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The antenatal ultrasonographic findings in a fetus with a left-sided congenital posterolateral diaphragmatic defect (CPLDD) are presented and discussed. Displacement of the heart towards the right and absence of a normally positioned fluid-filled stomach at repeated examinations are diagnostic. In the event of an intrathoracically displaced fetal stomach, which occurs in about 60% of the cases, a sonolucent area in the left chest may be found. In view of the dynamic nature of fetal stomach filling, more than one examination may be required to detect this feature. Antenatal recognition of congenital diaphragmatic hernia (CDH) has important consequences for perinatal management and can improve neonatal outcome.

Repair of a congenital posterolateral diaphragmatic defect (CPLDD) by direct suture results in a flat drum-head diaphragm, which has very little function. Other harmful effects of such a repair include enlargement of the thoracic cavity, resulting in more overexpansion of the hypoplastic lungs which may contribute to pulmonary vascular obstruction, and decrease in volume of the abdominal cavity, making closure of the laparotomy difficult. Reconstruction of a diaphragmatic dome would result in a more functional diaphragm and would prevent the above complications. This was substantiated in a series of 10 babies, all severely symptomatic from birth and treated according to the proposed technique. Eight babies survived, the two deaths occurring 36 hours and 3 months after surgery, in babies with severe cardiac anomalies. It is concluded that reconstruction of the dome of the diaphragm in patients with a CPLDD is well tolerated and may result in an increased survival.

A phenotypic boy presenting with gynaecomastia showed a mixed karyotype of 46,XX/46,XY/47,XXY. The left gonad was normally descended into the scrotum, but proved to be an ovary without any testicular structures. After left gonadectomy, plasma androgen and estrogen levels showed that the right gonad only contained testicular tissue. Seven patients with this form of triple mosaicism have been described but the clinical features are strikingly different among the described cases.

An experimental study was carried out investigating the feasibility of using only a portion of a donor liver in orthotopic, nonauxiliary transplantation, establishing a canine model. After being totally hepatectomized, 20 immunosuppressed adult beagles received a 60% donor liver graft, derived from tissue-typed identical littermates. Preservation time was 5 hr. In control experiments, 10 beagles, only half of them immunosuppressed, underwent an operation involving complete liver mobilization, vascular exclusion, cooling of the liver in situ, and a 40% partial hepatectomy with biliary anastomosis. The surgical procedure, including the method of cooling and preservation, is described in detail. Survival rate amounted to 90% for the control group and 50% for the transplanted group, while all surviving dogs were sacrificed 24 wk postoperatively. At sacrifice, the liver weight amounted to the weight of the total native liver at operation. Body weight profiles reflect good general condition of the surviving dogs. No major differences were noted between the immunosuppressed and the nonimmunosuppressed control dogs. No complications were related to the fact that only a partial liver was grafted or left in situ.

Perforation of the appendix in the neonatal period may be a complication of neonatal necrotizing enterocolitis and should be differentiated from perforating appendicitis in later life. A patient is presented together with a review of the literature to illustrate this concept. Perforation of the appendix occurred in a 12-day-old preterm baby. Th cause of this perforation is assumed to be localized full thickness necrosis of the appendiceal wall, a form of neonatal necrotizing enterocolitis. The similarity between the clinical histories of neonates with so called "appendicitis" and those with necrotizing enterocolitis is pointed out. It is argued that "idiopathic primary peritonitis" probably does not exist, but that the peritonitis may be secondary to similar small perforations of the bowel. The importance of a thorough search for such a perforation is stressed.

