Kinetics of the metal cations magnesium, calcium, copper, zinc, strontium, barium, and lead in chronic hemodialysis patients.

BACKGROUND: Dialysis patients are at risk of developing trace element imbalances. To further elucidate the origin of these potential trace element imbalances, plasma and dialysis fluids concentrations of the elements barium (Ba), calcium (Ca), copper (Cu), lead (Pb), magnesium (Mg), strontium (Sr) and zinc (Zn) of seven maintenance dialysis patients were investigated. PATIENTS AND METHODS: In each hemodialysis session 10 to 15 samples of each, whole blood and dialysis liquid before and after passing the artificial kidney were collected. Concentrations of elements were determined by inductively coupled plasma mass spectrometry following strict quality control schemes to guarantee the accuracy and precision of the results. RESULTS: Plasma concentrations of Cu and Zn continuously increased during hemodialysis. Plasma Cu remained within the reference range for healthy adults, whereas plasma Zn was always at or below the reference range in our patients. The behavior of Ca and Sr exhibited extraordinarily strong similarities both in plasma and dialysis liquids, although concentrations of Sr are approximately 2000 times lower. Plasma Ca and Sr were at or above the upper level of the reference range. Plasma Mg concentrations decreased during clinical treatment, but were at the end of dialysis still more than 50% higher than the high end of the reference range. Although concentrations of Ba in dialysis fluids were approximately 10 times lower than in plasma, plasma Ba concentrations (approximately 23 microg/l) were significantly elevated compared to plasma Ba of healthy adults. Initial concentrations of Pb in plasma (0.74 microg/l) were increased by approximately 15% during the clinical treatment and were always higher than the high limit of the reference range. Dialysis liquids had approximately the same Pb concentrations (0.5 to 1.3 microg/l) as found in the plasma of our patients but with higher concentrations at the inlet of the dialyzer. CONCLUSION: This study could give an insight into the kinetics of trace element concentrations during dialysis, the clinical relevance of which needs to be further elucidated.

Long-term changes of plasma trace element concentrations in chronic hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients are at risk of developing trace element imbalances. METHODS: The 12 trace elements Cd, Co, Cs, Cu, La, Mg, Mo, Pb, Rb, Sr, Tl and Zn were determined in the plasma (n = 52) of 6 chronic HD patients before and after HD sessions by inductively coupled plasma mass spectrometry. Plasma trace element concentrations were monitored for 6 months. Baseline data have been compared to the concentrations at the end of the observation period to identify a potential reduction or accumulation of trace elements in HD patients. RESULTS: Plasma Cd, Co and Pb levels were about 10 times higher than in healthy adults. Concentrations of Co and Pb increased during HD sessions, whereas plasma Co and Cd increased during the study period of 6 months. Plasma Cs, Mg, Mo and Rb continuously decreased in all patients. For plasma Cu and Zn, a statistically significant rise of their plasma concentrations during HD and during the period of 6 months could be established. Concentrations of La and Tl did not change distinctly. CONCLUSION: This study revealed that plasma trace element concentrations in HD patients are distinctly different compared to that of healthy adults. Elements such as Cs, Mg, Mo and Rb are reduced and Cd, Co and Pb are accumulated in HD patients. Further studies are needed to elucidate the clinical impact of these trace element imbalances.

Exchange of alkali trace elements in hemodialysis Patients: a comparison with Na(+) and K(+).

BACKGROUND: In the past, nephrologists have been troubled by electrolyte disturbances and consequently focused their attention on the importance of maintaining the concentrations of electrolytes within the normal range. However, information about the potential role of trace elements in chronic renal failure is scarce. METHODS: During hemodialysis sessions, the concentrations of the five alkali metal cations lithium (Li), sodium (Na), potassium (K), rubidium (Rb), and cesium (Cs) have been determined in plasma and dialysis fluids of chronic hemodialysis patients by inductively coupled plasma mass spectrometry (Li, Rb, Cs) and by ion-sensitive electrodes (Na, K). Strict quality control schemes were applied to all analytical procedures to ensure accuracy and precision of the results. RESULTS: The plasma concentrations of the elements Li, Cs, Rb, and K distinctly decreased to 29, 50, 69, and 71%, respectively, of their initial values during hemodialysis. Simultaneously, the concentrations of these elements in dialysis fluids at the outlet of the dialyzer increased approximately 13-fold for Rb, 11-fold for Li, 3-fold for Cs, and 2-fold for K as compared with the inlet values. The concentrations of Na in plasma and dialysis fluids were almost identical and did not change during hemodialysis. CONCLUSIONS: Li, Rb, and Cs were depleted in hemodialysis patients, although the plasma concentrations of these trace elements still remained within the reference ranges for healthy adults. Consequently, further studies are needed to elucidate the clinical importance and long-term effects of these trace element imbalances - for example, CNS disturbances associated with diminished concentrations of Rb - in hemodialysis patients.

