Rupture of splanchnic artery aneurysms

The results of surgical therapy for acute ruptured splanchnic artery aneurysms in 6 patients treated at Helsinki University Central Hospital from 1964 to 1984 were analyzed. There were 3 patients with ruptured splenic, 2 with ruptured hepatic and 1 with ruptured superior mesenteric artery aneurysms. The condition remained undiagnosed in all patients preoperatively, and the diagnosis was obtained only at emergency laparotomy performed for severe shock, abdominal pain, and distension. Five of the 6 patients survived, including a pregnant woman, who gave birth to a living baby by ceserean section. The results indicate that immediate, aggressive surgical approach dictated by the clinical condition of the patient affords good survival in patients suffering from acute rupture of splanchnic artery aneurysms.

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Resumen Se analizan los resultados del tratamiento quirúrgico de la ruptura aguda de aneurismas de arterias esplnicas en 6 pacientes manejados en el Hospital Central de la Universidad de Helsinki en el periodo 1964–1984. Se presentaron 3 pacientes con ruptura de aneurismas de la arteria esplénica, 2 de la hepática y 1 de la mesentérica superior. La condición clínica se mantuvo sin diagnóstico durante la fase preoperatoria, y el diagnóstico sólo fue hecho en el curso de la laparotomía, procedimiento que fue realizado por shock severo, dolor abdominal y distensión. Cinco de los 6 pacientes sobrevivieron, incluyendo una mujer embarazada, quien dio a luz un niño vivo mediante sección cesárea. Los resultados indican que el enfoque quirúrgico inicial agresivo indicado por la condición clínica del paciente ofrece una buena oportunidad de supervivencia en pacientes que presentan ruptura de aneurismas de las arterias esplácnicas.

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Résumé Les résultats du traitement chirurgical de 6 ruptures d'anévrysmes des artères splanchniques traités à l'Hôpital Central Universitaire d'Helsinki de 1964 à 1984 sont étudiés par les auteurs. Ils concernent la rupture anévrysmale de 3 artères spléniques, de 2 artères hépatiques, de 1 artère mésentérique. Le diagnostic ne fut porté qu'au moment de l'intervention d'urgence pratiquée en présence d'un état de choc sévère s'accompagnant de douleur et de distension abdominales. Cinq des 6 opérés ont survécu, dont une femme enceinte chez qui une césarienne fut pratiquée avec succès. Ces résultats plaident en faveur de l'action chirurgicale d'urgence.

     

The midsagittal area of the corpus callosum and total neocortical volume differ in three inbred strains of mice

Differences in the midsagittal area of the corpus callosum have been reported between human males and females, between handled and nonhandled rats, and both within and between various strains of mice. This measure has, in addition, been related to handedness in humans and "pawedness" in certain strains of mice. The present study investigated the between- and within-strain differences in three inbred strains of mice, two with autoimmune disorders and spontaneously occurring developmental neuropathology, in the midsagittal area of the corpus callosum, the total neocortical volume, and the asymmetry of the neocortex. These morphometric measures were obtained from coronally sectioned celloidin-embedded material from New Zealand Black (NZB/BINJ), BXSB/MpJ, and DBA/2J mouse strains. NZB mice had a total neocortical volume larger than that of either the BXSB or DBA strains, whereas the BSXB mice had a midsagittal area of the corpus callosum larger than that of either of the other two strains. In addition, there was a positive correlation between these two measures. There was no correlation between total neocortical asymmetry and midsagittal area of the corpus callosum in any of the three strains. Finally, there were no differences in any morphometric measure between animals with or without developmental neuropathology in any given strain.     

