Restrictive myocardiopathy in children

Four children, three males and one female, aged 1.5 months to 11 years, with restrictive cardiomyopathy are described. One had patent ductus arteriosus in association. Hepatomegaly, abnormal second heart sound and signs of pulmonary venous congestion in chest X-ray were the most consistent clinical findings. Diagnosis was based on echocardiographic findings, cardiac catheterization data and results of pathology. The most frequent echocardiographic sign was the enlargement of both atria but with the ventricles within normal size and normal systolic function. Abnormalities in second phase of the ventricular filling were recorded in 2D-echo Doppler and cardiac catheterization, where a dip and plateau morphology of ventricular tracings was recorded. Metabolic studies performed in two children were normal, and any child had hypereosinophilia. Two children died, one was lost for follow-up and another is asymptomatic. Remarks on medical and surgical management are made.     

Molecular genetic investigations of autism

Genetic factors are likely to play a major role in the etiology of autism. The genetics of the disorder is however complex, probably involving the action of several genes. In an attempt to identify autism susceptibility loci we are currently undertaking a systematic screening of the whole human genome using multiplex families. We describe the resources and the methods needed to achieve such a task, including extensive collection of family data, semiautomated genotyping technology, and specialized statistical approaches for linkage analysis of complex traits.     

An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3

Human adenoviruses (Ads) are attracting considerable attention because of their potential utility for gene transfer and gene therapy, for development of live viral vectored vaccines, and for protein expression in mammalian cells. Engineering Ad vectors for these applications requires a variety of reagents in the form of Ads and bacterial plasmids containing viral DNA sequences and requires different strategies for construction of vectors for different purposes. To simplify Ad vector construction and develop a procedure with maximum flexibility, efficiency, and cloning capacity, we have developed a vector system based on use of Ad5 DNA sequences cloned in bacterial plasmids. Expanded deletions in early region 1 (3180 bp) and early region 3 (2690 or 3132 bp) can be combined in a single vector that should have a capacity for inserts of up to 8.3 kb, enough to accommodate the majority of cDNAs encoding proteins with regulatory elements. Genes can be inserted into either early region 1 or 3 or both and mutations or deletions can be readily introduced elsewhere in the viral genome. To illustrate the flexibility of the system, we have introduced a wild-type early region 3 into the vectors, and to illustrate the high capacity for inserts, we have isolated a vector with two genes totaling 7.8 kb.     

Effects of high fat diet and cholecystokinin receptor blockade on pancreatic growth and tumor initiation in the hamster

The mechanism by which high-fat diet potentiates pancreatic cancer is not known, but trophic hormones may be involved. In preliminary growth studies, hamsters fed a high fat diet (17.5% lard, 17.5% corn oil) for 14 days showed a 16.3% increase (P < 0.01) in pancreatic weight compared to controls on low fat diet (2.5% lard, 2.5% corn oil). A significant increase was also seen at 28 days. Similar increases were seen in pancreatic DNA (29%, P < 0.01) and pancreatic RNA (22%, P < 0.05) at 14 days. Plasma cholecystokinin (CCK) levels at 14 days were 2.5 fold higher in the animals fed high fat (P < 0.01). Infusion of the CCK antagonist MK329 (25 nmol/kg/h) completely abolished the increase in pancreatic weight, pancreatic DNA and pancreatic RNA. The effect of CCK receptor blockade during the initiation period of carcinogenesis was investigated in hamsters fed the same diets used in the growth studies. One hundred animals received a single injection of N-nitrosobis(2-oxopropyl)amine, (BOP, 20 mg/kg). Half of the hamsters in each diet group received a 2 week infusion of MK329 (25 nmol/kg/h), beginning 8 days before carcinogen administration. At the time of death, 55 weeks after carcinogen administration, non-fasting plasma CCK levels were 31% higher in the high fat fed hamsters than in the low fat fed animals (P < 0.01). The high-fat diet group had a 3-fold increase in total cancer incidence and a 5-fold increase in advanced lesions (adenocarcinomas). Tumor incidence and yield were not changed in either diet group by CCK-receptor blockade during the initiation period. Cholecystokinin appears to mediate the short-term trophic effect that high-fat feeding has on the pancreas. However, potentiation of pancreatic cancer by high-fat diet in the hamster cancer model does not appear to be influenced by endogenous cholecystokinin at the time of tumor induction.     

Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia?

