Carbon fiber scaffolds in the surgical treatment of cartilage lesions.

We present a new method of treatment of chondral defects of the knee with the usage of carbon fibers. The prospective study describes experience with carbon fibers used as scaffolds in the drilled lesions to enhance ingrowth of regenerative tissue. We treated 35 patients for chondral defects with that method from December 93 to June 97. Average age was 46 years (range, 19-68 years) and average follow-up was 48 months (range, 24-55 months). The results were assessed by HSS knee scale, the Wallgren-Tegner activity score, VAS (visual analogue scale to measure pain) and patients assessment of the surgery. Twenty-five (71%) of 35 patients were rated good or excellent. The most striking result was good pain relief. Early follow-up results are good, but these must be confirmed in long-term observations.

[Vitamin D receptor gene polymorphism and the rate of bone loss of the femur neck and lumbar spine in hemodialized patients with chronic renal failure]. / Polimorfizm genu dla receptora witaminy D a szybkosc ubytku masy kostnej w zakresie szyjki kosci udowej i kregoslupa ledzwiowego u chorych na przewlekla niewydolnosc nerek leczonych hemodializami.

It has been suggested that the vitamin D receptor (VDR) gene Bsml-polymorphism is a genetic determinant of bone metabolism. To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 136 haemodialyzed patients. Lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1.25(OH)2D3, osteocalcin serum concentrations, bone alkaline phosphatase activity and intact 1, 84-PTH levels were measured. VDR genotype BB, Bb and bb were found in 24%, 46% and 30% of patients respectively. Initial BMD (g/cm2) of lumbar spine and femoral neck did not differ between genotypes, however the decrease of femoral neck BMD during 18 months of observation differ significantly (p < 0.02) between the particular genotype groups (femoral neck: BB -0.031 +/- 0.029; Bb -0.027 +/- 0.017; bb -0.017 +/- 0.019 g/cm2). Significantly lower serum level of 25OHD3 was found in patients with the BB genotype before and after 18 months of observation in comparison to the respective values obtained in bb genotype patients, (respectively, 21.0 +/- 16.8 ng/ml vs 30.8 +/- 17.9 ng/ml; p < 0.01 and 24.0 +/- 10.8 ng/ml vs 32.4 +/- 16.0 ng/ml; p < 0.02). BB genotype patients were also characterised by significantly lower serum level of 1.25(OH)2D3 both initially and after 18 month of the study (respectively in BB and bb patients 25.9 +/- 9.7 pg/ml vs 30.7 +/- 10.0 pg/ml; p < 0.02 and 18.4 +/- 12.3 pg/ml vs 24.3 +/- 13.0 pg/ml; p < 0.01). No significant differences were found in Ca, P, osteocalcin, iPTH serum concentrations and bone fraction of alkaline phosphatase activity between particular genotypes. Results from this study suggest that faster bone mineral loss and more exaggerated disturbances of vitamin D metabolism are present in haemodialyzed uraemic patients with BB than bb genotype of VDR.

[Analysing cause of death in chronically hemodialyzed patients]. / Analiza przyczyn zgonów chorych przewlekle hemodializowanych.

The documentation was analysed of 123 haemodialysed patients dying in the years 1984-1990 in nine extracorporeal dialysis centres in the Provinces of Bielsko, Czestochowa and Katowice. Among the dying haemodialysed patients were 61 men and 62 women. The mean age of these patients was 43.7 +/- 1.0 years. The mean time from starting the haemodialysis therapy to death was 29.2 +/- 3.9 months. Mortality among the haemodialysed patients in individual years ranged from 6.5 to 14.4% and was 9.7% on the average. The most frequent death causes in this group of patient in the studied time period were infections (45.5%) and cardiovascular complications (35%). The results of the analysis of death causes in haemodialysed patients suggest the need of constant monitoring of the risk factors contributing to the development of infections and cardiovascular complications.

[Requirement for blood in hemodialyzed patients with chronic renal failure in the period before and after introduction to erythropoietin (r-HuEPO) treatment]. / Zapotrzebowanie na krew u hemodializowanych chorych na przewlekla niewydolnosc nerek w okresie przed po wprowadzeniu do leczenia erytropoetyny (r-HuEPO).

