Renal pathology and premortem clinical presentation of Caucasian patients with AIDS: an autopsy study from the era prior to antiretroviral therapy.

PRINCIPLES: Renal disease in patients with HIV infection is becoming increasingly frequent. A particular form of HIV-associated nephropathy (HIVAN) has been found in patients of predominantly African-American and Hispanic origin. However, only limited data are available on renal pathology and premortem clinical presentation of kidney disease in Caucasian patients with AIDS. METHODS: To determine the prevalence, clinical presentation and aetiology of renal disease in Caucasian patients with AIDS at the time of death we have performed a prospective autopsy study with 239 patients who died of AIDS between 1981 and 1989. None of these patients had received HIV-specific antiretroviral therapy. Autopsies and histological analyses were performed on the basis of a standardised protocol. Clinical and laboratory data were gathered according to a uniform questionnaire. RESULTS: 95% of patients were of Caucasian race. 75% of all patients had extended AIDS (stage IV). Clinical signs of nephropathy prior to death were found in 36% of patients, including proteinuria (18%), abnormal urinary sediment (19.5%), and renal insufficiency (11%). Histopathological lesions were present in 43% of the autopsies, with two or more distinct structural lesions in 12.5% of patients. Of the pathological findings 28% were glomerular or vascular, 33% were non-glomerular, and 29% were combined lesions. The remaining 10% were renal infiltrations of infectious agents or neoplastic tissue. The most common findings were ischaemic changes and vascular scars (18% of patients), as well as pyelo- and interstitial nephritides (12.2%). Importantly, FSGS was present in only 1.7% of patients, and only a single African patient had classical HIVAN. CONCLUSIONS: Renal involvement in HIV disease is very common at the time of death among patients of Caucasian origin. However, classical HIV-associated nephropathy is absent in this population. These findings suggest that kidney disease affects all races and supports the hypothesis that HIVAN is specifically related to non-Caucasian ethnicity. The results reflect renal disease unaffected by HIV-specific antiretroviral therapy.

Aspirin-induced increases in soluble IL-1 receptor type II concentrations in vitro and in vivo.

This study examined the influence of low-dose aspirin on interleukin (IL)-1alpha , IL-1 receptor antagonist (IL-1ra), and soluble receptor type II (sIL-1RII) secretion in vivo and in vitro. Blood mononuclear cells were isolated from healthy young men who ingested 81 mg of aspirin on alternate days for 2 weeks and from unmedicated controls. Aspirin had minor effects on ex vivo secretion of IL-1beta and no influence on IL-1ra. In contrast, unstimulated ex vivo secretion of sIL-1RII was over twice as high by cells from aspirin-treated subjects (1115+/-123 vs. 460+/-77 pg/mL, P = 0.02). Lipopolysaccharide-stimulated sIL-1RII secretion was influenced similarly. Plasma sIL-1RII concentrations were 23% higher in aspirin-treated subjects (10.2+/-0.6 vs. 8.4+/-0.3 ng/mL, P = 0.03). In addition, cells from unmedicated subjects cultured in vitro with aspirin (10 microg/mL) secreted significantly greater amounts of sIL-1RII. Thus, low-dose aspirin therapy may prevent inflammation by increasing soluble receptor secretion, thereby preventing IL-1 from binding target cells.

Dynamic exercise shifts the operating point and reduces the gain of the arterial baroreflex in rats.

We tested the hypothesis that dynamic exercise resets the operating point and attenuates the gain of the arterial baroreflex regulation of heart rate (HR) in rats. Seven adult female spontaneously hypertensive rats (SHR) were chronically instrumented with left carotid arterial catheters. After the rats recovered, arterial baroreflex function was examined by recording reflex changes in HR in response to spontaneous changes in arterial pressure (AP) during a preexercise condition and during steady-state treadmill running at 6 and 18 m/min. Dynamic exercise at 6 and 18 m/min, respectively, reduced the spontaneous range (by 55 and 70%) and spontaneous gain (by 64 and 82%) of the arterial baroreflex control of HR. Dynamic exercise at 6 and 18 m/min, respectively, also increased the pressure at the midpoint of the spontaneous pressure range (by 7 and 12%), the spontaneous minimum HR response (by 35 and 59%), the HR at the midpoint of the spontaneous HR range (by 31 and 52%), and the spontaneous maximum HR response (by 27 and 46%). Sinoaortic denervation eliminated the relationship between AP and HR by reducing the spontaneous gain 95%. These results demonstrate that dynamic exercise shifted the operating point of the arterial baroreflex to a higher pressure and reduced the spontaneous gain in female SHR.

