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Biomedical subjects

H Adler

Publications and source records attributed to H Adler.

At least 37 records · Page 2Linked to original sources
PubMed1997

A simple electrocardiographic algorithm for detecting ventricular tachycardia.

The purpose of this study was to determine whether a simple ECG algorithm could be developed for predicting susceptibility to ventricular tachyarrhythmias (VT) as defined by sustained spontaneous or inducible VT. Two different QT dispersion algorithms were determined by the difference between the longest and shortest QT interval measured in three orthogonal leads (I, aVF, V1; QTD3), and at least 11 of 12 leads (QTD12) from the 12-lead ECG. These QT dispersion algorithms were investigated (with and without the QRS duration from the 12-lead ECG) and compared to the signal-averaged ECG (SAECG) in order to determine their sensitivity and specificity for detecting VT. Only patients who underwent SAECG and were referred for programmed electrical stimulation were included in this study. A positive SAECG was defined by filtered QRS duration > 114 ms, and/or low amplitude signal duration > 38 ms, and/or root mean square voltage in the last 40 ms of < 20 microV. Sixty patients were enrolled in this study with a mean age of 63 +/- 2 years. Fifty-five percent of the patients had coronary artery disease. A simple ECG algorithm consisting of the sum of QTD3 plus the QRS duration had a sensitivity and specificity of 90% and 63%, respectively, wheras the SAECG had a sensitivity and specificity of 60% and 63%, respectively (P = 0.022). We conclude that a simple ECG algorithm is more sensitive than the SAECG for predicting VT. This algorithm combines two easily measured variables obtained from the 12-lead ECG, and can easily be performed without expensive computer equipment.

Adolescent↗
PubMed1997

Serum factors, cell membrane CD14, and beta2 integrins are not required for activation of bovine macrophages by lipopolysaccharide.

The role of serum factors such as lipopolysaccharide (LPS)-binding protein (LBP) and of macrophage-expressed CD14 and beta2 integrins in the activation of bovine macrophages by LPS was investigated. Macrophage activation was determined by measuring tumor necrosis factor production, NO generation, and upregulation of procoagulant activity by LPS (Escherichia coli O55:B5) at concentrations of 100 pg/ml to 100 ng/ml. The 50% effective dose for LPS was 1 order of magnitude higher than that for activating human macrophages. Macrophages were activated by LPS in the presence of serum or in the presence of albumin demonstrated to be free of LBP. The capacity to react to LPS in the absence of LBP was not due to the acquisition of LBP during a previous culture in serum. It was then established which CD14-specific antibodies block LPS binding to monocytes. Among the CD14-specific antibodies recognizing bovine mononuclear phagocytes (60bca, 3C10, My4, CAM36, VPM65, CMRF31, and TUK4), the first four blocked the binding of LPS-fluorescein isothiocyanate to bovine monocytes at low concentrations. Anti-CD14 antibodies did not block LPS-mediated activation of bovine bone marrow-derived macrophages, monocyte-derived macrophages, and alveolar macrophages. This was observed in experiments in which anti-CD14 concentrations exceeded the 50% inhibitory dose by >30-fold (3C10 and My4) or >300-fold (60bca), as defined in the binding assay described above. Monocyte-derived macrophages from an animal deficient in beta2 integrins and control macrophages were activated by similar concentrations of LPS, suggesting that beta2 integrins are not important bovine LPS receptors. Thus, in bovine macrophages, LPS recognition pathways which are independent of exogenous LBP, of membrane-expressed CD14, and of beta2 integrins may exist.

Acute-Phase Proteins↗
PubMed1997

Macrophages infected with cytopathic bovine viral diarrhea virus release a factor(s) capable of priming uninfected macrophages for activation-induced apoptosis.

Bovine bone marrow-derived macrophages infected with the cytopathic biotype of bovine viral diarrhea virus released an antiviral activity into the supernatant which was tentatively characterized as type I interferon because of its physicochemical properties. Such supernatants primed both infected and uninfected macrophages for decreased nitric oxide production and apoptosis in response to lipopolysaccharide. This finding strongly suggests a role of this pathway in the pathogenesis of mucosal disease, a lethal form of infection with cytopathic bovine viral diarrhea virus in which the principal lesions are located in the oral cavity and the gastrointestinal tract, which are known to contain a high concentration of endotoxin.

Animals↗
PubMed1997

The cost and benefit of prophylaxis against deep vein thrombosis in elective hip replacement. DVT/PE Prophylaxis Consensus Forum.

