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Biomedical subjects

K Sack

Publications and source records attributed to K Sack.

At least 55 records · Page 3Linked to original sources

[C-reactive protein in the urine. The differential diagnosis of renal functional disorders following kidney transplantation].

A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.

Adult↗

Beta2-microglobulinuria as an early sign of cytomegalovirus infection following renal transplantation.

The frequency of cytomegalovirus infection was studied in a prospective study of 106 kidney recipients. The detection of cytomegalovirus-immediate-early-antigen and cytomegalovirus-immunoglobulin (IgM) antibodies in serum was used as the reference method and showed that 23.6% (25/106) of all patients were infected. In addition, four urinary proteins (IgG and transferrin as glomerular markers and alpha1-microglobulin and beta2-microglobulin as tubular markers) were quantitatively measured in 24-h urine samples from all of the patients using an immunoluminometric assay (ILMA). In all cytomegalovirus infection cases a pronounced but isolated increase of urinary beta2-microglobulin excretion was observed. In 20 of 25 infected patients, the beta2-microglobulinuria occurred 1-21 days (median 5.0) earlier than the appearance of the cytomegalovirus-immediate-early-antigen in blood. Thus, it can be seen that the quantitative measurement of beta2-microglobulin in urine is useful for the early detection of cytomegalovirus infection following renal transplantation.

Biomarkers↗

[Sacroiliitis in familial Mediterranean fever].

A 15-year-old girl of Turkish descent had for one year complained of severe recurrent fever-associated deep back pains. Since she was three years of age she had suffered from repeated attacks of fever and severe abdominal pain which ceased spontaneously in 1-3 days. On physical examination the sacrum and iliosacral joints were very painful to percussion, and she limped. Radiography revealed symmetric destructive sacroiliitis. Despite the unusual location of the arthritis, the triad of fever, abdominal pain and arthritis, as well as her belonging to an ethnic "at risk" group, pointed to the diagnosis of familial mediterranean fever (FML) or recurrent hereditary polyserositis. This diagnosis was confirmed by a positive metaraminol provocation test in that infusion of metaraminol reproduced the typical pains. Collagen diseases, rheumatic disease, acute porphyria and chronic infectious processes were excluded. The sacroiliitis quickly responded to long-term administration of colchicine, 0.5 mg twice daily. The patient also has Hageman factor deficiency whose significance remains unclear.

Adolescent↗

Proteinuria after renal transplantation: diagnosis with highly sensitive silver stain in sodium dodecylsulphate-polyacrylamide gradient gel electrophoresis.

Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of urinary proteins is becoming increasingly significant in monitoring renal allograft recipients. After conventional Coomassie Blue staining, changes in renal proteinuric patterns during acute renal transplant rejection could not be seen in many cases. Discrimination between rejection and nephrotoxic side effects of cyclosporine overdosage was also not possible. We therefore examined the possible advantages of a highly sensitive silver staining technique in this study. A total of 734 urine samples obtained from 38 patients after allogenic kidney transplantation were examined by SDS-PAGE with consecutive Coomassie Blue and silver staining. Twenty-two histologically proven rejections and 20 cyclosporine overdosage episodes were diagnosed in these patients within a time period of up to 524 days after transplantation. No changes in proteinuric patterns were seen in 9 of 22 patients after Coomassie stain during rejection, and only 12 cases showed a rise of glomerular protein bands, whereas silver stain revealed an increase in 19 of 22 cases. Discrimination between cyclosporine overdosage and rejection was possible with a probability of p less than 0.001 after silver stain when using the changes in the number of glomerular protein bands as a criterion. These findings suggest that application of a highly sensitive silver stain instead of the conventional Coomassie stain after SDS-PAGE reflects considerable progress in monitoring renal allograft recipients.

Adult↗

[Beta 2-microglobulinuria in cytomegalovirus infections following kidney transplantation].

In a prospective study the occurrence of cytomegalovirus (CMV) infection was diagnosed by demonstrating CMV-immediate early antigen (IEA) in the blood in 13 out of 68 (19%) patients who had undergone renal transplantation (27 women, 41 men, mean age 46.3 [21-64] years). Twenty-four hour urine samples were collected at the same time for quantitative determination of selected marker proteins by immunoluminometric assays (IgG and transferrin as glomerular markers, alpha 1-microglobulin and beta 2-microglobulin as tubular markers). In all 13 confirmed cases of CMV infection there was an isolated rise in urinary beta 2-microglobulin excretion amounting to more than three times the normal. In 11 of the 13 cases the beta 2-microglobulinuria was noted before the CMV-IEA test became positive. This suggests that quantitative assay of beta 2-microglobulin in the urine may be of value in the early diagnosis of CMV infection--a matter of some prognostic importance--and may hence offer additional support for therapeutic decisions.

