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G S Hill

Publications and source records attributed to G S Hill.

17 recordsLinked to original sources
PubMed1992

Role of pathology indices in the management of severe lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group.

The principal value of the renal biopsy in patients with SLE is as a therapeutic guide. Although semiquantitative indices of nephron loss (chronicity = CI) and acute potentially reversible inflammation (activity = AI) are reported by some to have separate values from traditional classifications of glomerular pathology as predictors of outcome and therapeutic guides, this point remains controversial. We have tested the predictive value of the AI and CI in a large group of patients with severe lupus glomerulonephritis (SLE GN) and a mean follow-up of 281 weeks +/- 116 (mean +/- SD). A total of 86 patients entered into the study of plasmapheresis in severe SLE GN by the Lupus Nephritis Collaborative Study Group, and long-term follow-up was available in 83. The predictive value of the AI and the CI was described over the entire range of cut-off points by the method of receiver operator characteristics (ROC). ROC analysis demonstrated that there was no level of either AI or CI that predicted the outcome of death or renal failure with sufficient sensitivity and specificity to be useful in the individual patient. The CI signifies renal damage and nephron loss, whereas the AI describes potentially reversible pathology. Neither the CI nor the AI taken by itself predicts individual outcomes of renal failure or death in patients with aggressively treated SLE GN. Since the indices fail to identify the patient whose disease will progress to renal failure, they are both insufficient as therapeutic guides and add little to the management of the patient with severe SLE GN.

Adult↗
PubMed1992

Adrenalectomy ameliorates ablative nephropathy in the rat independently of corticosterone maintenance level.

The roles of the adrenal gland and of dietary protein level in ablative nephropathy in the rat were examined by comparing adrenalectomized rats, replaced with corticosterone at low physiological (1 and 2) or high physiological (3 and 4) levels with intact rats (5 and 6). All groups were subjected to 5/6 nephrectomy and followed 12 weeks on a regular diet (2, 4 and 6) or a reduced protein diet (1, 3 and 5). Groups 1, 2, 5 and 6 all grew at the same rate but groups 3 and 4 grew less, though food intake was nearly the same in all. Higher dietary protein, higher corticosterone maintenance level, and the presence of intact adrenal glands all increased proteinuria significantly. Extracellular fluid volume (82Br space) was identical in all groups at 8 and 12 weeks, because the animals were given a choice of water or saline to drink. Mortality was highest (50%) in Group 6 and lowest (11%) in Group 1, but these differences were not significant. Final inulin clearance was significantly improved by adrenalectomy when non-survivors were scored as having zero clearance, but not if the analysis was limited to survivors. It was not affected by diet or by corticosterone level. Renal histopathological scores were also improved significantly by adrenalectomy and by protein restriction, but were not influenced by corticosterone level. Thus adrenalectomy and dietary protein restriction independently ameliorate ablative nephropathy, but corticosterone replacement level has no effects, except on proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Induction of specific tolerance to class I-disparate renal allografts in miniature swine with cyclosporine.

Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag----ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration of an immunosuppressive agent capable of inhibiting lymphokine production during this period to lead to the induction of tolerance to class I MHC antigens in two-haplotype class I mismatched renal allografts (i.e., gg----dd), which are otherwise uniformly and acutely rejected. This hypothesis was tested in eight two-haplotype class I disparate, class II matched donor-recipient pairs, in which recipients were treated with cyclosporine 10 mg/kg, i.v. q.d. for 12 days. This protocol led to the induction of long-term (greater than 100 days) specific tolerance in 100% of recipients, as compared with control animals that rejected grafts in 13.7 +/- 0.9 days (P less than 0.0001). The specificity of tolerance was assessed both in vivo with subsequent skin grafts and in vitro by mixed lymphocyte response (MLR) and cell-mediated lymphocytotoxicity (CML). Survival of donor-specific skin grafts was prolonged compared with skin grafts bearing third-party class I antigens (19.5 +/- 2.0 versus 11.5 +/- 2.0 days, n = 4, P less than 0.05). Tolerant recipients had markedly diminished or absent anti-donor MLR and CML responses, but maintained normal reactivity to third party. Four of eight CsA-treated recipients showed detectable levels of anti-donor IgM, while none demonstrated the presence of anti-donor IgG, which was found in all rejecting controls.

Animals↗
PubMed1991

The failure of skin grafting to break tolerance to class I-disparate renal allografts in miniature swine despite inducing marked antidonor cellular immunity.

