Very Long-term Survival of the Transplanted Kidney-Characteristics of Recipients.

BACKGROUND: After kidney transplantation (KTx), donor- and recipient-dependent factors, as well as the immunosuppression protocol, may have an impact long-term graft function. The aim of this retrospective study was to identify and describe recipients from a single center who had their transplanted kidney survive for more than 20 years. METHODS: The database of KTx recipients was searched to find identify patients with a functioning kidney graft for >20 years. Clinical, demographic, and immunologic data were recorded and analyzed. Moreover, the Charlson Comorbidity Index was calculated. RESULTS: We identified 25 patients, with graft survival of 23.9 ± 3.2 years (maximum, 31.5 years), with following characteristics: age at time of transplantation 36.2 ± 11.9 years; median of 4 human leukocyte antigen (HLA) mismatches; low risk of rejection (panel-reactive antibodies [PRA] 0%); and 14 recipients had delayed graft function (DGF) and 9 had a single episode of acute rejection successfully treated with steroid pulses. In 24 cases there was a deceased donor. There was a predominance of males aged <54 years. At 1 year after KTx, serum creatinine was 1.36 ± 0.26 mg/dL. All recipients were given cyclosporine + azathioprine + prednisone as primary immunosuppression. The majority of recipients have continued to visit the clinic on an oupatient basis, with a most recent creatinine average of 1.5 ± 0.82 mg/dL. CONCLUSION: Very long-term kidney graft survival is most likely associated with a low risk of rejection (0% PRA pre-KTx), a relatively weak immunosuppression protocol, and optimal function at 12 months post-KTx.

Lack of Impact of Presence of Positive C4d Staining in Capillaries in Myocardial Biopsies on Long-term Survival of Heart Transplant Patients.

BACKGROUND: The long-term survival of 209 consecutive patients (mean age, 46 ± 15 years) from a single center with ≥1 diagnostic myocardial biopsy after heart transplantation was analyzed. METHODS: Patients were considered as C4d positive if a capillary staining (immunohistochemistry in paraffin samples) was observed in ≥1 myocardial biopsy. Data were analyzed according to pathologic consensus of antibody mediated rejection definition of C4d+ positivity: 2004 definition in group A and the 2013 definition in group B and compared with their respective controls, composed of patients who do not meet those criteria. Age, follow-up time, and number of biopsies were comparable between patients with C4d+ and controls in both groups. Follow-up was 100% complete with mean of observation time 2143 days. RESULTS: During the follow-up period, 62 patients died (group A: C4d+ 32% vs controls 29%; group B: C4d+ 36% vs controls 29% [P = NS]). There were no differences in survival between patients with positive staining and without C4d+ staining when Kaplan-Meier survival curves were compared. CONCLUSIONS: The presence of C4d positive staining in myocardial capillaries of heart biopsies of patients after heart transplantation, as an isolated finding, was not related to worse long-term survival.

Total ischaemic time and 9-year outcomes in STEMI patients treated with pPCI.

BACKGROUND: Prolonged total ischaemic time (TIT) has been shown to independently predict poor myocardial perfusion in STEMI patients and affect in-hospital mortality. We aim to evaluate the influence of TIT on long-term follow-up (F/U) and identify the factors associated with TIT in patients with STEMI treated with pPCI at a high volume centre. METHODS: In a prospective "all-comer" registry, clinical, angiographic and procedural characteristics, TIT and 9-year mortality were determined in consecutive STEMI patients treated with pPCI. Patients were divided according to TIT into three groups: A) <3, B) 3-6 and C) >6h. RESULTS: Among 1064 patients, TIT was known in 1002 patients, 5 patients were lost to F/U. For censored observations F/U was 7.2-8.8 years. There were 350, 461, and 186 patients in groups A, B, and C, respectively. Patients in group A compared to B and C were younger, more often males and smokers, less frequently had history of CAD, and more frequently had occluded infarct related artery. However, final TIMI3 was obtained more frequently. Overall 30-day mortality was 4%, one-year mortality 7% and nine-year mortality 27%. Multivariable logistic regression models indicated that longer TIT was associated with a higher risk of 9-year mortality (A-21%, B-28%, C-37%, p<0.0005). TIT>6h was independently associated with advanced age, diabetes mellitus, history of CAD and higher rate of initial TIMI grade flow 3. CONCLUSIONS: TIT is strongly related with mortality in STEMI patients even after nine years of F/U. This finding reinforces the necessity of shortening the TIT in all STEMI patients.

