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Biomedical subjects

R Gold

Publications and source records attributed to R Gold.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Standardized bicycle ergometry test in mitochondrial myopathies. Indications, interferences and clinical parameters].

Exercise tests are widely used as simple, non-invasive screening methods in the differential diagnosis of metabolic myopathies. Exercise protocols have not been standardized with regard to duration of the test, workload, or monitored metabolic parameters. Potentially interfering parameters such as gender or maximal isometric force of the individuals have not been investigated. Here we describe a standardized bicycle ergometry protocol with a stepwise increasing workload between 30 and 100 watts. The venous lactate/pyruvate (L/P) ratio proved to be the one clinically most useful parameter in the functional diagnosis of mitochondrial myopathies with pathological exercise values in all nine examined patients. Additionally, the effects of coenzyme Q therapy in these patients were most clearly mirrored by changes in the L/P ratio. Nonspecifically elevated venous lactate concentrations above 5 mmol/l are rarely found in healthy female volunteers with low maximal isometric force of the M. quadriceps femoris. Other parameters such as serum free fatty acids, ketone bodies, intermediate products of the Krebs cycle or spirometric investigations add only little additional information. The exercise test described may be useful as an additional investigation in the differential diagnosis of metabolic myopathies.

Adult↗
PubMed1998

Metabolic changes in patients with mitochondrial myopathies and effects of coenzyme Q10 therapy.

We used a standardized bicycle ergometry protocol with a stepwise increasing workload (30-100 W) to evaluate various metabolic factors for the diagnosis and metabolic monitoring of mitochondrial encephalomyopathies. All patients (n = 9) showed pathological venous lactate/pyruvate (L/P) ratios, which normalized in three patients after 6 months of coenzyme Q10 (CoQ) therapy. Thus, the L/P ratio proved to be the clinically most useful parameter in the evaluation and monitoring of mitochondrial diseases, showing higher sensitivity than lactate measurements only. CoQ may exert a favourable effect in some patients with mitochondrial diseases.

Adolescent↗
PubMed1998

Plasma membrane phospholipid asymmetry precedes DNA fragmentation in different apoptotic cell models.

Biochemical alterations occurring in many cell types during apoptosis include the loss of plasma membrane phospholipid asymmetry and nuclear DNA fragmentation. Annexin V staining detects phosphatidylserine translocation into the outer plasma membrane layer occurring during cell death, while the in situ tailing (IST or TUNEL) reaction labels the DNA strand breaks typical of apoptosis. To compare the time course of these processes we investigated methylprednisolone-induced apoptosis of rat thymocytes, topoisomerase inhibitor-induced apoptosis in the human histiocytic lymphoma cell line U937, and serum deprivation-induced apoptosis in the rat pheochromocytoma cell line, PC12. At all time points, FACS analysis and quantitative fluorescence light microscopy showed a higher proportion of annexin V-positive than IST-positive cells, with significantly different time courses in the apoptotic cell models investigated (Anova test). Results were confirmed by confocal microscopy. Our data indicate that the exposure of phosphatidylserine, a potential phagocyte recognition signal on the cell surface of apoptotic cells in vivo, precedes DNA strand breaks during apoptosis in different cell types.

Animals↗
PubMed1998

Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus B conjugate vaccine administered to infants at two, four and six months of age.

Safety, immunogenicity and lot consistency of five-component pertussis combination vaccine (CPDT-IPV//PRP-T) in infants were compared to that of whole cell pertussis combination vaccine (DPT-IPV//PRP-T), as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV//PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in antibody responses were observed between lots of component pertussis vaccine. Higher concentrations of diphtheria and tetanus antitoxins were induced by separate than by combined injection of CPDT-IPV and PRP-T, but no other differences in immunogenicity were observed. Adverse reactions were more than twice as frequent after whole cell than after component pertussis vaccines. Antibody responses to pertussis toxoid, filamentous hemagglutin and pertactin were significantly greater after component vaccines, while the response to type 3 poliovirus was higher after whole cell vaccine. No significant differences were observed for other vaccine components. CPDT-IPV//PRP-T was safe and immunogenic in infants. Antibody results were similar to those observed in a Swedish field trial that demonstrated CPDT to be 85% effective in preventing clinical pertussis.

