Tp-/- mice. In summary, Tp-/- mice have a mild bleeding disorder and altered vascular responses to TXA2 and arachidonic acid. Our studies suggest that most of the recognized functions of TXA2 are mediated by the single known Tp gene locus.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Influence of different physicochemical conditions on the release of indium oxine from nanocapsules.

The main purpose of this study was to determine the influence of factors (pH, enzymes, etc.) chosen partially to mimic in vivo conditions on the release of a model drug, indium oxine, from polyepsiloncaprolactone (PCL) nanocapsules in vitro. A nanocapsule suspension, an emulsion (O/W), and a solution in olive oil were prepared in order to compare the release of a radioactive tracer, indium oxine, as a function of time by an in vitro dialysis method. Nanocapsules were prepared by interfacial deposition of PCL and characterized by particle size distribution (laser light scattering) and determination of the polymer molecular weight by gel permeation chromatography (GPC). The results of this study suggest that the partition coefficient between the acceptor medium and the olive oil is the major parameter governing the release of the isotope, at least in the absence of significant enzyme activity. The PCL wall of nanocapsules is a barrier that does not seem to retard the release of indium. The addition of porcine liver esterases accelerated the degradation of PCL. This study confirms that the release of a drug from nanocapsules may be very different depending on the in vivo location, that is, the administration site.

Dosage Forms↗
PubMed1998

Gait analysis in patients with Parkinson's disease and motor fluctuations: influence of levodopa and comparison with other measures of motor function.

Although clinical rating scales and simple timed tests of motor function are widely used to assess motor response to therapy, gait analysis may provide an alternative measure of this response. We studied 15 patients with PD complicated by motor fluctuations, first to determine changes in temporal and spatial gait parameters following levodopa, secondly to assess the stability of repeated gait measures and timed tests in "off" and "on" states, and thirdly to determine the use of gait analysis in the assessment of the dopaminergic response. Gait analysis (velocity, stride length, cadence, and double limb support), clinical rating scales (modified Webster scale and Hoehn and Yahr stage), and timed tests of motor function (hand tapping and stand-walk-sit time) were performed before ("off") and after ("on") a levodopa challenge. Stride length and gait velocity increased following medication whereas cadence and double limb support did not. Most gait measures and the stand-walk-sit time were stable over three consecutive trials in both "off" and "on" states. Of the gait measures, only cadence in the "off" state changed significantly whereas the tapping count improved with repeated trials in both "off" and "on" states. Changes in stride length, gait velocity, and tapping count following levodopa correlated with changes in clinical rating scales following treatment. Measurement of gait parameters provides a reliable, objective alternative to rating scales and timed tests in assessing the dopaminergic response in patients with PD and motor fluctuations.

Aged↗
PubMed1998

Anterior enterocele following cystectomy for intractable interstitial cystitis.

PURPOSE: We clinically define the development of an anterior vaginal wall hernia following cystectomy for the management of intractable interstitial cystitis and establish surgical technique for its correction. MATERIALS AND METHODS: Of 27 women who underwent simple cystectomy and urethrectomy for intractable interstitial cystitis an anterior vaginal wall hernia developed in 3 (71, 56 and 61 years old) at 8, 14 and 16 months, respectively, postoperatively. Clinical appearance was similar to a midline cystocele but it contained bowel contents in the form of an anterior enterocele. Anterior enterocele was associated with vaginal vault prolapse in 1 patient who was treated with transvaginal sacro-spinous colpopexy. Patients with isolated anterior enterocele required a transabdominal approach with mobilization of the intestinal hernia contents and obliteration of the intervaginal abdominal wall space. RESULTS: At 12, 19 and 33 months following reconstruction prolapse has not recurred, and sexual function was restored in 1 patient. CONCLUSIONS: These cases suggest that an extended simple cystectomy performed on women with intractable interstitial cystitis may result in a weakening of the anterior vaginal wall with resultant anterior enterocele formation. When it is associated with vaginal vault prolapse a transvaginal technique may be considered but we prefer a transabdominal approach for an isolated anterior enterocele. Prevention of this entity may be warranted at the time of cystectomy.

Aged↗
PubMed1998

Preparation and characterization of nanoparticles containing an antihypertensive agent.

Isradipine, an antihypertensive agent, was encapsulated by the nanoprecipitation method using polymers including poly(epsilon-caprolactone), poly(D,L-lactide) and poly(d, L-lactide-co-glycolide). In vitro scanning electron microscopy and differential scanning calorimetry were used to characterize the nanoparticles. The average diameters of the nanoparticles ranged from 110 nm to 208 nm. PCL nanoparticles were larger than nanoparticles prepared with the other polymers. The zeta potential of the nanoparticles was negative, with values of about -25 mV which promoted good stabilization of the particles. The amorphous state of PLA and PLAGA non-loaded nanoparticles and the semi-crystalline state of PCL were demonstrated with X-ray diffraction and differential scanning calorimetry. For all nanoparticles, isradipine was found to be totally amorphous in the polymer which suggested that the drug was molecularly dispersed in the matrix. The colloidal suspensions displayed a sustained release profile in comparison with the drug release profile of isradipine in a PEG solution. Results from this investigation suggest that these nanospheres will be a good candidate delivery system for oral administration, to reduce the initial hypotensive peak and to prolong the antihypertensive effect of the drug.

