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Biomedical subjects

T R Welch

Publications and source records attributed to T R Welch.

At least 73 records · Page 4Linked to original sources
PubMed1987

C4 isotype deficiency in IgA nephropathy.

C4 and factor B typing were performed in 37 pediatric patients with primary IgA nephropathy. Null alleles for C4B occurred with a frequency of 26% in patients, as compared to 15% in healthy controls (NS). The phenotype of C4B deficiency (homozygous C4B null), however, was found in 16% of patients and 4% of controls (P less than 0.05). Comparison of observed C4B phenotypes with those predicted from the Hardy-Weinberg equilibrium also confirmed an excess of C4B deficiency (P less than 0.0005). In contrast, there was no evidence of distortion in the frequencies of the C4A null allele or phenotype, or of the factor B alleles. The data suggest that C4B deficiency may be one of multiple interacting factors contributing to the development of this glomerulopathy.

Adolescent↗
PubMed1987

Differences between membranoproliferative glomerulonephritis types I and III in clinical presentation, glomerular morphology, and complement perturbation.

Data for 26 patients with membranoproliferative glomerulonephritis, type I (MPGN I) and 22 with membranoproliferative glomerulonephritis, type III (MPGN III), as distinguished by glomerular ultrastructure, were analyzed to determine differences in presentation, complement perturbation, and glomerular morphology by light microscopy. MPGN III was detected with greater frequency by the chance discovery of hematuria and proteinuria in the otherwise healthy individual (MPGN III, 63%; MPGN I, 30%; P = .01) and never, in the absence of renal failure, presented with systemic symptoms such as ease of fatigue, weight loss, and pallor, as may patients with MPGN I. The more frequent detection of MPGN III by chance is evidence that its onset is insidious and that for long periods it produces no symptoms or signs. Glomerular proliferation is also less than in MPGN I. Further, in MPGN III, the complement perturbation and glomerular immunofluorescence give no evidence of classical pathway activation, for which there is abundant evidence in MPGN I. Even with severe hypocomplementemia in MPGN III, C3 nephritic factor, another cause of hypocomplementemia, is rarely detectable and then in very low concentration. The cause of the complement perturbation in MPGN III has so far escaped identification. Although these observations give evidence that MPGN III is distinct from MPGN I, there is compelling evidence from other studies that a predisposition to both types is inherited and that similar genetic factors are operative in the two types. Because their genetic basis appears to be the same, it must be concluded that despite their differences, types I and III are variants of the same disease.

Complement C3↗
PubMed1987

Cutaneous mastocytosis with bleeding: probable heparin effect.

We describe here a child with diffuse cutaneous mastocytosis whose early clinical course was complicated by recurrent episodes of severe gastrointestinal bleeding. These episodes were preceded by formation of cutaneous bullae and were associated with prolonged coagulation times. In the child reported here, it is likely that the degranulation of mast cells in the skin resulted in gastrointestinal bleeding by the dual actions of heparin producing anticoagulation and histamine producing increased vascular permeability. It is possible that our patient's symptoms were related both to increased number of mast cells and increased releasability of mediators from these cells; his clinical course suggested that an alteration of the latter occurred spontaneously over time.

Gastrointestinal Hemorrhage↗
PubMed1987

C3 alleles in diseases associated with C3 activation.

C3 genetic polymorphism was examined by immunofixation electrophoresis in 100 healthy controls and in patients with three diseases in which this complement protein appears to be involved pathogenically (IgA nephropathy 31; membranoproliferative glomerulonephritis 33; systemic lupus erythematosus 30). C3*S (0.80) and C3*F (0.20) frequencies in controls were similar to those published in the literature, as were the frequencies of the C3 phenotypes C3S (0.65), C3SF (0.29), and C3F (0.06). No patient group had frequencies which differed significantly from controls. Thus, the previously reported association between C3*F and IgA nephropathy was not confirmed, and no relationships between C3 polymorphism and systemic lupus erythematosus or membranoproliferative glomerulonephritis were recognized.

Alleles↗
PubMed1986

Major-histocompatibility-complex extended haplotypes in membranoproliferative glomerulonephritis.

