Search PubMed⌕ Search

Biomedical subjects

J Laine

Publications and source records attributed to J Laine.

At least 37 records · Page 2Linked to original sources

Paediatric kidney transplantation.

Renal transplantation is the optimal form of renal replacement therapy leading to substantial improvement in the quality of life. It has rapidly become the standard treatment for end-stage renal disease in children. However, despite impressive short-term results significant long-term problems remain unsolved. Because of the lack of effective treatment for chronic rejection and common recipient noncompliance, allograft half-life has not improved significantly during the last decade. A paediatric recipient is likely to need several retransplantations in adulthood. Moreover, the immunosuppressive drugs used today have potentially serious side-effects including nephrotoxicity and de novo malignancy. These are especially relevant for paediatric recipients who will continue to receive therapy for several decades. Most therapeutic protocols used for children are derived from those used for adults. However, the metabolic differences between an adult and a growing and developing paediatric transplant recipient are not always adequately appreciated before these new therapies are initiated. In the near future, we are likely to see new and more efficient drugs become available. It is important that we try to understand their properties in children and use them and our current arsenal on an individual basis aiming at optimal graft survival but also at avoiding unnecessary adverse effects.

Adolescent↗

Kidney function after 1:1 conversion to the cyclosporine microemulsion formulation in children with liver allografts.

BACKGROUND: One-to-one (mg:mg) conversion from the conventional to the microemulsion formulation of cyclosporine (CsA) is advocated as a simple way to use the new therapeutic regimen. However, the potentially harmful effects of the conversion on kidney function in nonrenal transplant recipients are poorly known. METHODS: Renal effects of the conversion were prospectively investigated in 22 pediatric liver transplant recipients (mean age, 8.4 years; mean time from transplantation, 3.2 years). Patients were followed for 12 months. Pharmacokinetic studies were performed at baseline and 5 days and 6 and 12 months after conversion. RESULTS: Peak concentration, minimum concentration, average steady state concentration, and area under the concentration-versus-time curve increased by 60-130% after conversion. Graft losses, progressive deterioration of graft function, and acute rejection episodes did not occur. The mean glomerular filtration rate (GFR) was 103 ml/min/1.73 m2 at baseline and 100 ml/min/1.73 m2 after 12 months. However, 6 of the 22 patients showed at least a 15% (range, 16-38%) decrease in GFR between baseline and 6 months (P<0.01). They had a significantly higher increase in average steady state concentration between baseline and 6 months than the six patients with the best outcome in GFR during the same time period (164 ng/ml vs. 53 ng/ml, P<0.05). At this point (6 months), target CsA trough levels were reduced by 20-30%, while the mean area under the concentration-versus-time curve remained above that obtained at baseline. The GFR of three of the six patients subsequently improved. CONCLUSIONS: One-to-one conversion can be performed safely in liver transplant recipients if strict follow-up is feasible.

Adolescent↗

Apoptotic cell death in human chronic renal allograft rejection.

Chronic renal allograft rejection is characterized by gradual progression suggesting persistent low-grade injury. Apoptotic cell death may be initiated by low-grade injury secondary to external factors, making apoptosis a potential pathway of chronic rejection. In the present investigation, protocol kidney biopsies of 20 pediatric renal allograft recipients (12 with chronic rejection and 8 with normal histology), 9 pediatric liver allograft recipients, and 7 children with minimal change nephrotic syndrome were evaluated. The presence of apoptotic cell death was studied by determining apoptosis-induced oligonucleosomal DNA fragmentation in the biopsy specimens using 3' end labeling with terminal transferase, gel fractionation, and Southern blotting. The specific cell types with increased DNA fragmentation were determined by in situ 3' end labeling performed on sections of the biopsies. Significant DNA fragmentation was found only in the specimens from patients with chronic rejection. In situ investigation revealed increased apoptosis of both proximal and distal tubular epithelial cells, but not in the glomeruli or interstitium. The mean number of apoptotic tubular epithelial cells per 400x magnified field was higher in the renal allografts than in kidneys of liver transplant recipients or patients with minimal change nephrotic syndrome (2.3 vs. 0.8, P<0.05, in both cases). Our data provide biochemical evidence of increased apoptotic cell death of renal tubular epithelial cells in patients undergoing chronic renal allograft rejection.

