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Biomedical subjects

K E Holley

Publications and source records attributed to K E Holley.

At least 19 recordsLinked to original sources

Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis: a clinicopathologic study.

In 51 patients with type 1 and 9 patients with type 2 membranoproliferative glomerulonephritis, we found a male predominance in both types, a wide age range but with younger patients having predominantly type 2 disease, and clinical presentations that varied and included the nephrotic syndrome, an abnormal urinalysis only, acute nephritis, and recurrent hematuria. Hypertension and impaired renal function at the time of first evaluation, which were present in more than one-third of the patients, presaged a poor prognosis; in most of these patients end-stage renal failure or worsening of renal function occurred. Acute nephritis at onset was also related to a deteriorating course and was especially frequent in patients with type 2 membranoproliferative glomerulonephritis. Retrospective analysis of treatment regimens, in which patients were given an average of 1 year of therapy with prednisone alone or combined with cytotoxic agents, showed no effect in patients who had progressive forms of the glomerulopathy.

Adolescent

Use of combined plasmapheresis and immunosuppression in the treatment of Goodpasture's syndrome.

Five consecutive patients with well-documented Goodpasture's syndrome were treated with plasmapheresis and immunosuppression. In all patients, the antiglomerular basement-membrane antibody titers decreased with treatment. In three patients, hemoptysis responded promptly to plasmapheresis. Two patients presenting with severe renal failure required chronic dialysis, and three patients who had serum creatinine levels less than 2.1 mg/dl before treatment improved or had stabilization of their renal function. We confirm that the use of plasmapheresis and immunosuppression is a promising method of treatment in some patients with Goodpasture's syndrome.

Adult

Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide.

To evaluate the effectiveness of cyclophosphamide in the treatment of lupus nephritis, we designed a prospective study of patients with diffuse proliferative lupus nephritis. Twenty-six patients received prednisone (average dose, 40 mg per day) and 24 combined prednisone (average dose, 29 mg per day) and cyclophosphamide (average dose, 107 mg per day) for six months. Thereafter, all patients received maintenance doses of prednisone. Most of the patients improved (84 per cent) after six months of initial treatment with either program. Early progression of disease, ending mainly in end-stage renal disease, was equally frequent in the two treatment groups in patients with already advanced disease. In a four-year follow-up study there was a higher incidence (P approximately 0.04) and average rate (P approximately 0.02) of clinical recurrence of nephritis in the group initially given only steroid than in the group initially given both drugs. However, the proportion of patients alive after four years with stable or improved renal function was similar in the two treatment groups.

Adolescent

Immunological donor pretreatment in combination with pulsatile preservation in cadaveric renal transplantation.

The extended experience on the efficacy of pretreating the cadaveric renal allograft donor by means of large doses of cyclophosphamide and methylprednisolone (group A, 36 kidneys) was compared with the experience regarding untreated renal allografts (group B, 32 kidneys). Kidneys in both groups were perfused by pulsatile means using cryoprecipitated plasma. There was a significant difference in allograft survival (72% in group A versus 36% in group B at 3 years by actuarial means). Also, large doses of cyclophosphamide and methylprednisolone as pretreatment did not cause any detrimental effect to the allograft kidney when used in combination with cryoprecipitated plasma and pulsatile perfusion.

Cadaver

Class of immunoglobulin deposition and prognosis in lupus nephritis.

In the three major morphologic groups of lupus nephritis--diffuse, focal proliferative, and membranous--glomerular deposition of immunoglobulins is usually a combination of IgG, IgM, and IgA and is not a good indicator of initial renal severity or outcome. In this study of 60 patients with systemic lupus erythematosus and nephritis, patients with exclusive or predominant glomerular deposition of IgG did not have more severe renal disease or a worse prognosis than those with combined IgG-IgM deposition.

Adolescent

Recurrent Goodpasture's syndrome.

A 49-year-old woman had three distinct episodes of pulmonary hemorrhage over a 11-year period separated by symptom-free intervals of 6 and 5 years. The first and third episodes were associated with mild glomerulonephritis and linear deposition of IgG along glomerular/tubular basement membranes. The first episode was associated with a rising influenza A2 titer. Investigation of the third episode revealed circulating antiglomerular basement membrane antibodies detected by radioimmunoassay but not by indirect immunofluorescence. Antilung basement membrane antibodies were detected by both direct and indirect immunofluorescence. Recovery from each hemorrhage followed blood transfusion and oxygen therapy. This case demonstrates that (1) Goodpasture's syndrome, predominantly manifest by pulmonary hemorrhage, may have circulating antibodies with greater affinity for lung membrane compared with glomerular basement membrane, and (2) the antiglomerular basement membrane antibody response is not necessarily an acute self-limited event but may be a chronic or recurrent phenomenon.

