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Biomedical subjects

D Borochovitz

Publications and source records attributed to D Borochovitz.

At least 19 recordsLinked to original sources

Focal segmental glomerulosclerosis associated with nephrotic syndrome in cholesterol atheroembolism: clinicopathological correlations.

To better characterize the heavy proteinuria occasionally described in cholesterol atheroembolic renal disease (CAE), we reviewed the clinical features and histological findings of 24 patients found at renal biopsy to have CAE. Twelve (50%) had a typical clinical presentation soon after an invasive vascular procedure. Eight (33%) underwent biopsies to evaluate proteinuria and four (17%) with insidiously developing renal failure to exclude rapidly progressive glomerulonephritis. All had usual and similar risk factors for CAE; 71% were male, 96% had peripheral vascular disease, 79% had recently undergone an invasive vascular procedure, 74% were hypercholesterolemic, and all were hypertensive. Proteinuria was higher and serum creatinine lower in the proteinuria group. In the nine (38%) nephrotic patients, serum creatinine measurements were lower (2.7 +/- 1.2 v 5.6 +/- 2.4 mg/dL), duration of renal disease to biopsy longer, and time from biopsy to dialysis greater (23.5 +/- 14.8 v 0.03 +/- 0.098 mo, P < 0.05 for all). Focal segmental glomerulosclerosis (FSGS) was observed in 15 (63%) of the biopsy specimens. Although FSGS itself did not occur more commonly in nephrotic patients, these patients did have a higher fraction of segmentally sclerosed glomeruli (0.158 +/- 0.097 v 0.026 +/- 0.050, P < 0.01). A variant of FSGS, the cellular lesion with epithelial cell prominence and capillary loop collapse, was observed in 7 of 9 (78%) patients with nephrotic-range proteinuria, but in only 3 of 12 (25%) patients with lesser degrees of protein excretion (P < 0.05). The cellular lesion was accompanied by higher mean proteinuria, 7.6 +/- 4.3 versus 2.1 +/- 2.4 g/24 hr (P < 0.01). In a larger group of patients with a similar age range as the CAE group who were identified by search of a computerized biopsy database, membranous nephropathy was the only other form of idiopathic glomerulonephritis that occurred with CAE. One of 82 (1.2%) patients with membranous nephropathy also had CAE, compared with 20 of 102 (19.6%) with FSGS (P < 0.0002, chi2). Thus, the finding of FSGS with CAE was not coincidence. Mean follow-up was 20 +/- 26 months (range, 0 to 103 months). Six patients (25%) were followed-up at least 3 years after renal biopsy. These findings indicate that extended survival in CAE is not rare and that heavy proteinuria occurs as part of a chronic disorder with distinctive histological features. Cholesterol atheroembolism with FSGS should be considered in the differential diagnosis of nephrotic syndrome in elderly patients with advanced atherosclerosis.

Aged↗

Combined effects of FK506 (tacrolimus) and cyclophosphamide on atypical B220+ T cells, cytokine gene expression and disease activity in MRL/MpJ-lpr/lpr mice.

Groups of female MRL/MpJ-lpr/lpr mice received either saline or FK506 (tacrolimus; 2 mg/kg intraperitoneally) three times weekly, cyclophosphamide (CY; 20 mg/kg) once monthly, or both drugs from 8 weeks of age. Median survival for untreated and CY-treated mice was 26 weeks, and for FK506- and FK506 + CY-treated groups was > or = 44 weeks. Severity of skin lesions and lymph node hyperplasia was markedly reduced by the drug combination, whereas either drug alone was less effective. FK506 or CY alone delayed the onset of proteinuria, but by 24 weeks all of these animals were positive. In contrast, drug combination reduced the prevalence of proteinuria to < or = 60% throughout the 44 weeks of study. Sequential monitoring of peripheral blood lymphocytes revealed that combination therapy but not monotherapy markedly reduced the proportion of atypical CD3+ B220+ and CD3+CD4-CD8- T cells. Neither FK506 nor CY affected the reduction in IL-2 and IL-4 mRNA levels observed in lymph nodes of diseased animals compared with normals. Although the drug combination also did not affect IL-2 mRNA levels, IL-4 mRNA transcripts were increased six-fold compared with saline-treated controls. IL-10 and interferon-gamma (IFN-gamma) mRNAs were induced by FK506, CY and by the drug combination. Serum levels of anti-dsDNA antibodies were reduced in all treatment groups. These data demonstrate improved efficacy of combined T and B cell-directed immunosuppression in murine lupus, associated with marked inhibition of atypical T cells and selective augmentation of IL-4 within the affected lymphoid tissue.

