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Biomedical subjects

J Laine

Publications and source records attributed to J Laine.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differences in linear growth and cortisol production between liver and renal transplant recipients on similar immunosuppression.

Linear growth is more often impaired after liver than after renal transplantation (Tx) in childhood. As similar triple immunosuppression was used in our liver and renal transplant recipients, we were able to compare growth and endocrine function between 19 prepubertal liver and 35 renal transplant recipients. There were no significant differences in median age, weight-for-height index, or height standard deviation score at Tx. Seventy-eight percent of the liver Tx patients, but only 7% of the renal Tx patients, were below the normal range for height 3 years after Tx. Graft function was good in both liver and renal transplant recipients 3 years after Tx. There was no significant difference in growth hormone secretion, serum insulin-like growth factor (IGF)-I, and IGF-binding protein-3 levels, or in methylprednisolone and cyclosporine doses. However, the blood cyclosporine levels were significantly higher in the liver transplant recipients (P = 0.001 1 year and P = 0.005 2 years after Tx). Cortisol production was significantly lower in the liver transplant recipients (P = 0.002 1 year and P = 0.049 2 years after Tx), which suggests greater steroid-mediated suppression of adrenal function. Growth inhibition is more often observed in liver than in renal transplant recipients on similar triple immunosuppression, and may not be related to deficient function of the growth hormone-IGF-I axis. Similar cyclosporine doses result in higher plasma levels of the drug and similar methylprednisolone doses result in more inhibited adrenal cortisol production in liver transplant recipients. In children with organ transplants, cyclosporine and methylprednisolone should be administered on an individual basis.

Adrenocorticotropic Hormone↗
PubMed1995

Alphacalcidol oral pulses normalize uremic hyperparathyroidism prior to dialysis.

Alphacalcidol oral pulse therapy was given for secondary hyperparathyroidism to 22 children (mean age of 5.6 years) with renal insufficiency. At the beginning of the study, the glomerular filtration rate was < 50% of normal, serum intact parathyroid hormone (PTH) was > 100 ng/l and the serum phosphate and calcium concentrations were within the normal range. Alphacalcidol (0.5-3.0 micrograms) was given orally thrice weekly in the evening and adjusted according to PTH, ionized calcium and phosphate concentrations. Serum PTH (mean +/- SEM) decreased significantly from a pre-treatment level of 393 +/- 81 ng/l to 122 +/- 34 ng/l after 12 months, and stabilized at this level. Mean vitamin D metabolite concentrations were within the normal range. 1,25-Dihydroxyvitamin D did not increase during therapy, while PTH decreased. The estimated creatinine clearance remained almost unchanged (20 +/- 3 and 21 +/- 6 ml/min per 1.73 m2). Growth remained low normal (height standard deviation score -1.8 +/- 0.3 initially and -1.7 +/- 0.4 12 months later) and bone mineral density did not decrease. We concluded that feedback regulation of PTH with oral alphacalcidol pulse therapy is effective in the treatment of hyperparathyroidism in children with renal failure prior to dialysis.

Adolescent↗
PubMed1995

Synthesis and biodistribution of nitrido technetium-99m radiopharmaceuticals with dithiophosphinate ligands: a class of brain imaging agents.

The symmetrical complexes [99mTc][TcN(R2PS2)2] [R = CH3, CH2CH3, CH2CH2CH3, CH2(CH3)2], and the unsymmetrical complex [99mTc][TcN(Me2PS2)(Et2PS2)] have been prepared, at tracer level, through a two-step procedure involving the preliminary formation of a prereduced technetium nitrido intermediate followed by substitution reaction onto this species by the appropriate dithiophosphinate ligand [R2PS2]Na. The chemical identity of the resulting complexes have been established by comparison with the corresponding 99Tc-analogs prepared, at macroscopic level, by reacting the complex [99TcNCl4] [n-Bu4N] (n-Bu = n-butyl) with an excess of ligand in methanol, and characterized by elemental analyses and spectroscopic techniques. The complexes are neutral and lipophilic, and possess a square pyramidal geometry, with an apical Tc identical to N group and two dithiophosphinate ligands spanning the four positions on the basal plane through the four sulfur atoms of the > PS2 group. In vitro studies showed that these radiopharmaceuticals are stable in solution and that their chemical identity was not altered after incubation with rat blood. Biodistribution studies have been carried out in rats and primates. The results demonstrate that these compounds are significantly retained into the brain of these animals for a prolonged time. Planar gamma camera images have been obtained in monkeys showing a good visualization of the cerebral region. However, the existence of persistent blood activity yields a brain/blood ratio lower than that observed with other 99mTc-based brain perfusion imaging agents.

Animals↗
PubMed1995

Use of epinephrine for anaphylaxis by emergency medical technicians in a wilderness setting.

