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Biomedical subjects

A Penttilä

Publications and source records attributed to A Penttilä.

At least 109 records · Page 6Linked to original sources

Preneoplastic lesions of human liver.

In a consecutive autopsy series of 95 males, parenchymal hyperplastic nodules of clear cells occurred in 11.6% and liver cell dysplasia (LCD) in 7.4%. These two possible preneoplastic lesions never occurred together. Of the men, 50.5% had been alcoholics or had drunk more than an average of 80 g of alcohol daily, and 65.3% had been smokers, as established by interviewing a family member or a close friend of the deceased. Hyperplastic nodules of clear cells were found in association with liver cirrhosis (p less than 0.005), liver enlargement (p less than 0.025), and heavy alcohol consumption (p less than 0.05), and tended (n.s.) to be associated with smoking. The largest nodules of clear cells were found in nodular regenerative hyperplasia of the liver in a male who had used testosterone. In another case focal nodular hyperplasia coexisted. Hyperplastic nodules showed no association with the occurrence of cavernous hemangioma or benign bile duct tumors. Males with hyperplastic nodules of clear cells were significantly (p less than 0.01) younger (average 49.3 years) than those with LCD (average 61.1 years). Males with LCD were slightly (p less than 0.05) older, tended to have a small-sized liver, but were otherwise comparable with males without precursor lesions. The present results indicate that both hyperplastic nodules and liver cell dysplasia are common findings in male autopsy series comprising alcoholics and smokers. Hyperplastic nodules were associated with some of the predisposing factors of primary hepatocellular carcinoma.

Adult↗

Benign bile duct tumours, non-parasitic liver cysts and liver damage in males.

Pathogenetic associations between benign hepatic tumours and liver damage were studied in an autopsy series of 91 males with high incidence of alcoholism. Information on the consumption of alcohol was obtained by interviewing a family member or a close friend of the deceased. The reported use of alcohol correlated well with the increase of fatty and fibrotic changes and with the occurrence of liver cirrhosis, alcoholic hepatitis or pancreatitis. Benign bile duct tumours (bile duct adenomas and von Meyenburg's complexes) (n = 26) were associated with the occurrence of bridging (P less than 0.0005) and periportal (P less than 0.025) fibrosis of the liver and, independently from these, with chronic pancreatitis (P less than 0.05) and with non-parasitic liver cysts (n = 14) (P less than 0.01). The weight of the liver was greater (P less than 0.01) in males with focal nodular hyperplasia (n = 3). Cavernous hemangioma (n = 19) occurred independently of the parameters studied. None of the tumours showed significant correlation to liver cirrhosis, alcoholic hepatitis, fatty liver or diseases of the gallbladder. The results are in line with observations on the reactive nature and connections to fibropolycystic liver disease of benign bile duct tumours in laboratory animals and in man. Their presence in human liver specimens should be taken into account as a sign of liver damage, in this study related to heavy use of alcohol or to chronic inflammation of the pancreas.

Adult↗

Distribution of beta-adrenoceptor blocking drugs into cerebrospinal fluid in rats.

The distribution into cerebrospinal fluid (CSF) of five 3H- or 14C-labelled beta-adrenoceptor blocking drugs given intravenously was studied in urethane-anaesthetized rats. The doses (mg/kg) were: alprenolol 5, metoprolol 1, oxprenolol 5, pindolol 0.5, propranolol 0.1 and 5. Within 15 min. a marked fraction of the given radioactivity appeared in CSF with all substances. During the follow-up period of 315 min., only propranolol, independently of dose, caused high CSF/plasma ratios (0.54-0.73) of radioactivity. The other four beta-adrenoceptor blocking drugs caused levels of CSF radioactivity which were 0.05-0.28 of that in plasma and 0.05-0.14 of the calculated levels of activity in the whole body. Since propranolol is bound to plasma proteins to a higher degree than the other drugs studied, the penetration of the unbound fraction of propranolol into rat CSF is even more pronounced than what would be expected on the basis of CSF/plasma ratio measured.

Adrenergic beta-Antagonists↗

Occurrence of benign hepatocellular tumors in alcoholic men.

