INVITED REVIEW GASTROINTESTINAL MANIFESTATIONS IN PEDIATRIC AIDS

The pathologic changes in the gastrointestinal tract of children with AIDS are variable, clinically significant, and reflect multisystemic disease processes. Inflammation, changes in the lymphoid tissue, miscellaneous lesions, and tumors are documented in 58 patients in addition to cases reported in the literature. Cytomegalovirus infection of the gastrointestinal tract, associated with ulcerations, hemorrhage, perforation, and intestinal obstruction, carries a high morbidity and mortality, whereas the remaining infections are not life threatening. Special stains and electron micrographic examination are important to identify correctlycertain microorganisms such asmycobacterium avium intracellulare, cryptosporidia, and microsporidia. Lymphoproliferative changes of the gastrointestinal tract, a component of the generalized lymphoproliferative process, need to be characterized by tumor markers and cytogenetic studies. Within the miscellaneous lesions, AIDS associated arteriopathy can be complicated by intestinal ulceration and perforation. Both lymphomas and smooth muscle tumor in children with AIDS are related to Epstein-Barr virus infection. The smooth muscle tumors are frequently malignant and multiple.     

Consensus statement on the live organ donor

The Authors for the Live Organ Donor Consensus Group

JAMA. 2000;284:2919-2926.

Objective  To recommend practice guidelines for transplant physicians, primary care providers, health care planners, and all those who are concerned about the well-being of the live organ donor.

Participants  An executive group representing the National Kidney Foundation, and the American Societies of Transplantation, Transplant Surgeons, and Nephrology formed a steering committee of 12 members to evaluate current practices of living donor transplantation of the kidney, pancreas, liver, intestine, and lung. The steering committee subsequently assembled more than 100 representatives of the transplant community (physicians, nurses, ethicists, psychologists, lawyers, scientists, social workers, transplant recipients, and living donors) at a national conference held June 1-2, 2000, in Kansas City, Mo.

Consensus Process  Attendees participated in 7 assigned work groups. Three were organ specific (lung, liver, and kidney) and 4 were focused on social and ethical concerns (informed consent, donor source, psychosocial issues, and live organ donor registry). Work groups' deliberations were structured by a series of questions developed by the steering committee. Each work group presented its deliberations to an open plenary session of all attendees. This information was stored and shaped into a statement circulated electronically to all attendees for their comments, and finally approved by the steering committee for publication. The term consensus is not meant to convey universal agreement of the participants. The statement identifies issues of controversy; however, the wording of the entire statement is a consensus by approval of all attendees.

Conclusion  The person who gives consent to be a live organ donor should be competent, willing to donate, free from coercion, medically and psychosocially suitable, fully informed of the risks and benefits as a donor, and fully informed of the risks, benefits, and alternative treatment available to the recipient. The benefits to both donor and recipient must outweigh the risks associated with the donation and transplantation of the living donor organ.

     

The constitutive secretory pathway is a major route for islet amyloid polypeptide secretion in neonatal but not adult rat islet cells