STUDY OBJECTIVE: To describe a case series of emergency medical technician-basic (EMT-B)-administered epinephrine for anaphylaxis in a wilderness setting. DESIGN: Case series of patients in anaphylaxis who received epinephrine subcutaneously from EMT-Bs. SETTING: National park rural/wilderness emergency medical service system covering 863,000 acres and serving approximately 2 million annual visitors. PARTICIPANTS: Prehospital care providers were National Park Service rangers with EMT-B training. Patients in the series were visitors to Sequoia and Kings Canyon National Parks with anaphylaxis resulting from insect stings. INTERVENTION: Subcutaneous administration of epinephrine by EMT-Bs trained in recognition, understanding, and treatment of anaphylaxis. RESULTS: Eight patients with anaphylaxis resulting from Hymenoptera stings, from June 1992 through September 1993, received EMT-B-administered epinephrine. All patients improved clinically after treatment with epinephrine within 25 minutes. No major side effects occurred. CONCLUSION: Our data suggest that EMT-B-administered epinephrine is safe when used by EMT-Bs in the rural/wilderness setting, with appropriate physician supervision. Further study in large trials will be required to demonstrate safety and efficacy.

Adolescent↗
PubMed1995

Renal and adrenal mechanisms in cyclosporine-induced hyperkalaemia after renal transplantation.

CsA associated hyperkalaemia was investigated in 24 renal transplant recipients 6 months after transplantation. 51Cr-EDTA-, PAH-, lithium and sodium clearances, 24 h urinary creatinine and potassium excretions, plasma renin activity and aldosterone concentrations were measured. Transtubular potassium concentration gradient (TTKG) was calculated. An ACTH test was performed to document adrenal function. Eleven patients had hyperkalaemia. The TTKGs were low normal or reduced in both normo- and hyperkalaemic patients implying inhibition of K+ secretion. The hyperkalaemic patients received more CsA (mean dose 21.3 vs. 9.7 mg kg-1d-1, P = 0.01), and had lower lithium clearances (mean 9.9 vs. 17.0 mL min-1 1.73 m-2, P < 0.05). Adrenal function had no clear effect. Serum potassium concentration correlated with CsA dose (r = 0.773, P < 0.001) and inversely with lithium clearance (r = -0.568, P < 0.01) suggesting that CsA induced decrease in distal tubular flow rate reduced K+ excretion. Hyperkalaemia was not fully explained by renal mechanisms.

Adolescent↗
PubMed1995

The nephropathy of type I tyrosinemia after liver transplantation.

Type I tyrosinemia (HTI) is an autosomally recessively inherited disease caused by deficiency of fumarylacetoacetate hydrolase. The disease manifests with liver failure, renal tubular defects, and neurologic crises. Currently orthotopic liver transplantation (OLT) enables patients to survive. However, renal fumarylacetoacetate hydrolase deficiency is not corrected by OLT, and the long-term prognosis of the nephropathy is not known. We investigated tyrosine metabolism, GFR, renal tubular function, and histopathology before and 18-36 mo after OLT in eight patients with HTI. Progressive renal dysfunction was not documented despite continuing, although diminished, urinary succinylacetone excretion in all patients. The mean GFR was 82 mL/min/1.73 m2 before and 102 mL at 18 mo and 93 mL at 36 mo after OLT. All patients showed tubular dysfunction before OLT. At 18 mo, glucosuria occurred in one, amino aciduria and phosphaturia in three, and hypercalciuria in six patients. Only hypercalciuria was seen at 36 mo. Renal biopsies showed mild nonspecific changes caused either by minimal progression of the renal disease or by mild cyclosporine nephrotoxicity. In conclusion, patients with HTI had normal GFR, but showed signs of tubular dysfunction 18-36 mo after OLT. Renal function and histopathology should be monitored after OLT for HTI.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Renal allograft histology and correlation with function in children on triple therapy.

Histopathological findings of 13 LRD and 17 CAD renal allografts of paediatric recipients were prospectively semiquantitatively scored and correlated with clinical and functional parameters 18 and 36 months after transplantation. The most common findings at 18 months were diffuse interstitial fibrosis (incidence 57%), glomerular mesangial matrix increase (91%), arteriolar intimal proliferation (70%), and tubular atrophy (83%). Most changes were mild and most biopsies were scored normal or borderline (Banff classification). At 18 and at 36 months 30% of grafts showed mild chronic rejection (CR). Only two grafts showed grade II CR at 18 months and one graft grade III CR at 36 months. Progressive CR was not seen. Donor source or recipient age had no effect on graft histology. Vascular-interstitial cyclosporin (CsA) nephrotoxicity was not found. On the contrary, cumulative CsA dose (mg/kg/day) showed an inverse correlation with arteriolar intimal proliferation (P < 0.001). 51Cr-EDTA and lithium clearances showed inverse correlations with diffuse interstitial fibrosis and lymphocytosis. PAH clearance did not correlate with interstitial or vascular changes. The results indicate good prognosis in children on triple immunosuppression (with CsA administered in three doses/day to pre school children) regardless of donor source.

Adolescent↗
PubMed1994

Renal transplantation in children with emphasis on young patients.