Anti-Glomerular Basement Membrane Disease

Effect of high doses of intravenous methylprednisolone and cyclophosphamide on renal homografts.

The intravenous administration of high doses of methylprednisolone and cyclophosphamide during pretreatment of the heart-beating canine and human cadaveric allograft donor has caused no observable adverse effect on renal allografts. This is in contrast to that noted when high doses of these drugs are added to the preservation perfusate in which they are not metabolized and may possibly cause renal damage.

Animals

Membranous lupus nephropathy: a clinicopathologic study.

Twenty-eight patients with SLE and distinct, well-defined renal morphologic lesions of membranous nephropathy were followed up for 4 years. These patients comprised approximately 8% of the patients evaluated for SLE during a 12-year period. The patients with membranous lupus nephropathy had typical systemic features of SLE, and most of them had positive LE cell tests and ANA, low serum complement concentrations, and mildly elevated serum antinative DNA levels. Proteniuria and microscopic hematuria were usually discovered years after systemic symptoms of SLE had developed, Only two patients had slowly progressive renal failure, and most patients continued to have proteinuria. Prednisone treatment did not influence either proteinuria or renal function. In only one patient, the renal character of the disease changed drastically, demonstrating membranoproliferative glomerulonephritis. Six patients died (21%); most of these died of cardiovascular illnesses. The relatively benign and stable renal course of membranous lupus nephropathy in patients with otherwise typical SLE suggests that the renal pathogenesis is different from that of proliferative lupus nephritis.

Adolescent

Effect of storage on recovery of cytomegalovirus from necropsy tissue.

Cytomegalovirus (CMV) was isolated from lung tissue in 8 of 55 (14-6%) necropsies on patients who had received immunosuppressive therapy. Recovery of CMV was best (14 of 16 specimens, 87%) from fresh tissue that had been processed immediately. Storage of specimens at 4 degrees C before inoculation into cell cultures slightly reduced, to 58%, the recovery of CMV. However, conventional freezing of tissue to -- 20 degrees C for four to seven days significantly reduced the recovery of CMV, to 25% (p less than 0-001). In three of eight specimens from which virus was recovered, CMV inclusion bodies were found on tracheal smears. Sixty-five percent of the virus-negative group had measurable complement-fixing antibody in blood taken at necropsy, compared with 86% in the virus-positive group. However, there was no significant differences in antibody levels in the two groups. Our study indicates that specimens submitted for CMV isolation should be sent for virus isolation as rapidly as possible and should not be frozen. The level of antibody in a single serum taken in necropsy does not correlate well with morphological or cultural evidence of active infection.

Adolescent

Immunologic mechanisms in systemic vasculitis.

Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.

Adult

Progressive lupus glomerulonephritis. Treatment with prednisone and combined prednisone and cyclophosphamide.

We report a prospective randomized study of 39 patients with systemic lupus erythematosus and progressive glomerulonephritis who were assigned to treatment groups that received either prednisone alone or prednisone and cyclophosphamide combined. They received treatment for 6 months and were then followed up for an additional 18 months. No difference in outcome was seen in the two groups at the end of 6 months. Among patients followed up for an average of 24 months, fewer individuals showed later renal progression among those treated with cyclophosphamide and prednisone than among the group treated with prednisone alone.

Biopsy

Canine kidney preservation for 24 to 72 hours. Use of intracellular-like perfusate.

For universal application and usefulness, methods of renal preservation need simplification. Recent studies using initial brief perfusion with, and storage in, an intracellular, hyperosmolar type of perfusate have suggested the feasibility of this simple method. In the present study, 49 nephrectomized dogs received 16, 19 and 14 renal autografts preserved for 24, 48, and 72 hours, respectively, by this simple method. Long-term survivors in the three groups were seven of 16, ten of 19, and seven of 14, with return to normal or near-normal function. This method of preservation offers promise for wide clinical application in the near future.

Animals

Fanconi syndrome in adults. A manifestation of a latent form of myeloma.

From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded.

Aged

Cytomegalovirus studies of autopsy tissue. I. Virus isolation.