Acetaminophen↗
PubMed1998

Treatment of severe myasthenia gravis with protein A immunoadsorption and cyclophosphamide.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction caused by antibodies against the nicotinic acetylcholine receptor (AChR-Ab). We report a 16-year-old girl with severe MG who showed a poor response to plasma exchange and tryptophan-linked polyvinylalcohol gel immunoadsorption. Further improvement of muscle strength and decline of AChR-Ab could be achieved after initiation of protein-A immunoadsorption (PA-IA). Maintenance therapy with PA-IA and intravenous pulses of cyclophosphamide resulted in a stabilisation of the disease, with a complete remission during the follow-up period of six months. We suggest that PA-IA may be valuable and safe in the management of patients with severe MG, and maintenance therapy with PA-IA and cyclophosphamide may prevent serious and potentially life-threatening relapses of the disease.

Adolescent↗
PubMed1998

Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994-1995.

Of 145 patients admitted to our hospital because of encephalitis-like illness, 50 patients hospitalized for > or =72 hours underwent standardized microbiological investigations. A confirmed or probable etiologic agent was identified in 20 cases (40%), including Mycoplasma pneumoniae (9 cases). M. pneumoniae and enterovirus (2), herpes simplex virus (4), Epstein-Barr virus (1), human herpes-virus 6 (HHV-6) (1), HHV-6 and influenza virus type A (1), influenza virus type A (1), and Powassan virus (1). In 13 cases (26%), a possible pathogen was identified, including M. pneumoniae in nine cases. Presenting features included fever (80% of patients), seizures (78%), focal neurological findings (78%), and decreased consciousness (47%). The frequency of findings at the time of admission vs. later in hospitalization was as follows: pleocytosis, 59% vs. 63%; electroencephalogram abnormalities, 87% vs. 96%; and neuroimaging abnormalities, 37% vs. 69%, respectively. The outcomes at the time of discharge were as follows: normal results of physical examination, 32% (16) of the patients; death, 2% (1); motor difficulties, 26% (13); global neurological deficits, 16% (severe, 6; mild, 2); mental status changes, 14% (7); visual defects, 8% (4); and hearing impairment, 2% (1).

Acute Disease↗
PubMed1998

The role of the very late antigen-4 and its counterligand vascular cell adhesion molecule-1 in the pathogenesis of experimental autoimmune neuritis of the Lewis rat.

We have investigated the functional role of very late antigen-4 [VLA-4 (alpha4/beta1) integrin] and vascular cell adhesion molecule-1 (VCAM-1) in experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome, using neutralizing monoclonal antibodies (mAbs) as probes. Disease was induced by intravenous adoptive transfer of P2 specific T cells (AT-EAN), or by immunization with bovine myelin (active EAN). Preventive treatment with 500 microg anti-VLA-4 mAb (TA-2) or with an isotype control antibody was given in AT-EAN 4 h before cell transfer and at day 3. Intravenous injection of 500 microg anti-VCAM-1 mAb (5F10) or a corresponding isotype control was given in AT-EAN 4 h before disease induction, and at days 2, 4 and 6. Preventive treatment of active EAN with mAb to VLA-4 or VCAM-1 was performed at days 5, 9 and 13. On immunohistochemical examination, VCAM-1 in sciatic nerve was found to be upregulated at early stages of EAN (days 3-5 after T-cell transfer), whilst no expression was noted in healthy controls. In both EAN models, blockade of VLA-4 markedly attenuated disease severity. Blockade of VCAM-1 also significantly ameliorated the disease course and diminished T-cell infiltration in sciatic nerve, but to a lesser degree. These experiments demonstrate the critical role of VLA-4 in the pathogenesis of EAN and show that upregulation of VCAM-1 expression contributes, at least in part, to the progression of the disease in the early stages. Future studies are needed to assess the potential contribution of other VLA-4 ligands.

Animals↗
PubMed1998

Acute-phase neurologic complications of Haemophilus influenzae type b meningitis: association with developmental problems at school age.