Biotransformation of lovastatin--III. Effect of cimetidine and famotidine on in vitro metabolism of lovastatin by rat and human liver microsomes

The effects of the H2-receptor antagonists, cimetidine and famotidine, on the microsomal metabolism of [14C]lovastatin were investigated. Liver microsomes were prepared from control, phenobarbital- and 3-methylcholanthrene-pretreated rats and humans (male and female). Concentration-dependent inhibition of the metabolism of lovastatin (0.1 mM) was observed with cimetidine (0.1 to 1.0 mM). In contrast, famotidine at a similar concentration was a very weak inhibitor. The formation of 6'beta-hydroxy-lovastatin, the major microsomal metabolite of lovastatin, was similarly inhibited. The results suggest that in vivo metabolic interaction with concomitantly administered lovastatin is less likely with famotidine than with cimetidine. Phenobarbital pretreatment produced 58% stimulation in overall metabolism, whereas 3-methylcholanthrene pretreatment had no effect relative to control rats (5.4 nmol/mg protein/min). Liver microsomes from phenobarbital-pretreated rats produced 67% more of the 6'beta-hydroxy-lovastatin but 63-66% less of the 3'-hydroxy and 6'-exomethylene metabolites. Liver microsomes from 3-methylcholanthrene-treated rats also produced less 3"-hydroxy-lovastatin (49%) but similar quantities of the other two metabolites. 6'beta-Hydroxy-lovastatin was a major metabolite with human liver microsomes. Interestingly with these microsomes, hydroxylation at the 3'-position of the molecule was a negligible pathway and hydrolysis to the hydroxy acid form was not observed. The formation of 6'-exomethylene-lovastatin was also catalyzed by human liver microsomes (0.5 to 0.8 nmol/mg protein/min).     

Inhomogeneous exercise uptake and accelerated washout of a radioiodinated fatty acid analogue in syndromeX A SPECT study of the left ventricle

Myocardial metabolism in exercise was determined by studying 21 syndromeX patients and 14 healthy volunteers with an aromatic fatty acid analogue IPPA and a gamma camera. We developed criteria for visual semiquantitative assessment of relative segmental radiotracer uptake and washout, and tested a new computer program for quantitative evaluation. One volunteer (7%) and 12 patients (57%) showed visually inhomogeneous uptake (p=0.006, ²-test) in SPECT polar tomograms after a maximal ergometry test. Images in none of the volunteers and seven patients (33%) gave the impression of a slowed regional washout (p=0.057). Only six patients (29%) had a normal radial polarogram. Patients with irregular coronary angiograms (showing slow flow or minor sclerosis) and those with chest pain during the IPPA exercise test had a very low frequency of normalcy, but this was not significant.Total washout was higher in patients than in the reference population, as the exercise to rest activity ratio was 1.36 SD 0.13 versus 1.25 SD 0.11 in computerized quantitation (p=0.015, t-test). Washout did not correlate with age, sex or exercise heart rate. Regarding computerized analysis of uptake and slow washout, the number of deviant segments was not significantly higher in patients than in reference population. Semiquantitative and quantitative analysis correlated in the assessment of uptake, but not in the assessment of washout. Possible reasons for the discrepancy are discussed.Conclusions of this study are not straightforward. SyndromeX was associated with inhomogeneous IPPA uptake, which is not at variance with the theory of microvascular dysfunction. On the other hand, the analysis of washout presumably implies higher fatty acid utilization in patients than in normal controls, which is not a characteristic phenomenon in myocardial ischemia.     

Biomarkers of styrene exposure in lamination workers: levels of 06-guanine DNA adducts, DNA strand breaks and mutant frequencies in the hypoxanthine guanine phosphoribosyltransferase gene in T-lymphocytes