Long-term specific tolerance to one haplotype class I plus minor antigen disparate renal allografts develops without exogenous immunosuppression in approximately 35% of miniature swine (n = 128). Previous studies have suggested that this phenomenon is related to limited class I-specific helper T cell activity as evidenced by the failure of antibody class switching in vivo and the ability of exogenous interleukin 2 to elicit antidonor responses in vitro. To determine whether tolerance could be broken by inducing antidonor reactivity with donor antigen and a source of T cell help, multiple skin grafts bearing donor class I plus third-party class II antigens were placed on tolerant animals. Skin grafts were placed at least 3 months after the kidney transplant, at which time all recipients had normal renal function as measured by blood urea nitrogen and serum creatinine. First-set rejection of skin grafts by SLAad and SLAdd hosts occurred in 11.8 +/- 1.1 days (mean +/- SEM, n = 6) and in 9.3 +/- 0.9 days (n = 4), respectively. Coincident with skin rejection, most animals developed a transient rise in BUN to 62 +/- 11 mg/dl (n = 10) and a similar rise in Cr to 4.9 +/- 1.2 mg/dl (n = 10), with normal levels returning in all animals within two weeks. Subsequent skin grafts with the same disparity did not undergo second-set rejection and did not induce BUN or Cr elevations. Prior to skin grafting, animals showed no antidonor activity in mixed lymphocyte reaction or cell-mediated lymphocytotoxicity assays. After two skin grafts, all animals developed donor-specific CML and secondary MLR responses, and additional skin grafts amplified this cellular immunity. Development of marked antidonor immunity without a break in tolerance suggested that either graft adaptation or local suppression might be involved in maintaining tolerance to class I MHC antigens. In preliminary studies, an immunized SLAad animal and an immunized SLAdd animal were retransplanted with kidneys MHC matched to their first allografts. In both cases, the second graft was accepted permanently without immunosuppression, suggesting that graft adaptation is not necessary for the maintenance of tolerance to renal allografts in miniature swine.

Animals↗
PubMed1978

An unusual variant of membranous nephropathy with abundant crescent formation and recurrence in the transplanted kidney.

A patient with what initially appeared to be a typical membranous nephropathy had a progressive course to renal failure, nephrectomy, and transplantation. The nephrectomy specimen revealed abundant glomerular crescents and capsular synechiae. Post-transplantation the patient again developed a membranous nephropathy with florid crescents. Radioimmunoassay and indirect immunofluorescence tests failed to reveal anti-glomerular basement membrane antibody in the serum or kidney. It appears that there is a form of membranous nephropathy with crescent formation, unrelated to anti-GBM antibody, which has the capacity to recur after transplantation.

Adult↗
PubMed1977

Segmental gastric antral resection in experimental peptic ulceration.

In using the technique of histamine in beeswax peptic ulceration in dogs, these experimental preparations were studied as to their efficacy to protect against ulceration: laparotomy controls; bilateral truncal vagotomy and pyloroplasty; a 50 per cent gastrectomy and vagotomy plus a Billroth II gastrojejeunostomy; a 50 per cent segmental resection of the gastric antrum and corplus plus bilateral truncal vagotomy and pyloroplasty; a 75 per cent gastrectomy and Billroth II gastrojejeunostomy, and a 75 per cent segmental resection of the gastric antrum and corpus and bilateral truncal vagotomy and pyloroplasty. Only a 75 per cent gastrectomy Billroth II and a 75 per cent segmental resection of the antrum and corpus plus vagotomy and pyloroplasty consistently protected against histamine in beeswax induced ulceration.

Animals↗
PubMed1977

Tubulointerstitial nephritis and glomerulonephritis in Brown-Norway rats immunized with heterologous glomerular basement membrane.

Tubulointerstitial nephritis and glomerulonephritis were produced in Brown-Norway rats (BN) by a single immunization with 2 mg of lyophilized bovine glomerular basement membrane. Tubulointerstitial nephritis was evident before glomerulonephritis. Antibody first bound to tubular basement membranes (TBM), and then the renal cortex was infiltrated with inflammatory cells. The TBM was split, and many renal tubules, especially proximal tubules, were destroyed. Approximately 14 days after the beginning of the tubular phase, antibody was observed to be bound to glomerular basement membranes (GBM) in linear fashion. There was epithelial and mesangial cell proliferation, splitting and reduplication of GBM, crescent formation, and glomerular scarring and atrophy.

Animals↗
PubMed1976

Asymptomatic primary hyperparathyroidism.

With the advent of automated equipment for blood chemistry determinations, many patients are presenting with asymptomatic or "biochemical" hyperparathyroidism. In the present series, of 136 patients operated on for hyperparathyroidism, fifty-three were considered asymptomatic. In fifty-one patients, parathyroid pathologic conditions were found; in one patient, it is probable that an adenoma had been missed, and in the other, it is presumed that an error in diagnosis was made. We recommend that surgical exploration be considered as an acceptable alternative to watchful waiting for patients with asymptomatic hyperparathyroidism.

Adenoma↗
PubMed1976

Perfusion-related injury in renal transplantation.