Post-transplantation lymphoproliferative disorder of the T-cell/B-cell type: an unusual manifestation in a renal allograft.

Marked impairment of the cellular immune system predisposes renal transplant recipients to Epstein-Barr virus (EBV) associated clinical syndromes. This can culminate in post-transplantation lymphoproliferative disorders (PTLD) and malignant lymphomas. An unusual PTLD in a 59-year-old renal transplant recipient is reported here. Sonography and CT scan revealed a hypovascular infiltrating tumor mass in the lower pole of the graft which on histopathologic examination revealed a monotonous lymphoid proliferation. T-cell receptor and immunoglobulin heavy chain gene rearrangement as well as immunohistochemical analyses demonstrated a polyclonal origin of atypical lymphatic T- and B-cells. The Epstein-Barr viral genome was detected in the mass by Southern blot analysis, and a primary EBV infection was confirmed by serologic studies. Clinical follow-up showed a tumor-free course till the patient's sudden cardiac death 14 months after the operation.

Relapse of pulmonary Mycobacterium kansasii disease associated with large-cell cancer of the lung: a case report.

A 43-year-old caucasian male diabetic presented with purulent cough and a history of weight-loss, elevated temperature, night-sweat and dyspnea. Four years previously, the patient had undergone a 12-month antimycobacterial regimen because of pulmonary mycobacterium kansasii (MK) disease of the left upper lobe (LUL). Treatment had led to complete recovery with the exception of minor fibrous residuals in the involved pulmonary segments. Chest radiograph and computed tomography (CT), performed on recent admission, revealed a dense infiltration of these residual-containing segments. Microbiological evaluation of bronchial brushings, aspirates and histology of the transbronchial biopsies indicated a relapse of pulmonary MK disease. Although antimycobacterial treatment was started immediately, therapeutic effects were only minimal and remained to be limited to the initial phase of the treatment. After four weeks of treatment, the patient's general condition worsened again. Follow-up CT of the lung showed a marked increase of the infiltration in the left apicoposterior lobe and re-bronchoscopy showed a tumorous protrusion of the bronchial wall involving the apicoposterior segment ostium, a finding which was not seen in the previous bronchoscopy. Histology of the transbronchial biopsies revealed a carcinoma mainly from large-cell type.

Thromboembolic complications after arthroscopic knee surgery. Incidence and risk factors in 101 patients.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are less common after knee arthroscopy than after elective hip and knee arthroplasties. There is no consensus on the optimal prophylaxis. In this prospective cohort study, we used ultrasound, phlebography and lung scan pre- and postoperatively to assess the incidence of thromboembolic complications in 101 consecutive patients who underwent knee arthroscopy. Preoperatively, patients were screened for typical risk factors for DVT such as age, obesity, varicose veins, contraceptive pills and nicotine abuse. All patients received a once-daily injection of 5000 IU of low molecular weight heparin, at least 12 hours prior to surgery. 5 weeks after surgery, the same screening tests were repeated. In 12 of the 101 patients either DVT or PE was diagnosed. DVT occurred in 8 cases, 4 of which were silent and 4 symptomatic. The number of PEs was 9, 8 silent and 1 symptomatic. We found no correlation between DVT or PE and individual clinical risk factors, but there was a tendency towards the development of DVT and PE, with a higher number of risk factors. We found no correlation between DVT and intraoperative risk factors such as use of a tourniquet, type of anesthesia or duration of surgery. The relatively high rate of thromboembolic events after knee arthroscopy in our study suggests the need of all patients for routine use of thromboprophylaxis, probably in a higher dose than given.

Influence of ionic shifts during dialysis on volume estimations with multifrequency impedance analysis.

During dialysis the ion concentrations in many body fluids change significantly. The influence of these changes on the accuracy of volume measurements with bioimpedance spectroscopy is investigated by the following procedure: Plasma ion concentrations and impedance spectra (5-500 kHz) are measured during six standard haemodialyses. Intracellular ion concentrations are estimated using a multi-compartment model. Intra- (ICV) and extracellular (ECV) volumes are calculated using a fluid distribution model (FDM) based on Hanai's mixture theory. The input variables of the FDM are intra- and extracellular resistance data that have been fitted from impedance spectra with a Cole-Cole model. Resistivity changes (RCs) due to concentration changes of Na+, K+, Cl-, HCO3- and unspecified intracellular ions are estimated. The FDM is corrected for the RCs. Corrected ICVs and ECVs are calculated and compared with uncorrected values. The range of relative RCs between the start and end of the dialyses is -3.2% to 1.4% in the ECV and -3.7% to 1.7% in the ICV. From the RCs, volume estimation errors of -1.0% to 1.9% (ECV) and -1.2% to 2.1% (ICV) relative to the initial values have been calculated. At the end of dialysis, the percentage of the error with respect to the volume change is < 15% for the ECV but > 20% for the ICV. Consequently, a correction of the FDM for RCs is necessary to obtain more reliable ICV data.