Adolescent↗

Circulating luteinizing hormone receptor inhibitor(s) in boys with chronic renal failure.

Patients with chronic renal failure frequently have hypogonadism. To elucidate the molecular mechanisms involved, we tested the ability of serum from these patients to inhibit recombinant human luteinizing hormone receptors. Using a cell line expressing functional human luteinizing hormone receptors, we found that adenosine 3'5'-monophosphate (cAMP) production was markedly inhibited by sera from the patients, but not by sera from healthy subjects. Inhibition of cAMP production was associated with inhibition of 125I-human chorionic gonadotropin binding. Inhibition of LH receptors by sera from patients correlated with the glomerular filtration rate and after renal allograft transplantation, decreased. Fractionation of serum samples indicated the receptor-inhibiting activity in proteins of molecular weights from 30,000 to 60,000 Daltons. When characterized and purified, the factor responsible may well be a new LH receptor antagonist of clinical significance.

Blood Proteins↗

Contact allergy to dental restorative materials in patients with oral lichenoid lesions.

118 patients with oral lichenoid lesions (OLL) topographically related to dental fillings were patch tested (PT) to reveal contact allergy to restorative materials. 80 (67.8%) patients displayed positive PT reactions to metals of dental filling materials: 76 reactions were found to various mercury compounds, 4 to sodium aurothiosulphate, 3 to stannic chloride and 2 to silver nitrate. The positive patch test reactions appeared more commonly in patients with restricted contact lesions (85.1%, type-1 lesions) as compared to patients with lesions exceeding to the adjacent areas (38.6%, type-2 lesions). The replacement of dental fillings was carried out in 62/80 PT-positive and 15/38 PT-negative patients. 28 out of 62 (45.2%) PT-positive and 3/15 (20%) PT-negative patients showed complete healing of OLL after a mean follow-up time of 16 months. Complete healing occurred in 29/54 (54.0%) type-1 and 2/23 (8.7%) type-2 lesions. Topographical relation between the lesion and the filling material (restricted versus exceeding the contact area) indicated association of OLL lesion and the filling material, which could be further confirmed by patch testing in the majority of patients. The patch test series should include mercuric chloride (0.1%), mercury (0.5%) and mercury ammonium chloride (1.0%), each in pet.

Adult↗

In vitro lymphocyte proliferation test in the diagnosis of oral mucosal hypersensitivity reactions to dental amalgam.

Patch testing was carried out in 23 patients with oral lichenoid lesions (OLL) topographically related to dental amalgam fillings. Twelve patients displayed positive reactions to several mercury compounds, whereas 11 patients were negative. An in vitro lymphocyte proliferation (LyPro) test was carried out using different mercury compounds and other metal salts. Mercuric chloride and phenyl mercuric acetate caused positive proliferation in 3/12 patch test-positive and in 5/11 negative patients. One out of seven healthy control subjects had a positive LyPro result. The mean stimulation index (SI) values between the patient groups or compared with the control subjects did not differ significantly. Zinc, tin, copper or silver salts caused in vitro lymphocyte stimulation in most of the patients and in healthy control people. Total (14) or partial (4) replacement of amalgam fillings was carried out in 18 patients. Complete healing of lichenoid lesions was seen in 4/6 LyPro test-positive and in 5/10 patch test-positive patients at follow-up examinations 12 months after the replacement of amalgam fillings. The in vitro proliferation assay seems not to be a specific test for identifying the patients who would benefit from amalgam replacement.

Adult↗

Methylprednisolone exposure, rather than dose, predicts adrenal suppression and growth inhibition in children with liver and renal transplants.