Animals↗

Intraoperative imprint cytology for evaluation of mediastinal lymphadenopathy.

Frozen-section (FS) analysis of mediastinal lymph nodes is commonly used in the staging of lung cancer and the evaluation of diagnostic tissue at mediastinoscopy. This approach facilitates definitive surgical intervention in a single operation and reduces costs. However, FS analysis can be labor intensive for the pathology department and time-consuming while the patient is anesthetized. Imprint cytology is more rapid than the FS procedure (average, 2 minutes versus 11 minutes per node) and allows more extensive sampling of the specimen. In this prospective study, we compared the diagnostic accuracy of imprint cytology and permanent sections on 121 mediastinal lymph nodes from 38 patients. There were no false-positive results and one false-negative result, although that patient was correctly classified based on positive cytology from another node. The sensitivity was 96.6%, the specificity was 100%, and the predictive value of a positive result was 100%, as no false-positives results were observed. The predictive value of a negative result was 98.9%, and the overall efficiency was 99.2%. These results compare favorably with those in other studies comparing the diagnostic accuracy of imprint cytology with that of FS analysis and with reported accuracy rates of FS technique. Our findings confirm the usefulness of this technique as an adjunct or substitute for FS analysis in the intraoperative pathologic evaluation of mediastinal lymphadenopathy.

Adult↗

Interstitial hypertension in human breast and colorectal tumors.

The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean +/- SD of 20 +/- 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 +/- 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 +/- 14, 15 +/- 9, and 21 +/- 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 +/- 12.5 mm Hg, n = 12), cervical carcinomas (15.7 +/- 5.7 mm Hg, n = 12), and head and neck tumors (13.2 +/- 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy.

Adult↗

Cavernous hemangioma of the adrenal gland.

Cavernous hemangiomas of the adrenal gland are rare. We report on a patient with a left adrenal hemangioma successfully treated by radical excision. The literature pertaining to this interesting pathological condition is reviewed.

Adrenal Gland Neoplasms↗

Hemorrhagic cystitis with herpes simplex virus type 2 in the bladder mucosa.

A 67-year-old woman who had underlying rheumatoid arthritis and diabetes mellitus had an 8-year history of recurrent hemorrhagic cystitis. During her most recent episode of cystitis, a specimen of urine yielded herpes simplex virus type 2 in culture. A biopsy of the bladder mucosa revealed intranuclear inclusions in multinucleated and mononuclear giant cells that were positive for herpes simplex virus type 2 by immunoperoxidase staining. She had no evidence of infection with herpes simplex virus outside her bladder.

Aged↗

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged marrow for acute lymphoblastic leukemia.