UNLABELLED: A consensus forum was convened to evaluate the economic considerations associated with prophylaxis against thrombo-embolic disease in patients undergoing hip replacement therapy in South Africa. This forum consists of orthopaedic surgeons, vascular surgeons and a statistician. METHODS: The forum was instructed to evaluate the economic costs of the commonly used forms of prophylaxis of thrombo-embolism in patients undergoing hip replacement surgery in South Africa, looking at short-term events only. The methods used for the prophylaxis of thrombo-embolism in South Africa were determined by a postal survey. A decision tree was constructed to determine the events that will occur after a clinical decision to use no prophylaxis. The probabilities of these events were then determined. Protocols for and costs of prophylaxis and treatment were established. With the decision tree and these costs, the cost of the various modalities of prophylaxis was then determined. RESULTS: The probability, determined by the forum, of developing a deep-vein thrombosis (DVT) when no prophylaxis is used was 0.5, with a mortality rate of 2.1%. The cost of this decision was R875. No prophylaxis given, but a venogram performed on day 7, reduced the mortality rate to 0.7%; however, this cost R3 017. The cost of low-molecular-weight heparin was R1 223 (probability 0.26, mortality rate 1.1%), while unfractionated heparin with a graduated compression stocking (GCS) cost R1 351 (probability 0.24, mortality rate 1%). Aspirin with a GCS cost R777 (probability 0.35, mortality rate 1.5%).

Anticoagulants↗
PubMed1996

Inducible nitric oxide synthase of macrophages. Present knowledge and evidence for species-specific regulation.

An important mechanism by which macrophages (M phi) halt the growth of and eliminate a broad array of intracellular pathogens is the production of nitric oxide (NO). NO generation is catalyzed by inducible nitric oxide synthase (iNOS) converting arginine into citrulline and NO. In murine M phi, iNOS activity is regulated largely at the transcriptional level. LPS and IFN-gamma induce iNOS, IL-4 and TGF-beta down-regulate LPS or IFN-gamma induced iNOS. In human M phi, iNOS cannot be induced by conventional activating regimes in vitro. We studied iNOS induction in ruminant monocytes and M phi from various sources (bone marrow, alveolar lavage, peripheral blood) and found that there is a species-specific and differentiation stage-dependent pattern of iNOS regulation in vitro. Notably, cattle M phi and monocytes respond to distinct signals by iNOS expression. Goat monocytes and M phi resemble human, pig and rabbit M phi in that upon treatment with conventional activating stimuli, they express less iNOS than unstimulated murine or bovine M phi and fail to generate detectable amounts of nitrite and nitrate.

Animals↗
PubMed1996

Differential regulation of inducible nitric oxide synthase production in bovine and caprine macrophages.

Inducible nitric oxide synthase (iNOS) regulation in human and murine macrophages in vitro differs considerably. In this study, expression of macrophage iNOS in ruminants was addressed. Nitric oxide (NO) output by cattle and goat macrophages was as different as that by human and mouse macrophages. Bovine macrophages activated by heated Salmonella dublin or lipopolysaccharide (LPS) expressed high levels of iNOS mRNA, protein, and enzyme activity. Analogously cultured caprine macrophages did not respond to these and other activators by NO generation and iNOS expression. The lack of response was not due to general unresponsiveness to stimuli. Caprine iNOS mRNA was induced by stimulation of caprine macrophages with LPS, as shown by reverse transcription polymerase chain reaction. The level of mRNA expression in activated goat macrophages was lower than in resting bovine macrophages. A caprine 372-bp iNOS mRNA fragment that was sequenced closely resembled the bovine counterpart. This points to species-specific iNOS gene regulation.

Animals↗
PubMed1996

Cytokine regulation by virus infection: bovine viral diarrhea virus, a flavivirus, downregulates production of tumor necrosis factor alpha in macrophages in vitro.

Bovine bone marrow-derived macrophages were infected in vitro with noncytopathic or cytopathic strains of bovine viral diarrhea virus. Infection with both biotypes resulted in a decreased production of tumor necrosis factor alpha upon stimulation with heat-inactivated Salmonella dublin or lipopolysaccharide. Other macrophage functions were not downregulated, indicating that the observed effect was not due to a loss in macrophage viability. The downregulated production of tumor necrosis factor alpha in infected macrophages may contribute to the well-documented immunosuppression in animals infected with bovine viral diarrhea virus.