Some patients receiving glucocorticoids develop adverse effects even with very low doses, whereas others fail to achieve the desired effects with the usual therapeutic doses. We hypothesized that glucocorticoid exposure, rather than the dose, would predict the development of adverse effects in children receiving long-term glucocorticoid treatment. Sixteen liver and 10 renal transplant recipients on triple immunosuppression were studied. Serum total methylprednisolone (MP) and cortisol were determined before and up to 10 h after peroral MP administration. Heights were recorded 6 months before and after the study day. The MP dose (in milligrams per kilogram) was not correlated with the serum cortisol concentration or with the change in height SD score. The area under the serum MP time vs. concentration curve was inversely related to the serum cortisol concentration and to the height SD score, and was the best predictor of both adrenal function and growth. Dosing according to area under the serum MP time vs. concentration curve in children receiving long-term glucocorticoid treatment may substantially reduce the incidence of adverse effects without affecting therapeutic efficacy.

Adolescent↗

Kidney function in cyclosporine-treated pediatric heart transplant recipients.

BACKGROUND: End-stage kidney disease may develop in 1% to 3% of cyclosporine-treated heart transplant recipients, and most patients show a decreased glomerular filtration rate. There are little data on kidney function in pediatric recipients, although good function is needed for their optimal development. METHODS: Kidney function was prospectively investigated in 10 children receiving triple immunosuppression (cyclosporine, azathioprine, methylprednisolone) during the first 18 months after heart transplantation. The early cyclosporine trough level target was 300 to 500 micrograms/L and 100 to 200 micrograms/L after the first year. 51Chromium-ethylenediamine tetraacetic acid, para-amino hippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were obtained from four patients after 18 months. RESULTS: Heart function was good in all patients. Six patients (60%) remained rejection-free at 18 months. The mean glomerular filtration rate was 92.4 ml/min/1.73 m2 before transplantation, increased to 115 by 6 months (p < 0.05), and thereafter remained stable. The mean renal plasma flow was 487 ml/min/1.73 m2 after 18 months. Hypertension was seen in all patients at discharge but in only one at 18 months. Mild hyperuricemia was the most common sign of tubular dysfunction occurring in five patients at discharge but in only two patients at 18 months. The result of kidney histopathologic study was normal in three of four patients, and cyclosporine nephrotoxicity was not diagnosed. CONCLUSIONS: Triple immunosuppression with cyclosporine adequately protects the graft against acute rejection. It is compatible with normal glomerular function and leads to only minor tubular disturbances.

Adolescent↗

Comparison of conventional oral cyclosporine and cyclosporine microemulsion formulations in children with a liver transplant.

We studied 22 children (mean age: 8.42 years, range: 1.9-15.6 years) with a liver transplant to compare the pharmacokinetics of oral cyclosporine (CsA) microemulsion to the conventional formulation. The CsA treatment (mean dose: 5.9 mg/kg/day, range: 3.0-11.7 mg/kg/day) was converted 1:1 on a milligram-to-milligram basis to the microemulsion formulation. Five days after the conversion, the mean peak blood CsA concentration was higher (microemulsion: 963 ng/ml, range: 518-1864 ng/ml; conventional: 431 ng/ml, range: 98-888 ng/ml; P<0.0001) and it was reached faster (median time of peak concentration: 1.6 hr vs. 2.9 hr, range: 1.0-3.0 hr vs. 1.9-4.0 hr; P=0.0009). The absorption lasted on the average 19% longer after the conventional formulation. The area under the concentration versus time curve (AUC) was larger after the microemulsion formulation in all but one patient (P=0.001) by a mean factor of 1.80 (range: 0.72-3.04). The trough CsA level after the microemulsion formulation was more closely related to peak concentration (r2=0.86 vs. 0.45) and AUC (r2=0.84 vs. 0.47); thus, therapeutic drug monitoring may be more useful. After 6 months on the new formulation, the results for the whole group were similar, but in five children the AUC was comparable to the AUC obtained with the conventional formulation. No rejections occurred, and the liver and kidney functions remained unchanged. A 1:1 conversion can be safely performed in children, based on a 6-month follow-up. However, the total drug exposure changes in significant ways, which, on a long-term basis, may improve the immunosuppression in an underimmunosuppressed patient, but may increase the risk for dose-related adverse effects in others.