Characteristics of karyotypes were analyzed in de novo acute myeloid leukemia (AML) with trilineage myelodysplasia (AML/TMDS) at initial diagnosis and compared with myelodysplastic syndrome (MDS) cases that had evolved to AML (MDS/AML). Abnormal karyotypes were seen in 11 of 19 patients with AML/TMDS and 13 of 16 MDS/AML cases. Trisomy 8 was observed in 3 AML/TMDS cases as a sole anomaly and was also present in 3 MDS/AML cases but not as a sole finding. Although MDS/AML frequently displayed monosomies or long-arm deletions of chromosome 5, 7 and 9, only one case exhibited long-arm deletion (of chromosome 7) in AML/TMDS. Two or more chromosome aberrations were found in some cases in both groups. These findings suggest that AML/TMDS had passed through several preleukemic stages at diagnosis, as has been well documented in MDS and MDS/AML. Additionally, clonal evolution may have already occurred in AML/TMDS, as MDS transformed to AML is associated with clonal evolution.     

Laparoscopically assisted abdominal aortic aneurysm repair: first 20 cases

PURPOSE: Laparoscopic surgery decreases postoperative pain, shortens hospital stay, and returns patients to full functional status more quickly than open surgery for a variety of surgical procedures. This study was undertaken to evaluate laparoscopic techniques for application to abdominal aortic aneurysm (AAA) repair. METHODS: Twenty patients who had AAAs that required a tube graft underwent laparoscopically assisted AAA repair. The procedure consisted of transperitoneal laparoscopic dissection of the aneurysm neck and iliac vessels. A standard endoaneurysmorrhaphy was then performed through a minilaparotomy using the port sites for the aortic and iliac clamps. Data included operative times, duration of nasogastric suction, intensive care unit days, and postoperative hospital days. Pulmonary artery catheters and transesophageal echocardiography were used in seven patients. For these patients data included heart rate, pulmonary artery systolic and diastolic pressures, mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, and end diastolic area. Data were obtained before induction, during and after insufflation, during aortic cross-clamp, and at the end of the procedure. RESULTS: Laparoscopically assisted AAA repair was completed in 18 of 20 patients. Laparoscopic and total operative times were 1.44 +/- 0.44 and 4.1 +/- 0.92 hours, respectively. Duration of nasogastric suction was 1.3 +/- 0.7 days. Intensive care unit stay was 2.2 +/- 0.9 days. The mean length of hospital stay was 5.8 days excluding three patients who underwent other procedures. There were two minor complications, one major complication (colectomy after colon ischemia), and no deaths. For the eight patients who had intraoperative transesophageal echocardiographic monitoring, no changes were noted in heart rate, pulmonary artery systolic pressure, pulmonary capillary wedge pressure, and cardiac index. Pulmonary artery diastolic pressure and central venous pressure were greatest during insufflation without changes in end-diastolic area. Volume status, as reflected by end-diastolic area and pulmonary capillary wedge pressure, did not change. CONCLUSIONS: Laparoscopically assisted AAA repair is technically challenging but feasible. Potential advantages may be early removal of nasogastric suction, shorter intensive care unit and hospital stays, and prompt return to full functional status. The hemodynamic data obtained from the pulmonary artery catheter and transesophageal echocardiogram during pneumoperitoneum suggest that transesophageal echocardiography may be sufficient for evaluation of volume status along with the added benefit of detection of regional wall motion abnormalities and aortic insufficiency. Further refinement in technique and instrumentation will make total laparoscopic AAA repair a reality.     

Low sensitivity of computed tomography in the staging of gastric lymphomas of mucosa-associated lymphoid tissue: impact on prospective trials and ordinary clinical practice

The natural history and management of gastric lymphomas of mucosa-associated lymphoid tissue (MALTomas) are not completely understood. Most stage I cases are now entered into prospective trials to confirm the excellent results obtained with conservative treatment, whereas current therapeutic policies are based on accumulated experience. The limits of staging work-ups may have a significant impact on prospective trials and ordinary clinical practice. The authors explore the sensitivity of computed tomography scanning in detecting perigastric adenopathy in 20 patients with gastric MALToma treated by gastrectomy. Clinical staging identified 17 patients as having stage I MALTomas and three patients as having stage II1 MALTomas. Histopathologic staging showed that 8 of 17 patients formerly diagnosed with stage I MALToma had perigastric nodal involvement, whereas the three patients with clinical stage II1 were confirmed as such. Computed tomography scanning has low sensitivity in detecting perigastric lymphadenopathy in gastric MALTomas. This leads to understaging, with a significant impact on therapeutic decision, and distorts newly acquired knowledge about the disease's natural history and management, introducing a bias in prospective clinical trials. Endoscopic ultrasonography should be tested as a staging procedure both in prospective trials and in ordinary clinical practice.