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Biomedical subjects

B A Schwartz

Publications and source records attributed to B A Schwartz.

At least 19 recordsLinked to original sources
PubMed2004

Successful treatment for patients with von Willebrand disease undergoing urgent surgery using factor VIII/VWF concentrate (Humate-P).

von Willebrand disease (VWD) is characterized by insufficient von Willebrand factor (VWF) activity. It has been proposed that VWF:ristocetin cofactor (VWF:RCo) activity may be useful in evaluating the response to VWD treatment in patients who require replacement therapy. This prospective, open-label, non-randomized study evaluated the safety and efficacy of a factor VIII (FVIII)/VWF concentrate (Humate-P) used in treatment regimens based on VWF:RCo activity in subjects with VWD in situations requiring urgent and necessary surgery. This article summarizes the results for 39 subjects with 42 evaluable surgical treatment events, 100% of which were rated as excellent/good for overall efficacy (achievement of haemostasis). The median loading dose based upon VWF:RCo activity was 82.3 international units/kilogram (IU kg(-1); range 32.5-216.8 IU kg(-1)), and the median maintenance dose per infusion was 52.8 IU kg(-1) (range 24.2-196.5 IU kg(-1)) for a median of 3 days (range 1-50 days). The median number of infusions per event was 6 (range 1-67 infusions). Three unanticipated adverse events (peripheral oedema, extremity pain and pseudo-thrombocytopenia) from two surgical treatment events were reported that were potentially treatment-related. No serious drug-related adverse events (AEs) were observed, and no thrombotic events were reported in this study. This study supports the safety and efficacy of the FVIII/VWF concentrate Humate-P for the prevention of surgical haemorrhage in patients with VWD when administered in doses calculated in VWF:RCo units.

Adolescent↗
PubMed2003

Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy.

This prospective, open-label, non-randomized study evaluated the safety and efficacy of factor VIII (FVIII)/von Willebrand Factor (VWF) concentrate (Humate-P) using treatment regimens based on VWF:ristocetin cofactor (VWF:RCo) activity in patients with von Willebrand Disease (VWD) in (i) urgent bleeding episodes, or (ii) in patients undergoing urgent and necessary surgery. This article summarizes the results of treatment for the 33 patients with 53 urgent bleeding events. The median loading dose of FVIII/VWF concentrate was 67.0 international units per kilogram (IU kg(-1)) VWF:RCo (range 25.7-143.2 IU kg(-1)), and the median daily maintenance dose per infusion was 74.0 IU kg(-1) (range 16.4-182.9 IU kg(-1)) for a median duration of 2 days (range 1-34 days). The overall efficacy (achievement of haemostasis) of FVIII/VWF concentrate was rated as excellent/good for 98% of the urgent bleeding events. No unexpected treatment-related adverse events or serious drug-related adverse events (AEs) were observed. This study supports the safety and efficacy of Humate-P administered in doses calculated in VWF:RCo units for the treatment of urgent bleeding episodes in patients with VWD.

Coagulants↗
PubMed2003

Continuous intravenous infusion of a plasma-derived factor IX concentrate (Mononine) in haemophilia B.

This prospective, multicentre, open-label study evaluated the efficacy and safety of a plasma-derived factor IX concentrate [Mononine, Coagulation Factor IX (Human) Monoclonal Antibody Purified] administered by continuous intravenous (CIV) infusion to patients with haemophilia B. Admission criteria included documented diagnosis of haemophilia B (mild, moderate, or severe). Twenty-eight patients (25 surgery, two trauma, one severe spontaneous haemorrhage) were enrolled to receive a therapeutic bolus dose followed by CIV infusion of factor IX (FIX) to maintain FIX:C plasma levels of 0.4-1.0 IU mL(-1) (i.e. 40-100%). A median intravenous bolus dose of 54.2 IU kg(-1) FIX was administered to a subset of 13 non-emergency patients 7-21 days prior to CIV infusion to determine pharmacokinetic parameters in order to guide the dosing for CIV. For treatment, a bolus injection (median FIX dose; 89.6 IU kg(-1)) (range, 12.4-108.3), followed by a median total CIV infusion dose of 396.4 IU kg(-1) (range, 44.9-785.5) was administered at a median rate of 3.84 IU kg(-1) h(-1) (range, 1.74-7.33) for 107.17 h (range, 31.75-144). Twenty-four patients completed 72-120 h of FIX CIV infusion. Overall, 'excellent' (i.e. achievement of normal haemostasis) efficacy was reported in 23 of 24 (96%) evaluable patients, and 'good' (i.e. slight oozing) efficacy was reported in one (4%) patient. Median FIX:C was 72-86% for all patients receiving FIX by CIV on all days. Nine patients reported 13 adverse events that were possibly related to study medication but were not deemed serious by the investigator and were mainly because of local irritation at the infusion site. FIX CIV infusion therapy is safe and effective in the treatment of haemophilia B patients undergoing surgery, exposed to trauma, or experiencing severe spontaneous haemorrhage.