1. Blood clearances of lignocaine and indocyanine green together with indocyanine green half-lives were measured in 17 post-myocardial infarct patients (one patient was studied twice) between 8 h and 36 h after starting intravenous lignocaine infusions for the treatment of cardiac arrhythmias. 2. Mean +/- s.d. values of lignocaine clearance (ml min-1 kg-1) were higher in patients without heart failure (11.8 +/- 2.6, n = 9) than in those with heart failure (7.2 +/- 1.9, n = 9) (P < 0002). 3. Clearances of lignocaine and indocyanine green were not correlated but lignocaine clearance was directly related to the reciprocal of indocyanine green half-life (rs = 0.67, P < 0.01). 4. In eight patients who received both lignocaine and indocyanine green and in a further five patients received only lignocaine and whose lignocaine infusions lasted 24h or more, a 25% rise in lignocaine concentrations was observed between 8-12h and 24-28h. 5. The mean +/- s.d. post-infusion terminal half-life of lignocaine in four patients whose lignocaine infusions lasted 30h or longer was 7.2 +/- 2.1 h. 6. Heart failure was associated with greater changes in lignocaine kinetics than in indocyanine green kinetics. 72% of the variance between observed and predicted lignocaine clearances could be accounted for by multiple linear regression analysis incorporating indocyanine green half-life and the presence or absence of heart failure. Indocyanine green half-life contributed only 17% of the variance indicating that by itself it is of limited value in predicting lignocaine requirements. 7. Lignocaine kinetics during and after prolonged intravenous infusion were not predicted by data obtained after intravenous bolus injection. 8. A lowering of lignocaine dosage may be clinically desirable in the presence of heart failure and if an infusion lasts longer than 24 h.

The effects of three beta-adrenoceptor antagonists (propranolol, metoprolol and atenolol) on the serum kinetics and pharmacodynamics of warfarin given in a single oral dose (15 mg) were studied in six normal subjects. At the same degree of beta-adrenoceptor blockade, as assessed by the decrease of exercise tachycardia, propranolol increased the area under the serum warfarin concentration time curve (AUC) by 16.3 +/- 14.2 s.d.% (P less than 0.01) and the maximum serum warfarin concentration by 23.0 +/- 14.3 s.d.% (P less than 0.001). Atenolol increased the maximum serum warfarin concentration by 12.5 +/- 12.3% s.d. (P less than 0.05) but was without effect on warfarin AUC. Metoprolol had no effect on warfarin kinetics. The extent of changes in the prothrombin time and the plasma clotting Factor VII activity caused by warfarin were not altered by any of the beta-adrenoceptor antagonists.

Differences in the coagulation patterns between humans and dogs and the lack of reagents in the veterinary field to control haemostasis require a modification of existing screening techniques. The adaptations which were applied and which are described in this paper consist of greater dilutions of the samples. Two modified screening techniques in blood and plasma are described. The normal values of the different clotting factors and thrombokinetics, (thrombokinetogram, T.K.G.), using a normal beagle pool as a reference, are presented.

1 The cardiac effects of disopyramide (D) and lignocaine (L) were measured and compared in normal volunteers (D n=4; L n=3) following the establishment of a series of three steady-state drug plasma concentrations spanning the therapeutic range (1.5-5 micrograms base ml-1). 2 During control and steady-state periods multiple measurements were made of heart rate, blood pressure, drug concentrations and echocardiographic measurement of cardiac dimensions and estimated left ventricular function. 3 No change in heart size or estimated function occurred with L except for a small increase in estimated cardiac output (+0.5 1 min-1) secondary to a small rise in heart rate (maximum +7 beats min-1). Blood pressure rose slightly (maximum +11 mmHg). 4 D caused an increase in heart size, marked at end systole (+0.63 cm), and a decrease in echo indices of ventricular function (25-33%). These changes were related to plasma drug concentration but were not reflected in cardiac output estimation since heart rate rose (+15 beats min-1). Blood pressure also rose (+10 mmHg). 5 Significant differences were shown between D and L at similar plasma drug concentrations. The negative inotropic effect of D may be greater than previously suggested and clinically important.

A congenital hemangiopericytoma of the lower lip, first detected by prenatal ultrasound, was only partially resected and involuted over the next 20 months.

