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Biomedical subjects

B Brenner

Publications and source records attributed to B Brenner.

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

Willingness of male homosexuals to perform mouth-to-mouth resuscitation.

BACKGROUND: Providing mouth-to-mouth resuscitation (MMR) during cardiopulmonary resuscitation (CPR) is a proven effective lifesaving procedure. However, the perceived risk to the rescuer of contracting infectious diseases, especially acquired immunodeficiency syndrome (AIDS), by performing MMR on a possibly human immunodeficiency virus (HIV) positive individual is probably affecting the number of people willing to perform MMR. Physicians and nurses constitute a major part of citizen cardiopulmonary resuscitation (CPR) responders and serve as CPR educators and resource personnel. Currently, the fear of physicians and nurses of contracting infectious disease has dampened their willingness to perform MMR, and thus has reduced the number of strangers who will receive MMR. Homosexual males, like the medical community, have an increased perceived risk of acquiring infectious diseases, especially AIDS, and have been the target of intense educational efforts concerning the transmission of HIV. By (a) determining the willingness of various groups to perform MMR, (b) elucidating the factors which affect their willingness to perform MMR, and (c) comparing this willingness to the actual, not perceived, risk of acquiring HIV by performing MMR, either appropriate changes can be made to educate people in the performance of MMR, by informing them of the actual risks of contracting infectious diseases, or alternative methods of resuscitation, involving 'lay-on' masks, can be recommended. Thus the willingness of homosexual males to perform MMR was determined and compared to the previously determined actual reluctance of the medical community to perform MMR in similar hypothetical scenarios. METHODS: During interviews, 200 male homosexuals in Los Angeles were asked to assume that they knew how to perform CPR and MMR and to indicate how they would respond to four hypothetical cardiac arrest scenarios. These scenarios included cardiac arrests of a child, a trauma victim, a young man in a gay neighbourhood, and a victim of unknown history. Demographical data concerning the respondents was also obtained. RESULTS: Of the homosexual men surveyed, 93 and 85% stated they would perform MMR on a stranger of unknown history, if they, the rescuer, were HIV negative or positive, respectively, (P < 0.001). Similarly, a high percentage of the presumed HIV negative and HIV positive respondents stated a high willingness to perform MMR in response to hypothetical cardiac arrest scenarios involving a trauma victim, a child, and a young man in a gay neighbourhood. CONCLUSIONS: The willingness of male homosexuals to perform MMR is high, in contrast to the general reluctance of internists and medical nurses to perform MMR in the same outpatient scenarios. The different perceived risks of male homosexuals and physicians acquiring infectious diseases by performing MMR is probably responsible for the difference in willingness of these two groups to perform MMR. The high perceived risk of acquiring infectious diseases due to performance of MMR currently held by physicians in general may be lowered by increasing educational efforts. CPR courses should (a) discuss actual and perceived risks of acquiring infectious diseases by MMR, (b) discuss and weigh a small, and possibly not valid, risk of contracting an infectious disease while performing MMR on a victim, and (c) emphasize techniques involving 'lay-on' barrier masks. The availability of effective 'lay-on' barrier masks' should also be increased.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The reluctance of house staff to perform mouth-to-mouth resuscitation in the inpatient setting: what are the considerations?

