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Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 307 records · Page 17Linked to original sources

[Regulating intraoperative pressure in filtering glaucoma operations with a sterilizable tonometer].

BACKGROUND: Hypotony with shallow or flat chamber and hypertony without filtration are important short-term complications of filtering procedures in glaucoma. Both reflect the difficulty to adjust the tension of the scleral flap in a way that the artificial valve opens at pressures within the therapeutic range. Our aim was to avoid these complications by improving the filling test. PATIENTS AND METHOD: 22 eyes of 21 patients with chronic glaucoma of different etiology underwent a trabeculectomy. After preliminarily fixing the sutures, the anterior chamber was filled until fluid appeared at the rim of the scleral flap. Then, the pressure was measured using a newly developed, sterilizable applanation tonometer. By tightening or loosening the sutures the opening pressure was adjusted to values between 5 and 20 mm Hg. RESULTS: The IOP at the first postoperative day correlated well with the intraoperative flap opening pressure (correlation coefficient 0.771), but was 20% lower at the average. All cases had a sufficient filtering zone and IOP below 20 mm Hg. At the first day, all chambers were deep. After 2 to 9 days, 4 eyes developed temporarily a shallow chamber (minimum depth: 1 1/2 times corneal thickness). This complication occurred only in eyes with intraoperative pressures of 5 to 10 mm Hg. CONCLUSION: Intraoperative pressure control during trabeculectomy allows a fairly good determination of the postoperative IOP. Choosing a suitable pressure level (15 to 20 mm Hg), hypotony and shallow chambers should be avoided. Hypertony can be hindered, as well.

Equipment Design↗

Serotyping HIV type 1 by antibody binding to the V3 loop: relationship to viral genotype. WHO Network for HIV Isolation and Characterization.

We have investigated whether peptides representing the HIV-1 principal neutralization domain (V3) can be used as antigens in antibody-binding assays to predict the genotypes of the subjects' virus. Serum samples collected from HIV-1-infected subjects from the four WHO-sponsored vaccine evaluation sites (Uganda, Rwanda, Thailand, and Brazil) were characterized by antibody binding to a panel of synthetic V3 peptides that were derived from the consensus sequences of the V3 region of the HIV-1 subgroups according to the env phylogenetic analysis (A-E). An indirect V3 peptide-binding assay was used for primary screening, and a V3 peptide antigen-limiting ELISA was then used as a secondary assay to discriminate cross-reactivity if the screening assay was equivocal. In general, V3 peptide serology could predict HIV-1 genotypes. In sera for which the genotype of the virus was known, peptide assays could predict the correct genotype in approximately 90% of cases for genotypes A, B, C, and E; Ugandan sera of genotype D were more broadly reactive. There was considerable serological cross-reactivity between some HIV-1 genotypes, in particular between A and C, and, to a lesser extent, B and D subtypes. Owing to polymorphism at the crown of the V3 loop, an additional B peptide (B') was required to type Brazilian B genotype sera. These simple assays may help facilitate the determination and distribution of HIV-1 genotypes circulating in populations.

AIDS Vaccines↗

Autosomal dominant cerebellar ataxia with dementia: evidence for a fourth disease locus.

The autosomal dominant cerebellar ataxias have proved particularly difficult to classify due to the lack of phenotypic concordance both within and between families. Genetic heterogeneity has been established, and disease loci for spinal cerebellar ataxia have been assigned to chromosomes 6 (SCA1), 12 (SCA2) and 14 (Machado Joseph disease (MJD)). Genetic analysis performed on a large Thai kindred with autosomal dominant cerebellar ataxia, in which frontal lobe signs and dementia are commonly observed in affected family members, exclude linkage to the SCA1, SCA2 and MJD loci. This demonstrates that mutation in at least one further locus can cause spinal cerebellar ataxia, indicating the need for caution in the use of markers for predictive testing or prenatal diagnosis these disorders.

Chromosome Mapping↗

Local muscle hypertrophy due to an arterio-venous malformation.

A 20-yr-old man with progressive, painful diffuse swelling of his right shoulder muscles is reported. The diagnosis was muscle hypertrophy secondary to a congenital arterio-venous malformation (CAVM). Since a CAVM is not infrequently asymptomatic until the age of 20 to 30 yr and develops insidiously, the diagnosis may be delayed. In our patient, MRI rather than ultrasound and CT, led to the final diagnosis.

Adult↗

A phase I trial of intravenous interleukin-6 in patients with advanced cancer.