Administration, Oral↗

Recombinant human growth hormone treatment. Its effect on renal allograft function and histology.

Our objective was to investigate the effects of recombinant human growth hormone (rhGH) treatment on long-term renal allograft function and histopathology. RhGH is a potent therapy for poor growth after renal transplantation. However, rhGH has proinflammatory properties and may induce acute rejection or accelerate chronic rejection. Nine prepubertal rhGH-treated renal transplanted children and nine pair-matched controls were studied 18 (before the start of rhGH) and 36 months after transplantation (mean duration of rhGH-treatment 14 months). 51Cr-EDTA- and PAH-clearances were performed. A protocol renal biopsy was done at 36 months. Growth showed significant improvement during rhGH (P<0.01). One graft loss occurred in both groups. One acute rejection was seen in the control group. There was no difference in the rate pf change in 51Cr-EDTA-or PAH-clearance between the two groups. Histopathological findings were mostly mild. One new onset chronic rejection developed in both groups. Proximal tubular atrophy was more extensive in the rhGH-treated patients (P<0.05), but there was no uniform trend toward more severe findings. RhGH improved growth, and no significant differences were seen in allograft function or histopathology; however, larger trials controlled for pretreatment renal function and immunosuppression are needed.

Acute Disease↗

Chronic rejection and late renal allograft dysfunction.

Renal transplantation is currently standard therapy for end-stage kidney disease for children. Despite the considerable improvement in short-term results, the expected allograft half-life has remained the same. This is due to chronic rejection/late graft dysfunction which has proved resistant to therapeutic attempts. During the last few years the multifactorial pathogenesis of chronic renal allograft rejection has been clarified to some extent. Early injury by immunological and non-immunological mechanisms is followed by vascular remodelling due to repetitive cycles of cytokine release, upregulation of growth factors, and vascular smooth muscle cell proliferation. This leads to typical concentric arteriosclerosis and ischemia. Secondary kidney-specific mechanisms are initiated by the reduction in functioning renal mass and lead to gradual progression of chronic rejection. There is no single optimal therapy. Several attempts to influence the pathophysiological cascade have been promising. Attention should be focused on minimizing early immunological/non-immunological injury in order to attenuate future progression of chronic rejection. A significant prolongation of allograft half-life may be achieved during the next decade with the introduction of new therapeutic agents and comprehensive approach to treatment. This would be especially beneficial for pediatric recipients, reducing the need for retransplantation in adulthood.

Animals↗

Eradication of the long-term carriage of methicillin-resistant Staphylococcus aureus in patients wearing dentures: a follow-up of 10 patients.

To cure the long-term carriage of methicillin-resistant Staphylococcus aureus (MRSA), eradication treatment was given to 10 patients wearing complete dentures. In addition to multiple body sites, MRSA was cultured from the dentures of six patients. The contaminated dentures were rebased and sterilized with heat in order to prevent recolonization. The patients did not use their dentures during the decolonization therapy. Subsequently, MRSA was eradicated from three of these patients but three others remained MRSA-positive despite at least two courses of combined systemic and topical eradication treatment. These particular patients had persistent stomatitis and their dentures were a poor fit, in poor condition and repeatedly grew MRSA. Eradication treatment was successful in the remaining four patients whose dentures were MRSA-negative. These results confirm that dentures may function as foreign bodies and sustain persistent nasopharyngeal. MRSA colonization. Therefore, we suggest that whenever eradication of MRSA is deemed necessary in cases of nasal, oral or pharyngeal carriage, heat treatment of the dentures should be included. Further comparative studies with larger patient populations are needed to evaluate the contribution of dentures to the long-term carriage of MRSA, as well as to assess the value of denture sterilization during the eradication course.