OBJECTIVE: Medical house staff are required to perform cardiopulmonary resuscitation (CPR) as part of their job responsibilities. Previously it has been shown that house staff are reluctant to perform mouth-to-mouth resuscitation (MMR) in an out of hospital setting. Therefore, whether reluctance to perform MMR extends to the inpatient setting, and, if so, the reasons for this reluctance were investigated. DESIGN: All 74 internal medicine house officers of a large metropolitan hospital responded to presentations of hypothetical inpatient cardiac arrest scenarios to assess their willingness to perform MMR. SETTING: A 1200 bed university-affiliated teaching hospital in Los Angeles, California. SUBJECTS: All categorical internal medicine house officers at this hospital. INTERVENTIONS: This study is a survey which concerns whether the house officer would perform mouth-to-mouth resuscitation in different hypothetical cardiac arrest scenarios. RESULTS: Forty-five percent would perform MMR on an unknown patient and 39% would perform MMR in the elderly patient scenario. Only 16% would do MMR on a patient with a small amount of blood on his lips and only 7% would perform MMR on a patient with presumed acquired immunodeficiency syndrome. Medical housestaff were much more reluctant to perform MMR on elderly, trauma, or presumed immunodeficient patients in an inpatient setting than in an outpatient setting. All house staff that indicated their unwillingness to perform MMR cited fear of human immunodeficiency virus infection as their reason. CONCLUSION: Medical housestaff are quite reluctant to perform MMR in an inpatient setting. Thus, educating the medical house staff about the percent of patients that survive inpatient cardiac arrest and the actual risks of contracting infectious diseases, especially HIV infections, from MMR and preventative measures, such as effective barrier masks, should result in an increased willingness of physicians to perform MMR or mouth-to-mask ventilation on inpatients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Serum immunoreactive erythropoietin in hyper- and hypothyroidism: clinical observations related to cell culture studies.

Laboratory experiments have demonstrated that tetra- and triiodothyronine (T4, T3) enhance hypoxia-induced erythropoietin (Epo) production. In the present study serum immunoreactive Epo was measured in 29 patients with hyperthyroidism and in 10 patients with hypothyroidism. Epo levels were inversely correlated to the blood haemoglobin concentration [Hb] in both groups of patients. However, Epo levels at given [Hb] were significantly higher in the hyperthyroid state. In vitro studies confirmed that T4 and T3 stimulate Epo synthesis in the human liver cell line HepG2. This stimulating effect persisted for at least 1 day after the removal of T4 and T3 from the cultures. Thus, while thyroidal disorders affect steady-state levels of circulating Epo, it seems unlikely that thyroid hormones play a major role in abrupt adjustments of Epo production, such as the diurnal changes.

Carcinoma, Hepatocellular↗
PubMed1994

Inhibitory effect of 3'-azido-3'-deoxythymidine on proliferative responsiveness of CD8+ lymphocytes to interleukin-2.

Although several studies have shown that 3'-azido-3'-deoxythymidine (AZT) is not toxic for CD4+ lymphocytes, its effect on CD8+ cells has never been studied in a systematic way. We purified CD8+ cells from the peripheral blood mononuclear cells of both human immunodeficiency virus (HIV)-seronegative and HIV-infected individuals by means of magnetic beads that had been coated with monoclonal antibodies. We report that AZT, but not two other nucleosides tested, inhibited the interleukin-2-dependent proliferation of CD8+ lymphocytes in a dose-dependent manner. No such effect was observed with regard to CD4(+)-enriched populations. The AZT-mediated antiproliferative effect did not appear to be related to either the CD4+ count or to prior treatment with this drug in the case of HIV-seropositive subjects.

Antiviral Agents↗
PubMed1994

Coinfection with hepatitis viruses and human immunodeficiency virus in multiply transfused patients.

The prevalence, clinical manifestations and serological markers of hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections were studied in 112 multiply transfused patients (49 hemophiliacs receiving either nonheat-treated factor concentrates or cryoprecipitate, 33 thalassemic, 20 refractory anemia and 10 leukemia patients). Positive serological markers for HCV, HBV and HIV were found to correlate with number of donors and duration of disease (logistic regression P = 0.0001 and 0.01 respectively). Viral infectivity was significantly correlated with type of blood product. HCV seropositivity was more common in hemophiliacs treated with nonheat-treated factor concentrates (93%) compared to those receiving cryoprecipitate (37%) or nonhemophiliacs receiving red packed cells (20%) (P < 0.001). Likewise, HBV seropositivity in patients receiving the above blood products was 83%, 61% and 26% respectively (P < 0.001), and HIV seropositivity was 35%, 6% and 0% respectively (P < 0.001). Acute or chronic liver disease was documented in 4 of 14 (28%) HCV-positive patients. Increased liver enzymes were recorded in sera of 43% HCV-positive patients and 18% HBV-positive patients compared to 22% of HBV and 20% HCV-seronegative patients (P = 0.076). Of 47 HCV-positive patients 24 were coinfected by HBV and 9 had triple infection (HCV, HBV and HIV). No solitary HIV infection was found. HIV seropositivity was always accompanied by serologic evidence for HBV with or without HCV infection.