Islet amyloid polypeptide (IAPP or amylin) is a normal secretory product of the pancreatic beta-cell that is cosecreted with insulin and is the major constituent of islet amyloid deposits in individuals with type 2 diabetes or insulinomas. We have previously reported that glucose stimulates IAPP, but not insulin secretion, from neonatal rat beta-cells when regulated secretion is prevented by use of calcium-free media, suggesting that IAPP secretion occurs via a constitutive secretory pathway. To directly test this hypothesis, we examined the effects of 2 substances-brefeldin A (BFA) and cycloheximide (CHX)-that are predicted to selectively block constitutive secretion on the release of IAPP-like immunoreactivity (IAPP-LI) and immunoreactive insulin (IRI) from neonatal rat islet cell monolayer cultures. When regulated release was prevented by use of calcium-free media, glucose-stimulated IAPP-LI release was nearly abolished by blocking constitutive release with 10 microg/ml BFA (mean +/- SD: 8.7 +/- 7.7 vs. 29.3 +/- 14.3 pmol/l; n = 5; P < 0.05), an inhibitor of constitutive vesicle formation. Similarly, calcium-independent, glucose-stimulated IAPP-LI secretion was markedly suppressed when new protein synthesis was blocked by administration of 20 microg/ml CHX (4.6 +/- 2.1 vs. 29.5 +/- 14.0 pmol/l; n = 5; P < 0.005). Secretion of IRI was low in the absence of calcium, and neither BFA nor CHX had any further effect. When calcium was added to the incubation media to allow regulated secretion of both IRI and IAPP-LI, both BFA (47.7 micro 8.7 vs. 80.7 micro 10.3 pmol/l; P < 0.001) and CHX (37.3 +/- 5.8 vs. 73.3 +/- 6.2 pmol/l; n = 5; P < 0.0001) inhibited glucose-stimulated IAPP-LI secretion by approximately 40%, but again had no inhibitory effect on IRI secretion. These data indicate that approximately 40% of glucose-stimulated IAPP-LI release occurs via a constitutive secretory pathway in neonatal rat islet cells. By contrast, in adult rat islets, glucose-stimulated IAPP-LI release was almost abolished in the absence of calcium (86 +/- 3% inhibition; P < 0.05) and unaffected by addition of BFA (275 +/- 28 vs. 205 +/- 89 pmol/l; NS) or CHX (160 +/- 20 vs. 205 +/- 89 pmol/l; NS), suggesting that constitutive secretion of IAPP does not occur in mature beta-cells. Collectively, these data suggest that a significant proportion of glucose-stimulated IAPP secretion from neonatal, but not adult, rat islet cells occurs via a constitutive secretory pathway.     

A model to explore the interaction between muscle insulin resistance and beta-cell dysfunction in the development of type 2 diabetes

Type 2 diabetes is a polygenic disease characterized by defects in both insulin secretion and insulin action. We have previously reported that isolated insulin resistance in muscle by a tissue-specific insulin receptor knockout (MIRKO mouse) is not sufficient to alter glucose homeostasis, whereas beta-cell-specific insulin receptor knockout (betaIRKO) mice manifest severe progressive glucose intolerance due to loss of glucose-stimulated acute-phase insulin release. To explore the interaction between insulin resistance in muscle and altered insulin secretion, we created a double tissue-specific insulin receptor knockout in these tissues. Surprisingly, betaIRKO-MIRKO mice show an improvement rather than a deterioration of glucose tolerance when compared to betaIRKO mice. This is due to improved glucose-stimulated acute insulin release and redistribution of substrates with increased glucose uptake in adipose tissue and liver in vivo, without a significant decrease in muscle glucose uptake. Thus, insulin resistance in muscle leads to improved glucose-stimulated first-phase insulin secretion from beta-cells and shunting of substrates to nonmuscle tissues, collectively leading to improved glucose tolerance. These data suggest that muscle, either via changes in substrate availability or by acting as an endocrine tissue, communicates with and regulates insulin sensitivity in other tissues.     

Postinfarct refractory right ventricle: right ventricular exclusion. A possible option to mechanical cardiac support, in patients unsuitable for heart transplant

BACKGROUND: Postbypass refractory right ventricle (RRV) may develop due to right ventricular (RV) ischemia or infarction. In cases with RV infarction, recovery is often prolonged and salvage rate is extremely poor. In this retrospective study, we have examined the role of right ventricular exclusion (RVE), as a possible option to conventional weaning or bridging to heart transplant (B-HTX), in patients who were unsuitable for heart transplant. METHODS: During last 5 years, cumulative incidence of postbypass refractory circulatory failure (RCF) in our adult patients was 0.39% (26/6542). This problem was caused by a RRV in 17 (65%) patients. After CABG, these patients developed a grossly distended and poorly contracting RV (RVEDV: 330-400 ml, RVEF: 0-10%), high central venous pressure (> or =18 mmHg) and an inadequate aortic pressure for weaning off cardiopulmonary bypass. Three patients, who were unacceptable for HTX under UNOS program (age >65 years), were weaned off bypass after RVE, and remaining patients with RVAD (n=3) or BiVAD support, depending upon their concomitant moderate or poor left ventricular performance. RESULTS: The significant predictors of RRV by univariate analysis were; 2nd or 3rd redo CABG for a recent myocardial infarction, and failed graft angioplasty. Hospital mortality (14-60 days) was 0/3, 3/3 and 3/11 for the patients weaned off with RVE, RVAD and BiVAD respectively. At 3 years, overall salvage rate was 9/17 (RVE: 3/3, BiVAD B-HTX 4/6 + 2 weaned with BiVAD support). CONCLUSION: Right ventricular exclusion is a possible option to conventional B-HTX with mechanical support, in patients who develop postinfarct RRV and are unsuitable for transplant.     