Adult↗

[Kimura disease with minimally proliferative glomerulonephritis].

A 45-year-old Turk had a year ago noticed a submandibular and a retroauricular node-like swelling, about 2 cm in diameter each, firm and freely mobile. During the preceding two months he had polydipsia and polyuria. Recently he developed a nephrotic syndrome with lower-leg oedema and proteinuria (14 g albumin in 24-hour urine). The concentrations of IgE (250 IE/ml) and IgA (745 mg/dl) were raised, and there was eosinophilia of 14%. Renal needle biopsy revealed glomerulonephritis with minimal proliferation. Excision of part of the nodular tumour revealed histologically the typical signs of Kimura's disease (eosinophilic follicular lymphadenitis of the skin; subcutaneous angiolymphoid hyperplasia with eosinophilia). During treatment with prednisolone, 20 mg daily by mouth, the clinical and biochemical findings regressed within two weeks. But eight weeks later, after dose reduction to 10 mg daily, the nephrotic syndrome recurred so that the dosage had to be increased again to 20 mg prednisolone daily. On this treatment the patient has now been symptom-free for six months. This case demonstrates the unusual association of Kimura's disease with minimally proliferative glomerulonephritis.

Angiolymphoid Hyperplasia with Eosinophilia↗

Experimental studies on the nephrotoxicity of amphotericin B in rats.

The renal effects of amphotericin B alone and in combination with cyclosporin A, tobramycin, fosfomycin, D-glucaro-1,5-lactam and verapamil were studied in rats. The parameters for nephrotoxicity were urinary loss of tubular cells and malate dehydrogenase, as well as creatinine clearance. Repeated intraperitoneal injections of amphotericin B led to an increase of urinary tubular cell elimination and malate-dehydrogenase. After co-administration of amphotericin B and cyclosporin A, the urinary loss of tubular cells increased and creatinine clearance was reduced. A combination of amphotericin B and tobramycin reduced tubular cell elimination but the creatinine clearance improved. When verapamil was combined with amphotericin B, endogenous creatinine clearance increased, though the loss of tubular cells was elevated. Furthermore, fosfomycin reduced the loss of tubular cells and improved renal functional parameters in combination with amphotericin B. In addition, D-glucaro-1,5-lactam was found to reduce the urinary loss of tubular cells induced by amphotericin B.

Amphotericin B↗

Experimental studies on the nephrotoxicity of pentamidine in rats.

Renal side-effects are frequently observed after parenteral administration of pentamidine. In this study in a rat model, the nephrotoxicity was assessed by measuring urinary loss of tubular cells, malate dehydrogenase activity and creatinine clearance. In addition, we studied the influence of other nephrotoxins such as tobramycin, amphotericin B and cyclosporin on the pentamidine-associated nephrotoxicity and proved the possibilities of reducing this toxicity by coadministration with other drugs. The tubular toxicity of pentamidine (1, 10 or 20 mg/kg daily) is dose-related and reversible. The toxicity can be reduced by coadministration of fosfomycin (1 x 500 or 2 x 250 mg/kg daily) and D-glucaro-1,5-lactam (2 x 5 mg/kg daily) and enhanced by tobramycin (2 x 2.5 mg/kg daily), amphotericin B (1 mg/kg daily) and cyclosporin (10 mg/kg daily). Furthermore, an increase in the creatinine clearance in pentamidine-treated rats can be obtained with both verapamil (2 x 1.5 mg/kg daily) and enalapril (5 mg/kg daily).

Amphotericin B↗

Osteoarthritis of the knee: comparison of radiography, CT, and MR imaging to assess extent and severity.

Although conventional radiography is the method most frequently used for monitoring progression of osteoarthritis, it may not show osteoarthritic changes of the knee until late in the disease, and it may show involvement of only one or two compartments in patients who have tricompartmental disease. We compared radiography, CT, and MR imaging for assessing the extent and severity of osteoarthritis of the knee in 20 patients. Radiography included posteroanterior weight-bearing, true lateral, and sunrise patellar projections. Axial CT scans were reformatted in sagittal and coronal planes. MR imaging consisted of spin-echo (600-800/20; 2000/60, 120 [TR/TE]), and gradient-echo (600/30, theta = 30 degrees) sequences. The severity of osteoarthritic changes was graded from 0 to 3. MR frequently showed tricompartmental cartilage loss when radiography and CT showed only bicompartmental involvement in the medial and patellofemoral compartments. In the lateral compartment, MR showed a higher prevalence of cartilage loss (60%) than radiography (35%) and CT (25%) did. In the medial compartment, CT and MR showed osteophytes in 100% of the knees, whereas radiography showed osteophytes in only 60%. Notably, radiography often failed to show osteophytes in the posterior medial femoral condyle. On MR images, meniscal degeneration or tears were found in all 20 knees studied. Partial and complete tears of the anterior cruciate ligament were found in three and seven patients, respectively. MR is more sensitive than radiography and CT for assessing the extent and severity of osteoarthritic changes and frequently shows tricompartmental disease in patients in whom radiography and CT show only bicompartmental involvement. MR imaging is unique for evaluating meniscal and ligamentous disease related to osteoarthritis.