The influence of vascular diathesis on the localization of inflammatory foci in renal allografts with a specific antigranulocyte antibody.

Immunoscintigraphy with technetium-99m labelled BW 250/183, a murine monoclonal antibody specific for granulocytes, yielded a false-positive result in a patient suspected of having an abscess in his renal graft. To substantiate the presumption that diathesis and unspecific accumulation of the antibody may have caused this result, ten selected patients were investigated who presented with chronic vascular graft rejection but without signs of bacterial infection. Scintiscans were recorded 4 and 24h after administration of 99mTc-labelled BW 250/183. Graft-background ratios (GBRs) were calculated for each transplant. These were compared with the mean of physiological kidney-background ratios (KBRs) and with bone marrow-background ratios (BMBRs). After removal, the grafts were examined with pathological and immunohistological methods. Seven transplants demonstrated 4-h GBRs (mean: 3.9+/-1.1, P <0.001) significantly outside the range of normal KBRs while three were within the normal range (mean: 1.8+/-0.4). The relation between 4-h and 24-h GBRs varied. After 24h five GBRs still remained increased (mean: 3.2+/-1.4, P <0.05). By contrast the BMBRs decreased uniformly by 18%+/-5%. After graft removal, histopathology demonstrated no dominant granulocyte accumulations but various degrees of chronic vascular and tubulo-interstitial rejection. Immunohistochemical studies did not indicate cross-reactivity of BW 250/183. Increased GBRs of long-standing renal allografts indicate the passage of the antibody through injured vascular walls rather than the presence of granulocyte accumulations. Therefore, variability of GBRs with time reflects changes in transitory concentrations of 99mTc-labelled BW 250/183 in the tissues.

Mutant p53 expression and DNA analysis in human breast cancer comparison with conventional clinicopathological parameters.

Scientific research evaluates the prognostic importance of 53 expression and DNA flow cytometry controversially. To evaluate the prognostic relevance of mutant p53 protein overexpression and DNA flow cytometry in primary breast cancer we correlated these factors with the common prognostic parameters such as tumor size, lymph node status, grading, menopausal status and receptor status. Human breast cancer specimens from 180 previously untreated patients were collected and deep frozen. On each specimen DNA-analysis by Geohde's technique (Partec PAS II) and immunohistochemical evaluation of mutant p53 protein (PAb 1801 and 240, Novocastra Lab., Great Britain) were performed. Besides TNM- and histological classification, estrogen (ER)- and progesterone (PgR) receptor content was recorded. Overexpression of mutant p53 protein was found in 34 (19%) of all specimens. All these 34 tumors were aneuploid (p = 0.007), 86% of them were receptor negative (p 0.0001), 79% had a high tumor grade (p 0.0001), 73% a high S-phase-fraction (SPF) (p = 0.045) and 53% were premenopausal (p 0.0001). Tumor size and node status did not correlate significantly with p53 expression. 27 (15%) out of 180 carcinomas were diploid. There was a significant correlation between ploidy and the tumor grade (p = 0.003) and SPF (p 0.0001), but not correlation between ploidy and tumor size (p = 0.21), node status (p = 0.33) or receptor status (p = 0.18). A low SPF was predominantly found in tumors less than 2 cm in diameter (p 0.0001); no significant correlation was found between SPF, receptor status, tumor grade, node and menopausal status. Mutant p53 protein expression and DNA analysis in combination with common prognostic parameters might help to detect prognostically unfavourable subgroups of breast cancer patients.

Increased susceptibility for CsA-induced hepatotoxicity in kidney graft recipients with chronic viral hepatitis C.

CsA-induced hepatotoxicity is a rare disorder in renal transplant recipients when low doses are administered and whole blood trough levels of CsA are regularly monitored. However, there is controversy about the clinical value of measuring CsA-metabolites, whose contribution to immunosuppression and toxicity is not fully understood. To assess the relation between low-dose CsA therapy and hepatotoxicity, we studied 128 renal transplant recipients attending our nephrology clinic. Eight of these patients had markedly elevated liver function tests. Three patients while receiving very low doses of oral CsA (< 3.8 mg/kg of body weight) presented marked derangements of CsA metabolism with abnormally increased CsA-metabolite levels. Parent drug levels were in the normal range. All 3 patients had chronic infection with hepatitis C virus and revealed histomorphologic evidence of hepatotoxicity. Hepatic dysfunction normalized when CsA was withdrawn or reduced by 50%. It is likely that hepatitis C virus infection interferes with CsA metabolism and/or biliary CsA-excretion and thus is responsible for CsA and/or metabolite-induced hepatotoxicity despite very low doses of CsA.