Adolescent↗
PubMed2002

Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease.

The present study was initiated to evaluate the safety and efficacy of Haemate-P (Humate-P in North America) (anti-hemophilic FVIII/VWF complex [human] dried, pasteurized) dosed in ristocetin cofactor units (VWF:RCo) in the treatment of von Willebrand disease (VWD) patients in Canada. This retrospective data collection reviewed the medical records of VWD patients treated under the Canadian Emergency Drug Release Program from November 22, 1991, to April 30, 1996. Data collection was accomplished by on-site retrieval from source data for 97 patients. Dosing was based on the German package insert, which lists only Factor VIII:C (FVIII:C) units, which were converted in the study analysis to VWF:RCo units based on the analysis of the individual manufactured lots of product used in these patients (average ratio of 2.6 IU VWF:RCo per IU FVIII:C). Twenty five different lots of Haemate-P/Humate-P were used to treat 437 different events in the 97 study patients (344 hemorrhagic events, 73 surgical interventions and 20 prophylactic infusion cycles). Overall, the median dose of concentrate per infusion used to treat surgical events was 69.1 IU VWF:RCo/kg (range 11.9-222.8); bleeding events 55.3 IU VWF:RCo/kg (range 17.1-227.5) and prophylaxis 41.6 IU VWF:RCo/kg (range 34.6-81.0). Treatment periods varied, with the majority of events treated for < or = 10 days (91%). Fifty percent of events that were treated longer than 10 days were given for prophylactic reasons. Efficacy was determined in a standardized manner by the physician, based on dosing in VWF:RCo activity. An overall clinical result of "excellent" or "good" was reported in 97% (424/437) of treatment events. A pediatric sub-population analysis of the patient population reported "excellent/good" efficacy in 100% (17/17) of treatment events in infants, 95% (155/164) in children, and 94% (76/81) in adolescent patients. Related adverse events (AEs) were observed in only 4 (4%) patients and were not deemed to be serious. The findings in this study confirm the safety and efficacy of Haemate-P/Humate-P using VWF:RCo dosing in pediatric and adult patients with various types of VWD.

Adolescent↗
PubMed2000

Progression of radiographic joint erosion during low dose corticosteroid treatment of rheumatoid arthritis.

OBJECTIVE: The reported prevention of joint damage during treatment with prednisolone 7.5 mg daily in patients with early rheumatoid arthritis (RA)3 may have important implications for management of RA. We evaluated this observation in another patient population. METHODS: Radiographic progression rates in paired hand radiographs were analyzed in 824 patients with RA who participated in a 3 year prospective, randomized clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (150 or 500 mg bid) and ibuprofen (600 mg qid). Disease modifying antirheumatic drugs (DMARD) were not permitted. Prednisone < or=5 mg daily was continued by 197 patients (mean dose 4.37 mg daily) who had started prednisone therapy at least 6 mo before study entry, but new prednisone starts were not allowed. Standardized hand/wrist radiographs were done yearly and at dropout; joint erosion and narrowing scores of 3 readers were averaged and progression rates were compared. RESULTS: Mean duration of RA was 3.6 years (range 1-7); patients' ages were 21-78 years; 71% were women. Among the 824 patients, those taking prednisone were more likely to have had previous DMARD, and at study entry had higher radiographic scores for joint erosion and joint space narrowing and slightly higher swollen joint counts, C-reactive protein values, and rheumatoid factor titers than those not taking prednisone. However, for the subgroup of 252 patients with RA duration of 12-24 months, prestudy radiographic scores were not different in those taking or not taking prednisone. The mean (+/-SD) monthly rate of increase in erosion scores was 0.228 +/-0.37 for the prednisone patients and 0.206+/-0.35 for patients not taking prednisone (p = 0.994 by ANCOVA). The subgroup with 12 to 24 months' disease duration at entry also showed no significant effect of prednisone treatment on erosion progression. CONCLUSION: Clinically indicated low dose prednisone did not prevent progressive radiographic damage in 197 NSAID treated patients whose physicians had initiated < or =5 mg daily before study entry. The risk/benefit ratio of chronic low dose prednisone in early RA remains uncertain.