Ten patients age 13-52 years with acute lymphoblastic leukemia (ALL) in first complete remission (CR) (1), second CR (6), or relapse (3) were treated with cyclophosphamide 50 mg/kg daily x 4 and total body irradiation 3 Gy daily x 4 followed by infusion of autologous marrow purged with 4-hydroperoxycyclophosphamide (4-HC) at 100-120 micrograms/ml. The patients transplanted in relapse also received 2 mg vincristine and corticosteroids. All marrows were harvested while patients were in CR. The nucleated marrow cell dose was 3.5 +/- 0.7 x 10(8)/kg, and the CFU-GM content of the transplant was 0.4 +/- 0.5 x 10(3)/kg after purging with 4-HC. Median time from transplantation is 48 months. The neutrophil count (ANC) exceeded 1.0 x 10(9)/L at a median of 26 days and platelets exceeded 50 x 10(9)/L at 34 days. All patients were in remission after transplantation (ABMT). Five patients relapsed 2-9 months after ABMT (actuarial rate 60%). Three patients are alive and in CR at 17+, 43+, and 54+ months after ABMT. Purging marrow with 4-HC did not adversely affect engraftment, but it is not clear if the high relapse rate was due to incomplete ex vivo purging or inadequacy of the conditioning regimen.

Adolescent↗

A case of multiple pilar tumors and pilar cysts involving the scalp and back.

The case of a patient with multiple proliferating trichilemmal tumors and trichilemmal cysts of the scalp and back is discussed. The multicentric presentation of this tumor is unusual and, to our knowledge, has not been described previously. The appearance of trichilemmal cysts in association with multiple proliferating trichilemmal tumors suggests a common histogenesis of these two neoplasms. The typical presenting features, histologic description, and recommended treatment for these tumors are reviewed.

Back↗

Acute respiratory failure caused by pulmonary vasculitis after L-tryptophan ingestion.

This report describes two women who presented with severe respiratory failure and diffuse pulmonary infiltrates in the fall of 1989. Both required prolonged assisted ventilation because of severe shunt physiology. Open lung biopsies on admission revealed a small vessel vasculitis as the sole morphologic abnormality in both patients. Both responded to high dose corticosteroids. Neither patient exhibited evidence of systemic vasculitis, and neither had serologic evidence of an immune disorder. Common to both patients was ingestion of L-tryptophan. One patient exhibited several features of the eosinophilia-myalgia syndrome. The other patient did not appear to have the syndrome, but the temporal relationship between the onset of symptoms and initiation of L-tryptophan treatment was striking. The presentation of these patients alters our notions concerning the spectrum of clinical manifestations caused by this agent, and the response to methylprednisolone supports its efficacy in the treatment of this disorder.

Acute Disease↗

Cimetidine protection against alpha-amanitin hepatotoxicity in mice: a potential model for the treatment of Amanita phalloides poisoning.

The ingestion of the mushroom Amanita phalloides is associated with hepatic necrosis appearing clinically two to three days after ingestion. The mechanism of this toxicity is unknown, and no reliable antidote is available. Because of the similarity of Amanita poisoning to other toxins affecting cytochrome P450, we investigated the use of cimetidine (as a P450 cytochrome inhibitor) as an antidote against a primary toxin of the mushroom alpha-amanitin. Mice injected with alpha-amanitin and given cimetidine either prophylactically or within six hours showed histologic protection from the hepatic damage seen in control mice. Control animals displayed significant mitochondrial changes when examined by electron-microscopy, while the mitochondria of the cimetidine-treated animals were preserved, suggesting a possible site for toxin action. Further trials will be necessary before treatment of human cases with cimetidine is indicated.

Amanita↗

Membranous glomerulonephritis associated with the Guillain-Barré syndrome.

A 63-year-old white man had simultaneous onset of the Guillain-Barré syndrome and the nephrotic syndrome, three weeks after having an upper respiratory tract infection. Many granular casts were noticed in the urine sediment. Renal biopsy specimens showed early membranous glomerulonephritis and acute interstitial nephritis by light microscopy, with fine granular deposition of IgG, IgM, and C3 along the basement membrane by immunofluorescence. Electron microscopy revealed subepithelial electron-dense deposits (Stage 1 membranous glomerulonephritis). The association of these two syndromes is rare, although evidence of immunologic dysfunction has been described in both. The recent literature is reviewed and possible pathogenetic mechanisms are discussed.

Complement C3↗