Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition.

AIMS/HYPOTHESIS: A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients. METHODS: For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n = 15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients. RESULTS: Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n = 10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results. CONCLUSIONS/INTERPRETATION: Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Effect of alpha 2-interferon on hairy cells and cell lines: a role for type I interferon receptors and RNA synthesis.

The binding of alpha 2-interferon to highly purified plasma membrane proteins of malignant human lymphoid cells was assessed by Western Blotting. The human hairy cell leukemia cell line JOK-1 revealed three major alpha-interferon binding proteins with molecular weights of 120, 100, and 32 kD. Pretreatment of JOK-1 cells with alpha-interferon in vitro results in a disappearance of these proteins, which is in concordance with receptor down-regulation on JOK-1 cells. In a case of T chronic lymphocytic leukemic (CLL), a differential binding pattern of two proteins with 100 and 85 kD was observed, whereas a case of B-CLL did not yield any signal detection. In addition, mononuclear cells from patients with hairy cell leukemia and CLL were found to differ with respect to the in vitro incorporation of nucleic acid precursors. alpha 2-Interferon enhances [3H] uridine incorporation into hairy cells, whereas this phenomenon can be detected in CLL cells only to a much lesser extent.

Non-radioactive detection of the rearranged BCR/ABL sequences amplified by polymerase chain reaction.

The polymerase chain reaction (PCR) is a powerful technique for the detection of the bcr/abl rearrangement in chronic myelogenous leukemia (CML). It allows the exponential amplification of the rearranged region, thus facilitating its detection. The specificity of the bcr/abl cDNA sequence amplified by PCR is most commonly verified by hybridization to a 32P-labeled probe. In this paper, an assay for the colorimetric detection of the amplified bcr/abl fragment is described, which offers several advantages over the use of radioactive probes. We adapted the PCR for synthesis and simultaneous labeling of DNA fragments with a non-radioactive steroid compound called digoxigenin. This labeling procedure was used to generate a digoxigenin-labeled internal probe for the chimeric bcr/abl mRNA. The assay described is based on the hybridization of the amplified bcr/abl sequence to the non-radioactively labeled probe and on the subsequent detection by an enzyme-linked immunoassay and enzyme-catalyzed color reaction. Using this protocol, we investigated 20 patients with CML along with six healthy individuals and two cell lines derived from patients with CML for the presence of the bcr/abl rearrangement. It is shown that the assay is both highly sensitive and specific and that it is readily applicable to the routine diagnosis of CML. In addition, the assay could be adapted to a number of clinical diagnostic uses.

The influence of ACE-inhibition on myocardial mass and diastolic function in chronic hemodialysis patients with adequate control of blood pressure.

The objectives of this study were to evaluate the specific effect of the ACE-inhibitor lisinopril on myocardial mass and diastolic function in uremic patients using a protocol designed to leave blood pressure unchanged. Nineteen hemodialysis patients (7 males; mean age: 55 +/- 13 years; mean time on dialysis: 44 +/- 35 months) received lisinopril for 6 months in addition to their preexistent antihypertensive treatment regimens (mean: 1.4 +/- 0.8 drugs). Doses of antihypertensive drugs were adjusted to keep both systolic and diastolic blood pressure stable. Nine patients were withdrawn from lisinopril treatment after 43 +/- 33 days because of hypotension (n = 4), withdrawn consent (n = 3), stroke (n = 1) and cough (n = 1). Seven of them were further studied as controls. Ten patients received 6.4 +/- 4 mg lisinopril as a mean for 6 months. Mean myocardial mass, calculated by M-mode echocardiography, was 324 +/- 103 g before, and 313 +/- 79 g after 6 months of lisinopril treatment. In the control patients, myocardial mass was 318 +/- 110 g initially, and after 6 months, it was 334 +/- 159 g. Early and late transmitral diastolic flow velocities were not significantly influenced by lisinopril. Throughout the study, both the systolic and diastolic 24-h mean blood pressure levels remained stable (systolic: before: 145 +/- 19 mmHg, at 6 months: 147 +/- 17 mmHg; diastolic: before: 87 +/- 12 mmHg, at 6 months 87 +/- 10 mmHg). Thus, no specific effect of lisinopril on regression of myocardial hypertrophy or improvement of diastolic function could be observed within a 6-month period in this small group of hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden onset of paralysis in a twenty year-old male patient.

