Developmental Progression in Children's Knowledge of AIDS: Implications for Education and Attitudinal Change

The effectiveness of curricula designed to enhance a child'sunderstanding of AIDS may hinge partially upon incorporatinginformation adjusted to the child's developmental status. Accordingly,we examined the developmental progression of children's understandingof illness transmission in general and AIDS in particular, aswell as explored the relation between a child's knowledge ofAIDS and his/her attitudes toward persons with AIDS. Knowledgeof AIDS was manipulated through use of a brief educational intervention.Results support a developmental progression in knowledge aboutAIDS that is consistent with progressions related to illnessesin general. Knowledge enhancement was associated with positivechanges in attitude.     

Managing pain: The Challenge in Underserved Populations: Appropriate Use Versus Abuse and Diversion

ISSUE: Inadequate pain management is a serious public health problem that affects a wide cross-section of Americans. Patients are often denied sufficient medication, because physicians lack training and fear scrutiny from federal and state regulatory agencies. In addition, even the state-financed system of care, Medicaid, has been increasingly denying payment for the best treatment for pain management. These factors are complicated by physician bias about various subgroups and poor physician-patient communication. Comprehensive patient assessment plays a crucial role in determining appropriate treatment and identifying potential abuse problems. Physicians must routinely document medications analgesic effects and screen for potential ill effects and drug abuse. OBJECTIVE: To examine the prevalence of the undertreatment of pain, particularly among African Americans, and to recommend relevant proactive policy and practice changes to aid in eliminating this health problem. CONSENSUS PROCESS: In July 2002, the NMA convened the "Managing Pain: The Challenge in Underserved Populations: Appropriate Use versus Abuse and Diversion" Consensus Meeting in Washington, DC. The country's most renowned experts in the area of pain management and substance abuse reviewed substantial information regarding pain management and substance abuse including the following: --A draft summary paper on pain management and substance abuse that served as briefing material for consensus members; --Annotated bibliographies; --Articles on pain management and substance abuse; and --Key presentations on pain management and substance abuse.     

Expression microdissection: operator-independent retrieval of cells for molecular profiling.

Tissue microdissection is an important method for the study of disease states. However, it is difficult to perform high-throughput molecular analysis with current techniques. We describe here a prototype version of a novel technique (expression microdissection) that allows for the procurement of desired cells via molecular targeting. Expression microdissection (xMD) offers significant advantages over available methods, including an increase in dissection speed of several orders of magnitude. xMD may become a valuable tool for investigators studying cancer or other disease states in patient specimens and animal models.     

No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity

In light of evidence of linkage of obesity to chromosome 2q31-q37, we hypothesized that the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus (NIDDM) is involved in early onset obesity. We screened the NIDDM 'high-risk'-haplotype combination formed by the alleles 112 and 121 of the polymorphisms UCSNP-43, -19, and -63 in 166 families consisting of an extremely obese child or adolescent (mean BMI percentile: 99.3+/-1.38), one or more obese sibs (mean BMI percentile: 97.42+/-2.88), and both of their parents. Genotyping for three calpain-10 gene polymorphisms was performed by polymerase chain reaction (PCR) with (a) length polymorphism detection (UCSNP-19) or (b) allele-specific PCR (UCSNP-43 and -63). To allow for correct haplotype assignment all individuals were additionally genotyped for two microsatellite markers (D2S125 and D2S2338). We followed a hierarchical test procedure. As the first step, model-free linkage analysis was performed using maximum likelihood binomial statistics. The second stage consisted of a one-sided asymptotic pedigree disequilibrium test for the UCSNP-43 and on an exploratory level for the other SNP-markers and all haplotypes formed by the three SNPs. The final stage investigated the reported haplotype combination. We failed to detect an initial linkage of obesity to this region (LOD score <0.4). All subsequent exploratory analyses were negative. Our analysis of the relationship between the NIDDM 'high-risk' haplotype combination and extreme early onset obesity revealed no evidence for linkage and association.     

Comparison of antireflux surgery among ethnicity

African Americans appear less likely than caucasians to undergo surgery for gastroesophageal reflux disease (GERD). When they do, they appear to have higher conversion and complication rates. Nevertheless, satisfaction with surgery is similar to caucasians. BACKGROUND: There is little information comparing the prevalence and treatment of GERD in various ethnic populations. The purpose of this study was to examine the variations in outcomes between caucasians and African Americans undergoing antireflux surgery. METHODS: The records of all patients who underwent antireflux surgery for GERD or paraesophageal hernia by a single surgeon from January 1997 through December 2001 were reviewed for preoperative and postoperative symptoms, complications, and postoperative satisfaction with surgery. RESULTS: Of the 204 procedures performed, 198 patients were either African American (24) or caucasian (174). Of the 18 African Americans undergoing laparoscopic antireflux surgery (LARS), five were converted to open and four had grade-1 or -2 complications. Of the 160 caucasians undergoing LARS, 27 were converted, and 17 had grade-1, -2, or -3 complications. African-American females had a heavier weight (222 lbs. versus 175 lbs., p<0.05) and conversion rate (55% versus 18%, p<0.05), compared to caucasian females. Satisfaction rates for African Americans were 88%, compared to 82% for caucasians. CONCLUSION: This study demonstrated significant differences between conversion rates in African Americans and caucasians with respects to frequency of surgery for GERD and conversion rates for LARS. Nevertheless, African Americans appear more satisfied with their surgical outcome. Further research is needed to determine whether African Americans truly have a lower incidence of GERD or if bias exists in referral patterns or cultural attitudes.     

