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G S Hill

Publications and source records attributed to G S Hill.

At least 19 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↗
PubMed1989

Predictive value of renal pathology in diffuse proliferative lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group.

We tested the value of the activity (AI) and chronicity (CI) indices devised by Austin et al as predictors of outcome in lupus patients with diffuse proliferative glomerulonephritis (DPGN). Four renal pathologists independently scored the AI and CI on 84 renal biopsy specimens from patients with lupus DPGN followed for 109 +/- 74 weeks (mean +/- SD), and the mean score was compared to the development of renal failure and to adverse outcome (combined data for renal failure, death and predefined clinical stop points). Receiver operator characteristic curves were derived from a series of 2 x 2 tables in which one variable was renal failure or adverse outcome and the other variable was AI or CI dichotomized by a cut-off point. Over the entire range (0 to 10) of the CI there was no value that separated patients who developed renal failure from those who did not. The ROC curve analysis indicated that the sensitivity and specificity of the CI were too low to allow it to function as a good test. Once patients entering renal failure were identified, the mean CI approached but did not reach a significant difference when compared to the mean CI of those who did not go into renal failure (4.38 +/- 0.42, mean +/- SE vs. 3.19 +/- 0.23, P = 0.0620). The CI did not predict the adverse clinical outcomes. There was no cut-off value of the CI which separated patients who had an adverse outcome from those who did not, and this result was confirmed by ROC analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Sweet's syndrome associated with acute renal failure.

We describe two patients with Sweet's syndrome and acute renal failure requiring dialysis. One patient developed end-stage renal disease; the other died from acute renal failure. We recommend that patients with Sweet's syndrome be evaluated for concomitant renal disease and suggest that a common pathogenesis may produce cutaneous and renal lesions in some cases.

Acute Kidney Injury↗
PubMed1986

Urethral prolapse in children: insights into etiology and management.

The pathophysiology of urethral prolapse has never been clearly elucidated. Following en bloc removal of the urethra, bladder, vagina, uterus and pelvic floor tissues from a 4-year-old burn victim with urethral prolapse at the time of death and from a female newborn cadaver, careful step-sectioning of the specimens at 5 mm. intervals for histological examination was performed. The anatomical defects of urethral prolapse noted were marked eversion of the urethral mucosa, vascular congestion of the "corpus spongiosum urethrae muliebris", and a cleavage plane between the inner longitudinal and outer circular-oblique smooth muscle layers of the urethra. We propose that urethral prolapse results from poor attachments between the smooth muscle layers of the urethra in association with episodic increases in intra-abdominal pressure. A clinical review of 12 cases revealed that at least 8 (67 per cent) had antecedent episodes of marked increases in intra-abdominal pressure. Obliteration of the cleavage plane between the smooth muscle layers is important for successful treatment of this lesion.

Abdomen↗
PubMed1986

Long-term renal responses to high dietary protein in dogs with 75% nephrectomy.

It has been proposed that ingestion of large amounts of dietary protein leads to sustained renal hyperperfusion and progressive glomerulosclerosis in rats. This hypothesis was tested in dogs, with 75% reduction in renal mass, maintained for 4 years on either 56, 27, or 19% dietary protein. Twelve of 21 dogs survived 4 years, and death due to renal failure was not correlated to diet. Dogs fed 56 and 27% protein had increased GFR and CPAH before and after reduction of renal mass compared to the 19% group. A pattern of deterioration of renal function, including proteinuria, was not found in any diet group. Nine of 11 dogs, fed 56, 27, or 19% protein had minimal glomerular lesions, including mesangial proliferation, GBM irregularities, adhesions, and sclerosis. Two other dogs, fed 56% protein, had more severe glomerular lesions. No significant ultrastructural differences were found in glomeruli among the three diet groups. These results do not support the hypothesis that high protein feeding had a significant adverse effect on either renal function of morphology in dogs with 75% nephrectomy.

Animals↗
PubMed1986

Drug-associated glomerulopathies.

The renal glomeruli are vulnerable to injury by a number of drugs and other toxic agents. These agents may lead to damage by one of two basic mechanisms: direct, dose-related toxic injury; indirect, immunologically mediated injury, largely dose-independent. Proteinuria is the simplest and most important functional indicator of glomerular injury. It occurs almost immediately in direct toxic injury, but there is a latent period of weeks to months with immunologically mediated processes. Of the two mechanisms, the second is by far the more common in clinical settings. The best studied experimental agent causing direct toxic injury is the aminonucleoside of puromycin. Clinically, perhaps the most important agent is Cyclosporine A. Although this agent is usually thought of primarily as a tubular toxin, it is capable of giving rise to a microangiopathic glomerular lesion similar to that in the hemolytic uremic syndrome. The classic model for immunologic glomerular lesion is Heymann nephritis, which produces a membranous glomerulopathy. Clinically, most drug mediated glomerulopathies also take the form of a membranous nephropathy, usually with a frank nephrotic syndrome. Among the more common offenders are penicillamine, gold salts used in rheumatoid arthritis, and captopril used in hypertension. The other common type of drug-related glomerulopathy occurs as part of a lupus-like syndrome induced by a variety of drugs, including hydralazine, procainamide, and penicillamine. All of these give rise to a variety of antibodies, most prominently antinuclear antibodies, and in the more severe cases there may be lupus-like glomerular lesions as well.

Amyloidosis↗
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↗