The present paper aimed to assess the influence of EPO-therapy on the requirement of blood transfusion in haemodialysed patients with end-stage renal failure. As shown in this paper, introduction of r-HuEPO into the therapy of uraemic anaemia almost completely eliminated the request for blood transfusion in these patients. EPO therapy did not influence significantly to the serum creatinine concentration and mean arterial blood pressure in these patients.

Methods for the isolation and culture of human articular chondrocytes.

The tissue engineering of cartilage implants may open new paths for the surgical treatment of joint surface defects. Autologous chondrocyte transplantation (ACT) has been gaining in clinical significance over the last several years. This study presents the methods used for isolation, monolayer culturing, multipication and assesment in transmission light microscopy of human chondrocytes. The tissue was gained from resected fragments of joint during total knee replacement.

Angiotensin converting enzyme inhibitors, calcium channel blockers, and their combination in the treatment of glomerular disease.

BACKGROUND: Glomerular diseases may progress to end-stage renal failure via the development of glomerulosclerosis. Systemic hypertension and intraglomerular hypertension are important, although not the only, determinants of this process. Proteinuria (albuminuria) is a surrogate marker for glomerular damage and renal prognosis. EFFICACY OF ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS: In animal experiments and in controlled clinical studies, ACE inhibitors have proved to be effective in reducing proteinuria and in preventing glomerulosclerosis or progression to end-stage renal failure, possibly more than can be explained by their effects on blood pressure. EFFICACY OF CALCIUM CHANNEL BLOCKERS: In contrast to the uniform efficacy of ACE inhibitors, the effect of calcium channel blockers is less uniform. It depends on the model of renal damage used, the extent of the fall in systemic blood pressure and the type of calcium channel blocker used. Nevertheless, clinical studies have shown a reduction in proteinuria and at least an attenuation of progression with the use of long-acting calcium channel blockers. RATIONALE FOR THE COMBINATION OF ACE INHIBITORS AND CALCIUM CHANNEL BLOCKERS: If angiotensin II influences the progression of renal failure, as is universally accepted, then the combination of an ACE inhibitor (reducing the generation of angiotensin II) and a calcium channel blocker (reducing target-organ responsiveness to angiotensin II) appears a promising one. EVIDENCE FOR THE EFFECTIVENESS OF THIS COMBINATION: In animal experiments, co-administration of an ACE inhibitor and a calcium channel blocker caused a more marked reduction in glomerulosclerosis, and this was seen in the stroke-prone spontaneously hypertensive rat model even at non-antihypertensive doses. In human diabetic nephropathy at least, proteinuria (measured as a surrogate marker of the illness) was lowered more effectively by the combination of an ACE inhibitor and a calcium channel blocker than either drug used as monotherapy despite a similar fall in blood pressure.

The use of carbon fibers to restore cartilage defects in the knee.

Research on carbon biomaterials has Bern in progress at the Warsaw Orthopedic Clinic for more than 20 years. Recently these materials have also been used in clinical practice as matrix material for repairing tissue defects in the motor organs. In this article, a new method is presented using carbon fiber to treat cartilage defects in the knee. This study describes the authors experience with carbon fibers used as scaffolds in drilled cartilage lesions to enhance the in growth of regenerative tissue. The research involved 35 patients treated for cartilage defects from December 1993 to June 1997. The average age was 46 (range 19-68), and the average follow-up was 48 months (range 24-55 months). The results were assessed by applying the HSS knee scale, the Wallgren-Tegner activity score, the VAS (visual analogue scale of pain), and the patients subjective judgment of the surgery. Good or excellent outcomes were obtained in 25 of the 35 patients (71%). The most striking aspect of the outcome was good pain relief. Early follow-ups are necessary, but the results must be confirmed in long-term observations.

[Molecular basis of achondroplasia, hypochondroplasia, and thanatophoric dysplasia]. / Molekularne podloze achondroplazji, hipochondroplazji i dysplazji tanatoforycznej.

Fibroblast growth factor 2 (FGF2) inhibits proliferation and hypertrophy of chondrocytes in the growth plate, synthesis of cartilage matrix, terminal differentiation of hypertrophic chondrocytes and matrix calcification. Recent studies have found that mutations in the receptor for fibroblast growth factor 3 (FGFR3) cause achondroplasia, hypochondroplasia and thanatophoric dysplasia. These mutations evoke uncontrolled stimulation of the receptor, leading to inhibition of bone growth. Inactivation of the receptor in experimental animals causes excessive chondrocyte proliferation and abnormal bone length. Chondrocyte stem cells proliferate in the ossification groove of Ranvier and contribute to both peripheral and longitudinal growth of the growth plate. They express FGFR3, have a potential to differentiate into chondrocytes and are therefore considered adequate for healing cartilage defects in the articular surface. It is at present unknown what happens to the chondrocyte precursor cells in the ossification groove of patients with FGFR3 mutation.