Antihypertensive Agents↗
PubMed1998

Malignant melanoma in Cape Town, South Africa.

There is a world-wide increase in the incidence of cutaneous malignant melanoma among white people. Absence of accurate population-based data on the incidence of melanoma in South Africa prompted a study to determine the incidence, anatomical sites and pathological details of melanoma in Cape Town. In a prospective study from 1 January 1990 to 31 December 1995, all the histopathology reports of melanoma presenting in a geographically defined area of Cape Town, were actively retrieved from every pathologist practising in this area. The data evaluated included information on age, sex, ethnic group and location of residence. Details of melanoma comprised body site, Clark level of invasion, Breslow thickness in millimetres and histogenetic type. The histology slides were reviewed by a panel in those cases where the recorded information was ambiguous or incomplete. A final number of 595 reports of primary invasive cutaneous melanomas in white people was analysed. Of these 50.3% were men and 49.7% women. The overall age-standardized incidence rate was 24.4 per 100,000 per annum (27.5 for men and 22.2 for women). There was no change in the incidence rate over the study period. Most melanomas in both sexes (74% of women and 71% of men) were < 1.5 mm Breslow thickness. Results of this study indicate a high incidence rate of melanoma in white South Africans, comparable with that in Australia, which demands urgent preventive health measures.

Adolescent↗
PubMed1998

Newer concepts of blood coagulation.

In this report we describe an in vitro model of blood coagulation reactions that mimics as closely as possible the in vivo condition. Our model indicates that the tissue factor-factor VIIa complex initiates coagulation by activating small amounts of both factor IX and factor X in the environment of the tissue factor bearing cell. Factor Xa and factor IXa formed in the initial reaction then play very distinct roles in the subsequent interactions of the clotting mechanism leading to a burst of thrombin generation on the platelet surface. Our results also indicate that factor XI can be activated by thrombin in the absence of factor XII and that the function of factor XI is simply to enhance conversion of factor IX to factor IXa resulting in enhanced thrombin generation on the platelet surface.

Animals↗
PubMed1998

Determination of heparin in aqueous solutions.

OBJECTIVE: To develop a volumetric method for assaying heparin in aqueous media. METHOD: Heparin is precipitated out with an aqueous solution of an organic amine by titration and the end-point is based on the measurement of the medium dielectric permittivity. We studied the titration of a 500 IU/ml heparin solution with a 0.08 M cetylpyridinium chloride solution at pH 6.8. Then, we assayed sulphate groups selectively at pH 2. The results were compared against a classical method of SO2 determination. The sensitivity and reproducibility of the volumetric method were evaluated at pH 6.8 and compared with the characteristics of a chromogenic method, usually used for the assay of heparin in biological fluids. RESULTS: A linear relationship between anticoagulant activity and sulphate and carboxyl group concentration was observed. The method was less sensitive but more reproducible than the chromogenic method. CONCLUSION: The proposed method can be used for aqueous solutions and is easy to carry out. It can be fully automated and applied to formulation studies.

Cetylpyridinium↗
PubMed1998

A randomized trial of recombinant human interleukin-11 following autologous bone marrow transplantation with peripheral blood progenitor cell support in patients with breast cancer.

This study assessed the safety and efficacy of recombinant human interleukin (rhIL)-11 in decreasing platelet transfusion requirements in patients with breast cancer who were undergoing autologous bone marrow transplantation (ABMT) with peripheral blood progenitor cell (PBPC) support. After high-dose therapy with cyclophosphamide, cisplatin, and carmustine, 80 patients were randomized to one of three treatment groups: placebo (26), 25 microg/kg of rhIL-11 (28), and 50 microg/kg of rhIL-11 (26). Of those randomized, 75 (94%) received at least one dose of the masked study drug and the remaining 5 (6%) withdrew consent before study drug administration. In the placebo group, each patient received an average 12.4 (+/-10.2) platelet transfusions vs. 9.2 (+/-5.0) in the 25-microg/kg rhIL-11 group (p = 0.17) and 9.9 (+/-3.5) in the 50-microg/kg rhIL-11 group (p = 0.34). There was no statistically significant difference between the rhIL-11 groups and the placebo group in the median number of days to platelet recovery. Neutrophil and red blood cell recovery were similar for all treatment groups. The imbalance in the number of patients already alloimmunized at study entry in the rhIL-11 groups (12) and in the placebo group (1) may have confounded the primary efficacy assessment. Most adverse events were related to the high-dose chemotherapy. Generally mild edema and minor conjunctival bleeding (grades 1 or 2) were statistically associated with rhIL-11 administration (p < 0.04). There was no association between rhIL-11 and the occurrence of atrial arrhythmias, although there was a suggestion of an association with rhIL-11, 5 of 50 cases vs. 1 of 25 in the placebo group. Two cardiovascular events, tachycardia and hypotension (grade 1 or 2), occurred in the 50-microg/kg rhIL-11 group. The number of patients who discontinued study drug dosing because of an adverse event was distributed across all treatment groups. In summary, rhIL-11 was safe and well tolerated in this study. The results did not demonstrate that rhIL-11 treatment significantly decreased platelet transfusion requirements after high-dose chemotherapy with ABMT and PBPC support.

Adult↗