Adrenal Cortex Hormones↗
PubMed1998

Thermogenic and corticosterone responses to intravenous cytokines (IL-1beta and TNF-alpha) are attenuated by subdiaphragmatic vagotomy.

The brain orchestrates changes in behavior and physiology as a consequence of peripheral immune activation and infection. These changes require that the brain receives signals from the periphery that an immunological challenge has occurred. Previous research has established that cytokines play a role in signalling the brain. What remains unclear, however, is how peripheral cytokines signal the central nervous system. A recent proposal is that cytokines signal the brain by stimulating peripheral nerves. The hypothesis states that following infection and the release of cytokines such as IL-1beta into local tissue or microvasculature, IL-1beta stimulates IL-1 receptors on vagal afferent terminals, or more likely on cells of vagal paraganglia. Vagal afferents, in turn, signal the brain. Previous work has demonstrated that transection of the vagus below the level of the diaphragm blocks or attenuates many illness consequences of intraperitoneally (i.p.) administered lipopolysaccharide (LPS) or IL-1beta. The present studies extend these findings by examining the effect of subdiaphragmatic vagotomy on illness consequences following intravenously (i.v.) administered IL-1beta and TNF-alpha. Subdiaphragmatic vagotomy attenuated both the fever response and corticosterone response produced by i.v. administered cytokines. This effect was dose dependent. The results add support to the hypothesis that vagal afferents are involved in peripheral cytokine-to-brain communication.

Animals↗
PubMed1997

Inescapable shock-induced potentiation of morphine analgesia.

Exposure to various stressors potentiates nociceptive and nonnociceptive responses to morphine. These phenomena have received little study despite their seeming generality and importance for understanding analgesia and opiate action. The present experiments characterize inescapable shock (IS)-induced potentiation of morphine analgesia. Rats were exposed to IS, equal escapable shocks (ESs), or restraint (control). Potentiation of analgesia (tail-flick [TF] test and hotplate test) was observed only in rats given IS 24 or 48 hr earlier, in agreement with previously reported learned-helplessness effects. Finally, no change in tail temperature or motor function was found that could be inaccurately interpreted as analgesia. The relevance of these findings to stressor-induced enhancement of morphine analgesia and potential substrates of IS effects are discussed.

Analgesics, Opioid↗
PubMed1985

Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: role of red cell glutathione.

Intact erythrocytes placed into the tracheobronchial tree of hyperoxic rats dramatically improved their chances for survival. Over 70 percent of the animals so treated survived more than 12 days during continuous exposure to 95 percent oxygen, whereas all of the control animals died within 96 hours. Lungs from erythrocyte-protected rats showed almost none of the morphologic damage suffered by untreated animals. Erythrocytes containing cyanomethemoglobin were as beneficial as normal erythrocytes, but cells in which glutathione was partially blocked were significantly less protective. Analogous results were obtained in vitro: 51Cr-labeled target cells released 70 to 90 percent of their label when exposed briefly to hydrogen peroxide or to toxic oxygen species generated by phorbol ester-stimulated neutrophils. Addition of intact erythrocytes decreased release by approximately 75 percent, but significantly less than this if red blood cell glutathione was partially blocked. These results suggest that insufflated erythrocytes, through their recyclable glutathione, protect rats from toxic oxygen species engendered by hyperoxia.

Animals↗
PubMed1985

Cigarette smoking causes accumulation of polymorphonuclear leukocytes in alveolar septum.

The polymorphonuclear leukocyte (PMN) may play an important role in the pathogenesis of emphysema. Cigarette smoking is associated with the accumulation of PMN in the lung as determined by bronchoalveolar lavage. We enumerated alveolar wall PMN on histologic sections from lungs of humans and hamsters with and without cigarette smoke exposure. In human nonsmokers, there were 0.9 +/- 0.2 PMN/mm alveolar wall. In cigarette smokers without emphysema, there were 2.1 +/- 0.3 PMN/mm alveolar wall (p less than 0.01), and in cigarette smokers with emphysema, there were 2.4 +/- 0.7 PMN/alveolar wall (p less than 0.05). There were 1.7 +/- 0.3 PMN/mm alveolar wall in the lungs of hamsters unexposed to cigarette smoke compared with 3.1 +/- 0.3 PMN/mm alveolar wall in smoke-exposed hamsters (p less than 0.005). Although cigarette smoking causes PMN to accumulate within alveolar septa, the accumulation does not seem to be closely related to the development of emphysema. This suggests that additional or other factors are important in the pathogenesis of emphysema.