The purposes of this study were to describe the incidence of acute-phase neurologic complications in a sample of 126 children with Haemophilus influenzae type b meningitis, and to determine if these complications were associated with higher rates of learning and behavior problems at school age. Risks were assessed by comparing rates of adverse psychoeducational outcomes in the 53 children in the sample with complications to corresponding outcome rates in the 67 children who were free of neurologic complications and who did not have abnormal electroencephalograms (EEGs) or computed tomographic (CT) scans. Comparisons were made by means of logistic regression analysis. Twenty-nine children (23% of the sample) had seizures, 16 (13%) were comatose or obtunded, 15 (12%) had sensorineural hearing loss, 8 (6%) had hemiparesis, and 7 (6%) had cranial nerve deficits other than hearing loss. Relative to children without complications, those with complications had higher rates of grade repetition and substandard performance on neuropsychological and achievement testing. Adverse outcomes, however, consisted primarily of more subtle cognitive and learning problems; only two of the children in the sample obtained prorated IQ scores below 70. Sequelae were associated with persistent neurologic deficits and bilateral hearing loss, as well as with transient symptoms including seizures, coma, and hemiparesis. While study findings argue against adverse consequences for the vast majority of children treated for this disease, the results clarify learning and behavior outcomes and indicate which children are at greatest risk.

Adolescent↗
PubMed1998

Sexual functioning in ambulatory men with HIV/AIDS.

Sexual functioning is often neglected in the care of HIV-infected patients. Little information exists about the relationship between hormonal factors, psychological factors, medication, HIV disease stage and sexual functioning among persons with HIV disease. In this study, 50 HIV+ men completed the Derogatis Sexual Functioning Inventory (DSFI), and had serum hormonal assays drawn (testosterone, thyroid function test, leuteinizing hormone, prolactin and oestradiol). Although all the subjects reported some degree of sexual dysfunction, persons with symptomatic HIV/AIDS reported more negative mood, lower sexual satisfaction scores and worse body image than persons with asymptomatic HIV. Persons with asymptomatic HIV also tended to have normal testosterone levels compared with persons with symptomatic HIV/AIDS. No relationship was found between medications and low testosterone, although numbers were small. These results suggest that sexual dysfunction is prevalent among persons with HIV disease, is more common as patients become symptomatic and progress to AIDS and that both physiological (low testosterone) and psychological issues play a role.

Adult↗
PubMed1997

Apoptosis of myelin-reactive T cells induced by reactive oxygen and nitrogen intermediates in vitro.

Apoptosis is a major mechanism of T cell elimination during ontogeny and tolerance induction as well as in autoimmunity. To assess the possible involvement of reactive oxygen and nitrogen intermediates (ROI and NO.) in T-cell apoptosis during autoimmune demyelination we investigated the effects of H2O2 and NO. in vitro on activated autoreactive CD4+ T cell lines capable of transferring experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). For detection and quantitation of apoptotic cells, DNA fragmentation was assessed by in situ tailing with fluorescein-ddUTP and subsequent flow cytometric analysis. H2O2 applied directly to the cell cultures for 6 to 18 hr at concentrations of 10 to 300 microM and ROI released by combination of hypoxanthine and xanthine oxidase (HX/XO) caused apoptosis in a dose-dependent manner in 13-33% of T cells of neuritogenic and encephalitogenic T cell lines. Apoptosis induction could be suppressed by the H2O2-neutralizing enzyme catalase. NO. released by the penicillamine derivative SNAP induced apoptosis to a similar extent as ROI. Maximum values were 38% in an encephalitogenic V beta 8.2-T cell receptor-bearing T cell line and 26% in a neuritogenic T cell line. T cell lines with specificity to ovalbumin revealed slightly lower susceptibility to apoptosis induction by all three kinds of trigger, which is, however, most probably not due to the different antigen specificity, but rather a result of fewer in vitro restimulation cycles of these cells. In neuritogenic cells high-dose (100 units/ml) exogenous interleukin-2 (IL-2) prevents H2O2-induced apoptosis. In conclusion, macrophage-derived reactive oxygen and nitrogen intermediates have the potency to limit inflammatory demyelination by elimination of autoreactive and bystander T cells via apoptotic cell death, and IL-2 is a rescue factor.

Animals↗
PubMed1997

A practical guide for the diagnosis and treatment of pediatric pneumonia.