Neuropsychological dysfunctions in siblings discordant for schizophrenia

Although cognitive impairments are well recognized in patients with schizophrenia, it is unclear which impairments are due to a genetic predisposition and which are caused by secondary disease effects or phenotype. The aim of this study is to investigate the possible relationship between genetic vulnerability to schizophrenia and cognitive functioning. Three groups of subjects were compared: 14 patients with schizophrenia, 15 healthy siblings and 32 healthy control subjects. All subjects were tested neuropsychologically. The raw test data were rescaled to standard equivalents (z-scores). Subjects' z scores on tests assessing the same cognitive domain were clustered and analyzed. Differences in cognitive functioning were found in the domains of abstraction, attention, executive functioning, spatial memory, and sensory-motor functioning. The schizophrenic probands were impaired on all these five domains whereas the healthy probands showed impairments on executive functioning and partially on sensory-motor functioning. Furthermore, for spatial memory the significant finding could mainly be attributed to impaired functioning in the patients, but not healthy siblings or control subjects, whereas for executive functioning patients and healthy siblings seemed equally impaired as compared to control subjects. The planning time of the Tower of London (TOL) and the initiation time of the Motor Planning Task (MPT) were used for measures of executive functioning, while the 'time to move of the Motor Planning Task' was used as measures of sensory motor functioning. These results suggest that the cognitive abnormalities in schizophrenia that may be related to genotype are represented in the domain of executive functioning and to some extent in the domain of sensory-motor functioning.     

Children's use of motor vehicle restraints: maternal psychological distress, maternal motor vehicle restraint practices, and sociodemographics.

OBJECTIVE: To determine the relative contribution of maternal psychological distress, maternal restraint use, and sociodemographic characteristics to the likelihood that a child would not be restrained in a motor vehicle. METHODS: We examined data on 6251 children aged 0-17 years from the 1998 National Health Interview Survey. The level of children's motor vehicle restraint use (low vs high) was examined by maternal psychological distress and motor vehicle restraint use. Multivariate regression analyses were used to model the odds of children's low use of motor vehicle restraints, controlling for potential confounders. RESULTS: According to maternal reports, more than 10% of children and nearly 13% of mothers reported low use of motor vehicle restraints. Multivariate analyses revealed that maternal use of restraints and psychological distress were both independently related to children's use of restraints, with maternal low use as the stronger correlate. Older children were more likely than younger children to be low users of motor vehicle restraints if the mother reported that she was a low user of restraints. Families with male children, black and Hispanic mothers, and 4 or more members reported lower use of restraints for their children. CONCLUSIONS: Children's low use of motor vehicle restraints was associated with low levels of maternal motor vehicle restraint use and maternal psychological distress. Moreover, maternal motor vehicle restraint practices become increasingly important as children age. Health care providers should consider maternal motor vehicle restraint use, maternal psychological distress, and child age in addition to sociodemographics when assessing children's motor vehicle safety.     

Video-laparoscopic diagnosis and follow-up of a peritoneal tuberculosis

A 21-year-old woman suffering from abdominal pain and a fever of 39 degrees C was hospitalized. Ultrasonography and computed tomographic scan showed a large amount of ascites and one hepatic node. The serum CA 125 level was elevated. Protein Chain Reaction (PCR) searching tuberculosis antigen in ascitic fluid was normal. A diagnosis of peritoneal tuberculosis was supposed and an exploratory laparoscopic procedure performed. Peroperative observation of the ascites, with multiple sites of adhesion, and pathological examination of the hepatic nodule and peritoneum confirmed initial diagnosis. Antituberculous treatment was given for one year. A second laparoscopic procedure was performed and found no disease remaining.