Animals↗
PubMed1996

The role of urodynamics in the evaluation of voiding dysfunction in men after cerebrovascular accident.

PURPOSE: The etiology of voiding dysfunction was determined in men after a cerebrovascular accident who were at risk for obstructive uropathy to evaluate whether the cause of voiding dysfunction could be predicted by the type (obstructive or irritative) or onset of symptoms. MATERIALS AND METHODS: We evaluated 38 men with complaints of voiding dysfunction following a cerebrovascular accident. All patients were of the age when bladder outlet obstruction secondary to benign prostatic hyperplasia would otherwise be prevalent. After a comprehensive history and physical examination, all patients underwent multichannel urodynamic studies at a medium fill rate (20 to 50 ml. per minute). Findings were classified by the Abrams-Griffiths nomogram as obstruction, no obstruction or equivocal. RESULTS: Mean patient age was 70 years (range 54 to 87). Patients were grouped according to the presenting voiding complaints (purely irritative in 42%, purely obstructive in 34% or mixed in 24%). In 34 patients (89%) the onset of symptoms paralleled the occurrence of the cerebrovascular accident. Detrusor hyperreflexia was noted in 82% of the patients. There was no statistically significant difference in the occurrence of detrusor hyperreflexia among the 3 symptom groups (Fisher's exact test). Pressure-flow analysis clearly showed obstruction in 24 patients (63%), no obstruction in 9 (24%) and equivocal results in 5 (13%) according to the nomogram. There was no statistically significant difference in the incidence of obstruction among the 3 symptom groups (Fisher's exact test). CONCLUSIONS: Presenting symptoms did not predict the urodynamic findings of bladder outlet obstruction or detrusor hyperreflexia. The significant incidence of onset of symptoms after stroke suggests that the cerebrovascular accident induced voiding dysfunction in the face of preexisting bladder outlet obstruction may exacerbate the symptoms of the latter condition or vice versa.

Aged↗
PubMed1996

[Use of polymerase chain reaction to reduce the use of animal studies: a project for the expression of the structural proteins of tick-borne meningoencephalitis virus].

Tick-borne encephalitis virus is difficult to propagate because with consecutive passages in cell culture the virus titer will decrease. Stockvirus has to be propagated in young mice. Therefore, every production of virus for research, diagnostic assays or vaccination demands the use of laboratory animals. We decided to clone the part of the viral genome which codes for the structural proteins, and to produce the structural proteins in a suitable expression system. Using reverse transcription, followed by the polymerase chain reaction, we amplified exactly this part of the viral genome, added restriction sites for cloning and a stop-codon. Cloning of this DNA-fragment and expression of the structural proteins of tick-borne encephalitis virus in the baculovirus expression system has thus been possible. Replacement of traditional viral antigen by these recombinant proteins may reduce the need for laboratory animals.

Animals↗
PubMed1995

Interferon-alpha primes macrophages for lipopolysaccharide-induced apoptosis.

Apoptosis plays an important role in generating and maintaining an effective immune system. Many pathogens can perturb the homeostasis of the immune system by either inducing or suppressing cell death of immune cells. Using bovine macrophages as a model, we found that interferon-alpha, one of the host's responses to viral infection, can prime macrophages for activation-induced apoptosis. Exposure of bovine bone-marrow-derived macrophages to interferon-alpha and subsequent activation with lipopolysaccharide led to a strong downregulation of the macrophages' nitric oxide production when compared to lipopolysaccharide stimulation alone. We could show that this was due to induction of apoptosis after activation of the cells. Herpesvirus-induced type I interferon also primed bovine macrophages for lipopolysaccharide-induced apoptosis. Our studies describe how in a novel pathway an antiviral immune response could contribute to pathological sequelae of viral diseases.

Animals↗
PubMed1995

Inducible nitric oxide synthase in cattle. Differential cytokine regulation of nitric oxide synthase in bovine and murine macrophages.

