Pseudolymphoma of the lung in a patient with systemic lupus erythematosus.

A 47 year old woman with systemic lupus erythematosus was found to have asymptomatic pulmonary nodules. Histologically they represented benign reactive lymphoreticular hyperplasia compatible with the diagnosis of pseudolymphoma. Immunofluorescence and electron microscopy demonstrated immunoreactants and electron-dense deposits in the alveolar and vascular walls, suggesting that an immune complex mechanism may be involved in this case.

Asymptomatic IgA nephropathy associated with pulmonary hemosiderosis.

A glomerular lesion identical to that of IgA nephropathy was demonstrated unexpectedly in a 17 year old boy who presented with clinical manifestations of pulmonary hemosiderosis and with no evidence of renal disease. This subclinical glomerular lesion would have remained undetected in this patient unless kidney tissue was obtained and examined by immunofluorescence or electron microscopy. It is unknown if the glomerular lesion in this case is causally related to pulmonary hemosiderosis.

Childhood primary aldosteronism due to an adrenal adenoma: preoperative localization by adrenal vein catheterization.

Primary aldosteronism resulting from an adrenal adenoma is rare in children. An 8 1/2-year-old girl was found to have hypertension and spontaneous hypokalemia, both detected as incidental findings. Subsequent investigations revealed inappropriately elevated levels of plasma and urinary aldosterone with suppressed plasma renin activity. Adrenal vein blood sampling and venography suggested the presence of left adrenal adenoma which was confirmed at surgical exploration and pathologic examination. All the clinical and biochemical abnormalities were corrected by the adrenalectomy. The differential diagnoses of various types of hyperaldosteronism and/or hypokalemia in such a clinical setting are discussed.

Acute tubulointerstitial nephritis attributable to indinavir therapy.

Indinavir sulfate has been reported to cause asymptomatic crystalluria and nephrolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients taking indinavir may present with asymptomatic crystalluria, nephrolithiasis with frank renal colic and obstruction, flank pain in the absence of nephrolithiasis, and dysuria or urgency. Asymptomatic crystalluria has been described as benign. Discontinuation of the drug has not been recommended in the absence of nephrolithiasis. We report two HIV-positive patients receiving indinavir who developed acute interstitial nephritis with foreign body giant cell reaction on renal biopsies. Both patients had asymptomatic crystalluria, although crystals were associated with clumps of white blood cells (WBCs) on urinalysis in one patient. Both cases show that the inflammatory response was significant enough to lead to tubular injury and acute renal impairment. Our findings suggest that asymptomatic crystalluria attributable to indinavir may illicit an inflammatory response with acute renal insufficiency, warranting monitoring of renal function, especially in patients with crystalluria.

Adenosquamous carcinoma of the pancreas.

HYPOTHESIS: Adenosquamous carcinoma of the pancreas is a rare but particularly virulent variant of invasive ductal carcinoma. This review will demonstrate the aggressive biologic activity, histopathologic features, and DNA flow cytometric characteristics of this aggressive lesion. In addition, the outcome is less favorable than in other pancreatic neoplasms, in spite of aggressive surgical and postoperative adjuvant therapy. DESIGN: A retrospective review of 6 patients treated during an 8-year period. SETTING: A major urban university tertiary referral hospital. PATIENTS: There were 6 patients with this unusual tumor seen between 1990 and 1998. There were 4 men and 2 women, all white, with a mean+/-SD age of 63.5+/-14.7 years. Symptoms were similar to those in patients with more common pancreatic malignant neoplasms. RESULTS: Four patients with tumors in the head of the pancreas had pancreatoduodenectomy, and 2 with body and or tail lesions had distal pancreatectomy and splenectomy. Pathologically, all the tumors were poorly differentiated and aneuploid, and 5 of the 6 were locally metastatic. All but 1 patient had postoperative complications, but there were no operative deaths. One half of the patients received postoperative adjuvant chemotherapy and radiation therapy. Only 1 patient is still alive at 9 months after surgery, but has known residual cancer around his portal vein noted during palliative distal pancreatectomy. CONCLUSIONS: Adenosquamous carcinoma of the pancreas is an uncommon variant of exocrine pancreatic neoplasm. It is characterized by an admixture of adenomatous and squamous cell elements and demonstrates aggressive biologic behavior. This series of 6 patients is similar to the 134 cases reported since 1907, in that survival is short despite aggressive surgical therapy. Few patients with this disease live more than 1 year. Aggressive therapy should be tempered by the realization of the uniform poor prognosis associated with this malignant neoplasm.