We report on a twenty year-old male patient who presented with sudden onset of flaccid paralysis. After exclusion of central nervous system involvement, marked hypokalemia pointed to the diagnosis of hypokalemic periodic paralysis, which was completely reversible on oral and parenteral potassium substitution. A provocation test with glucose and insulin administration leading to hypokalemia and incipient paralysis of the limbs confirmed the diagnosis. Pathogenetically, this syndrome is characterized by an excessive shift of potassium ions into the muscle cells. Therapeutic measures include potassium-sparing diuretics, beta blockers, acetazolamide or diclofenamide. In less severe cases, oral potassium may be sufficient to reverse the symptoms.

[Comparison between ambulatory 24-hour blood pressure measurement and occasional blood pressure measurement in hemodialysis patients with left heart hypertrophy]. / Vergleich zwischen ambulanter 24-h-Blutdruckmessung und Gelegenheitsblutdruckmessung bei Hämodialysepatienten mit Linksherzhypertrophie.

Since 24-hour blood pressure monitoring seems to be superior to occasional blood pressure measurement as far as risk stratification is concerned, we compared the two methods in patients with secondary hypertension and left ventricular hypertrophy. In 26 haemodialysis patients (12 male, mean age 54 +/- 13 years), the mean occasional blood pressure values during haemodialysis were 147 +/- 18/82 +/- 9 mmHg, the mean 24-hour blood pressure values were 145 +/- 21/ 85 +/- 13 mmHg, during the day 145 +/- 23/86 +/- 13, during the night 143 +/- 25/81 +/- 13 mmHg. The nocturnal reduction of mean blood pressure was -3.6 +/- 7%. Both methods of blood pressure monitoring showed a significant correlation with the relevant echocardiographic parameters of left ventricular hypertrophy, cardiac mass and interventricular septum diameter. Patients with and without a nocturnal reduction in blood pressure could not be differentiated by the mean occasional blood pressure values. Therefore, 24 h ambulatory blood pressure monitoring seems warranted in this high risk group, especially to monitor antihypertensive drug therapy.

Gadolinium and nephrogenic systemic fibrosis.

Nephrogenic systemic fibrosis (NSF) is characterized by red skin areas or plaques that over several weeks successively develop to painful thickened skin with a 'woody' texture, resembling 'peau d'orange'. Starting at the extremities, it may spread to the trunk, and may progressively inhibit flexion of adjacent joints. In skin biopsies of affected areas, thickened collagen bundles, mucin deposition, and proliferation of fibroblasts and elastic fibers are seen. Originally described as nephrogenic fibrosing dermopathy (NFD) because of its primarily cutaneous manifestation, this entity was then named NSF because of systemic involvement of other organs like lungs, myocardium, or striated muscles. The pathogenesis of the disease is not yet known, but our observations suggest a close association between development of NSF and exposure to gadolinium-containing contrast agents, thereafter confirmed by other authors. Recently, gadolinium was demonstrated to be detectable in skin tissue samples of affected patients. In this short review, the development of NSF and its sequential association with the exposure to gadolinium-containing contrast agents is presented. The mechanisms likely to cause NFD/NSF are discussed.

A special technique of compound osteosynthesis of the distal humerus. A case report about extramedullary blast crisis in chronic myelogenous leukemia.

In a rare case of chronic myelogenous leukemia, extramedullary myeloblast crisis occurred in the distal humerus after 27 years. The pathological fracture was stabilized with double-plate compound osteosynthesis. The small distal fragment was stabilized without restriction of the range of movement of the elbow joint. The osteosynthesis remained stable until the patient died.

Value of flumazenil in benzodiazepine self-poisoning.

The efficacy of the benzodiazepine-antagonist flumazenil (Ro 15-1788) was evaluated in 26 patients with coma due to benzodiazepine self poisoning, alone or in combination with alcohol or other psychoactive drugs. 77% of the patients responded to the administration of a mean dose of 1.73 mg (range 0.2 to 8 mg) with immediate awakening or an improvement of at least 2 coma grades. In the patients without response (n = 3) or with minor improvement (n = 3) other psychoactive drugs turned out to be predominantly responsible for their comatose state. Adverse effects of flumazenil treatment such as altered blood pressure or increased heart rate were observed, but were generally mild. An acute benzodiazepine withdrawal syndrome was seen in 2 cases. In conclusion, flumazenil proved to be effective in the treatment of severe benzodiazepine intoxication. Beyond that, in cases of mixed overdosage or initially unknown diagnosis the antidote assisted in the clarification of the clinical condition.

[Mechanism of action of interferon-alpha 2 in hairy cells and lymphoblastoid cell lines: the significance of type I interferon receptors and RNA synthesis]. / Zum Wirkungsmechanismus von Interferon-alpha 2 bei Haarzellen und lymphoblastoiden Zellinien: Die Bedeutung von Typ-I-Interferon-Rezeptoren und RNS-Synthese.