Membranoproliferative glomerulonephritis is often associated with evidence of immune derangement, especially hypocomplementemia. We studied genetic markers for membranoproliferative glomerulonephritis within the major histocompatibility complex in 34 patients and their families and in 29 normal families. We examined the frequencies of extended haplotypes (combinations of alleles that tend to occur together) in patients and controls. The extended haplotype HLA-B8,DR3,SC01,GLO2(glyoxalase I 2) was observed in 9 of 68 disease-associated haplotypes (13 percent), but in only 3 of 205 controls (1 percent) (relative risk, 14.79; P less than 0.001). An extended haplotype similar except for a different glyoxalase allotype (B8,DR3,SC01,GLO1) did not occur with increased frequency, nor did any other extended haplotypes. Patients with the extended haplotype B8,DR3,SC01,GLO2 had a higher incidence of renal insufficiency than those without it (P less than 0.01). The data support the hypothesis that a specific extended haplotype of the major histocompatibility complex is associated with susceptibility to membranoproliferative glomerulonephritis, and that patients with glomerulonephritis who have this extended haplotype have a poorer prognosis for kidney survival than those without the haplotype.

Alleles↗
PubMed1986

Relationship between the component and regulatory proteins of the classical pathway C3 convertase.

A relationship was found between the sums of the component proteins of the classical pathway C3 convertase (C2 and C4) and their regulators (C4bp and 1) in 184 normal controls. The relationship was maintained in most patients with low levels of individual components resulting from congenital deficiency and urinary losses, as well as in most cord sera. On the other hand, classical pathway activation in membranoproliferative glomerulonephritis type I, systemic lupus erythematosus, hereditary angioneurotic edema, and bacteremia resulted in loss of this relationship. Patients with alternative pathway-mediated complement activation (membranoproliferative glomerulonephritis type II) had a normal relationship between the classical component and regulatory proteins. In situations in which classical pathway activation is suspected, simultaneous examination of C4, C2, C4bp, and I may be helpful.

Angioedema↗
PubMed1986

Minoxidil for control of acute blood pressure elevation in chronically hypertensive children.

Twenty-three episodes of acute elevation of BP related to renal disease in 13 chronically hypertensive children 2 to 18 years of age were treated with a single oral dose of minoxidil. All except one patient were receiving a diuretic and all but one a beta-blocking agent at the time of minoxidil treatment. The goal of lowering BP to or below the 95th percentile for age within four hours of minoxidil administration was achieved in 14 of 23 treatment episodes. The goal was achieved in nine of 11 (82%) when the dose of minoxidil was greater than or equal to 0.2 mg/kg and in five of 12 (42%) when the dose was less than 0.2 mg/kg (P less than .05). In patients treated with greater than or equal to 0.2 mg/kg of minoxidil, mean systolic and diastolic BP decreased significantly from pretreatment values within one hour. In patients receiving less than 0.2 mg/kg, mean systolic BP was never significantly reduced and mean diastolic BP did not change significantly for two hours. Adverse effects were minimal. The results indicate that minoxidil in a dose of 0.2 mg/kg in combination with a diuretic and beta-blocking agent will lower BP to safe levels in most patients with severe hypertension related to renal disease within four hours with minimal side effects.

Adolescent↗
PubMed1985

C4 uremic variant: an acquired C4 allotype.

The major histocompatibility complex (MHC)-linked complotype region includes alleles for B, C2, and C4 loci. These loci are closely linked to each other and to HLA-DR on chromosome 6. The duplicated C4 loci, C4A and B, are especially polymorphic. In seven patients with renal insufficiency, we observed a C4 variant with electrophoretic mobility between C4B2 and C4B3. Four of these patients were detected during a study of MHC markers in membranoproliferative glomerulonephritis. Complete complotype and HLA data from families of five of the seven patients demonstrated that the variant was not inherited. The pattern was revealed by immunofixation electrophoresis and also by C4-specific hemolytic overlay. In serial plasma specimens taken from one patient, the C4 variant appeared only after the patient became uremic. However, the variant could not be produced in normal plasma after incubation with C4-depleted uremic plasma. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions of immunoprecipitated C4 from these patients showed C4A and C4B alpha chains of normal molecular mass; incompletely processed forms of C4 were not observed. We believe that this variant is probably acquired in the presence of uremia and may represent the C4B2.9 allele found by Wank and co-workers in many patients with glomerulonephritis. Family studies are mandatory to distinguish genetic variants from acquired alterations in the C4 phenotype.