Occupational exposure to styrene was studied in nine workersof a hand lamination plant in Bohemia. Personal dosimeters wereused to monitor the styrene workplace exposure, and the levelsof styrene in blood and mandelic acid in urine were measured.Blood samples were taken at four occasions during a 7 monthperiod to determine styrene-specific 0⁶-guanine DNA adductsin lymphocytes and granulocytes, DNA strand breaks and hypoxanthineguanine phosphoribosyltransferase (HPRT) mutant frequency inT-lymphocytes. Seven administrative employees in the same factory(factory controls) and eight persons in a research laboratory(laboratory controls) were used as referents. DNA adduct levelsdetermined by the ³²P-postlabelling method in lymphocytes oflamina-tors were remarkably constant and significantly higher(P < 0.0001) than in factory controls at all four samplingtimes. HPRT mutant frequencies (MF) measured by the T-cell cloningassay were higher in the laminators (17.5 x10^–6, groupmean) than in the factory controls (15.7x10^–6, group mean)at three of the four sampling times, but the differences werenot statistically significant. However, a statistically significant(P = 0.021) difference between MF in the laminators (18.0 x10^–6,group mean) and laboratory controls (11.8 xl0^–6, groupmean) was observed at sampling time 4 (the only sampling timewhen this latter group was studied). This result indicates thatstyrene exposure may induce gene mutation in T-cells in vivo.DNA strand breaks were studied by the ‘Comet assay’at the fourth sampling time. The laminators were found to havesignificantly higher levels of DNA strand breaks than the factorycontrols (P = 0.032 for tail length, TL; P = 0.007 for percentageof DNA in tail, T%; and P = 0.020 for tail moment, TM). A statisticallysignificant correlation was also found between the levels oflymphocyte DNA adducts and all three DNA strand break parameters(TL P = 0.046; T% P = 0.026 and TM P = 0.034). On the contrary,no significant correlations were found between DNA adduct levelsand the HPRT mutant frequencies or between the mutant frequenciesand DNA strand breaks. Taken together, these results add furthersupport to the genotoxic and possibly mutagenic effects of styreneexposure in vivo. However, no simple quantitative relationshipseems to exist between the levels of styrene-induced DNA damageand frequency of HPRT mutation in T-lymphocytes.     

Piriformis pyomyositis mimicking epidural abscess in a parturient

A case is presented of a patient who developed fever, leukocytosis, severe back pain, local overlying spinal tenderness, and left leg weakness on the fifth day postpartum. The patient had epidural anaesthesia for ten hours duration, before and during a forceps delivery. Computerized axial tomography (CT) and magnetic resonance imaging (MRI) of the pelvis and lumbar spine revealed swelling of the left iliacus and piriformis muscles, but no epidural abscess. A diagnosis of isolated piriformis pyomyositis with secondary sciatic nerve irritation was made, and the patient was treated with intravenous antibiotics, non-steroidal anti-inflammatory agents, and morphine analgesia. She made a full, uneventful recovery within 50 days, and was discharged requiring no medications.     

Distribution of bratton-marshall-positive material in mice following intravenous injections of nitrosoureas

Summary As determined by a colorimetric assay measuring parent compounds plus ether-extractable, nitroso-containing metabolites, N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) disappeared more rapidly than N-(2-chloroethyl)-N cyclohexyl-N-nitrosourea (CCNU) and N-(2-chloroethyl)-N-(4-transmethylcyclohexyl)-N-nitrosourea (MeCCNU) and their products from the tissues of mice injected IV. Assay of selected samples by high-pressure liquid chromatography revealed that the colorimetric assay for BCNU was specific in that the two assays gave equivalent results. Following IV-injections of CCNU and MeCCNU, however, levels of the parent compounds decreased much more rapidly than the total, color-producing material.Of seven tissues, the largest Cxt values for BCNU, as determined by the colorimetric assay, were noted for blood (442 g-min/ml) and large intestine (285 g-min/g). Liver (29 g-min/g) had the lowest Cxt value, reflecting rapid metabolism of the compound by this organ. Color-producing material related to CCNU disappeared from the solid tissues of mice in a manner generally parallel to that for blood. Of the Cxt values for this compound and its products, those for lung (1753 g-equivalents-min/g), kidney (1633 g-equivalents-min/g), and small intestine (1557 g-equivalents-min/g) were highest. Consistent with its slower rate of metabolism, MeCCNU and its color-producing metabolites remained in most tissues of mice for 12 h following injection. Except for brain (1434 g-equivalents-min/g), Cxt values for this nitrosourea and its metabolites in tissues were higher than those of blood (5485 g-equivalents-min/ml), with kidney (15,324 g-equivalents-min/g), liver (12,921 g-equivalents-min/g), and large intestine (11,501 g-equivalents-min/g) being highest. For each nitrosourea, a fair correlation was observed between the Cxt values for tissues and the toxic and/or antitumor effects at those sites.     