Adult↗

Glomerular proteinuria as an early sign of renal-transplant rejection.

The introduction of cyclosporin gave rise to an additional problem in the surveillance of renal transplant patients, namely the differentiation between cyclosporin toxicity and acute transplant rejection. The development of assays for specific proteins in urine has produced a non-invasive solution to this problem. In 55 renal transplant patients the following proteins were determined daily in 24 h-urine samples: IgG, transferrin (TF), albumin, beta 2-microglobulin (beta 2-MG), retinol binding protein (RBP), alpha 1-microglobulin (alpha 1-MG) and alpha 1-antitrypsin (alpha 1-AT). All proteins were determined quantitatively using immunoluminometric assays and 10 microliters urine in dilutions from 1:1-1:100. The urinary protein excretion was related to the actual creatinine clearance as this index gave the best differentiation between normal and abnormal status. In 24 h-urine, intraindividual peaks of IgG, TF and albumin were seen regularly in acute rejection episodes. However, a peak in the "tubular" proteins (RBP, beta 2-MG, alpha 1-MG) could not be detected. After effective treatment of the rejection episode, the renal function improved and the protein excretion returned to prerejection episode levels. In bacterial infection of the urogenital tract, urinary alpha1-AT levels rose. They returned to normal after successful antibiotic treatment. In two cases of cyclosporin toxicity neither glomerular nor tubular proteins were excreted in abnormal amounts when compared with transplant patients without complications, the only changes being an increase in serum creatinine as a result of reduced renal function.

Cyclosporins↗

Danazol therapy in autoimmune hemolytic anemia associated with systemic lupus erythematosus.

We describe a patient with systemic lupus erythematosus (SLE) complicated by severe autoimmune hemolytic anemia. Therapy with corticosteroids, splenectomy, azathioprine, chlorambucil, and intravenous immunoglobulin was unsuccessful. She responded to danazol, however, with maintenance of her hemoglobin and reductions in her transfusion and corticosteroid requirement. Thus, danazol may represent an important therapeutic option in the treatment of autoimmune hemolytic anemia.

Adrenal Cortex Hormones↗

Deforming arthropathy complicating primary biliary cirrhosis.

A 53-year-old woman with concurrent systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) developed a deforming but minimally symptomatic arthropathy. The simultaneous occurrence of SLE and PBC is believed to be rare. Moreover, destructive arthritis, in the absence of serum rheumatoid factor, has not been previously reported with either disease. We review the association of liver disease with arthritis and propose a possible mechanism to account for the severe joint destruction seen in our patient.

Arthritis↗

[Acute kidney failure during psoriasis therapy with fumaric acid derivatives].

24 days after starting treatment of psoriasis with fumaric acid derivatives (0.8-1.0 g orally, plus unknown quantities locally) a 21-year-old woman developed acute oliguric renal failure with a rise of serum creatinine levels to 1094 mumol/l (12.4 mg/dl). Deterioration of renal function had been preceded by severe abdominal symptoms with nausea, vomiting and colicky pain. On admission to hospital she was dehydrated with hyponatraemia and hypokalaemia. There was glomerular microhaematuria, increased excretion of renal epithelia, and tubular proteinuria. Renal biopsy demonstrated acute tubular damage with vacuolization of proximal epithelia, dilated tubules and scattered necroses. After intermittent haemodialysis (13 courses over two weeks) renal function gradually recovered, as demonstrated at a follow-up examination four months after discharge.

Acute Kidney Injury↗

Experimental studies on nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) in rats.

The nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) were studied in an experimental rat model. Nephrotoxicity was assessed by measuring urinary loss of tubular cells and malate dehydrogenase. LY 146032 (10-250 mg/kg daily iv) led to a dose-dependent and reversible increase of cell elimination. The tubulo-toxic threshold dose is stated to be 10 mg/kg daily. Nephrotoxicity induced by LY 146032 can be reduced by coadministration of fosfomycin or D-glucaro-1.5-lactam, and enhanced by combination with tobramycin. LY 146032 accumulated in renal tissue during repeated administration. Electron microscopy revealed histopathological changes in the kidneys. Therefore the nephrotoxic potential of LY 146032 should be taken into consideration in clinical trials.

Animals↗