Long-term complete remission of melanoma liver metastases after intermittent intra-arterial cisplatin chemotherapy and surgery.

This paper presents the case of a female patient with liver metastases of a malignant melanoma showing complete remission after 10 courses of regional, intra-arterial chemotherapy with cisplatin. The drug was administered as continuous infusion for 5 days. The daily dosage amounted to 30 mg/m2. The interval between courses was 6 weeks. Nausea and vomiting were seen after each course, while pathological serum creatinine levels only appeared after the eighth course. The only lesion in the liver still visible on CT scan after chemotherapy was removed by left hemihepatectomy. Meticulous histological examination revealed a big focus of necrotic tissue without any tumour cells. At the time of publication the patient is alive and disease-free over 9 years later.

[Phenprocoumon-induced cholestatic hepatitis]. / Phenprocoumon-induzierte cholestatische Hepatitis.

HISTORY AND CLINICAL FINDINGS: A 78-year-old woman had 4 years age received phenprocoumon as prophylaxis against thromboembolism after implantation of a left total knee prosthesis. Ten weeks later she developed hepatitis with negative hepatitis serology. 6 weeks before her latest hospitalisation a right total knee implantation had been performed and she again received phenprocoumon. She was admitted now because of cholestatic jaundice with rapid deterioration of her general state. There were no significant abnormal findings other than jaundiced skin and sclerae. INVESTIGATION: Bilirubin concentration was clearly elevated to 11.5 mg/dl, and the transaminase activities were increased, together with raised gamma-GT and alkaline phosphatase levels. The Quick value was below 8%. Hepatitis serology was positive for hepatitis A antibodies, but negative for B and C antibodies. No antigens were demonstrated. The eosinophil count was elevated in the differential blood count. Sonography showed a normal-sized liver with slightly dense echo pattern, but no evidence of abscess or dilatation of the bile duct system. Liver biopsy revealed severe acute hepatitis of viral type and discrete eosinophilic infiltration. TREATMENT AND COURSE: After all medication had been discontinued, transaminase activities decreased while bilirubin concentration rose. Thus, prednisone treatment was started (initially 50 mg/d), the dose then gradually reduced. The cholestasis parameters became normal and the patient's general state was much improved so that she could be discharged. CONCLUSION: Cholestatic hepatitis is a rare side effect of phenprocoumon. The associated eosinophilia suggests the cause to be an allergic genesis in the sense of a hypersensitivity reaction.

Imaging diagnosis of sclerosing peritonitis and relation of radiologic signs to the extent of the disease.

BACKGROUND: Sclerosing peritonitis (SP) is a serious complication of chronic ambulatory peritoneal dialysis (CAPD) that is characterized by thickened peritoneal membranes, leading to impaired ultrafiltration and intestinal obstruction. The aim of this study was to analyze the radiographic signs of SP in symptomatic patients and to compare them with the histological severity of the disease. METHODS: In 14 patients with symptoms of intestinal obstruction related to SP, plain films of the abdomen, upper GI follow-through examinations, ultrasonography, and computed tomography were evaluated retrospectively. Imaging findings such as bowel motility, bowel wall and peritoneal thickness, and the presence of intraperitoneal fluid collections were correlated to the histological degree of the fibrosis. RESULTS: Signs of intestinal obstruction and disturbed motility were present in all cases. In addition, patients with histologically severe SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications, and thickened peritoneal membranes, and suffered more often from postoperative complications. CONCLUSION: The detection of characteristic radiographic signs in CAPD patients presenting with symptoms of intestinal obstruction may suggest the presence of severe SP and should lead to cautious surgical interventions.

Karyomegalic interstitial nephritis: further support for a distinct entity and evidence for a genetic defect.

Karyomegalic interstitial nephritis was first described in 1979 by Mihatsch, who was reporting three such cases. We report here four additional cases as well as two family investigations. Our findings support the association of karyomegaly and interstitial nephritis as a distinct entity. Typical clinical features are asymptomatic progressive renal failure in the third decade of life and recurrent infections, mostly of the upper respiratory tract. Histologic alterations consist of markedly enlarged and hyperchromic nuclei in many tubular epithelial cells throughout the nephron accompanied by interstitial fibrosis in the surrounding atrophic tubules. Karyomegaly is not limited to the kidneys. In one case, autopsy revealed karyomegaly in epithelial and mesenchymal cells of many other organs. However, no association of karyomegaly with further histologic damage is evident except in the kidneys. Because of the familial clustering, karyomegalic interstitial nephritis seems to be an inherited disease. Examination of the nuclear proliferation-associated structures proliferating cell nuclear antigen/cyclin, Ki 67, and p53 suggests an inhibition of mitosis in karyomegalic cells. The finding of the same HLA haplotype, A9/B35, in four of six HLA-typed cases suggests the possibility of a genetic defect on chromosome 6, which is inherited and linked to the HLA locus.