Lymphoblastoid cells were subjected to Western Blot analysis for detection of Interferon-alpha-binding proteins. JOK-1 cells--a human hairy cell leukemia line--revealed three proteins with apparent molecular weights of 120, 100 and 32 kD, respectively. Down-regulation of the receptor was observed. A differential binding pattern of two proteins (100 and 85 kD) was observed in T-CLL, whereas no signal detection was achieved in B-CLL. Mononuclear cells from 6 patients with hairy cell leukemia and 6 patients with CLL were found to differ significantly in terms of nucleic acid precursor incorporation.

Initial subcutaneous embedding of the peritoneal dialysis catheter--a critical appraisal of this new implantation technique.

BACKGROUND: The objectives of this open non-randomized study were to evaluate the impact of a new peritoneal catheter placement technique on catheter maintenance, and complications possibly related to the access, e.g. leakage, infectious complications, or drainage failure. METHOD: In a routine clinical setting, a two-cuff swan-neck catheter was implanted surgically, but its external segment was embedded in a subcutaneous pouch initially without exit site to enable uncontaminated wound healing and tight ingrowth of the cuffs. After 4 weeks at the earliest the distal catheter tip was set free by a small incision under local anaesthesia, and CAPD was started. RESULTS: Using this technique, 26 catheters were implanted in 17 males and nine females (mean age 52.3 +/- 17.4, range 19-83 years). The catheters were buried subcutaneously for a median of 79.5 (mean +/- SD 132.2 +/- 157.2, range 28-675) days, and were activated in 21 patients. No leaks were seen, and only one abdominal wall abscess secondary to a haematoma was found. Long-term follow up (mean duration of CAPD 467.0 +/- 338.1, range 32-1320 days) revealed a very low overall incidence of infectious complications, i.e. 0.80 per patient-year (1 episode per 14.9 patient-months), and the incidence of catheter-related peritonitis amounted to 0.036 per patient-year (1 episode per 27.2 patient-years), only. However, the postoperative course was complicated by seromas in two of 26, and subcutaneous haematomas in 12 of 26 patients, five of which were revised surgically. At catheter activation, fibrin thrombi were found in nine of 21 patients and two had to be operated. Omental catheter obstruction was diagnosed in four patients, and followed by omentectomy. No relationship was seen between thrombus formation and omental obstruction and duration of subcutaneous embedment (P = 0.27 and P = 0.5 respectively) or patient age (P = 0.06 and P = 0.13 respectively; Mann-Whitney-test). There was also no relationship with primary omentectomy or haematoma. CONCLUSION: We conclude that although the very low incidence of infectious episodes favours the new technique, further improvement is necessary to decrease the unacceptable rate of perioperative complications. Subcutaneous embedding of the catheter may then be considered in patients with expected problems of wound healing, and those who wish to be prepared for peritoneal dialysis in time.

Acute leukemia with mediastinal mass, lymphadenopathy, and monocytic precursor cells.

Cell marker analysis with monoclonal antibodies (MoAb) as well as differentiation studies with the chemical inducer TPA were used to identify a population of apparently lymphoid cells as monocytic precursor cells in a patient with acute leukemia. The initial manifestation of the disease with mediastinal mass and lymphadenopathy was followed by the appearance of small lymphocyte-like blast cells in bone marrow (BM) and peripheral blood (PB). Although a lymph node biopsy revealed an infiltration with monoblasts, the leukemic cells in BM and PB were not classifiable. However, when the patient relapsed after chemotherapy with large monoblasts and again with morphologically lymphoid blast cells, the latter could be classified by treatment with TPA. After incubation with the inducer (12-48 hr) the cells became positive with the MoAB VIM-D5, showed a strong reaction with alpha-naphthyl-acetate-esterase and developed macrophage like morphology, as well as phagocytic properties. During the terminal phase of the disease, small, lymphocyte-like blast cells predominated. These cells could be classified by a panel of MoABs. They expressed myeloid determinants (VIM-D5, VIM-2, MY 9, VIM-12, VIM-13) but showed no reactivity with MoABs specific for lymphocytic cells.

Duration of first remission as an indicator of long-term survival in chronic myelogenous leukaemia.

Approximately 31 patients with chronic myelogenous leukaemia (CML) are documented in the literature who survived more than 10 years after diagnosis. We present a CML-patient whose survival of 27 years is probably the longest reported so far. The analysis of the course of disease in these patients revealed that the duration of unmaintained first remission after chemotherapy is of high prognostic significance. In 17 of 24 evaluable patients the remission lasted more than 1 year and in another five at least 6 months (mean 73.8 months, range 0-240 months). In most patients busulfan was used as initial therapy. There was no correlation between the amount of drug given and the duration of remission or survival. Other parameters such as sex, age, initial leucocyte counts, differential count, haemoglobin, platelet count or spleen size seemed to have no prognostic relevance. While approximately 25% of CML patients with typical duration of survival exhibit a Ph1 chromosome mosaicism only, this finding was present in nearly half of the long-term survivers.