Blood Component Transfusion↗
PubMed1993

Increased risk of cancer in patients with Gaucher disease.

BACKGROUND: An increased incidence of cancer, especially hematopoietic in origin, has long been suspected but never established in patients with Gaucher disease. METHODS: To determine whether patients with Gaucher disease have an increased risk of cancer, the authors conducted a retrospective cohort study, comparing the incidence and type of cancer in 48 patients with Gaucher disease with those of 511 control subjects without the disease. RESULTS: Among patients with Gaucher disease, 10 of 48 (20.8%) had cancer, as compared with 35 of 511 (6.8%) of the control group (P = 0.0027; relative risk, 3.6; 95% confidence interval, 1.7-7.5). As compared with the control group, patients with Gaucher disease had a 14.7-fold risk of having cancer of hematopoietic origin (10.4% [5 of 48] versus 0.78% [4 of 511], respectively; P = 0.00037; 95% confidence interval, 5.2-41.7). The mean age at cancer diagnosis in the group with Gaucher disease was 57 +/- 18 years. CONCLUSIONS: The authors conclude that patients with Gaucher disease have a significantly increased risk of cancer, occurring in late adulthood. Of all the cancers, hematologic cancers are significantly more prevalent.

Adult↗
PubMed1993

On the regeneration of the actin-myosin power stroke in contracting muscle.

The transient behavior of muscle in double-or multiple-step length perturbations [Lombardi, V., Piazzesi, G. & Linari, M. (1992) Nature (London) 355, 638-641] is simulated with a "conventional" cross-bridge model, which has been reported [Eisenberg, E., Hill, T. L. & Chen, Y. (1980) Biophys. J. 29, 195-227] to account for many mechanical, as well as biochemical, muscle data. The quick recovery of tension after double- or multiple-length perturbations was calculated for the model without any readjustment of its original parameters. The regeneration rate of the quick tension recovery of the model is fast and comparable to that measured experimentally by Lombardi et al. For multiple-step "stair-case"-type length releases, the tension response reaches a steady-state shape after three or four steps, and the average ATP turnover is much slower than the regeneration of the quick tension recovery. Our simulation shows that the experimental findings of Lombardi et al. can easily be reproduced by this simple conventional cross-bridge model, in which the completion of one work-producing power stroke is coupled to the hydrolysis of one ATP molecule. Thus, to account for the data of Lombardi et al., there is no need to assume that cross-bridges can execute multiple power strokes per ATPase cycle, although cross-bridges may well be able to do so. The mechanism that underlies the fast regeneration of the quick tension recovery in the conventional model used here is discussed.

Actins↗
PubMed1993

Structural changes in the actomyosin cross-bridges associated with force generation.

It is generally thought that to generate active force in muscle, myosin heads (cross-bridges) that are attached to actin undergo large-scale conformational changes. However, evidence for conformational changes of the attached cross-bridges associated with force generation has been ambiguous. In this study, we took advantage of the recent observation that cross-bridges that are weakly attached to actin in a relaxed muscle are apparently in attached preforce-generating states. The experimental conditions were chosen such that there were large fractions of cross-bridges attached under relaxing and activating conditions, and high-resolution equatorial x-ray diffraction patterns obtained under these conditions were compared. Changes brought about by activation in the two innermost intensities, I10 and I11, did not follow the familiar reciprocal changes. Instead, there was almost no change in I11, whereas I10 decreased by 34%. Together with the changes found in the higher-order reflections, the results suggest that the structure of the attached force-generating cross-bridges differs from that of the weakly bound, preforce-generating cross-bridges and possibly also differs from that of the cross-bridges in rigor. These observations support the concept that force generation involves a transition between distinct structural states of the actomyosin cross-bridges.