Alleles↗
PubMed1985

The effect of null C4 alleles on complement function.

C4 is encoded at two polymorphic genetic loci (C4A and B), and "null" or unexpressed alleles are relatively common. An increased frequency of nulls has been reported in a variety of diseases. In the present study, C4 allotypes and C4 hemolytic efficiencies (the ratios of functional to antigenic levels) were determined for a population of 75 normal unrelated individuals. Of these, 28 had three gene products (single null at C4A or B) while three had no expressed C4A products and three had no C4B products (homozygous null). Mean antigenic C4 levels correlated with the number of expressed gene products but there was a wide spread of individual values. Those homozygous null for C4A had greater, and for C4B less, hemolytic efficiency than those with four gene products. However, there was no difference in the in vitro kinetics of C3 convertase formation between homozygous null C4A or C4B individuals. Therefore, the presence of null genes for C4 does not appear to compromise complement function sufficiently to account for the reported disease associations. Some of the associations may result from the fact that null genes for C4, as part of an extended HLA haplotype, may be genetically linked to disease susceptibility.

Adult↗
PubMed1985

Components of the alternative pathway of complement in otitis media with effusion.

An evaluation of the alternative pathway of complement was undertaken in patients with otitis media with effusion (OME). Middle ear fluid (MEF) and serum specimens were obtained from 34 patients at the time of elective myringotomy for OME. Bacterial, viral, and mycoplasma cultures were made for all specimens of the fluids. Immunochemical determinations by radial immunodiffusion were performed for C3, C5, factor B, properdin, factor H, factor I, and albumin. Each patient's recent clinical course and past history were reviewed. The results of all viral and mycoplasma cultures were negative. Three of 55 bacterial cultures were positive for type B Haemophilus influenzae. All components of the alternative pathway measured were found to be present in varying amounts in MEF. When the levels of the complement components were compared to the clinical factors studied, there were no observable differences. These data suggest that components of the alternative pathway of complement are present in OME and are not useful in predicting the clinical course or outcome of this disorder.

Adolescent↗
PubMed1984

An abnormality of the fourth component of complement associated with benign recurrent hematuria.

A group of 9 children with persistent isolated hematuria in the absence of other evidence of renal disease is presented. The children represent about one third of our patients with benign recurrent hematuria and are unique in that their C4s, in a functional assay, are lower than one would expect from their immunochemical level, resulting in an abnormally low C4 hemolytic efficiency. This feature occurs in the absence of any other evidence of complement dysfunction. Similar abnormalities were not seen in patients with other hypocomplementemic renal disease or congenital C4 deficiency. The patients' C4 molecules were identical to normal in charge, mobility, antigenic configuration, and ability to participate in an immune reaction. All patients had at least one C4 null gene on genetic analysis and 3 had double null genes. A similar pattern of C4 abnormality was not found in other patients with hypocomplementemic renal disease.

Adolescent↗
PubMed1977

Clonazepam overdose resulting in cyclic coma.

Cyclic coma in a 4-year-old boy followed an ingestion of clonazepam, a new benzodiazepine, utilized in treatment of convulsive disorders. Alternation between coma and a hyperalert state occurred even after further gastrointestinal absorption had, presumably, been precluded. Laboratory identification by routine examination for benzodiazepines was unsuccessful.

Benzodiazepinones↗
PubMed1976

Recurrent urinary tract infection in girls. Group with lower tract findings and a benign course.

A group of girls is described with recurrent urinary tract infections characterized by predominantly lower tract symptoms. Clinical, laboratory, and radiography findings during the period of follow-up are presented. Infection persisted in most patients over several years. Response to medical and surgical treatment was unsatisfactory. The mean interval between the initial and most recent radiological study was 6 1/2 years. No case of renal parenchymal scarring was seen.

Anti-Bacterial Agents↗