Rapidly progressive glomerulonephritis in adults: clinical and histologic correlations.

The clinical and histological features of 43 patients with rapidly progressive glomerulonephritis were reviewed. All had extensive crescent formation in more than 50 per cent of glomeruli. Three distinct patterns of immunofluorescent staining were identified: linear, granular, and sparse staining. Electron microscopy was valuable in corroborating the results of immunofluorescence. The prognosis was poor, with no patient regaining normal renal function regardless of treatment. Significant differences were observed among patients categorized by immunofluorescent staining. Those with a linear pattern were younger and more commonly had hemoptysis. Patients with sparse immunofluorescent staining had better renal function at the time of presentation and a longer duration of illness.

A beneficial effect of splenectomy in sickle cell anemia and chronic renal failure.

A 25-year-old black male with known sickle cell disease developed progressive chronic renal failure. Eight months after the initiation of chronic hemodialysis, he developed a rapidly-increasing transfusion requirement. The requirement was one unit of blood per week in order to maintain a hematocrit of 16%. His spleen was found, at that time, to be enlarged both on physical examination and radioisotopic scan. A radiochromium study disclosed a red blood cell half-life of 17 days. No evidence of splenic sequestration could be demonstrated isotopically. Splenectomy produced a marked decrease in the patient's transfusion need. Presently, this patient needs one unit of blood every 10 to 12 weeks to maintain a hematocrit of 18%.

Effects of chronic tubular obstruction in Necturus kidney.

The effects of chronic single nephron or mesonephric duct obstruction on renal pressures were measured in anesthetized Necturi by servo-null techniques. Glomerular capillary hydrostatic pressure (PGC) averaged 11.3 +/- 1.2 (SD) cmH2O in 18 normal nephrons. Chronic tubule blockade for 2-6 days produced no significant change in PGC. Light and electron microscopy of the juxtaglomerular apparatus (JGA) revealed juxtaglomerular cell granules widely dispersed along the course of preglomerular arterioles, a deficient macula densa, and no polkissen. The absence of a detectable change in PGC with chronic tubule blockade, i.e., a tubuloglomerular feedback response, may reflect poor development of the JGA in this amphibian.

Carcinoid tumor arising in a treated primary germ cell tumor of the mediastinum.

A 33-year-old man had a locally aggressive anterior mediastinal carcinoid tumor, manifested as an enlarging mass refractory to chemotherapy two years after initially successful treatment of a primary germ cell tumor. Ultrastructurally, the tumor contained dense-core endocrine-type secretory granules. Many mediastinal carcinoid tumors have been reported, but we found no examples of such a tumor arising as a sequel to or as a refractory component of a mediastinal germ cell tumor after initially effective therapy.

The effect of antimacrophage antiserum on immune complex glomerulonephritis.

The effect of anti-M IgG on acute IC GN was assessed in rabbits. Nephritis was induced in sensitized animals with BSA. Anti-M IgG and the other immunoglobulins given to the various groups were administered by intra-aortic injection at the orifice of the left renal artery to avoid pulmonary sequestration of the antibodies. The animals were nephrectomized on the right to permit unilateral renal perfusion. The immunoglobulins were given to the study groups every 8 hr for 4 days, which corresponded to the period of IC formation and deposition in this model. Renal arteria perfusion with anti-M IgG reduced glomerular cellularity and preserved renal function. The groups given the other immunoglobulins were not afforded the same protection.

IgA nephropathy in children: significance of glomerular basement membrane deposition of IgA.