Renal disease and hypertension in non-insulin-dependent diabetes mellitus.

Recent epidemiologic data demonstrate a dramatic increase in the incidence of end-stage renal disease (ESRD) in patients with non-insulin-dependent diabetes mellitus (NIDDM), thus dispelling the mistaken belief that renal prognosis is benign in NIDDM. Currently, the leading cause of ESRD in the United States, Japan, and in most industrialized Europe is NIDDM, accounting for nearly 90% of all cases of diabetes. In addition to profound economic costs, patients with NIDDM and diabetic nephropathy have a dramatically increased morbidity and premature mortality. NIDDM-related nephropathy varies widely among racial and ethnic groups, genders and lifestyles; and gender may interact with race to affect the disease progression. While the course of insulin-dependent diabetes mellitus (IDDM) progresses through well-defined stages, the natural history of NIDDM is less well characterized. NIDDM patients with coronary heart disease have a higher urinary albumin excretion rate at the time of diagnosis and follow-up. This greater risk may also be associated with hypertension and hyperlipidemia, and genes involved in blood pressure are obvious candidate genes for diabetic nephropathy. Hyperglycemia appears to be an important factor in the development of proteinuria in NIDDM, but its role and the influence of diet are not yet clear. Tobacco smoking can also be deleterious to the diabetic patient, and is also associated with disease progression. Maintaining euglycemia, stopping smoking and controlling blood pressure may prevent or slow the progression of NIDDM-related nephropathy and reduce extrarenal injury. Treatment recommendations include early screening for hyperlipidemia, appropriate exercise and a healthy diet. Cornerstones of management should also include: (1) educating the medical community and more widely disseminating data supporting the value of early treatment of microalbuminuria; (2) developing a comprehensive, multidisciplinary team approach that involves physicians, nurses, diabetes educators and behavioral therapists; and (3) intensifying research in this field.

[Effect of elevated blood pressure and proteinuria on progression of mesangioproliferative glomerulonephritis]. / Wplyw nadcisnienia tetniczego oraz bialkomoczu na przebieg klebuszkowego rozplemowego mezangialnego zapalenia nerek (glomerulonephritis proliferativa mesangialis).

UNLABELLED: Mesangioproliferative glomerulonephritis (GNpm) is one of the most frequent histopathological forms in patients with proteinuria and erythrocyturia. The aim of this study was to assess the rate of deterioration of renal function in 39 patients with mesangioproliferative glomerulonephritis. All patients (25 M and 14 F, age from 19 do 55 year) were diagnosed in the Department of Nephrology Silesian University School of Medicine in Katowice two times: before and at least 12 month after renal biopsy respectively. 21 patients with mesangioproliferative glomerulonephritis was oligosymptomatic. In 6 patients the leading sign of GNpm was moderate arterial hypertension while in the other 22 nephrotic syndrome. 17 patients with mesangioproliferative glomerulonephritis received immunosuppressive medication while in the other 22 patients these drugs were not used. Deterioration of renal function was assessed using a progression index (PI) which is calculated by dividing delta of serum creatinine (mumol/l) by the observation period (months). Deterioration of renal function was faster in nephrotic patients (PI = 0.27 +/- 0.11 mumol creat./month) and in patients with the hypertensive form of mesangioproliferative glomerulonephritis (PI = 0.69 +/- 0.29 umol creat./month) than in patients with oligosymptomatic mesangioproliferative glomerulonephritis (PI = 0.06 +/- 0.04 mumol creat./month). Significantly slower deterioration of renal function was noticed in patients treated with immunosuppressive drugs than medicated only symptomatically (PI = 0.05 +/- 0.007 mumol creat./month vs 0.70 +/- 0.06 mumol creat./month). CONCLUSIONS: 1) Presence of hypertension and of a nephrotic syndrome does influence adversely the progression of mesangioproliferative glomerulonephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

The ET(A) receptor blocker LU 135252 prevents chronic transplant nephropathy in the "Fisher to Lewis" model.