Requirement for tumor necrosis factor receptor 2 expression on vascular cells to induce experimental cerebral malaria

Using tumor necrosis factor receptor type 2 (TNFR2)-deficient mice and generating bone marrow chimeras which express TNFR2 on either hematopoietic or nonhematopoietic cells, we demonstrated the requirement for TNFR2 expression on tissue cells to induce lethal cerebral malaria. Thus, TNFR2 on the brain vasculature mediates tumor necrosis factor-induced neurovascular lesions in experimental cerebral malaria.     

Changes in the nuclei of astrocytes following portacaval shunting and portacaval transposition in the rat.

Structural abnormalities are found in the astrocytes of the dentate nuclei of animals after portacaval shunting (PCS). These changes are also found in man in association with portal-systemic encephalopathy. To investigate the relationship between portal-systemic shunting and hepatocellular dysfunction in the pathogenesis of these changes, PCS and protacaval transposition (PCT) were performed in rats. PCT diverts portal blood into the systemic circulation, but retains normal total hepatic blood flow by perfusion with systemic venous blood. Liver function and mass are better preserved than after PCS. Abnormal glial cells were found in 4.03% of animals following sham operation, 13.45% following PCT, and 19.09% following PCS. Both experimental groups differed significantly from control animals, and the number of abnormal cells was significantly higher after PCS than after PCT. These findings are in keeping with the hypothesis that hepatocellular dysfunction plays an important role in addition to portal-systemic shunting in the aetiology of the structural changes in the brain associated with hepatic encephalopathy.     

Natural History of Mouse Syngeneic Lymphoma: Morphologic and Immunologic Aspects

The morphologic changes in lymphoreticular tissues and development of antitumor immune reactions of specific pathogen-free mice injected with syngeneic lymphoma cells were sequentially analyzed. The regional (right inguinal) lymph node demonstrated mild changes indicative of immunologic response. Systemic lymph nodes revealed a moderate degree of immune response on morphologic basis. The spleen was the site of marked activity, characterized by the presence of large pyroninophilic cells and germinal centers. Foci of necrosis in the local tumor accompanied by mature lymphocytes suggested cell-mediated immune rejection. Mice developed circulating antibodies 2 days after implantation. No antibodies were demonstrated attached to fresh tumor cells. Lymphocyte cytotoxic activity was demonstrated beginning on day 4. Both cytotoxic activity and circulating antibodies were no longer detectable after the third week following tumor implantation. Tumor-bearing mice also had an impaired capacity to mount a primary immune reaction to sheep red blood cells. The spleen demonstrated a marked loss of lymphocytes and the subsequent appearance of masses of amyloid material. It is suggested that amyloidosis in lymphoreticular organs is the result of a derangement in the immune response of the host following a prolonged and sustained antigenic stimulation. It appears that in syngeneic pathogen-free mice the spleen plays the major role in immune rejection mechanisms while the draining node only plays a modest role.     

Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms

Mutations in the melanocortin-4 receptor gene (MC4R) represent the commonest monogenic cause of human obesity. However, information regarding the precise effects of such mutations on receptor function is very limited. We examined the functional properties of 12 different mutations in human MC4R that result in severe, familial, early-onset obesity. Of the nine missense mutants studied, four were completely unable to generate cAMP in response to ligand and five were partially impaired. Four showed evidence of impaired cell surface expression and six of reduced binding affinity for ligand. One mutation in the C-terminal tail, I316S, showed reduced affinity for alpha-MSH but retained normal affinity for the antagonist AgRP. None of the mutations inhibited signaling through co-transfected wild-type receptors. Thus, in the most comprehensive study to date of the functional properties of naturally occurring MC4R mutations we have (1) established that defective expression on the cell surface is a common mechanism impairing receptor function, (2) identified mutations which specifically affect ligand binding affinity thus aiding the definition of receptor structure-function relationships, (3) provided evidence against the notion that these receptor mutants act as dominant-negatives, and (4) identified a potentially novel molecular mechanism of receptor dysfunction whereby a mutation alters the relative affinities of a receptor for its natural agonist versus antagonist.