1 The effects of two beta-adrenoceptor antagonists (propranolol and metoprolol), and of the beta-adrenoceptor agonist, terbutaline, on the plasma kinetics of antipyrine were studied in five normal subjects. In addition, the influence of propranolol on the clearance of antipyrine to three of its major metabolites was investigated. 2 At the same level of beta-adrenoceptor blockade, assessed by lowering of exercise tachycardia, propranolol decreased antipyrine clearance by 37.3 +/- 9.9 s.d. % (P less than 0.001) and metoprolol decreased it by 18.0 +/- 4.7 s.d. % (P less than 0.01). Terbutaline had no effect on antipyrine clearance. The volume of distribution of antipyrine was unchanged following treatment with all three drugs. 3 Only the metabolic clearance of antipyrine to its 3-hydroxymethyl product was impaired to a statistically significant degree by propranolol. However, four of the five subjects also showed impaired clearance to 4-hydroxyantipyrine and three of the five to norantipyrine after propranolol treatment. In four of the five subjects propranolol lowered the renal clearance of antipyrine. 4 Inhibition of the metabolism of antipyrine by beta-adrenoceptor antagonists may be related to their lipid-solubility and extent of metabolism and is independent of their effect on beta-adrenoreceptors.

The effects of two beta-adrenoceptor antagonists, penbutolol (administered on separate occasions as (+/-)- and (-)-forms) and propranolol, on the kinetics of antipyrine were studied in eight normal subjects. At the same degree of beta-adrenoceptor blockade, as assessed by the lowering of exercise tachycardia, propranolol decreased antipyrine clearance by 31 +/- 11 s.d.% (P less than 0.001) whereas neither of the two penbutolol formulations had a significant effect. The volume of distribution of antipyrine was unchanged following any of the beta-adrenoceptor antagonist treatments. The lack of effect of penbutolol on oxidative drug metabolism is not consistent with in vitro data suggesting a relationship between the lipid solubility of beta-adrenoceptor antagonists and inhibition of metabolism.

In theory, beta-adrenoceptor antagonists could lower the clearance of free lignocaine in three ways (a) by decreasing hepatic blood flow, (b) by competing for plasma binding sites or (c) by inhibiting the enzymes responsible for metabolising lignocaine. The first mechanism has been demonstrated for propranolol and is probably common to all agents lacking intrinsic sympathomimetic activity. The second mechanism is discounted by data showing that propranolol, one of the more highly bound beta-adrenoceptor antagonists, does not alter the free fraction of lignocaine in plasma. In vitro studies support the third mechanism for the more lipid-soluble beta-adrenoceptor antagonists, as does the fact that observed decreases in the clearance of lignocaine in vivo are generally greater than the anticipated maximum lowering of hepatic blood flow.

To account for a 40% lowering of the systemic clearance of lignocaine by propranolol treatment it has been proposed that propranolol reduces liver blood flow by 25% and causes a 50% decrease in the intrinsic clearance of lignocaine by enzyme inhibition. In theory, the contribution of direct enzyme inhibition is best evaluated using oral administration of lignocaine when models of hepatic drug clearance predict that propranolol could increase the AUCpo of lignocaine by 100-140%. This hypothesis was tested in six healthy men who received 200 mg lignocaine HCl X H2O orally with and without propranolol pre-treatment (80 mg twice daily for 3 days). Propranolol treatment increased the mean plasma AUCpo of lignocaine by 113 +/- 58 s.d.% (P less than 0.005); it increased the peak plasma lignocaine concentration by 79 +/- 50 s.d.% (P less than 0.025) and it prolonged the elimination half-life of lignocaine by 20 +/- 13 s.d.% (P less than 0.05). Propranolol treatment lowered indocyanine green clearance by 11 +/- 15 s.d.%, but this change was not significant statistically. These experimental results are in accord with the theoretical predictions suggesting that propranolol lowers the systemic clearance of lignocaine mainly by direct inhibition of its metabolism rather than by a lowering of the hepatic blood flow.

We describe 4 patients with a neonatal small left colon. From these cases and from the literature we know that in 40 to 50% the mother has diabetes mellitus. We describe the differential diagnosis with morbus Hirschsprung, meconium plug and the occurrence of a microcolon in atresias and meconium ileus. Three of the four patients were prematures. From the literature we know this abnormality is found mostly in term infants.