Biomedical subjects
Publications and source records attributed to J Perheentupa.
Dental and craniofacial features of 17 children and young adults suffering from the recently discovered mulibrey nanism syndrome are described and discussed. The present data do not allow any definite craniofacial typification of the syndrome. However, several findings suggest that we may be dealing with persistence of infantile structural relationships in the craniofacial area.
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A 2-hour adrenocorticotrophic-hormone (A.C.T.H.) test was given to 23 children in their first attack of idiopathic nephrotic syndrome, after treatment with prednisone according to the schedule of the International Study of Kidney Disease in Children. The length of the first remission was correlated with the response to the postmedication A.C.T.H. test. In 11 children this response was subnormal, and 10 of them had the first relapse within a year. Of the 7 children who stayed in remission for more than a year, 6 had normal responses. The treatment scheme should be adjusted to prevent postmedication adrenocortical suppression.
Congenital chloride diarrhea is an inherited defect of active intestinal Cl- transport which results in a large wastage of electrolytes and water. The effects of this disease and of replacement therapy on renal histology, function, growth, and the renin-angiotensin-aldosterone system were studied in 18 patients. When the patients were given KCl supplement, histologic findings included juxtaglomerular hyperplasia hyalinized glomeruli, calcifications, and arteriolar changes. Renal function and growth were reduced, and the hormonal activities were high. These abnormalities were evidently due to chronic dehydration. The dehydration could be corrected by increasing the dose of KCl, but only the addition of NaCl corrected the hyperaldosteronism. Adequate replacement therapy prevented the renal involvement.
Clinical findings in 21 Finnish children with congenital chloride diarrhoea are reported. Inheritance of this disease by the autosomal recessive mode is established. All children were born 1-8 weeks prematurely. Hydramnios was present in every case and no meconium was observed; intrauterine onset of diarrhoea is thus apparent. In most cases the diarrhoea or passing of large volumes of "urine" was noted on the first day of life and the abdomen was usually large and distended. The neonatla weight loss was abnormally large, and was associated with hypochloraemia and hyponatraemia. Some infants survived the neonatal period without adequate therapy. They presented later with failure to thrive and usually had hypochloraemia, hypokalaemia, and metabolic alkalosis associated with hyperaldosteronism. However, these features may be absent and the diagnosis is based on a history of hydramnios and diarrhoea, and a faecal Cl- concentration which always exceeds 90 mmol/l when fluid and electrolyte deficits have been corrected. Lower faecal Cl- concentrations were seen only in chronic hypochloraemia, which is also associated with achloriduria. Adequate treatment consists of full continuous replacement of the faecal losses of water, NaCl, and KCl. This should be given intravenously in the early neonatal period; later a solution can be taken orally with meals. The dose has to be adjusted to maintain normal serum electrolyte concentrations, normal blood pH, and some chloriduria. This therapy prevents the renal lesions and the retarded growth and psychomotor development which were seen in the children who were diagnosed late and in those who received inadequate replacement therapy. The watery diarrhoea persists and increases slightly with age, though patients learn to live with their disease and to make an adequate social adjustment.
Different parameters of the response to the 5-day metyrapone test were evaluated for their diagnostic accuracy in tests given to 58 children and adolescents as part of an investigation for short stature. Insulin test, vasopressin test and ACTH test were used for diagnostic reference. A log transformation of the data was clearly appropriate. The maximal daily excretion of 17-ketogenic steroids was distinctly positively correlated with the basal excretion. Consequently, the most correct parameter of the response is the SD score of the deviation of the maximal excretion from the regression of the maximal excretion on the basal excretion in the reference population. This parameter, 'relative maximal excretion' was shown to be the diagnostically most accurate index of the response of 11 parameters studied.
The threshold of serum osmolality causing release of vasopressin (antidiuretic hormone) was shifted to an abnormally low level (262 mosmol/kg H2O) in a 14-year-old girl with hypertension and signs of hypoplastic corpus callosum. There was a physiologically meaningful control of vasopressin release in response to water restriction and water load. Plasma vasopressin concentrations (range 1.2--11.9 pg/ml) were of the same magnitude as those of healthy adults, being abnormally high only when related to the hypotonicity of serum observed. Plasma concentrations of angiotensin II were higher than expected from the suppressed levels of plasma renin activity. Blood-pressure response to angiotensin II infusion was increased. Resetting of the osmostat and hypertension may both be explained by lesions of the central nervous system.
Excretion of urinary cyclic adenosine 3',5'-monophosphate (cAMP) was determined in twenty-four children of short stature and in sixteen normal children. Of the patients, eight suffered from anterior panhypopituitarism, six from isolated deficiency or somatotropin, seven had a family history of short stature, and three had growth failure of pre-natal onset. In children suffering from anterior panhypopituitarism or from isolated somatotropin deficiency, excretion of cAMP was found to be depressed. Short-term administration of purified somatotropin in normal therapeutic dose (3.4 mg per 1.7 m2 i.m. daily for 5 days) had no effect on urinary cAMP, but reduced urine volume in all patient groups. During somatotropin treatment there was a positive correlation between changes in urine volume and nitrogen balance (r = 0.67).