[Specific therapy of acute benzodiazepine poisoning using flumazenil (Ro 15-1788)]. / Spezifische Therapie der akuten Benzodiazepinintoxikation mittels Flumazenil (Ro 15-1788).

In 20 patients with coma (grade 4: n = 7, grade 3: n = 8, grade 2: n = 2, grade 1: n = 3) due to benzodiazepine intoxication, solely or combined with alcohol or other psychoactive drugs, the effect of a specific benzodiazepine antagonist, Flumazenil (Ro 15-1788), was evaluated. In terms of coma depth, 80% of the patients responded to application of 1.96 mg Flumazenil as a mean with immediate awakening or improvement of at least two steps in coma grading. In those 3 patients, who failed to respond to Flumazenil, the history revealed amitriptyline or barbiturates to be responsible for the comatose state. The observed side-effects of Flumazenil included increase (n = 4) or decrease (n = 3) of blood pressure, increase of heart rate (n = 7), cutaneous flush (n = 1) and ventricular extrasystoles (n = 1). Agitation and generalized convulsions, each observed in 1 patient, presumably were due to an acute benzodiazepine-withdrawal rather than an intrinsic side effect of the antagonist. In conclusion, Flumazenil proved to be a potent antagonist of benzodiazepines in patients with severe coma and even may serve as a valuable diagnostic in cases of suspected benzodiazepine intoxication.

Ventricular late potentials in haemodialysis patients and the risk of sudden death.

Cardiovascular diseases account for approximately 50% of deaths in patients on chronic haemodialysis. Therefore we prospectively studied 54 consecutive patients on dialysis for the presence or absence of ventricular late potentials (LP). LP, i.e. low-amplitude potentials in the terminal part of the QRS complex, have been shown to be highly indicative of life-threatening arrhythmias and sudden death. The results were correlated with echocardiographic studies and the clinical outcome during a follow-up period of 18 months. Fifty patients were suitable for evaluation (29 males, 21 females; mean age 55 years; mean time on dialysis 32 months; coronary artery disease present in 5) Our analysis revealed LP in seven of 50 patients only. Left ventricular hypertrophy, i.e. mean wall diameter > 12 mm, was present in 78%, a compromised left ventricular function, i.e. shortening fraction < 28%, was found in 28% of the patients. With respect to echocardiographic parameters, patients with and without LP were similar. During follow-up, sudden cardiac death was observed in three of 11 patients deceased. LP were detectable in one of the three only. From the remaining six patients with LP, four are still alive, and two patients died due to atherosclerosis and pulmonary embolism. Our data underline the crucial role of sudden cardiac death in dialysis patients. Ventricular late potentials, however, are of no prognostic relevance with respect to identification of dialysis patients at risk of sudden death.

Interferon alpha-2 for hairy cell leukemia: evidence for induction of RNA synthesis in hairy cells and failure to correlate enhancement of natural killer cells with elimination of hairy cells.

The effect of human recombinant interferon alpha 2 (IFN alpha 2) on hairy cells obtained from 16 patients was evaluated. All patients promptly responded to induction of remission with 2 X 10(6) U/m2 interferon alpha 2 b, three times a week, sc. In order to achieve a more detailed insight into the mode of action of interferon in this disease, we determined the influence of IFN alpha 2 on the incorporation of radiolabeled thymidine and uridine into hairy cells. While both 3H-thymidine and 3H-uridine incorporation were unaffected by IFN alpha 2 in a 3-hour incubation period, a significant increase in uridine incorporation into hairy cells, but not CLL cells, was observed after 24 h. Cell surface marker analysis performed with monoclonal antibodies did not reveal a quantitative alteration of the immunophenotype of hairy cells in vitro. In addition, natural killer cells, assessed by monoclonal antibodies and a cytotoxicity assay against K 562 cells, were found to be decreased in 9 out of 10 patients prior to therapy. Although IFN alpha 2 could stimulate natural killer cells in vivo, we did not find a consistent correlation between the activation of these cells and the response to therapy. We conclude, therefore, that NK cells play no major role in the regression of hairy cells. Furthermore, IFN alpha 2 does not alter antigenic determinants in vitro, but leads to an enhanced incorporation of 3H-uridine into hairy cells in vitro, thus indicating a possible role for the induction of RNA synthesis in vivo.