[Proliferation markers, enzyme markers and oncogene expression profile of intraocular melanoma]. / Proliferationsmarker, Enzymmarker und Onkogenexpressionsprofile bei intraokularen Melanomen.

In this study 9 uveal melanomas, 1 iris melanoma and 1 conjunctival melanoma were evaluated for their proliferation activity with antibodies to KI67 protein. In addition, the distribution of glutathion-S transferase (alkaline and acid isoforms) and lysosomal cathepsin D protease was demonstrated immunohistochemically. The expression of the oncoproteins c-neu (internal and external domaine) and ras (mutated and non-mutated isoform) were also analyzed with specific monoclonal antibodies. In the case of the metastasing melanoma significant Ki67 protein expression and marked expression of the oncoproteins ras p21 and pan ras were obvious. All other melanomas showed less proliferation and enzymatic activity with a moderate expression pattern for oncoproteins. Regarding the results of the proliferation and enzymatic markers, the tumors were heterogeneous; single cells or clusters may play a role in the prognosis of the tumor if there is an intense immunohistochemical reaction. The influence of histomorphological criteria, e.g., cell subtype, seems to be minor compared to immunohistochemical criteria.

Tuberculosis of the small bowel with perforation and hematogenous spread in a renal transplant recipient.

A 41-year-old male was admitted because of acute abdomen. A flat plate of the abdomen suggested pneumoperitoneum and a chest X-ray an infiltrate in the right upper lobe. The patient was a renal allograft recipient and was on immunosuppressive therapy with azathioprine, cyclosporine and steroids. At laparatomy inflammatory thickening of the bowel wall was found in the terminal ileum with necrotic areas and two sites of perforation. The involved terminal ileum was removed together with a right hemicolectomy. The resected segment showed exudative ileal tuberculosis and fibrinous and purulent peritonitis. During the postoperative period rapid hematogenous spread of tuberculosis developed with progressive reduction of respiratory function followed by ARDS. Autopsy revealed tuberculosis in all organs including the transplanted kidney.

Sclerosing encapsulating peritonitis: differential diagnosis to peritoneal encapsulation and abdominal cocoon--a case report.

A 59 year old man presented with symptoms of partial bowel obstruction. Small bowel x-ray studies did not allow to identify the nature of the intestinal process in the upper ileum. At laparotomy small bowel encapsulation with a whitish membrane was encountered. Despite partial removal of this membrane small bowel obstruction persisted and two weeks postoperatively the patient died of peritonitis and cardiac insufficiency. Autopsy findings revealed massive fibrous adhesions in the abdomen with granulomatous inflammation. The presence of foreign body giant cells and bifringent crystals were characteristic for talcum powder. The latter suggested a causal role of an appendectomy 45 years earlier. The diagnosis of sclerosing encapsulating peritonitis as established in our patient needs to be separated from peritoneal encapsulation, a congenital malformation, and abdominal cocoon, which contains histological elements of inflammation. This case report should draw attention to these entities in the differential diagnosis and surgical management of small bowel obstruction.

Diagnostic immunohistochemistry of neuroblastic tumors.

Eighteen commercially available antibodies were applied to formalin-fixed, paraffin-embedded neuroblastomas (NBLs, n = 20), ganglioneuroblastomas (GNBLs, n = 7), and ganglioneuromas (GNs, n = 7) to assess their reliability as markers for neuroendocrine differentiation and degree of tumor cell maturation. Incubations with a monoclonal antibody to neuron-specific enolase resulted in positive reactions in all tumors, with consistently strong staining intensities in moderate and well-differentiated NBLs, GNBLs, and GNs. Antibodies to dopamine beta-hydroxylase and protein gene product (PGP) 9.5 reacted with all tumors except two NBLs. Among the antibodies directed to chromogranins and related proteins, HISL19 was most reliable (33/34) followed by endocrine granule constituent (EGC) (30/34), chromogranin A (LK2H10) (21/34), and chromogranin A + B (CGA + B) (19/34), in proving the existence of endocrine granules in tumor cells and Neurofilament (70 + 200 kD) immunoreactivity was demonstrated in all tumors except two undifferentiated NBLs. S-100 protein-immunoreactive cells were visualized with increasing frequency in highly differentiated GNBLs and GNs, whereas Leu 7 immunoreactivity was restricted to ganglioneuromas. We conclude that antibodies directed to neuron-specific enolase, HISL19, dopamine beta-hydroxylase, neurofilaments, EGC, LK2H10, and leucocyte common antigen represent markers that might be useful in the discrimination of GNBLs from non-neuroendocrine round and small cell tumors in routinely processed tissue. Antibodies to neuron-specific enolase, PGP 9.5, different chromogranins, neurofilaments, vasoactive intestinal peptide (VIP), and S-100 protein may help to determine the grade of tumor cell maturation.