Actomyosin↗
PubMed1993

Evidence for structural changes in crossbridges during force generation.

During muscle contraction, it is generally thought that myosin heads undergo large scale conformational changes, such as an oar-like rotation between 90 degrees and 45 degrees while attached to actin. However, evidence for conformational changes of the attached crossbridges associated with force generation has been ambiguous. In this study, we compared the conformations of attached crossbridges in (i) the pre-force generating state, (ii) force generating state, (ii) rigor state. High resolution equatorial X-ray diffraction patterns have been obtained from single chemically skinned rabbit psoas fibers under relaxed, fully Ca(2+)-activated and rigor conditions. The experimental condition was chosen (ionic strength = 50 mM and temperature = 5 degrees C) such that there are large fractions (80-100%) of crossbridges attached in all the three states, and the attached crossbridges in the relaxed muscle represent the pre-force generating state. Upon activation, changes in the two innermost intensities I10 and I11 did not follow the familiar reciprocal changes. Instead, there was almost no change in I11 while I10 decreased by 30%. Similarly, greater changes were found in I10 as the fiber goes into rigor from the activate state. Changes were also found in the higher order reflections suggesting that the structure of the force generating crossbridges is not a mixture of those found in the weakly bound and rigor crossbridges. Therefore, our data provides evidence that the average conformation of the force generating crossbridges is different from the weakly attached and from rigor crossbridges.

Actins↗
PubMed1993

Dynamic actin interaction of cross-bridges during force generation: implications for cross-bridge action in muscle.

The force response of Ca(2+)-activated, permeabilized segments of rabbit psoas muscle fibers to stretches and releases was studied. These length changes were imposed (i) during isometric steady state contraction, (ii) as a restretch at the end of a ramp-shaped prerelease, and (iii) during isotonic steady state shortening. The speed of the stretches/releases was varied between about 10 and 10(5) (nm/half-sarcomere)/s. At physiological ionic strength and at low temperature (5 degrees C), the force response to stretches apparently is neither affected by cross-bridges that occupy weak-binding states nor by redistribution among various attached force-generating states. Plots of force vs. imposed length change ("T-plots") and plots of apparent fiber stiffness vs. speed of the imposed length change ("stiffness-speed relations") recorded under all these conditions suggest that cross-bridges, even during force-generation, dissociate and reassociate from and to actin on a time scale that is fast compared to active cross-bridge cycling (> 50- 1000s-1 vs. 1-10s-1). This rapid dissociation/reassociation of force-generating cross-bridges may provide a mechanism to account for the unexpectedly low ATPase activity during high-speed shortening and for filament sliding exceeding 10-20nm while a cross-bridge passes through the force-generating states.

Actins↗
PubMed1993

Lower limb ischaemia in primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder manifested by recurrent thrombosis in the venous and arterial system. We report a group of seven patients with lower limb ischaemia associated with PAPS. Four were male patients and three were females, with a mean age of 37 years. All had a previous deep vein thrombosis and the majority, five out of seven, had a prior cerebrovascular accident (CVA). Prolonged activated thromboplastin time was demonstrated in all our patients and PAPS was established by positive thromboplastin titration index, circulating anticoagulant index and increased anticardiolipin levels. Symptoms included claudication in three, rest pain in four and gangrene in five patients. Angiography demonstrated thrombosis of various segments of the arterial tree including: aorta, iliac, femoral and popliteal arteries. Two patients were treated conservatively and one by percutaneous transluminal angioplasty (PTA) of the distal aorta. A total of eleven vascular surgical procedures were performed in four patients resulting in early postoperative thrombosis (2h-30 days) in 10 cases. Only one graft remained patent, when full heparinisation (1000 units/h) was used perioperatively. We conclude that PAPS patients are at high risk for graft thrombosis and should only be operated upon on full anticoagulation, starting at operation and proceeding indefinitely.

