Effects of hydralazine on cardiac performance in infants receiving extracorporeal membrane oxygenation

To determine the effects of afterload reduction on cardiac performance during partial cardiopulmonary bypass, we administered hydralazine to infants who were either normotensive (n = 11) or hypertensive (n = 12) 1 hour after extracorporeal membrane oxygenation (ECMO) was begun. Load-dependent and load-independent measures of cardiac performance and indexes of cerebral blood flow were measured. Infants in both groups had similar weight, heart rate, blood pressure, and inotropic support before ECMO. Shortening fraction was normal in both groups before ECMO (47 +/- 11% vs 49 +/- 10%; p greater than or equal to 0.05), decreased during ECMO (31 +/- 18% vs 39 +/- 12%; p greater than or equal to 0.05), and did not change after administration of hydralazine (31 +/- 12% vs 37 +/- 8%; p greater than or equal to 0.05). Cardiac output was normal in both groups before ECMO (176 +/- 71 vs 157 +/- 72 ml/kg per minute; p greater than or equal to 0.05), decreased during ECMO (120 +/- 80 vs 105 +/- 64 ml/kg per minute; p greater than or equal to 0.05), and did not change after hydralazine administration. Velocity of circumferential fiber shortening, an index of contractility (circumference per second), was normal in both groups before ECMO (1.96 +/- 0.57 vs 1.90 +/- 0.43 circ/sec; p greater than or equal to 0.05), decreased during ECMO (1.18 +/- 0.83 vs 1.56 +/- 0.58 circ/sec; p greater than or equal to 0.05), and did not change after hydralazine administration. The relationship between velocity of circumferential fiber shortening and wall stress was similar in both groups before ECMO, during ECMO, and after hydralazine administration. The cerebral blood flow resistance index was similar in both groups before ECMO (0.70 +/- 0.16 vs 0.70 +/- 0.20; p greater than or equal to 0.05), decreased during ECMO (0.45 +/- 0.13 vs 0.43 +/- 0.09; p greater than or equal to 0.05), and did not change after administration of hydralazine. We conclude that hydralazine does not improve cardiac performance during ECMO.     

Mutagenicity of o-anisidine to the bladder of lacI- transgenic B6C3F1 mice: absence of 14C or 32P bladder DNA adduction

Earlier studies have established that the rodent bladder carcinogeno-anisidine (OA) gives negative results hi all of the standardrodent genetic toxicity assays. In the present study, a singleoral administration of the maximum tolerated dose level (750mg/kg) of OA to B6C3F1 mice yielded negative results in ³²P-post-labellingassays of bladder and liver DNA (24 h after dosing). Likewise,¹⁴C-ring-labelled OA administered orally to B6C3F1 mice gaveno evidence of DNA binding 6, 12 or 24 h later. Administrationof OA (750 mg/kg) to transgenic lacl{small tilde} mice (BigBlue^TM led to a small increase in mutation frequency (MF) inthe bladder, but not in the liver. Increased MFs were observedin the bladder following 1, 3 or 10 daily doses with samplingtimes of 1 or 2 weeks after the final dose. However, statisticalsignificance (P < 0.01) was only reached 2 weeks after either3 or 10 daily administrations of OA. The positive control chemical(dimethylnitrosamine) gave a positive result (P < 0.01) inthe liver, but not the bladder, 7 days after a single administrationof 10 mg/kg. The possibility that OA is mutagenic and carcinogenicto the rodent bladder via formation of radical species is suggested.     

Contraceptive effects of levonorgestrel implants in a marsupial

The effect of subcutaneous levonorgestrel implants on reproduction in female tammar wallabies was investigated during the breeding and non-breeding season. Female tammars were given either a control or a levonorgestrel implant and their pouch young were removed to terminate embryonic diapause. Both the control and the levonorgestrel-implant animals treated during the months of May and June gave birth, demonstrating that levonorgestrel does not prevent the reactivation of the diapausing blastocyst or its subsequent development when given at these times. However, none of the levonorgestrel-treated animals mated post partum, whereas all of the control females that gave birth had a post partum oestrus and mated. Control animals gave birth again when the neonate was removed, and continued to breed normally during the following 36 months of the investigation. None of the levonorgestrel-treated animals gave birth again or mated during the next 36 months. Animals given control implants during December did not reactivate or give birth until the normal start of the breeding season in late January. Animals treated with levonorgestrel implants during December did not reactivate with the control animals at the beginning of the breeding season and did not give birth during the next 36 months. There were no effects of levonorgestrel treatment on early lactation. Levonorgestrel implants were removed from six females and four of these animals resumed reproductive activity, confirming that the contraceptive effect of the implants is reversible. Levonorgestrel implants therefore provide a highly effective, reversible and long-term method of contraception for tammar wallabies. This contraceptive system appears to offer a method of population control for the management of overabundant captive and selected wild populations of macropodid marsupials.     