Seventeen children with IgA nephropathy were grouped according to the absence (group I, n = 10) or presence (group II, n = 7) of glomerular basement membrane (GBM) deposition of IgA to determine whether GBM deposition of IgA correlated with laboratory or pathologic data at diagnosis or clinical status at follow-up. Children in group II had significantly (p less than 0.01) more proteinuria at diagnosis than children in group I. The percentage of glomeruli demonstrating crescent formation was significantly (p less than 0.05) higher in group II biopsies. Chronic changes of fibrous crescents, segmental sclerosis, global obsolescence, tubular atrophy, and interstitial fibrosis were also significantly (p less than 0.001) more common in group II biopsies. After a mean follow-up period of 2 years, all children in group II have persistent proteinuria of more than 1 g/24 h, and 3 of 5 have renal insufficiency (2 require dialysis). In contrast, 2 of 9 group I children have proteinuria exceeding 1 g/24 h, and only 1 has renal insufficiency. We conclude that, as compared to children with IgA localized to the mesangium, children with IgA nephropathy and GBM deposition of IgA have a higher urinary protein excretion at the time of diagnosis, more severe histologic alterations including a greater percentage of glomeruli demonstrating crescent formation, more chronic changes of segmental or global sclerosis, tubular atrophy, and interstitial fibrosis. Such children usually have persistent proteinuria and are more likely to develop progressive renal disease.

Epithelioid hemangioendothelioma of the clitoris: a case report with immunohistochemical and ultrastructural findings.

A 30-year-old woman was referred for evaluation of a small nodule of the clitoris. This was subsequently diagnosed as epithelioid hemangioendothelioma. This rare vascular tumor of intermediate malignancy has not been previously described in the vulva. The patient underwent a modified radical vulvectomy and bilateral inguinal lymph node dissection, and subsequently received photon therapy. She is alive with no evidence of disease 27 months after diagnosis.

The effect of concomitant mercuric chloride and gentamicin on kidney function and structure in the rat.

In order to define the possible effects of gentamicin on the course of experimental acute renal failure, the interaction between gentamicin and mercuric chloride was studied in rats. Acute renal failure was induced with 1 mg. of HgCl2 per kilogram intravenously. When given alone, HgCl2 produced a uniform, reproducible, nonoliguric, acute renal failure with a low mortality rate. Animals receiving gentamicin over the course of HgCl2-induced acute renal failure, in doses sufficient to produce a 1 hour postinjection serum concentration of 10 mug/ml., recovered glomerular filtration in a fashion similar to animals receiving only HgCl2(p greater than 0.05). Animals that recovered from HgCl2-induced acute renal failure were given 10 mg./Kg. of gentamicin every 4 hours for 15 days and developed proteinuria and decline in urine osmolality to the same degree as animals given gentamicin alone, but failed to develop azotemia. Nevertheless, morphological changes associated with gentamicin nephrotoxicity were found which were similar in severity to those seen with gentamicin alone. Animals pretreated with 10 mg./Kg. of gentamicin every 4 hours for 7 days were then given HgCl2. Acute renal failure in these animals was more severe than in animals receiving HgCl2 alone, as manifest by a greater degree of azotemia and death (p less than 0.05). The data indicate that in the rat the concomitant administration of gentamicin did not interfere with recovery from HgCl2-induced renal failure. Rats recovering from HgCl2-induced acute renal failure were resistant to a depression in glomerular filtration when given gentamicin. The prior administration of gentamicin enhanced the nephrotoxicity of HgCl2.

Comparative nephrotoxicities of netilmicin and gentamicin in rats.

The relative nephrotoxicities of netilmicin (Sch 20569) and gentamicin were compared in rats at doses of 30, 60, 90, and 120 mg/kg per day for 15 days. Both drugs caused proteinuria and a decrease in urine osmolality; however, netilmicin produced significantly less changes at all doses than gentamicin. Whereas gentamicin resulted in a decline in creatinine clearance at all doses, netilmicin failed to cause a decline in creatinine clearance. Renal-cortical concentrations of antibiotic at sacrifice were similar in animals receiving either drug. Light-microscopic changes were less severe with netilmicin than gentamicin. Cytosegresomes with myeloid bodies were identified electron microscopically in the kidneys of animals receiving either netilmicin or gentamicin at all doses. Electron-microscopic manifestations were similar. The data indicate that in the rat, netilmicin is distinctly less nephrotoxic than gentamicin.

Glomerular lesions in Hodgkin disease.

Three cases of Hodgkin disease with renal manifestations were studied with electron microscopy and immunofluorescence. The first patient had lipoid nephrosis that disappeared after chemotherapy for Hodgkin disease. Immune-complex nephritis was observed in the second patient who also had Sjogren syndrome. The third patient developed amyloid nephrosis five years after the onset of Hodgkin disease. Apparently, diverse lesions and mechanisms are involved in the development of the nephrotic syndrome in Hodgkin disease and the diagnosis can only be established by appropriate studies of kidney specimens.