Adolescent↗
PubMed1993

Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders.

Haemostatic efficacy and pharmacokinetic analysis of solvent/detergent (S/D) treated, virus inactivated plasma (Octaplas, Germany) was evaluated in eight patients with hereditary factor VII, X and XI deficiency and in three patients with acquired coagulation disorders due to liver disease. The patients received the S/D plasma for treatment of haemarthrosis, menorrhagia or before surgical procedures. In all the patients the S/D plasma was sufficient to prevent or stop bleeding. Side effects included urticaria (one patient) and moderate anaphylactoid reaction (one patient). No evidence of plasma-born viral infections was observed up to 12 months after the treatment (95% confidence limits 0-22%). Calculated mean half-life of coagulation factors VII, X and XI was 4.36 h, 49.21 h and 44.5 h, respectively, similar to that observed with fresh-frozen plasma. Because of retained coagulation factor integrity and improved viral safety, S/D plasma could be considered a superior alternative to standard fresh-frozen plasma.

Adult↗
PubMed1993

Carbamazepine (Tegretol)-induced thrombocytopenia.

A case of carbamazepine-induced thrombocytopenia is reported. The patient, a 38-year-old female, developed thrombocytopenia 10 days after receiving 400 mg carbamazepine daily. The presence of an anti-IgG carbamazepine-dependent platelet-reactive antibody was documented. Using flow cytometry, the drug-induced antibody was detected at a drug concentration as low as 10(-6) M.

Adult↗
PubMed1993

State-dependent radial elasticity of attached cross-bridges in single skinned fibres of rabbit psoas muscle.

1. In a single skinned fibre of rabbit psoas muscle, upon attachment of cross-bridges to actin in the presence of ADP or pyrophosphate (PP(i)), the separation between the contractile filaments, as determined by equatorial X-ray diffraction, is found to decrease, suggesting that force is generated in the radial direction.2. The single muscle fibres were subjected to compression by 0-8% of dextran T(500). The changes in lattice spacings by dextran compression were compared with changes induced by cross-bridge attachment to actin. Based on this comparison, the magnitude and the direction of the radial force generated by the attached cross-bridges were estimated. The radial cross-bridge force varied with filament separation, and the magnitude of the radial cross-bridge force reached as high as the maximal axial force produced during isometric contraction.3. One key parameter of the radial elasticity, i.e. the equilibrium spacing where the radial force is zero, was found to depend on the ligand bound to the myosin head. In the presence of ADP, the equilibrium spacing was 36 nm. In the presence of MgPP(i) the equilibrium spacing shifted to 35 nm and Ca(2+) had little effect on the equilibrium spacing.4. The equilibrium spacing was independent of the fraction of cross-bridges attached to actin. The fraction of cross-bridges attached in rigor was modulated from 100% to close to 0% by adding up to 10 mM of ATPgammaS in the rigor solution. The lattice spacing remained at 38 nm, the equilibrium spacing for nucleotide-free cross-bridges at mu = 170 mM.5. Radial force generated by cross-bridges in rigor at large lattice spacings (38 nm </= d(10) </= 46 nm) appeared to vary linearly with lattice spacing.6. The titration of ATPgammaS to fibres in rigor provided a correlation between the radial stiffness of the nucleotide-free cross-bridges and the equatorial intensities. The relation between the equatorial intensity ratio I(11)/I(10) and radial stiffness appeared to be approximately linear.7. The fibres under different conditions showed a wide range of radial stiffness, which was not proportional to the apparent axial stiffness of the fibre. If the apparent axial stiffness is a measure of the fraction of cross-bridges bound to actin, it follows that the radial elastic constant is state dependent; or vice versa.8. Differences in equilibrium lattice spacing and in radial elastic constant, most probably reflect differences in the molecular structure of the acto-myosin complex and there is more than one single conformation of the various strongly bound cross-bridge states.9. Determining equilibrium spacings of the radial elasticity appears to be an effective new approach in detecting structural differences among the attached cross-bridges, since this approach is independent of the fraction of cross-bridges attached, a factor that frequently encumbers the interpretation of structural studies of attached cross-bridge states.