Focal nodular hyperplasia (FNH) and liver cell adenoma (LCA) are benign hepatocellular tumors, found mainly in females in association with the use of oral contraceptives. In adult male clinical patients and in retrospective male autopsy cases, both tumors were often found in association with chronic abuse of alcohol. This association was also found (p less than 0.025) in a prospective autopsy series on alcoholic and non-alcoholic males, in which a family member or close friends of the deceased were interviewed for estimating the consumption of alcohol. Nine of the 12 tumors found in males were FNH and three were LCA. In the average males with FNH were as old (51.0 years) as those with LCA (48.7 years). In two of the FNH cases two tumors were found. In the prospective autopsy series the weight of the liver of males with FNH was significantly (p less than 0.001) higher than that of non-alcoholic controls. A correlation (p less than 0.05), independent of age or liver weight, was found between the size of cavernous hemangioma, another hepatic tumor suggested to respond to estrogens, and daily alcohol dose. It is suggested that alcohol-induced liver cell hypertrophy or the feminizing effect of chronic use of alcohol on male sex hormone metabolism might contribute to the growth of pre-existing benign hepatocellular tumors in males.

Adenoma↗

Screening for barbiturates in vitreous humor by the EMIT-st serum enzyme immunoassay.

In 16 medical examiner's cases, which were found to be barbiturate-positive by thin-layer chromatographic screening of the liver, blood barbiturate concentrations were determined by gas chromatography. The corresponding vitreous humor samples were screened by the enzyme multiplied immunoassay technique, the EMIT-st serum barbiturate assay. By using the recommended dilution for detecting serum barbiturates, it was possible to detect barbiturates in vitreous humor at a toxic concentration. By using one fourth the amount of diluent, the barbiturates could be detected also at a therapeutic concentration. The EMIT-st assay proved to be useful in the screening for barbiturates in vitreous humor, a material that is readily available in forensic toxicology.

Barbiturates↗

Multi-score estimation of catecholamine fluorescence for clinical purposes.

Experience accumulated at multi-score semiquantitation of catecholamine fluorescence of glyoxylic acid-treated stretch preparations of human clinical specimens is presented. The methodology and criteria of quantitation are described in detail. For an example, comparison between 3 different methods for analyzing neural-bound noradrenaline in human myocardial tissue in various heart diseases (obtained during the course of cardiac surgery) is presented: Biochemical determination of tissue noradrenaline content multi-score estimation of catecholamine fluorescence of glyoxylic acid-treated stretch preparations microfluorimetric analysis of the same stretch preparations. The results show that the multi-score estimation method gives a reliable concept of the relative amounts of noradrenaline stored in the intrinsic adrenergic nerve net (corresponding closely to the individual and group differences observed at biochemical noradrenaline determination). In addition, possible regional differences, alterations in the structural integrity of the inbuilt intrinsic nerve net, and other structural changes (e.g. pathological catecholamine accumulations) are easily recognized, whereas biochemical estimation cannot give information on structural aspects, which may have important clinical repercussions. Microfluorimetry does not seem suitable for studies on human myocardial specimens for several reasons which are discussed. The method of multi-score estimation of catecholamine fluorescence described and discussed is recommended for other similar and related studies on human clinical materials.

Catecholamines↗

Bumetanide kinetics in renal failure.

To study the effects of renal failure on bumetanide kinetics, we administered single intravenous doses of 1.0 mg/3.08 microCi 14C-bumetanide to six healthy subjects and 22 patients with variable degrees of renal failure. The kinetics of 14C-bumetanide and total 14C were adequately described by a two-compartment open model in the control subjects and in the patients. The volume of the central compartment and the distribution t1/2 were of the same order in both groups, whereas the mean (+/- SE) volume at steady state was larger (22.1 +/- 1.6 and 16.9 +/- 1.0 L) and the elimination t1/2 was longer (1.9 +/- 0.2 and 1.4 +/- 0.1 hours) in patients with renal failure than in healthy controls. Bumetanide renal clearance was lower (10 +/- 3 and 90 +/- 13 ml/min) in patients than in subjects and correlated with creatinine clearance (r = 0.784) and log serum creatinine level (r = -0.843), whereas nonrenal clearance was significantly higher in the patients (153 +/- 14 and 99 +/- 6 ml/min). Bumetanide total plasma clearance did not significantly change. The non-protein-bound, free fraction of bumetanide was higher in patients and correlated with plasma albumin levels (r = -0.777). The kinetics of total 14C showed similar but greater changes than those of 14C-bumetanide. Thus the most important changes in bumetanide kinetics in patients with renal failure are low renal clearance and a high free fraction, with a consequent increase in nonrenal clearance, volume of distribution, and elimination t1/2.