We assessed bovine bone marrow-derived macrophages and monocyte-derived macrophages for expression of inducible nitric oxide synthase (iNOS) activity. Both cell types expressed iNOS activity upon stimulation with Salmonella dublin (S. dublin) or with LPS. A 372-bp fragment of the bovine iNOS mRNA could be amplified by reverse transcription-PCR from mRNA of stimulated macrophages. Cloning and sequencing of the fragment revealed a high degree of homology to human hepatocyte, rat vascular smooth muscle cell, and mouse macrophage iNOS both at the nucleotide (87 to 92%) and amino acid levels (94 to 97%). iNOS mRNA was expressed maximally 6 h after stimulation with S. dublin, whereas maximal nitrite accumulation in supernatants was measured at 24 to 48 h. Significant differences with regard to cytokine regulation of iNOS were observed between murine and bovine macrophages cultured under identical conditions. The most striking difference was the inability of homologous IFN-gamma to induce iNOS both at the level of nitrite production and of mRNA expression in bovine macrophages. TNF-alpha, IL-2, and IL-1 alone or together with IFN-gamma neither induced iNOS nor primed bovine macrophages for enhanced iNOS expression or activity upon stimulation with S. dublin. RhuIL-4, but not rhuTGF-beta, down-regulated S. dublin-induced iNOS activity and mRNA expression in bovine macrophages. Thus, an enzyme with a high degree of homology to rodent iNOS is inducible by stimulation of bovine macrophages with bacteria, but induction and regulation by cytokines occur under more restricted conditions than in rodent macrophages.

Amino Acid Oxidoreductases↗
PubMed1995

Recall and repetition of a severe childhood trauma.

This study focuses on a patient who at the age of 3 survived the extended suicide of her parents. The account concentrates on the way in which this woman repeated the experiences of her trauma in the highly emotional therapy process (initially infrequent), and then how she recalled them at different stages and with variations, and it shows the decisive involvement of the analyst in this activity, in parallel processes of defence and reconstruction. The distinction needs to be drawn between the reproduction of the trauma, the form in which the extreme trauma is indelibly tattooed on the memory, and actual recalling. This is to be regarded as a method of analytical understanding, general in its applicability, as an evolving retrospective imposition of sense, by means of which the previously valid construction of knowledge is revised in accordance with the central relationship in the present. What the patient recalled as trauma events in evolving perspectives revealed itself as an overpowering prefiguration (attainable a posteriori) of the vicissitudes of transference. With regard to extreme trauma in childhood, this study develops the following hypotheses: (1) the overwhelming, shattering blow of an external event is met by an equally strong, archaic defence, even in the historical situation itself, as an escape from the unbearable, unspeakable pain; (2) the Janus face of the victim/perpetrator introject is manifest in the masochistic character-structure; (3) these splits can be attenuated in the course of a person's life, with the appropriate help, although they cannot be fully integrated.

Adolescent↗
PubMed1994

Noncytopathic strains of bovine viral diarrhea virus prime bovine bone marrow-derived macrophages for enhanced generation of nitric oxide.

Bovine bone marrow-derived macrophages (BBMM) were infected in vitro with a cytopathic (cp) and a noncytopathic (ncp) biotype of bovine viral diarrhea virus (BVDV). The virus strains used, TGAN (ncp) and TGAC (cp), originate from one animal and are antigenically closely related. Both TGAC and TGAN infected a subset of BBMM. Only cp BVDV induced a cytopathic effect. Infection of BBMM resulted in the modulation of certain macrophage functions. Only ncp strains of BVDV primed BBMM for enhanced reactive nitrogen production in response to Salmonella dublin. In contrast, infection with both biotypes did not influence bacteria-induced procoagulant activity and both biotypes equally reduced PMA-induced superoxide production. This suggests that the two biotypes differentially and selectively affect certain macrophage functions related to host defense. For the first time, a BVDV biotype-associated difference has been related to a biochemical parameter of the host cell.

Amino Acid Oxidoreductases↗
PubMed1994

Inducible L-arginine-dependent nitric oxide synthase activity in bovine bone marrow-derived macrophages.

In rodent macrophages, cytokines or bacterial constituents induce a Ca(2+)-independent nitric oxide (NO) synthase which plays a key role in antimicrobial and tumoricidal activity. Firm evidence for expression of a similar enzyme in other mammals has been lacking. Here we show that bovine bone marrow-derived macrophages produce nitrite in an L-arginine-dependent manner upon stimulation with heat-killed gram-positive or gram-negative bacteria. NO2- production was markedly diminished by arginase, and by the arginine analogue, NG-monomethyl-L-arginine. Bacteria-induced NO2- production was enhanced by concomittant exposure to interferon-gamma, tumor necrosis factor-alpha or both combined, although these cytokines alone (in the absence of bacteria) induced little NO2-. This is one of the first demonstrations of NO2- production by non-rodent macrophages.

Amino Acid Oxidoreductases↗