Aged↗
PubMed1985

Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase.

To test the feasibility of using liposomes to deliver therapeutic agents to the lungs, the effect of liposome-encapsulated superoxide dismutase (SOD) or catalase on pulmonary oxygen toxicity was studied in rats. The SOD or catalase was encapsulated in negatively changed multilamellar liposomes and administered directly into the trachea of adult rats, which were subsequently exposed to hyperoxia (greater than 95% O2). Response to hyperoxia was examined by studying lung SOD and catalase activities, survival rates, and lung morphology. Rats receiving liposome-encapsulated SOD or catalase showed increased levels of enzyme activities in the lung homogenates compared with those in the control groups after 24 to 72 h of hyperoxic exposure. Elevated enzyme levels in the lungs of rats treated with liposome-encapsulated SOD or catalase were accompanied by a significant improvement in survival rates after 72 h of hyperoxic exposure and less lung injury than in the other control groups.

Animals↗
PubMed1984

Lung T cells in hypersensitivity pneumonitis.

Monoclonal antibodies OKT3 (all T cells), OKT4 (T-helper/inducer), and OKT8 (T-suppressor/cytotoxic) were used to determine surface phenotypes of bronchoalveolar lavage and peripheral blood lymphocytes in patients with chronic hypersensitivity pneumonitis. Similar studies were done in asymptomatic pigeon breeders, patients with sarcoidosis, and nonsmoking controls. Increased numbers of lavage T cells were found in patients with hypersensitivity pneumonitis and sarcoidosis and in asymptomatic pigeon breeders. The predominant T-cell subset in patients with hypersensitivity pneumonitis and in asymptomatic pigeon breeders was T8 +; in contrast, the predominant subset in those with sarcoidosis was T4 +. Peripheral blood T-cell subsets were normal in all groups. Thus, most lung T lymphocytes in chronic hypersensitivity pneumonitis belong to the T8 + subset; the local cellular immune response in hypersensitivity pneumonitis and sarcoidosis are different; and the pattern of alveolitis, as determined by bronchoalveolar lavage, is not the sole determinant of lung impairment after exposure to hypersensitivity pneumonitis antigens.

Adult↗
PubMed1978

Mycolic acids. A reinvestigation.

Mycolic acids derived from the cell walls of Mycobacterium bovis BCG, Mycobacterium bovis Bovinus I, Mycobacterium smegmatis, and Mycobacterium tuberculosis H37Rv have been fractionated as their p-bromophenacyl esters by a two-step high performance liquid chromatographic procedure: 1) adsorption chromatography on 10-micrometer particle size silica gel, and 2) reverse phase partition chromatography on a 10-micrometer particle size support containing a C18 bonded phase. This procedure has resulted in the isolation of approximately 24 mycolic acids from each bacterium (very likely homologs of various mycolate types) instead of the two to four that have previously been described. The implication of these results on the previously determined structures of these fatty acids is discussed.

Molecular Weight↗
PubMed1978

Proteins containing reductively aminated disaccharides: chemical and immunochemical characterization.

Synthetic glycoproteins can be prepared by reductive amination of proteins and reducing carbohydrates in the presence of sodium cyanoborohydride. The reaction proceeds readily in aqueous solution at pH 6--9 to give high degrees of substitution. The degree of substitution can be determined by amino acid analysis, as the 2 degrees amine linkage formed with the epsilon-amino groups of lysine is stable to acid-catalyzed protein hydrolysis conditions. Antisera have been obtained to bovine serum albumin conjugates containing reductively aminated cellobiose, lactose, and maltose. Preliminary experiments demonstrate that antiserum to the cellobiose-BSA conjugate is hapten-specific, and the structural features of the hapten recognized by the antibodies were established by hapten inhibition experiments. These studies demonstrate that antibodies recognize both the terminal beta-glucosyl and acyclic reduced glucosyl residues.

Amination↗