Effect of Different Respirator Adjustments on Central Haemodynamics in Open-Heart Surgery Patients

Changes in cardiac index (CI) mean pulmonary artery pressure (PAP), mean pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and pulmonary artery vascular resistance (PVR), associated with spontaneous respiration (SR) and two different types of intermittent positive pressure ventilation (IPPPV and IPNPV) were studied in a total of 17 patients undergoing aortic valve replacement or myocardial revascularization. Swan-Ganz thermodilution pulmonary artery cardiac output catheters were used and the aim was to determine: whether postoperative cardiac output may paradoxically be greater during IPPPV than during IPNPV or SR; whether the use of "negative" pressure in the expiratory phase during controlled ventilation may be responsible for bringing about the central haemodynamic conditions prevailing during spontaneous respiration; and whether, in weaning from postoperative IPPPV to SR, there is a risk of pulmonary congestion as a consequence of possible autotransfusion. IPPPV connected with anaesthesia induction caused a highly significant deterioration central haemodynamics. The use of positive end-expiratory pressure (PEEP) is not to be recommended for such patients at this stage. On the first postoperative day, the mean CI was lower during IPPPV than during IPNPV (P less than 0.1) or during SR (P less than 0.05). The changes observed in CI, were, however, so slight that the authors consider the routine use of PEEP to be beneficial during controlled ventilation following major open-heart surgery. In some patients, the CI was paradoxically higher during IPPPV than during IPNPV or SR. The mean CI was nearly the same during IPNPV (3.32) as during SR (3.38). However, PAP, PCWP and PVR values were significantly higher during SR than during IPNPV. Thus, according to this study, the use of "negative" end-expiratory pressure during controlled ventilation did not in these patients produce central pressure conditions corresponding to spontaneous respiration. The present study supports the finding that in weaning from controlled ventilation with PEEP to SR there is a danger of pulmonary congestion. This could be predicted by measurement of pulmonary wedge pressure, but not by measurement of central venous pressure.     

Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus monkey.

Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal reabsorption of a drug. Drug recycling through EHR can lead to a change in pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half-life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong the pharmacological effect of drugs. In the present study, the compound (Cpd A) was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from 2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A population four-compartment model was constructed based on recirculation loops incorporating all possible inputs (bile secretion, a lag-time model for gall bladder emptying, routes and amounts of a single dose administration) to fully evaluate the EHR of Cpd A. The plasma concentrations versus time profiles predicted from the model had a good fit to the values observed in the subjects and were further simulated with 90% confidence interval to demonstrate its utility. Thus, the model could be applied as a useful tool to evaluate the drugs or compounds that undergo EHR in different species.     

Familial lung cancer and aggregation of smoking habits: a simulation of the effect of shared environmental factors on the familial risk of cancer.

BACKGROUND: Tobacco smoking is the principal cause of lung cancer. The risk of lung cancer in the offspring of lung cancer patients is about twice higher than the risk in the general population. The present study investigated the contribution of shared smoking habits to the familial clustering of lung cancer. METHODS: We estimated the relative risk of lung cancer attributable to smoking according to the extent to which smokers transmit their smoking habits to the offspring (heritability of smoking), the prevalence of smoking in the general population, and the risk of lung cancer for smokers compared with nonsmokers. FINDINGS: The relative risk of lung cancer for the offspring of lung cancer patients attributable to smoking was 1.19 when published data on smoking practice were modeled (i.e., assuming that the heritability of smoking was 0.5, the smoking prevalence 40%, and the odds ratio of lung cancer for smokers versus nonsmokers was 20). INTERPRETATION: Most familial cases of lung cancer cannot be attributed to shared smoking habits. The example of smoking can be used for other familial cancers, for which no strong environmental risk factors are usually known, to infer the primary role for heritable genes.