From January through September 1973, 55 virus isolates were recovered from lung and kidney specimens from 44 (8.8%) of 502 unselected autopsy cases. Cytomegalovirus (CMV) was isolated 42 times in 34 cases (36 from lung, four from kidney, and one each from pleural and bronchial tissues). Virus isolation was approximately six times more sensitive than histologic detection of CMV infections. Major causes of death included solid malignant tumors, leukemia, lymphoma, and renal allograft rejection; 13 patients had a variety of other diseases, predominantly cardiopulmonary. CMV was recovered from more males than females. The mean age of the CMV-positive group did not differ significantly from that of the CMV-negative group. CMV-positive cases were not preselected on the basis of specimen processing time. Serologic results indicate that recovery of CMV from an autopsy case was seven times more likely when the complement-fixing antibody titer was 1:16 or more.

Autopsy

Cytomegalovirus studies of autopsy tissue. II. Incidence of inclusion bodies and related pathologic data.

Cytomegaloviruses (CMV) were recovered from lung tissue in 34 (6.8%) of 502 unselected autopsy cases. Inclusion bodies were detected in the lung in nine of these cases (26%) and in organs other than the lung in three others. Overall, the incidence of inclusion bodies in this series of 502 cases was 2.4%. Our data strongly indicate that virus isolation is more sensitive than histopathologic study in establishing the presence of CMV infection. However, CMV was not recovered from one kidney and one liver in which inclusion bodies were present, although the virus was isolated from lung. Four of five cases of renal allograft rejection were positive for both CMV and inclusion bodies. The incidence of CMV recovery and inclusion body detection in leukemia and lymphoma cases was more than twice that in cases with other diseases. CMV inclusion bodies with or without associated inflammation were found, in descending order of frequency, in the lung, kidney, liver, pancreas, adrenal gland, esophagus, prostate, testes, thyroid gland, parathyroid gland, stomach, small intestine, large intestine, and heart.

Autopsy

Time course and zonal variations of ischemia-induced myocardial cationic electrolyte derangements.

Myocardial cationic electrolytes were determined at regular time intervals up to 24 hours after coronary artery ligation in the dog. Replicate electrolyte ratios were computed for different areas of the heart at each time interval. For purposes of statistical analysis, ratios from two border areas and four areas remote from the infarct were pooled as values for ZONE B and ZONE N, respectively, and compared with those from the infarct proper, ZONE I. Ischemia-induced tissue Mg++/Ca++ changes paralleled those of K+/Na+ with respect to time course and zonal variations. In ZONE I, both K+/Na+ and Mg++/Ca++ fell precipitously during the first hour, and the falls became more gradual thereafter, approac hing those of extracellular fluid at 24 hours. Changes in ZONE B, which appeared normal histologically, followed a similar downward trend but differed in magnitude from those in ZONE I (P smaller than 0.01). Changes in ZONE N were small but did not always overlap values in sham-operated dogs. It was concluded that lowered tissue K+/Na+ and Mg++/Ca++ were sensitive, but not specific, indices of myocardial ishemia, and multiple samplings of ionic ratios were essential for proper interpretation of ischemia-induced myocardial electrolyte derangements.

Animals

Focal sclerosing glomerulonephropathy: a clinicopathologic study.

Forty cases of focal sclerosing glomerulonephropathy with nephrotic syndrome or proteinuria were studied retrospectively in regard to clinical presentation, response to steroid therapy and clinical course, and histopathology of the lesion. Morphologically there was a focal segmental and global sclerosis with subendothelial hyaline deposits, collapse of the capillary loops, intracapillary hyaline material or foam cells, filling and widening of the mesangium with mesangial matrix, focal tubular atrophy, and focal interstitial fibrosis. Thirty-four patients had been treated with prednisone; initial complete remission of the nephrotic syndrome occurred in only 4 patients and partial remission in 10. Nine of these 14 patients had nephrotic relapse or became resistant to steroids. Thirty-three percent of the patients progressed to end-stage renal failure and an additional 25 percent had impairment of renal function after a mean of 8 years from onset. Three patients received kidney allografts, and in two the disease recurred in the transplanted kidney. Focal sclerosing glomerulonephropathy associated with nephrotic syndrome or proteinuria appears to be a clinicopathologic entity characterized by resistance to steroid treatment, frequent progression to end-stage renal disease, and recurrence in the transplanted kidney.

Adolescent