Acute Kidney Injury↗

Changes in germinal tissue and Leydig cells correlated with ethanol consumption in males with and without liver disease.

The weight of testicles and morphometric changes in testicular germinal tissue and Leydig cells were correlated with chronic consumption of ethyl alcohol and liver diseases in 44 consecutive autopsies. The mass and volume of seminiferous tubules decreased with the increase in alcohol consumption (p less than 0.05). The atrophy and fibrosis of testicles were most advanced in males with liver cirrhosis (p less than 0.005) and in males with moderate or heavy fatty liver (p less than 0.01) whereas these parameters were only slightly decreased in alcoholic males with normal liver despite the greater amount of ethanol consumed. The changes in Leydig cells were mainly inconspicious. These results indicate that the most sensitive tissue to chronic alcohol-induced injury in testis is the germinal tissue and point out the role of liver diseases in testicular damage found in alcoholics.

Alcoholism↗

Pharmacokinetics of tolfenamic acid: disposition in bile, blood and urine after intravenous administration to man.

To study its pharmacokinetics and especially microCi/100 mg was infused i.v. in 8 patients with a T-tube inserted in the common bile duct at choledocholithotomy 7-10 days prior to the study. Bile was collected in fractions by continuous suction over a 24 h period. Blood samples were taken and urine collected up to 48 h after the dose. Tolfenamic acid and its metabolites were separated by TLC and were quantitated by liquid scintillation counting. The pharmacokinetics of tolfenamic acid could be described by a two compartment open model with V1 of 3.67 +/- 0.681 and VSS of 8.0 +/- 1.01. The total plasma clearance of tolfenamic acid averaged 106 +/- 8 ml/min and t1/2 beta was 1.38 +/- 0.32 h. A three compartment open model was required to describe the kinetics of total 14C. The plasma clearance of total 14C was 15.4 +/- 3.9 ml/min and its terminal half life averaged 19.0 +/- 4.1 h. The long half-life was caused by the slow elimination of tolfenamic acid metabolites. Four metabolites were measured in plasma and bile. The principal metabolites in bile were glucuronide/sulphate conjugates of hydroxylated derivatives of tolfenamic acid. The recovery of tolfenamic acid in bile was 1.1 +/- 0.3% of the dose, whereas the recovery of total 14C was 18.6 +/- 4.9%. The biliary clearances of tolfenamic acid and total 14C were 1.2 +/- 0.3 and 5.0 +/- 2.1 ml/min, respectively. Thus, biliary excretion plays a considerable part in the pharmacokinetics of tolfenamic acid.

Aged↗

Clinical versus autopsy diagnosis of cranio-cerebral injury.

The accuracy of the clinical diagnoses of the victims who died at the Department of Neurosurgery, Helsinki University Central Hospital in 1975 and 1976 of a lethal injury to the head was investigated. Standard clinical and X-ray means were used without computed tomography whose value as an additional tool will be reported later. Most of the patients were traffic accident victims of which 71% died within 24 h after trauma. The rate of the correct diagnoses of fractures was 87% in the vault, 76% at the base of the skull, and 67% in the facial bones. Of all intracranial lesions, 75% were correctly and 9% partially diagnosed. The discrepancy would have been more marked if such entities as cerebral contusion and laceration and hemorrhage had been presented separately. This study indicates that many head injuries remained undiagnosed by standard clinical means. The value of X-ray examination also appeared small in the postmortem diagnostics of skull fractures and intracranial lesions.

Adolescent↗