The association of precipitating anti-adrenal antibodies with different subgroups of idiopathic Addison's disease were studied. We had previously found these antibodies in patients with the moniliasis-polyendocrinopathy syndrome. Sera of 36 adult patients suffering from different froms of Addison's disease were examined for the presence of adrenal antibodies demonstrable either by immunofluorescence (IFL) or by gel diffusion. 3 of the 17 patients with tuberculous and 17 of 19 patients with idiopathic Addison's disease had IFL antibodies but only one had precipitating antibodies. There was one typical case of Schmidt's syndrome, and four additional cases with Addison's disease combined with diabetes or thyroiditis, who may later develop the syndrome. None of htese patients had precipitating anti-adrenal antibodies. The only patients with precipitating adrenal antibodies had the moniliasis-polyendocrinopathy syndrome. He was not typical as Addison' disease appeared unusually late and he did not have hypoparathyroidism. The presence of precipitating anti-adrenal antibodies in this patient, and the absence of these in other groups of Addison's disease, is further evidence for the association of precipitating antibodies with the moniliasis-polyendocrinopathy syndrome.
Lysinuric protein intolerance (LPI), an autosomal recessive defect of diamino acid transport, is characterized chemically by renal hyperdiaminoaciduria, especially lysinuria, and by impaired formation of urea with hyperammonemia after protein ingestion. Our 20 patients thrived during breast-feeding, but ingestion of cow's milk caused diarrhea and vomiting. When able to select their diet, they rejected all protein-rich foods. They were short staturated and had weak atrophic muscles, osteoporosis, hepatomegaly and often splenomegaly. Four patients were mentally retarded. Fifteen patients had leukocyte counts below 4,000/mm3, and 17 patients had platelet counts below 150,000/mm3. Serum lactate dehydrogenase activity was constantly increased, and transaminase and aldolase activities were often increased. In the infants' livers, changes were only revealed by electron microscopy: increased and vesicular smooth endoplasmic reticulum, and abundance of glycogen particles in the hepatocytes. In the older patients, light microscopy demonstrated clearly limited areas where hepatocytes had large pale cytoplasm and small pyknotic nuclei. The diamino acids lysine, arginine and ornithine had plasma concentrations only one-third to one-half the normal mean; the renal clearances were clearly increased. Oral diamino acid loading tests suggested impaired intestinal absorption. Urea is built in the liver through transformation of ornithine to arginine, and cleavage of arginine to ornithine and urea. The addition of ornithine to an intravenous I-alanine loading prevented the hyperammonemia and normalized the urea production. Therefore, the diet has been supplemented with arginine, and more protein has been added. This therapy has lead to a remarkable catch-up growth in some patients. The pathophysiology of LPI is explained. Because of defective intestinal absorption and incrased renal loss, the diamino acids have a low plasma concentration. Their transport from plasma to hepatocytes is also impaired, and the liver becomes deficient in ornithine. This retards the urea cycle, and leads to postprandial hyperammonemia and protein aversion. The presence of the transport defect in the hepatocytes distinguishes LPI from other hyperdibasicaminoacidurias.
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Congenital chloride diarrhea (CCD) is a rare autosomal recessive disorder, characterized by watery stools with C1- concentration around 150 meq/liter. We have perfused the colon of three patients and their three healthy siblings with different salt solutions containing 36C1- to determine the nature of the colonic defect in CCD. In the controls, net absorption of Na+ and C1- occurred against steep concentration gradients. The influx (lumen-to-plasms flux) of C1- was twice the effux. Omission of HCO3- from the perfusate caused a clear decrease in C1- efflux which suggests a coupling of C1- effux to HCO3- influx. In CCD, net Na+ absorption occurred normally when HCO3- was present in the lumen. However, Na+ absorption was always impaired when the luminal contents were acid, a situation that prevails in CCD. Net K+ secretion was clearly increased. Both influx and efflux of C1- were practically absent. Only slight net secretion occurred along a steep gradient. Net appearance of HCO3- was not observed, in contrast to controls. These findings and earlier studies of ileal function in CCD are best explained by a defect in the C1-/HCO3- exchange mechanism, which operates in both directions in the normal ileum and colon.
Mulibrey (muscle, liver, brain, eye) nanism is probably an autosomal recessive condition characterized by progressive growth failure of prenatal onset, triangular face with hydrocephaloid skull, general thinness and muscular hypotonicity, peculiar voice, venous congestion caused by pericardial constriction, and pigment dispersion and yellowish dots in ocular fundi. Two thirds of the patients had cutaneous nevi flammei and one third cystic fibrous dysplasia of the tibia. Probably a substantial portion of the affected are lost by early abortion and others by infantile death. The physical capacity and life expectancy seem to vary depending on the degree of the cardiac affection.
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