Left ventricular outflow tract gradient decrease with non-surgical myocardial reduction improves exercise capacity in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was undertaken to evaluate mid-term clinical results of non-surgical myocardial reduction in patients with hypertrophic obstructive cardiomyopathy. METHODS: Twenty-five patients with left ventricular outflow tract obstruction (mean gradient of 84. 54+/-31.38 mmHg) and symptoms of dyspnoea, angina and/or syncope were treated with non-surgical myocardial reduction. The patients were followed-up for a mean period of 10.44+/-1.8 months. In all patients clinical examination with echocardiography was repeated after every 3 months of follow-up, and a symptom-limited treadmill test was repeated at the 6 month follow-up. Eighteen patients underwent simultaneous respiratory gas analysis. RESULTS: Clinical follow-up examinations were achieved in all 25 patients. Persistent left ventricular outflow tract gradient reduction was seen in 23 patients. Seventeen patients had a reduction of left ventricular outflow tract gradient >50% of baseline value. Twenty patients showed a clinical improvement from 2.8+/-0.5 up to 1.2+/-0.5 NYHA class (P<0.001). The clinical improvement was matched by an improvement in objective measures of exercise capacity in patients with significant left ventricular outflow tract gradient reduction. Exercise time increased from 571.9+/-192.2 to 703.5+/-175.4 s, P<0. 001, and peak VO(2)increased from 14.6+/-5.2 to 20.5+/-8.6 ml. kg(-1)min(-1), P<0.05. CONCLUSION: Significant left ventricular outflow tract gradient reduction with exercise capacity improvement was achieved in the majority of patients treated with non-surgical myocardial reduction. We recommend this method as an alternative to surgery for symptomatic patients with hypertrophic obstructive cardiomyopathy.

Purification and partial characterization of thiol protease inhibitors from embryos of the brine shrimp Artemia.

Thiol protease inhibitor (TPI) proteins in embryos of the brine shrimp Artemia were purified to apparent homogeneity and several of their properties were studied. Four protein fractions containing thiol protease inhibitor activity were obtained by high performance liquid chromatography of Artemia embryo proteins on a C-18 reverse-phase column and these were designated as TPI-1a, -1b, -2, and -3. Acrylamide gel electrophoresis showed that TPI-1a and TPI-1b each consisted of two bands of 11.8 and 13.6 kilodaltons (kDa), while TPI-2 and TPI-3 consisted of only one band of 12.5 kDa. Isoelectric focusing experiments demonstrated that TPI-3 contained one band at pH 5.3, while both TPI-1b and TPI-2 yielded bands at pH 5.2 and 5.3. TPI-1a did not yield any major bands. Amino acid composition analyses of the Artemia TPI proteins showed them to be remarkably similar to one another. All were rich in valine and aspartic and glutamic acids, and devoid of cysteine. Partial trypsin digestion of TPI-1b, TPI-2, and TPI-3 yielded several peptides with identical mobilities on a reverse-phase column and several other peptides with different mobilities, suggesting that the multiple forms of Artemia TPIs may have originated from the same parental protein. N-terminal amino acid sequence analyses of TPI-3 suggest that Artemia TPI proteins are members of the type I cystatin family of protease inhibitors.

Hepatitis B virus-associated glomerulonephritis: electron microscopic studies in 98 children.

Ninety-eight children with glomerulonephritis concomitant with hepatitis B surface HBs antigenemia were studied, the antigenemia being first documented at the clinical onset of glomerulopathy. Initial diagnoses, based on examination of the paraffin sections, varied, membrano-proliferative, mesangial, and membranous glomerulonephritis being most frequently considered. However, electron microscopic examination showed that 77 children had a uniform type of glomerulopathy, irrespective of the light microscopic appearance. This type was diagnosed as secondary membranous glomerulonephritis. The clinical course of this nephropathy was relatively indolent and short. Moreover, in many children, elimination of some hepatitis B virus (HBV) antigens from the circulation was also associated with clinical remission of glomerulopathy. The remaining 21 children with HBs antigenemia had various morphological forms of glomerulonephritis, these being similar to their idiopathic counterparts in both morphology and clinical course. The distinct clinical and morphological picture of secondary membranous glomerulonephritis with HBs antigenemia occurring in 77 of 98 children supports the hypothesis that HBsV-associated glomerulonephritis is of the secondary membranous type. Thus, we conclude that in children HBV antigenemia associated with glomerulonephritis other than secondary membranous is coincidental.

Striatal and nucleus accumbens D1/D2 dopamine receptors in neuroleptic catalepsy.