Journal Article↗
PubMed1993

State-dependent radial elasticity of attached cross-bridges in single skinned fibres of rabbit psoas muscle.

1. In a single skinned fibre of rabbit psoas muscle, upon attachment of cross bridges to actin in the presence of ADP or pyrophosphate (PPi), the separation between the contractile filaments, as determined by equatorial X-ray diffraction, is found to decrease, suggesting that force is generated in the radial direction. 2. The single muscle fibres were subjected to compression by 0-8% of dextran T500. The changes in lattice spacings by dextran compression were compared with changes induced by cross-bridge attachment to actin. Based on this comparison, the magnitude and the direction of the radial force generated by the attached cross-bridges were estimated. The radial cross-bridge force varied with filament separation, and the magnitude of the radial cross-bridge force reached as high as the maximal axial force produced during isometric contraction. 3. One key parameter of the radial elasticity, i.e. the equilibrium spacing where the radial force is zero, was found to depend on the ligand bound to the myosin head. In the presence of ADP, the equilibrium spacing was 36 nm. In the presence of MgPPi the equilibrium spacing shifted to 35 nm and Ca2+ had little effect on the equilibrium spacing. 4. The equilibrium spacing was independent of the fraction of cross-bridges attached to actin. The fraction of cross-bridges attached in rigor was modulated from 100% to close to 0% by adding up to 10 mM of ATP gamma S in the rigor solution. The lattice spacing remained at 38 nm, the equilibrium spacing for nucleotide-free cross-bridges at mu = 170 mM. 5. Radial force generated by cross-bridges in rigor at large lattice spacings (38 nm < or = d10 < or = 46 nm) appeared to vary linearly with lattice spacing. 6. The titration of ATP gamma S to fibres in rigor provided a correlation between the radial stiffness of the nucleotide-free cross-bridges and the equatorial intensities. The relation between the equatorial intensity ratio I11/I10 and radial stiffness appeared to be approximately linear. 7. The fibres under different conditions showed a wide range of radial stiffness, which was not proportional to the apparent axial stiffness of the fibre. If the apparent axial stiffness is a measure of the fraction of cross-bridges bound to actin, it follows that the radial elastic constant is state dependent; or vice versa.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1993

The recruitment of research participants: a review.

Social workers are involved in the recruitment of research participants in a variety of ways. Increased knowledge regarding recruitment issues will allow social workers to expand their role and improve their performance in this area. These individuals should be aware that there is a large body of literature addressing recruitment. This selective review of the literature prior to mid-1992 will focus on the Coronary Primary Prevention Trial, volunteer effects, recruitment sources, the recruitment process, impediments to recruitment, bias in recruitment, the amount of time required to recruit and the impact of recruitment and participation on individuals. This will be followed by a discussion of issues to be addressed in arriving at solutions to recruitment problems.

Clinical Trials as Topic↗
PubMed1992

Effect of Ca2+ on weak cross-bridge interaction with actin in the presence of adenosine 5'-[gamma-thio]triphosphate).

In the presence of the nucleotide analog adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]), effects of Ca2+ on stiffness and equatorial x-ray diffraction patterns of single skinned fibers of the rabbit psoas muscle were studied. It is shown that cross-bridges in the presence of ATP[gamma S] have properties of the weak-binding states of the ATP hydrolysis cycle. Raising the Ca2+ concentration up to pCa 4.5 has little effect on actin affinity of cross-bridges in the presence of ATP[gamma S]. However, the rate constants for cross-bridge dissociation and reassociation from and to actin are reduced by about 2 orders of magnitude. In addition, nucleotide affinity of the cross-bridge is much smaller at high Ca2+ concentrations. Implications for interpretation of fiber stiffness recorded during isotonic shortening and the rising phase of a tetanus are discussed.

Actins↗