The implantation and one hour post-transplant renal biopsies from three types of allograft recipients were compared with a blind grading system: (1) 25 cadaver kidneys preserved by pulsatile perfusion, (2) seven cadaver kidneys preserved by simple hypothermia following electrolyte solution flush, (3) 18 kidneys from living-related donors. Significant lesions were found only in cadaver kidneys which had received pulsatile preservation. Microscopic findings were correlated with perfusing agent, length of perfusion and its characteristics, and subsequent clinical course of the patient. Perfusion-related injury was found to be morphologically identical to hyperacute rejection, although the lesion is produced by quite different mechanisms. Pulsatile preservation appears to be associated with a spectrum of mechanical endothelial injury ranging from minute breaks visible only ultrastructurally to areas of complete denudation baring the basement membrane. The exposed collagen activates the clotting sequence resulting in platelet and fibrin deposition, whereas in classical hyperacute rejection the triggering mechanism is cytotoxic recipient antibody. The extent of perfusion-related injury correlates well with length of preservation, quantity of fibrin deposited, and, most importantly, with both the immediate and long-term post-transplant failure rate. In some patients the injury appears to be produced by cytotoxic antibodies in the plasma perfusate, which combine with antigens in the kidney ex vivo. The Ag-Ab complex activates complement and coagulation sequences in vivo after reimplantation. Early results with albumin or purified plasma fraction perfusates suggest this portion of perfusion-related injury can be eliminated. Comparison of pre- and postimplantation biopsies of the kidneys preserved by simple hypothermia or by pulsatile preservation suggests that perfusion-related injury is much more common than is true hyperacute rejection mediated by recipient cytotoxic antibodies. We suggest that the term "hyperacute rejection" be reserved for situations where significant endothelial drainage has been excluded by preimplantation biopsy and where recipient cytotoxic antibodies can be proved.

Cadaver↗
PubMed1976

Tuberculous enteritis.

Tuberculous enteritis occurs in about 2 percent of patients with pulmonary tuberculosis. Although it is uncommon in the United States, tuberculous enteritis should be considered in any patient with active pulmonary tuberculosis and abdominal complaints. Eight cases of T. enteritis have been treated at Harbor General Hospital in the last 25 years. Associated pulmonary disease was shown radiologically to be present in seven of eight patients. Findings on contrast studies of the gastrointestinal tract showed disease in six of six patients examined. In five patients, surgical operation was required for diagnosis or complications. Resection of diseased bowel with primary anastomosis was done in five patients. Although medical therapy is the mainstay in the treatment of both pulmonary and intestinal tuberculosis, one staged resection of diseased bowel with primary anastomosis is the procedure of choice for complications such as obstruction, hemorrhage or perforation.

Adult↗
PubMed1975

Alternative C3 pathway activiation in pneumococcal glomerulonephritis.

Glomerulonephritis following pneumococcal infection has been observed, but possible immunopathologic mechanisms have not been adequately explored. Multiple serologic studies as well as light, immunofluorescence and electron microscopic evaluation of kidney biopsy tissue from a 4 year old girl with pneumococcal glomerulonephritis were performed. Clinical studies at the onset of the disease showed normal serum C3 and C4 levels (third and fourth components of complement) with progression to selective C3 hypocomplementemia from days 2 to 58. A serum factor capable of breaking down C3 in normal human serum was present during the period of maximum C3 hypocomplementemia. Renal glomerular histology revealed a mesangial proliferative glomerulonephritis. Glomerular bound C3 and type 14 pneumococcal antigen were associated with similar, but less extensive, deposits of properdin. Minimal immunoglobulin M (IgM) and C4 were seen, but immunoglobulin G (IgG) and fibrinogen were absent. Ultrastructurally, subepithelial "humps" and intramembranous electron dense deposits were noted. It is hypothesized that the pneumococcal polysaccharide can activate the alternate complement pathway and may be responsible for a limited course of glomerulonephritis.

Antigens, Bacterial↗
PubMed1975

Immune injury from organ preservation. A potential cause of hyperacute rejection in human cadaver kidney transplantation.

Two pairs of plasma-perfused human cadaver kidneys were rejected in a hyperacute manner by recipients who had not previously received a transplant. Crossmatches between recipient sera and donor lymphocytes were negative in all cases. A fifth kidney was plasma-perfused but not transplanted because the perfusate was shown to be cytotoxic to donor lymphocytes. IgM and complement, but not IgG, were demonstrated in these kidneys by immunofluorescent microscopy and confirmed by further immunological studies. The IgM was broadly reactive against multiple HL-A specificities and was present in 11 percent of sera from normal, healthy male donors. It appears from our studies that cytotoxic IgM may be present in homologous plasma and cause immune injury to the kidney during ex vivo pulsatile preservation. This may be responsible for some cases of otherwise unexplained accelerated allograft rejection.

Blood Donors↗