Oligohydramnios sequence and renal tubular malformation associated with maternal enalapril use

We present the case of a child who died of pulmonary hypoplasia as a result of the oligohydramnios sequence. The mother was taking enalapril, as well as propranolol and hydrochlorothiazide, for treatment of hypertension associated with systemic lupus erythematosus. Autopsy examination revealed severe renal tubular malformation. Correlation of animal data with previous case reports of neonatal anuria in association with maternal angiotensin converting enzyme inhibitors suggests that these agents may have a deleterious effect on fetal renal development and general well-being.     

Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia

To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed.     

Role of intraoperative fibrinolytic therapy in acute arterial occlusion

Nineteen patients with acute onset of ischemia affecting the lower extremities were studied from January 1985 to March 1987. Patients with preoperative Doppler and angiographic studies consistent with arterial occlusions subsequently underwent a thromboembolectomy using a Fogarty catheter. All patients were given a bolus injection of 5,000 units of heparin intravenously at the start of the surgical procedure. In all patients studied, a clot was retrieved on the first pass, but after two additional passes, total distal blood flow was not shown to be restored on angiogram. Intraoperative angiograms showed distal emboli. All patients underwent intraoperative fibrinolytic therapy by local bolus infusion. Streptokinase, ranging from 50,000 to 200,000 units, was administered in 50,000 unit injections in ten to 15 minute intervals. Repeat attempts at thromboembolectomy with the Fogarty catheter resulted in an additional clot retrieved in all 19 patients with intraoperative angiographic, Doppler and clinical improvement. No perioperative or postoperative complications were observed, including anaphylactic reactions, uncontrollable bleeding or amputation. Four patients had nonacute femoropopliteal bypass operations within the next six months. Intraoperative fibrinolytic therapy can be a safe and effective adjunct in acute arterial embolic occlusion requiring balloon catheter thromboembolectomy.     

The treatment of malignant cerebral tumours

Malignant cerebral tumours are uncommon. While a large proportion are resistant to conventional therapies there are a significant number of curable malignant brain tumours that require recognition and appropriate therapy.     

Extracorporeal membrane oxygenation in the management of respiratory failure in the newborn

The history of ECMO and the development of its present-day use is discussed. The results of the National ECMO Registry and the first 100 patients at Children's Hospital National Medical Center are presented. Future developments and directions of ECMO are presented.     

Serum Ornithine Carbamoyl Transferase as a Surrogate Marker in Malaria

Ornithine carbamoyl transferase (OCT) activity and other liver function tests were studied in a total of 50 patients of clinical malaria and 15 controls. They were grouped as group I (positive for malarial parasite on peripheral blood smear, n=18), group II (negative for malarial parasite on peripheral blood smear (PBS) but responded to antimalarials, n=17) and group III (peripheral blood smear negative and did not respond to antimalarial therapy, n=15). The mean OCT levels were significantly raised in group I (6.79 ± 1.84 IU/L, p value = 0.006) and group II (5.0 ± 1.15 IU/L, p value = 0.014) as compared to controls (2.5 ± 1.13 IU/L) and returned to normal after treatment In contrast, group III had normal levels except in a case of kala azar and septicemia where OCT levels were high and increased further on treatment. Taking PBS positivity as a gold standard of diagnostic criteria, OCT had a sensitivity of 83% and specificity of 86% with a high positive predictive value of 88% as compared to ALT which had a lower sensitivity of 55% and specificity of 80%. The clinical response rate in PBS negative cases of fever having high OCT level was 83% as compared to 35% in cases with normal OCT level, making OCT a good surrogate marker of malaria. OCT levels could also be of prognostic significance as 2 cases of cerebral malaria had high OCT levels of 11.1 UAL and 10.7 IU/L, respectively.Key Words: Malaria, Ornithine carbamoyl transferase