Aged↗

Contact allergy to gold in dental patients.

Gold sodium thiosulphate (GSTS) in patch test series commonly yields positive reactions. In this study of dental patients, the clinical relevance of these positive reactions, the suitability of gold compounds as patch test materials, and value of the lymphocyte proliferation test in gold contact allergy, were evaluated. The frequency of positive patch test reactions to GSTS was 12.4% in the dental series. Fifty-two patients, only two of whom were male, were studied. Thirteen (25%) had had symptoms from jewellery or dental restorations. However, in most cases gold allergy was subclinical. A 10% aqueous solution of gold sodium thiomalate (GSTM) was almost as good as 0.5% GSTS in petrolatum as a marker of gold contact allergy, but 0.001% potassium dicyanoaurate (PDCA) yielded a high percentage of false-negative results. Seventy-three per cent of the subjects with positive patch tests to GSTS responded to gold compounds in vitro in the lymphocyte proliferation test, whereas 13 controls without gold contact sensitivity were negative. Consistent results in skin and lymphocyte proliferation tests provide support for the concept that gold salt-induced 'allergic-like' reactions are truly allergic in nature.

Adolescent↗

Mechanisms of hyperuricemia in cyclosporine-treated renal transplanted children.

Mechanisms of hyperuricemia were investigated in 19 pediatric renal transplant recipients 6 months after transplantation. 51Cr-EDTA, PAH, lithium and sodium clearances, 24-hour urinary creatinine and urate excretions were measured. Ten patients had hyperuricemia. The hyperuricemic patients had lower EDTA, PAH, and urate clearances (mean 69.5 vs. 92.5, p < 0.05, 234 vs. 421, p < 0.05 and 4.3 vs. 10.6 ml/min/1.73 m2, p < 0.001, respectively). Serum urate concentration correlated with cyclosporine dose (r = 0.46, p < 0.05) and inversely with urate (r = -0.88, p < 0.001), and lithium (r = -0.55, p < 0.05) clearances. Urate clearance showed a significant positive correlation with lithium clearance (r = 0.66, p = 0.01) and an inverse correlation with fractional proximal tubular reabsorption (r = -0.63, p = 0.02). Results were not influenced by diuretic administration. Our data support increased proximal tubular urate reabsorption rather than decreased secretion as the mechanism in cyclosporine-induced hyperuricemia.

Azathioprine↗

Congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) can be caused by neonatal infections, renal diseases which exceptionally occur in early infancy and syndromes with a renal histology of DMS. The most common CNS is the Finnish-type (CNF), an autosomal recessively inherited disease characterized by intrauterine onset of massive proteinuria. The CNF gene has been localized to the long arm of chromosome 19, but the pathogenesis remains unclear. Forty-six CNF patients have been treated at our institution. The diagnosis was based on family history, severe proteinuria of intrauterine onset (serum albumin < 10 g/liter at presentation and urinary protein > 20 g/liter when serum albumin was corrected to > 15 g/liter), a large placenta (> 25% of birth wt), exclusion of other CNS-types and normal glomerular filtration rate during the first six months. Treatment included i.v. albumin substitution, optimal nutrition, thyroxine and anticoagulation. Forty-one patients had been nephrectomized bilaterally at a mean age of 1.2 years and after 3 to 25 months on peritoneal dialysis renal transplantation (Tx) had been performed on 34 who were a mean age of 2.2 years. Growth and development has been normal. Patient survival after Tx was 97%, graft survival 94%, 81% and 81% one, three and five years after Tx was (50% cadaver grafts). Mean GFR was 75 ml/min/1.73 m2 after three years, mean height SDS -1.42, and the nine oldest patients attend school in a normal class.

Humans↗