Effect of antigen charge on immune complex interaction with glomerular cells in culture.

The effect of antigen charge on immune complex (IC) interaction with glomerular cells was evaluated using cultured rabbit glomerular cells. Rat albumin (Alb) was modified to produce a cationic charge; isoelectric point (pI) 7.4-8.0; anionic charge, pI 4.0-4.2; or left unmodified, pI 6.2-6.4. I125-IC (100 micrograms Alb in complex) was incubated with cells for 44 hr. Cationic Alb IC (CAT IC) interaction was 7 and 10 times greater than unmodified (UM) and anionic (AN) IC, 7596 +/- 613 vs 1016 +/- 176 and 746 +/- 106 pg I125-Alb/micrograms cell protein, mean +/- SE (P less than 0.01). A 10-fold excess of unlabeled CAT Alb decreased CAT IC interaction (6342 +/- 432 vs 1246 +/- 296 pg I125-Alb/micrograms cell protein, P less than 0.01) increased UM IC (981 +/- 186 vs 3994 +/- 394 pg I125-Alb/micrograms cell protein, P less than 0.01), and had no effect on AN IC. A 10-fold excess unlabeled CAT IC increased interaction of both CAT IC (7067 +/- 514 vs 37,416 +/- 3026 pg I125-Alb/micrograms cell protein) and UM IC (994 +/- 123 vs 12,922 +/- 566 pg I125-Alb/micrograms cell protein) but not of AN IC. Incubation of cells with CAT, UM, or AN Alb followed by specific antibody demonstrated increased antibody interaction with cells exposed to CAT Alb (15,212 +/- 676 vs 3866 +/- 406 and 1785 +/- 206 pg I125-IgG/microgram cell protein for UM and AN Alb, respectively).

Recovery from aminoglycoside nephrotoxicity with continued drug administration.

To examine the nephrotoxicity of prolonged gentamicin administration compared to the effect obtained when a less toxic aminoglycoside is substituted during the course of treatment, we gave gentamicin (67.5 mg/kg per day) to rats for 21 days, gentamicin for 14 days followed by either netilmicin or tobramycin for 7 days, or gentamicin for 14 days followed by saline diluent. After initial tubular, necrosis, the animals recovered from renal injury whether the drug was continued or discontinued or another drug was substituted. These data are consistent with the observation that regenerating renal epithelium is resistant to continued or additional nephrotoxic insults. These findings suggest that improvement in renal function during aminoglycoside therapy cannot necessarily be attributed to the substitution of another aminoglycoside or other therapeutic interventions.

Comparative nephrotoxicities of dibekacin, amikacin, and gentamicin in a rat model.

The nephrotoxicity of dibekacin was compared with those of gentamicin and amikacin in a rat model. The doses used were 3, 10, and 30 times the suggested human therapeutic dose on a weight basis. Indices of glomerular and tubular function failed to clearly differentiate the drugs. Dibekacin and gentamicin produced equally severe injury to the renal tissue. Slightly less damage occurred with amikacin.

Experimental aminoglycoside nephrotoxicity.

The nephrotoxicities of gentamicin and three other experimental aminoglycosides were compared at a single 60 mg. per kilogram per day dose in rats. Renal function, lysosomal enzymuria, and antibiotic concentrations in plasma, urine, and renal tissue were measured at regular intervals throughout the course of treatment. Kidney tissue was examined by light and electron microscopy in animals killed at intervals throughout the period of antibiotic administration. Proteinuria and enzymuria were early indicators of nephron dysfunction, whereas endogenous creatinine clearance declined later in the course of treatment. All animals were killed 24 hours after a previous antibiotic injection and displayed sustained renal tissue antibiotic concentrations which were 5 to 10 times higher than those in serum or urine. When assayed separately, renal cortical tissue had a fivefold greater antibiotic concentration than renal medulla. Light microscopy displayed necrosis of the pars convoluta of the proximal tubule. Electron microscopy revealed appearance of cytosegrosomes with myeloid bodies. It is possible that impaired cytoplasmic degradation of sequestered organelle membranes, resulting from aminoglycoside accumulation, is responsible for the myeloid body formation and subsequent tubular necrosis.