[Hemolytic-uremic syndrome following kidney transplantation: prognostic factors]. / Hämolytisch-urämisches Syndrom nach Nierentransplantation: prognostische Faktoren.

Posttransplant hemolytic uremic syndrome (P-HUS) is a rare complication following kidney transplantation and is due to thrombotic microangiopathy. The aim of the present study was to determine patients at risk for this condition and to describe the follow-up in patients who developed P-HUS. The study is based on 557 consecutive patients who underwent either renal or combined renal and pancreatic transplantation in the cyclosporin era. P-HUS occurred in 19 out of 557 patients (3.4%). The reasons for developing P-HUS were: vascular rejection in 10 patients, association with cyclosporin in 5 patients, recurrence of an original HUS in 3 patients, and a transplanted shock-damaged kidney in 1 case. Patients with retransplants, grafts procured from non-heartbeating donors, high levels of anti-HLA antibodies, high HLA-DR mismatch, and HUS or Alport syndrome as the original disease, were found to be at increased risk for developing P-HUS. One-year graft survival for the P-HUS group was 42% and 88% for patients without this complication. Despite full therapy the prognosis of a P-HUS remains poor. Therefore, prevention of P-HUS, which consists in avoidance of the combination of the risk factors mentioned above, is emphasised.

[Whipple's disease with reactive (AA) amyloidosis]. / Morbus Whipple mit reaktiver (AA-)Amyloidose.

A 59-year-old man had been known for two years to have a clearly elevated blood sedimentation reaction and intermittent arthralgia in the hand. His general condition had progressively deteriorated over the last six months, with weight loss, recurrent vomiting and constipation. At first malignant lymphoma had been suspected because numerous lymph nodes were enlarged. But a lymph-node biopsy revealed massive macrophages with PAS-positive inclusion material, diagnosed as Whipple's disease. The patient died suddenly of a heart attack on the day of diagnosis. At necropsy generalized amyloidosis with marked cardiac involvement was found. Immunohistochemically the amyloid deposits gave a strongly positive reaction to anti-AA, while other amyloid syndromes were excluded using appropriate anti-sera. This was therefore a case of reactive (AA) amyloidosis in the presence of Whipple's disease.

[The imaging diagnosis of sclerosing peritonitis (SP) following continuous ambulatory peritoneal dialysis (CAPD)]. / Bildgebende Diagnostik der sklerosierenden Peritonitis (SP) nach kontinuierlicher ambulanter Peritonealdialyse (CAPD).

Sclerosing peritonitis is a serious complication of CAPD characterised by thickened peritoneal membranes which lead to decreased ultrafiltration and intestinal obstruction. The roentgenographic signs of SP were analysed in 11 patients who underwent plain x-ray of the abdomen, follow-through examinations of the small bowel, ultrasonography and computed tomography. Results were correlated with the histological degree of SP. Besides the non-specific findings of intestinal obstruction, patients with histologically marked SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications and thickened peritoneal membranes. Due to the fact that postoperative complications often occur in patients with SP, detection of the radiological signs should lead to cautious surgical interventions and changeover to haemodialysis.

Long-term low-dose cyclosporin A in steroid dependent nephrotic syndrome of childhood.

Therapy of steroid-dependent idiopathic nephrotic syndrome is often unsatisfactory. Since 1986 we have treated nine children (six male and three female), aged 3-16 years, with cyclosporin A (CsA) during 2.0-5.2 (median 3.1) years. All had minimal change disease on renal biopsy and had previously received cyclophosphamide. Mean daily dosage of CsA was 4.1 mg/kg (range 2.7-5.8) and mean whole blood trough level was 220 ng/ml (range 141-271). The relapse rate decreased from 3.4/patient year before CsA to 0.55 on CsA. Discontinuation of CsA or reduction below 2 mg/kg daily was always followed by a relapse. The overall relapse rate, including the period with very low-dose CsA, was 0.95/patient year. Four patients required additional low-dose alternate-day prednisone. Repeat renal biopsy showed minimal change disease in eight patients and focal segmental glomerulosclerosis in one; CsA-toxicity was mild in two and moderate in one. The latter was the only patient with slightly reduced glomerular filtration rate. Two boys with delayed puberty spontaneously matured and reached expected final height. We conclude that long-term low-dose CsA is very effective and steroid-sparing. Its use is justified in selected patients, particularly in those with numerous relapses and in male patients before and during puberty, as long as renal function and CsA-toxicity are carefully monitored.