OBJECTIVE: To develop guidelines for the diagnosis and management of community-acquired pediatric pneumonia. OPTIONS: Clinical assessment, radiography, laboratory testing, and empirical antimicrobial therapy. OUTCOMES: Increased awareness of age-related causes, improved accuracy of clinical diagnosis, better utilization of diagnostic testing and the rational use of empirical antimicrobial therapy resulting in more rapid diagnosis, initiation of appropriate therapy and decreased morbidity and mortality. EVIDENCE: A MEDLINE search for relevant articles published from 1996 to September 1996 using the MeSH terms "pediatric," "pneumonia," "respiratory tract infection," "pneumonitis," "etiology," "diagnosis," "therapy," "antibiotics," "resistance," "radiology," "microbiology" and "biochemistry." VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. When application of the hierarchy was not feasible or appropriate, different evaluation criteria were used. BENEFITS, HARMS AND COSTS: Increased awareness of the causes of pneumonia, accurate diagnosis and prompt treatment should reduce costs associated with unnecessary investigations and complications due to inappropriate treatment. RECOMMENDATIONS: Age is the best predictor of the cause of pediatric pneumonia, viral pneumonia being most common during the first 2 years of life. The absence of a symptom cluster of respiratory distress, tachypnea, crackles and decreased breath sounds accurately excludes the presence of pneumonia (level II evidence). Bacterial cultures of samples from the nasopharynx and throat have no predictive value; however, Gram staining and culture of sputum from older children and adolescents are useful (level III evidence). Oral antimicrobial therapy will provide adequate coverage for most mild to moderate forms of pneumonia in children (level III evidence). Parenteral therapy is typically reserved for neonates and patients with severe pneumonia admitted to hospital (level III evidence). VALIDATION: These recommendations are based on consensus of Canadian experts in infectious diseases and microbiology. They are the only guidelines to address antimicrobial treatment from an age-related, etiologic perspective. SPONSOR: The development of these guidelines and the technical support and assistance of Core Health Inc. in preparing this manuscript were funded through an unrestricted educational grant from Abbott Laboratories Canada. The sponsoring company was not involved in determining the membership of the consensus group or the content of the guidelines.

Adolescent↗
PubMed1997

Antigen therapy eliminates T cell inflammation by apoptosis: effective treatment of experimental autoimmune neuritis with recombinant myelin protein P2.

Exposure of T cells to their specific antigen normally results in proliferation, but in the presence of high and repeatedly administered doses of antigen, T cells may undergo apoptosis. Here we demonstrate that i.v. administration of as little as 100 microg of recombinant P2 protein twice daily completely prevents experimental autoimmune neuritis induced by adoptive transfer of neuritogenic P2-specific T cells or by immunization with the neuritogenic P2-peptide-spanning amino acids 53-78. Antigen treatment started after disease onset markedly ameliorated experimental autoimmune neuritis. The mechanism of action may be through programmed T cell death; a profound increase of the rate of apoptosis was seen in inflammatory foci of peripheral nerves and in the spleen. There was no cytokine switch by our Th1 cells after exposure to their specific antigen, but increased secretion of interferon gamma and tumor necrosis factor alpha was demonstrated. High antigen dose therapy using recombinant, pathogen-free protein may prove useful for the treatment of autoimmune inflammatory disorders of the nervous system.

Adoptive Transfer↗
PubMed1997

Failure of intravenous immunoglobulin (IVIg) therapy in experimental autoimmune neuritis (EAN) of the Lewis rat.

Experimental autoimmune neuritis (EAN) is an animal model for Guillain-Barré syndrome (GBS). Intravenous immunoglobulins (IVIg) are an effective treatment for GBS, but their mechanism of action is not well understood. Here we tested whether IVIg treatment, a potent modulator of proinflammatory assaults, reduces inflammation in EAN. The evaluation of IVIg treatment failed to demonstrate a salutary effect in different models of EAN. IVIg appears not to suppress the acute inflammatory insult on the peripheral nerve, but may have beneficial long-term effects not looked for in the present investigation.

Animals↗
PubMed1997

T-cell apoptosis in autoimmune diseases: termination of inflammation in the nervous system and other sites with specialized immune-defense mechanisms.

We have studied T-cell apoptosis in animal models of human autoimmune disorders of the nervous system and in other tissues devoid of specialized immune-defense mechanisms. Our data suggest that the CNS has high potential for elimination of T-cell-dependent inflammation, whereas this mechanism is less effective in the PNS, and is almost absent in other tissues such as muscle and skin. Interestingly, several conventional and novel immunotherapeutic approaches, such as glucocorticosteroid and high-dose antigen therapy, induce T-cell apoptosis in situ. In vitro experiments suggest different scenarios for the mechanisms by which specific cellular and humoral elements in the nervous system synergize and sensitize T cells for apoptosis in vivo. We also discuss regulatory, proapoptotic mechanisms, such as the Fas-FasL system and galectin-I, that have been utilized in other tissues to mediate immune protection.

Animals↗