The effect of the orally highly bioavailable and specific endothelin A (ET(A)) receptor antagonist LU 135252 was assessed in a model of chronic renal allograft nephropathy. Kidneys of Fisher rats were orthotopically grafted to Lewis rats. Fisher autografts and kidneys after uninephrectomy served as controls. All animals received low-dose cyclosporin A (CsA; 1.5 mg/kg body wt) for 10 d after surgery. Allotransplanted animals were then randomized to receive standard diet or a diet designed to deliver 30 mg of LU 135252/kg body wt per d for 35 wk. BP was monitored telemetrically. Treatment with LU 135252 did not affect systolic or diastolic pressure. Indices of glomerulosclerosis (GSI), and tubulointerstitial and vascular damage were measured. Chronic transplant nephropathy was almost completely prevented by LU 135252 compared with untreated allografts or kidneys of uninephrectomized controls, i.e., GSI 0.7 +/- 0.12 versus 1.6 +/- 0.25 (P < 0.001) versus 0.7 +/- 0.06 (P < 0.001). Allograft weight and serum creatinine were significantly lower in treated versus untreated animals. The results are consistent with the notion that ET(A) receptor-mediated events play a role in the genesis of chronic transplant nephropathy.

[Relationship between renal biopsy histopathology and profile of changes in serum protein, lipids and proteinuria in patients with nephrotic syndrome due to chronic glomerulonephritis]. / Zaleznosc pomiedzy obrazem histopatologicznym bioptatu nerki, a profilem zmian proteinogramu i lipidogramu surowicy oraz proteinuria u chorych z zespolem nerczycowym spowodowanym przewleklym klebuszkowym zapaleniem nerek.

UNLABELLED: Relationship was assessed between the type of renal pathology and the degree of plasma protein and lipid abnormalities in 59 patients with nephrotic syndrome due to chronic glomerulonephritis (GN). All patients were divided into 5 subgroups according to the type of renal pathology (extracapillary proliferative GN--23, mesangioproliferative GN--18, membranous GN--5, minimal changes--5, other--8 patients) and according to the presence (22 patients) or absence (37 patients) of altered interstitium (inflammation and/or fibrosis). In all patients the following parameters were analyzed: plasma levels of creatinine, total cholesterol and lipids, triglycerides, total protein, electrophoretic fractions of plasma proteins and urinary protein excretion. Type of renal pathology as well as presence of interstitial lesion did not influence the degree of protein and lipid abnormalities in nephrotic patients. Significantly more marked (p < 0.05) abnormalities in the serum and lipid profile were found in patients in whom 76-100% of all glomeruli were abnormal than in patients with a lower percentage of damaged glomeruli. CONCLUSION: Percentage of damaged glomeruli but not the type of renal pathology (glomerular or/and interstitial) are the main factors influencing the magnitude of abnormal serum protein and lipid profiles in nephrotic patients.

Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients?

BACKGROUND: It has been suggested that the vitamin D receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone metabolism. DESIGN: To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 88 haemodialysed patients not receiving active vitamin D metabolites. METHODS: Whole body, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline phosphatase activity and intact 1,84 PTH levels were measured. RESULTS: VDR genotype BB, Bb and bb were found in 27, 49 and 24% of patients. Initial BMD (g/cm2) of whole body, lumbar spine and femoral neck did not differ between genotypes (whole body: BB 1.055 +/- 0.120, Bb 1.082 +/- 0.102, bb 1.128 +/- 0.120; lumbar spine: BB 1.075 +/- 0.199, Bb 1.079 +/- 0.185, bb 1.099 +/- 0.170; femoral neck: BB 0.808 +/- 0.160, Bb 0.862 +/- 0.127, bb 0.842 +/- 0.125; mean +/- SD), but the decrease of whole body and femoral neck BMD during 18 months was significantly (P < 0.02) different between the genotype groups (whole body: BB -0.048 +/- 0.028, Bb -0.031 +/- 0.029, bb -0.024 +/- 0.023; femoral neck BB -0.044 +/- 0.069, Bb -0.032 +/- 0.081, bb -0.012 +/- 0.029 g/cm2). CONCLUSION: This preliminary study suggests faster mineral loss in BB genotype of VDR in haemodialysed patients.