We report the results of 41 consecutive renal transplantations performed on 39 children (median age 2.7 years). Twenty-six recipients were less than 5 years old. Twenty-one recipients (13 under the age of 5 years) received cadaver (CAD) grafts. All grafts except 2 were from adult donors and were placed extraperitoneally. Patients were on triple immunosuppression (cyclosporine plus azathioprine plus methylprednisolone). Mean follow-up time was 2.3 years. No vascular and only one ureteral complication was seen. Acute tubular necrosis occurred in 3 patients (7.3%). No grafts were lost due to acute rejection. Three-year patient survival and 1-year graft survival were 100%. The overall 3-year actuarial graft survival was 86%. Three-year survival of grafts from living-related donors (LRD) was 92% and that of CAD grafts 75%. In recipients younger than 5 years, 3-year LRD graft survival was '89% and CAD graft survival 73%. No significant differences in graft survival between recipients of different age groups or between LRD and CAD grafts were found. We conclude that results of renal transplantation in children under 5 years of age are comparable to those of older children, even using CAD grafts, when adult donors and triple immunosuppression are used.

Adolescent↗
PubMed1994

Renal function and histopathologic changes in children after liver transplantation.

Up to 60% reduction of renal function has been reported after orthotopic liver transplantation (OLT) in patients receiving cyclosporine. We prospectively investigated renal function and histopathology in 16 children on triple immunosuppression therapy during 3 years after OLT. Cyclosporine was administered in 3 doses/day to preschool children. The median age at OLT was 5.4 years. Determinations of chromium 51-labeled ethylenediaminetetraacetic acid, p = aminohippuric acid, lithium, and sodium clearances, measurements of serum and urinary electrolytes, and urinary concentration tests were performed. Renal biopsy specimens were taken 18 and 36 months after transplantation. The mean glomerular filtration rate was 121.5 ml/min per 1.73 m2 before transplantation, 86.3 at discharge, and 119.4 36 months after OLT. Hyperuricemia, hyperkalemia, and reduced urinary concentrating capacity were common. Hyperkalemia occurred in 13% to 19% of the patients, only during the first 6 months. Hyperuricemia and reduced concentrating capacity occurred with incidences of 17% to 44% and 40% to 63%, respectively. Histopathologic changes were mild, and severe nephrotoxic effects of cyclosporine was not seen. However, tubular atrophy, mesangial matrix increase, and mesangial cell proliferation were common. We conclude that triple immunosuppression with cyclosporine administration, in three doses per day, to small children and careful renal follow-up ensure good renal function after OLT.

Adolescent↗
PubMed1994

Chronic alcohol intake and carbachol-induced acute pancreatitis in the rat.

Alcohol-induced changes in cholinergic and pancreozymin pathways regulating exocrine pancreatic secretion have been proposed to play a crucial role in the pathogenesis of acute alcoholic pancreatitis. In the present study we investigated the role of chronic alcohol intake in an experimental acute pancreatitis induced in rats by cholinergic hyperstimulation. Chronic alcohol intake interfered with the function of rat pancreatic muscarinic receptors in carbachol-induced acute pancreatitis. However, chronic alcohol intake did not sensitize the experimental animals to cholinergic hyperstimulation. Whether this increased resistance at the level of pancreatic muscarinic receptors contributes to acute alcoholic pancreatitis is discussed in the present article.

Acute Disease↗
PubMed1994

Identification of a stop mutation in five Finnish patients suffering from hereditary tyrosinemia type I.

Hereditary tyrosinemia type I is a metabolic disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH, EC 3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. The molecular basis of FAH deficiency was examined in five Finnish patients suffering from this severe metabolic disease. No immunoreactive FAH nor enzymatic activity were found in their liver. Direct sequencing of the 14 exons of the FAH gene showed a G to A transition, which predicts a change from tryptophan to a stop codon (TGG-->TGA) at position 262 (W262X). Four of the five patients examined were homozygous for the mutation. Allele specific oligonucleotide hybridization showed a predominance of the W262X mutation in Finland (9 of 10 alleles) and the absence of this mutant allele in patients from other parts of the world. The loss of a BsaJI restriction site in those patients may be used for diagnosis.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Effect of donor source on renal allograft function in children on triple immunosuppression.

Results of renal transplantation using cadaver donors (CAD) are usually inferior to those using living related donors (LRD). We have previously reported 100% 1-year CAD and LRD graft survival using adult cadaver donors and triple immunosuppression. In the present study glomerular and tubular function of 23 LRD and 22 CAD grafts (median ages 3.5 and 2.6 years) were compared during 3 years after transplantation. Glomerular filtration rate (GFR) and renal plasma flow were lower in CAD grafts but remained stable in both groups. The mean GFRs were 87.3 and 63.2 ml/min/1.73 m2 at discharge and 82.8 and 72.5 ml/min/1.73 m2 at 36 months in LRD and CAD grafts respectively. No significant differences were found after 6 months. Tubular function was good in both groups. The only significant difference was in urate handling at 36 months (mean serum urate 396 mumol/l in CAD, 301 in LRD grafts, P < 0.05). Cyclosporin nephrotoxicity manifested as hyperkalaemia due to reduced distal potassium secretion and/or adrenal suppression. In conclusion, donor source had little effect on the development of progressive allograft dysfunction using adult CAD grafts and triple immunosuppression with CsA administered in three daily doses to preschool children.

Adolescent↗