Eighteen patients were treated with escalating doses of recombinant, Escherichia coli-derived human interleukin-6 (IL-6) intravenously every 8 h. Therapy was given for two cycles of 7 days each separated by a week off therapy. Fevers and chills were observed in most patients. Mild renal and liver function abnormalities were noted at higher doses of IL-6. Dose-limiting toxicity was reached at 30 micrograms/kg i.v. every 8 h due to reversible neurotoxicity, but significant rapidly reversible anemia and hyperglycemia were seen at lower doses. Platelet counts, white blood cell counts, and acute phase reactant levels were substantially elevated. No antitumor responses were seen. A maximum tolerated dose of 10 micrograms/kg i.v. every 8 h for two 7-day cycles is recommended for future phase II trials.

Acute-Phase Proteins↗

The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis.

Human T-cell leukemia virus type I (HTLV-1) causes T-cell leukemia and tropical spastic paraparesis (TSP) in a minority of infected people, whereas the majority remain healthy. No association between a particular HTLV-I sequence and disease manifestation has been found in previous studies. We studied here the sequence variability of the gene for the HTLV-I Tax protein, which is the dominant target antigen of the very strong cytotoxic T-lymphocyte response to the virus. In HTLV-I infection, the intraisolate nucleotide variability is much greater than the variability between isolates. The predicted protein sequence of Tax was significantly more variable in the healthy seropositive individuals' provirus than in those of the patients with TSP. Thus, tax sequence heterogeneity, rather than the presence of particular sequences, distinguishes healthy HTLV-I-seropositive individuals from patients with TSP.

Base Sequence↗

Circulating anti-Tax cytotoxic T lymphocytes from human T-cell leukemia virus type I-infected people, with and without tropical spastic paraparesis, recognize multiple epitopes simultaneously.

CD8+ T cells were freshly isolated from a human T-cell leukemia virus type I (HTLV-I)-infected patient with tropical spastic paraparesis. These cells, which were specific for HTLV-I Tax, simultaneously recognized a minimum of five, and possibly as many as seven, distinct peptide epitopes within the protein. A further Tax epitope was recognized after a short period of culture without exogenous peptide stimulation. All but one of these epitopes were clustered in the N-terminal third of Tax, and one of the epitopes was clearly immunodominant on two separate occasions of testing. Recognition of the immunodominant epitope was restricted by human leukocyte antigen (HLA) B15, and recognition of all the others was by HLA A2. Similar patterns of cytotoxic T lymphocyte recognition of the HLA A2-restricted Tax peptides in two healthy HTLV-I-seropositive individuals, each of whom carried the HLA A2 allele, were observed.

Adult↗

In vitro effects of amino-acid-based versus glucose-based continuous ambulatory peritoneal dialysis fluids on peritoneal macrophage function.

We studied the in vitro effects of peritoneal dialysis fluids (PDF) containing 1 and 1.5% amino acids (AA) as compared to approximately equiosmolar glucose (GLU)-based PDF (1.5 and 4.25%) and control buffer, respectively, on peritoneal macrophage (PMO) function. The media were tested at original pH (5.3-5.5) and after pH adjustment to 7.4. PMO were isolated from the effluents of 10 on continuous ambulatory peritoneal dialysis (CAPD) patients and tested for luminol- and lucigenin-enhanced chemiluminescence (CL), superoxide generation measured by cytochrome c reduction, killing capacity and phagocytosis after incubation (30 min, 37 degrees C) in the PDF used. All AA-based PDF exhibited a statistically significant depressive effect on integral CL response, O2- production and bacterial killing of PMO at pH 7.4 in comparison with pH-adjusted GLU-based PDF of similar osmolality and buffer. Exposure of PMO to acidic AA-based media did not result in a significantly different suppression of the oxidative metabolism and the killing capacity as compared to fresh GLU-based fluids. Phagocytosis of PMO did not show significant differences after incubation in the solutions studied. Thus, the AA-based PDF employed compromise the oxidative metabolism and the killing capacity of PMO at pH 7.4 in vitro significantly more than GLU-based fluids. Since pH-identical and almost equiosmolar PDF were compared, the specific composition of the AA-based fluids, especially the high content of lactate and several essential AA, could be responsible for this detrimental impact.

Amino Acids↗

Adverse effects of drugs used in the management of opportunistic infections associated with HIV infection.

Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS-defining diagnoses. First-line therapy is cotrimoxazole (trimethoprim-sulfamethoxazole), despite a high incidence of toxic effects, and a greater incidence of hypersensitivity reactions among HIV-positive patients compared with the seronegative population. Alternative agents such as intravenous pentamidine, or clindamycin with primaquine, and trimethoprim with dapsone, also have a wide range of serious adverse effects, but remain treatment options. Atovaquone appears promising for the treatment of both PCP and toxoplasmosis, and has a lower reported incidence of toxicity than the alternative agents. The most toxic antifungal drugs are reserved for serious infections, such as cryptococcal meningitis. Liposomal amphotericin B has less renal toxicity than standard formulations, and exemplifies that new formulations of existing drugs, although often expensive, may have a better adverse effect profile. There are 2 different drugs currently available for cytomegalovirus (CMV) infections, ganciclovir and foscarnet. Both have a high incidence of serious adverse effects; ganciclovir mainly causes bone marrow toxicity and foscarnet leads to renal toxicity. The drugs used for mycobacterial infection (including mycobacteria as well as tuberculosis) have a wide range of adverse effects, particularly skin rashes and drug-induced hepatitis. Some of these compounds are quite new, such as rifabutin and clarithromycin, and it is important to be ever vigilant for previously unreported adverse effects.

AIDS-Related Opportunistic Infections↗

Can aspirin prevent gallstone recurrence after successful extracorporeal shockwave lithotripsy?

Extracorporeal shockwave lithotripsy (ESWL) is a feasible procedure for the treatment of gallbladder stones in humans. Well-selected patients can achieve stone-free rates in a high percentage. With the gallbladder in situ, these patients are at risk of stone recurrence. There is considerable evidence that aspirin prevents cholesterol gallstone formation in animal models and may prevent gallstone recurrence in man. We attempted to clarify the risk of gallstone recurrence after successful piezoelectric lithotripsy in patients taking either low-dose aspirin or no medication. The first 45 patients shown to be completely free from stones after ESWL were randomized into two groups. One group received 100 mg aspirin daily; the other group did not receive any further medical therapy. Patients were further examined on an average of 19.6 months and 21.9 months, respectively. In the aspirin group the recurrence rate was 18.2%, whereas 21.7% of the patients in the control group developed recurrent stones. Seventy-eight per cent of these patients also had a recurrence of biliary pain. By life-table analysis we had, after a follow-up period of 24 months, a stone recurrence rate of 25% (+/- 11) in the aspirin group and 34% (+/- 14) in the control group. Our results indicate that recurrence prophylaxis remains one of the central questions in ESWL. In this preliminary study, 100 mg of aspirin daily was not able to reduce the recurrence rate after successful ESWL. Further studies will have to show whether higher doses of aspirin or other ways of preventing gallstone after ESWL are possible.

Adult↗

[Results of therapeutic management of vesico-urethral and anorectal disorders in 20 patients with cauda equina syndrome].

Twenty patients (7 females and 13 males) with cauda equina lesions (12 herniated lumbar disks, 4 tumours, and 4 compression fractures of the lumbar spine), were treated according to a standardized management of their urinary and digestive symptoms, after surgery. The bladder emptying inability was managed by Crédé manoeuver facilitated by appropriate drugs completed by self intermittent catheterization. The constipation was treated by non irritant osmotic laxatives, and defecation obtained by abdominal straining, was facilitated by a suppository. All the patients recovered a sphincteric autonomy, without invalidating incontinence. Within 3 to 6 months, eleven patients improved enough bladder emptying to stop drugs and self-catheterization. None presented urinary incontinence. Within the same time, 14 had a stool daily, but medical treatment of the constipation had to be carried on in all of the 20 patients. None of the patients had incontinence for the solid stools, but only the patients who improved (spontaneously or after biofeedback therapy) the voluntary anal sphincter contraction were continent for the gaz, and liquid stools. The intermittent self-catheterization release (a complete emptying of the bladder being achieved) was more frequent after tumor treatment than after herniated disk, or compressive fracture treatment; the same release happened in case of immediate management if compared with delayed management of the urinary symptoms. Adversely, the digestive recovering was not influenced by either the etiology of the cauda equina lesions or the therapeutic management delay. Defecography demonstrated anatomical disturbances of the rectoanal apparatus such as perineal descent and/or mucosal prolapse, which could be secondary to the abdominal straining necessary to complete bladder and rectum emptying.

Adult↗

[Patient contact supported effectiveness evaluation of legal guidelines on ambulatory care].