Haloperidol (2.5-10 micrograms) injected bilaterally into the ventro-rostral striatum or into the nucleus accumbens induced dose-dependent catalepsy whereas its injection into the dorso-rostral striatum (2.5 micrograms) was ineffective. Similarly, the specific antagonist of D1 receptors, SCH 23390 (1-5 micrograms), injected into the ventro-rostral striatum or nucleus accumbens, as well as the specific antagonist of D2 receptors, sulpiride, injected into the ventro-rostral striatum (0.02-15 micrograms) or nucleus accumbens (1-15 micrograms), induced a dose-dependent catalepsy. Both drugs (SCH 23390 2 micrograms, sulpiride 0.5 micrograms) were ineffective when injected into the dorso-rostral striatum. Doses of sulpiride about 100 times lower than those injected into the nucleus accumbens were sufficient to evoke an equipotent catalepsy when injected into the ventro-rostral striatum. However, similar doses of haloperidol and SCH 23390, injected into the ventro-rostral striatum and nucleus accumbens, evoked a similar catalepsy. It is concluded that (1) the catalepsy induced by systemic administration of haloperidol seems to result from the action of this drug on both the ventro-rostral striatum and the nucleus accumbens, (2) both D1 and D2 dopamine receptors in the ventro-rostral striatum are involved in the cataleptogenic action of neuroleptics, and (3) in the nucleus accumbens, only D1 dopamine receptors seem to play an important role in this phenomenon.

Prognostic factors in the hemolytic-uremic syndrome.

During 1972-1986, 142 children with the hemolytic-uremic syndrome were treated. Most of them were infants (73%). The total mortality rate reached 25.4%. Computer analysis revealed the following risk factors of a fatal outcome: severe gastrointestinal symptoms during the prodromal period, coma, convulsions, malignant hypertension, persistence of prodromal symptoms over 7 days, hyperkalemia over 7 mmol/l, acidosis with bicarbonate level less than 15 mmol/l, a delay of over 5 days in starting dialysis, and transport to dialysis unit of over 100 km. The greatest risk of death existed during the first 3 weeks from onset. Among 142 children, 106 survived the acute phase. They were followed up from 2 to 16 years. Nine were lost to follow-up. Twelve children developed chronic renal failure.

Henoch-Schönlein nephritis in children--a clinicopathological study.

36 children with Henoch-Schönlein nephritis had their renal biopsy specimens studied by light and electron microscopic and immunofluorescence antibody techniques. Though no pathognomic changes were found the histological picture was characteristic. The severity of histological changes correlated well with the clinical manifestation and disease persistence. IMF studies showed characteristic mesangial IgA staining. The most prominent ultrastructural feature was segmental mesangial and subendothelial deposits with basement membrane changes. The amount of deposits was a good exponent of disease activity-children with few deposits recovering shortly. In spite of long duration, the outcome after an average 4 year follow-up was good, the majority of children having improved and renal insufficiency developing rarely. Renal biopsy is essential for an estimation of severity of renal disease and enables prognosis of disease persistence and long term outlook.

[Gastrointestinal complications in children with hemolytic-uremic syndrome]. / Gastrointestinale Komplikationen bei Kindern mit hämolytisch-urämischem Syndrom.

Eight children out of 106 with haemolytic-uraemic syndrome (HUS) had marked gastrointestinal complications requiring close cooperation between the paediatrician and paediatric surgeon. These children showed signs of ileus and peritonitis. Six children hat these complications in the prodromal stage, whereas the other two children showed them in the anuria stage. The complications were closely connected with multiple erosions of the mucosa and ulcerations of the intestinal wall which resulted in perforation of the intestinal wall in two cases. In two further cases, intestinal vagination was seen which was limited toward the small intestine. All operated children died. The authors are of the opinion that prognosis in HUS with severe gastrointestinal complications is very infaust.

Mesangial proliferative glomerulonephritis in children.

Over a ten year period 105 children with a histological diagnosis of a mesangial proliferative glomerulonephritis were diagnosed. Patients were divided into two groups according to their clinical presentation at the time of diagnosis. Ninety two children presented with nephrotic syndrome (NS) of whom 82 received steroid therapy. No response was observed in 26 children and in 56 remissions were short in duration and subsequent relapses were frequent. Eighty nine children with the nephrotic syndrome were treated with cyclophosphamide (CP) of whom 26 had a steroid resistant NS, 53 were steroid dependent and 10 were previously untreated. Eighty four entered remission with a mean duration of 46 months. Only 5 children did not respond to treatment with CP. No correlation could be found between the results of therapy and the degree of morphological changes on examination of renal biopsy. The second group consisted of 13 children presenting with a persistent nephritic syndrome and or proteinuria. These children were untreated and no progression of renal disease was observed after several years follow up.