[Primary amyloidosis of the liver]. / Primäre Amyloidose der Leber.

For 2 years a 72-year-old man had suffered from nonspecific upper abdominal discomfort and hepatomegaly. The gamma-glutamate transaminase concentration was increased to 121 U/l, the erythrocyte sedimentation rate was 80 mm in the first hour. Histological examination of tissue from the enlarged liver (22 cm in the midclavicular line) revealed the diagnosis of amyloidosis. The gastric mucosa, duodenum and rectum were not involved. Two years later ascites developed; six months after this he was again hospitalized in hepatic coma. Now, for the first time, a type IgA-lambda paraprotein was demonstrated by serum immunoelectrophoresis. The patient died of slowly progressing anicteric liver failure after having been ill for a total of 4 1/2 years. At autopsy there were extensive amyloid deposits throughout the liver and spleen so that the structure of these organs was hardly recognizable. The amyloid deposits in the liver were restricted to the glomerular region, while there was no amyloid in the heart. Histochemical tests showed that the deposits were strongly positive to the anti-lambda antibody. This was thus a case of primary (AL-lambda) amyloidosis of the liver and spleen which had taken an unusually prolonged course, because the heart was not involved at all and the kidneys only slightly.

Morphological and cytogenetic aspects of renal-cell carcinoma.

The medical history of 'hypernephroma' is characterized by errors which arose from the notion of 'disseminated adrenocortical foci.' Its origin from tubule epithelia of the kidney is on the other hand to be substantiated both in morphological and in immunological terms. Many attempts to arrive at a clinically serviceable establishment of the prognosis on the basis of the morphology have proved to be inadequate for the large group of the classical forms. Only the sarcomatous tumors and the oncocytes could be classified prognostically with sufficient certainty. An attempt is made in the present study to propagate the idea that besides the histogenetic, morphologically more or less tangible characteristics, molecular biological features are also important for the biological behavior of a tumor and should be used to appraise the prognosis.

[Spontaneous kidney rupture]. / Spontane Nierenruptur.

Spontaneous rupture of the kidney may occur as a complication of various congenital or acquired renal lesions. We describe three patients with non-traumatic rupture of the kidney, recently seen in our hospital. The rupture was related to polyarteritis nodosa in one case, and in the other two respectively to urothelial carcinoma and to acquired renal cystic disease in end-stage renal disease with continuous ambulatory peritoneal dialysis. In all patients the hemorrhagic complication led to a previously unsuspected diagnosis. After nephrectomy all patients did well. While spontaneous rupture of the kidney is very rare, it is important to consider this complication in the evaluation of a corresponding clinical picture. The possible causes of renal rupture are discussed.

[Alveolar hemorrhage]. / Alveoläre Hämorrhagien.

Alveolar hemorrhage (AH) is the result of diffuse bleeding into the acinar portion of the lung. Cardinal symptoms of AH include hemoptysis, dyspnea, alveolar filling opacities on chest roentgenogram, anemia and hypoxemia. However, AH is often misdiagnosed as pneumonia or pulmonary edema at the time of initial presentation. Isolated AH may occur but is more often seen in diffuse connective tissue diseases or in rapidly progressive glomerulonephritis. - At the Medical Clinic of the University Hospital of Zurich we have diagnosed AH in 18 patients (13 males, 5 females) over the last ten years (1978-1988). In 2 patients AH occurred as an isolated symptom: once due to occupational inhalation of fumes containing trimellitic anhydride, and once as so-called idiopathic pulmonary hemosiderosis. In 16 patients AH was associated with kidney disease, including the following disorders: vasculitis and collagen vascular disorders (9), rapidly progressive glomerulonephritis (4) and Goodpasture's syndrome (3). In 5 patients the presenting symptom was AH. 9 patients presented initially with renal symptoms and in 2 patients renal and pulmonary features occurred simultaneously. 7 patients died of the underlying disease or its complications. Both patients with isolated AH have survived. In the remaining 9 patients 1 required dialysis temporarily and 4 permanently. All patients except the one with AH due to inhalation of trimellitic anhydride were treated with immunosuppressive agents. - Since the pulmonary features are similar in each of the AH syndromes, diagnosis of the underlying disorder is heavily dependent upon pathologic evaluation of diseased extrapulmonary organs. Moreover, immunologic studies are essential. Failure to diagnose or treat AH syndromes in the early stages may have lethal consequences.