A network of about 100 physicians (general practitioners, internists) has been introduced in Lower Saxony, Germany. The participating physicians report on a sample of their patient contacts involving frequent complaints (e.g. vertigo, leg problems, pain due to rheumatic conditions, and gastrointestinal disturbances). The project combines individual, problem-specific patient monitoring with the physicians' estimation of both the conditions under which they conduct their practice and the state of the regional health care system. A standardized questionnaire records sociodemographic variables and major reasons for the patients' visit. It also records data about diagnoses, diagnostic and therapeutic strategies and changes in therapy. In 1993 special attention was given to an assessment of recent health care cost containment legislation and its effects upon the quality of ambulatory medical care. 1400 patient contacts have been reported on in the first two surveys. Results are presented in this article.

Ambulatory Care↗

Validity of two-dimensional data obtained with the Heidelberg Retina Tomograph as verified by direct measurements in normal optic nerve heads.

The Heidelberg Retina Tomograph (HRT) was recently developed to measure two- and three-dimensional parameters of the optic disc. The instrument gives measurement results on an absolute scale; the validity of the scaling has never been proven in the living eye. Eight phakic eyes (eight patients) scheduled for subsequent pars plana vitrectomy were selected for this study. The optic disc was scanned using the HRT. During vitrectomy, the disc was measured directly using a modified retina spatula that had a 2.5-mm scale with a grading of 1/10 mm at the tip. The measurement was recorded with a high-resolution video system adapted to a Zeiss operation microscope. We used a vitrectomy contact lens with a flat surface. First we looked for reference points along the disc margin that could be clearly identified on both images, then we determined the distances between these points. Calculations from HRT data followed according to the software used in this instrument. Calculations from video images were related to the grading of the intraocular scale instrument. As determined using HRT software version 1.08, the mean ratio of HRT distances obtained by direct video measurements was 1.031 (SD, +/- 0.099; SE, +/- 0.035). No significant correlation between the ratio and the ametropia of the eyes could be verified (r = 0.506, P = 0.20). On average, the two-dimensional measurements of the HRT were correct. Furthermore, we used software version 1.07, which does not correct the image size depending on refraction, and found that the mean ratio of HRT distances obtained direct video measurements was 0.985 (SD, +/- 0.108; SE, +/- 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity.

OBJECTIVE: To address the issues of immunogenicity and local and systemic reactions to vaccination with influenza vaccine in patients with rheumatoid arthritis (RA). METHODS: One hundred and twenty-six patients with RA were stratified into 3 groups: (1) those with a history of vaccination with influenza vaccine within 24 months who were receiving usual therapy for RA, (2) those receiving usual therapy for RA but without prior vaccine, and (3) those receiving immunosuppressive medication or prednisone > or = 7.5 mg/day, irrespective of their prior immunization status. Within each group, patients were randomized to receive vaccine or placebo. A group of age matched, healthy controls were also vaccinated. RESULTS: During a one month followup period, adverse reactions occurred with equal frequency among patients with RA and healthy controls. Similar significant increases in titers to the vaccine were seen in all groups of patients with arthritis and in the controls. CONCLUSION: The potential increase in susceptibility to influenza and death from respiratory illness in patients with RA and the demonstrated safety and immunogenicity of influenza vaccine should require the inclusion of patients with RA in standard immunization programs.

Arthritis, Rheumatoid↗

Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation.

We have initiated a series of experiments to explore the effect of changes in density of the surface Ig receptor (mIg) on Ag:mIg interactions. We transfected into the surface Ig-negative B cell line M12.4 H and L chain constructs known to effect a 10-fold change in antibody binding affinity for the naturally occurring hapten phosphocholine (PC). Two sets of stable transfectants were generated and those expressing levels of mIg comparable to the range normally seen on splenic B cells were studied. One set expressed an unmutated VH and an unmutated VL. The second set expressed the same pair of V regions except for a single somatic change in CDR3 of VH; this substitution increases the affinity of antibody for PC from 3 x 10(4) M-1 to 3 x 10(5) M-1. Ag:mIg interactions were assessed in the transfected cell lines by measuring calcium mobilization induced by stimulation with soluble PC Ag. As expected, the mutation that increased affinity for PC increased the sensitivity of transfectants to PC Ag. Relatively small changes in receptor number had a dramatic effect in the quantity and quality of a calcium response. Significantly, we found that Ag-specific signaling could occur with only a few thousand receptors per cell. Signaling differences were most noticeable with PC protein Ag (T-dependent form) compared with PC polysaccharide Ag (T-independent form). These results suggest that the down-regulation of mIg that follows B cell activation may have evolved to assist in the selection of B cell clones with higher affinity for Ag. Furthermore, the results also provide an explanation for why selection of higher affinity clones can occur with protein Ag but only poorly so with polymeric Ag.

Animals↗