Atypical cases of gallstone ileus evaluated with multidetector computed tomography

OBJECTIVE: To describe the multidetector computed tomography (CT) findings in 3 patients with atypical gallstone ileus. METHODS: We retrospectively evaluated computed radiography and CT images from three cases of surgically proven gallstone ileus. Two radiologists evaluated by consensus all images for the presence of ectopic gallstone, small bowel obstruction, intrahepatic pneumobilia, cholecystic pneumobilia. One author recorded whether diagnosis of gallstone ileus was made prospectively on radiologic reports and correlated findings to pathology. RESULTS: All cases of gallstone ileus were atypical in that one patient had porcelain gallbladder, one had recurrent pyogenic cholangitis, and one was only 35 years of age. Prospective clinical diagnosis of gallstone ileus was made in only 1 patient at computed radiography and all 3 patients at CT. Retrospectively, small bowel obstruction and cholecystic pneumobilia were identified retrospectively in all 3 patients at both computed radiography and MDCT, and an ectopic gallstone, intrahepatic pneumobilia, and choledochoduodenal fistula was seen in 2, 1, and 0 patients at computed radiography and 3, 2, and 3 patients at CT respectively. CONCLUSION: Multidetector CT is an accurate means to diagnose gallstone ileus, even in patients with atypical features. In particular, multidetector CT is useful for identifying the ectopic gallstone at the transition point between dilated and decompressed bowel.     

Acculturation and health beliefs of Mexican Americans regarding tuberculosis prevention

Mexican Americans are at particular risk of contracting tuberculosis. Yet too little is known about perceptions influencing their health. This study investigated gender and acculturation differences in TB-specific Health Belief Model (HBM) constructs, and the applicability of the HBM's traditional configuration to Mexican Americans. Acculturation and gender substantially influenced the findings. Traditional Mexican Americans reported higher perceived susceptibility and seriousness, more barriers, and greater attention to cues regarding TB prevention than Highly Integrated Biculturals. Women reported greater benefits, attention to cues, and intent to engage in TB prevention behaviors than men. Highly Integrated Bicultural men reported less attention to cues and less intent to engage in health behaviors than other groups. The traditional HBM configuration did not fit this sample. Reconfiguration did, however, result in adequate fit. Overall, higher perceived susceptibility, action benefits, attention to media cues, and female gender predicted greater intent to engage in TB health behaviors.     

Constitutive Ras activity induces hippocampal hypertrophy and remodeling of pyramidal neurons in synRas mice

The small G protein Ras, which is involved critically in neurotrophic signal transduction, has been implicated in neuronal plasticity of both the developing and the adult nervous systems. In the present study, the cumulative effects of constitutive Ras activity from early in postnatal development into the adult upon the morphology of hippocampal pyramidal neurons were investigated in synRas mice overexpressing Val12-Ha-Ras postmitotically under the control of the rat synapsin I promoter. In synRas mice, stereologic investigations revealed hypertrophy of the hippocampus associated with an increase in perikaryal size of pyramidal neurons within the CA2/CA3 region and the gyrus dentatus. Morphometric analyses of Lucifer Yellow-filled CA1 pyramidal neurons, in addition, demonstrated considerable expansion of dendritic arbors. The increase in basal dendritic size was caused primarily by alterations of intermediate and distal segments and was associated with an enlarged dendritic surface. Apical dendrites showed similar but more moderate changes, which were attributed mainly to elongation of terminal segments. Sholl analyses illustrated higher complexity of both basal and apical trees. Despite significant morphologic alterations, dendritic arbors preserve their major design principles. The synaptic density within the stratum radiatum of CA1 remained unchanged; however, increases in the total hippocampal volume and in apical dendritic size imply an increment in the absolute number of synaptic contacts. The data presented here suggest a critical involvement of Ras dependent signaling in morphoregulatory processes during the maturation and in the maintenance of hippocampal pyramidal neurons.     

Different immunogenicity of H-2 Kb-restricted epitopes in natural variants of the hepatitis B surface antigen

The small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long-term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8(+) T cell responses to two K(b)-restricted HBsAg epitopes primed by four different HBsAg variants using protein- and DNA-based vaccination protocols. The K(b)-binding S(208-215) epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross-reactive CD8(+) T cell responses. In contrast, the exchange of an N-terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The K(b)-binding S(190-197) epitope 2 is processed from endogenous but not exogenous HBsAg. A single-residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8(+) T cell repertoires, suggesting an impressive complexity and flexibility of the CD8(+) T cell repertoire to antigen variants from viruses with limited diversity.     

Kompetenznetz HIV/AIDS

Thanks to a nationwide network of specialized, clinic-associated outpatient facilities and competent registered physicians, the quality of care for HIV-infected patients in Germany is high. Although basic HIV research is also well advanced in several centers, in contrast Germany's clinical HIV research is barely discemable on an international level. This deficit is primarily due to a lack of clinical studies involving patients from across the country and the fact that no national patient cohort system exists which could provide a basis for such clinical studies. The competence network HIV/AIDS aims to overcome this shortcoming by serving as a comprehensive, nationwide research alliance. The established patient cohort is linked to 13 projects. The infrastructure required for communications and data exchange will be based on a telematics platform. There will also be various service facilities established within the network, creating an organizational structure to promote the horizontal exchange of information between centers, as well as establish the vertical exchange of knowledge between physicians, patients, public health policy makers, and the general public.     

The pharmacokinetic and pharmacodynamic characteristics of a long-acting growth hormone (GH) preparation (nutropin depot) in GH-deficient adults

A pharmacokinetic-pharmacodynamic study of a long-acting GH [Nutropin Depot; somatropin (rDNA origin) for injectable suspension] was performed in 25 patients with adult GH deficiency. Single doses of 0.25 mg/kg and 0.5 mg/kg, based on ideal body weight, were administered sc. After either dose, serum GH concentrations rose rapidly in both sexes. In men, the lower dose maintained serum IGF-I levels within 1 SD of the mean for age and sex for 14-17 d; the higher dose raised IGF-I levels 2 SD above the mean. In most women, all of whom were receiving oral estrogen, the lower dose did not normalize IGF-I levels; the higher dose maintained IGF-I near the mean for approximately 14 d. Increases in IGF binding protein-3 and acid-labile subunit levels were observed in both sexes; however, a sex-related difference was not obvious. Fasting glucose and insulin concentrations were transiently elevated in men receiving the higher dose. Patients tolerated the injections well. We concluded that a single injection of Nutropin Depot at these doses in patients with adult GH deficiency increased serum IGF-I to within normal limits for 14-17 d. Estrogen-treated women required approximately twice the dose needed in men to produce comparable IGF-I concentrations.     

Modulation of gene-gun-mediated Th2 immunity to hepatitis B surface antigen by bacterial CpG motifs or IL-12

Using different DNA vaccination techniques, we studied the IgG1/IgG2a antibody and MHC-I-restricted cytotoxic T lymphocyte (CTL) responses to the hepatitis B surface antigen (HBsAg) in mice. A single intramuscular injection of 100 microg HBsAg-encoding pCI/S plasmid DNA efficiently primed IgG2a antibody (IgG1/IgG2a ratio <0.3) and CTL responses to HBsAg (Th1 immunity). In contrast, a single intradermal injection of 1 microg of particle-coated pCI/S DNA with the gene-gun-primed IgG1 antibody responses to HBsAg (IgG1/IgG2a ratio >80) but there was no CTL response (Th2 immunity). Injection of immune-stimulating CpG-containing oligodeoxy-nucleotides (ODN) into the skin area used for gene-gun-mediated pCI/S DNA delivery shifted the polarization of the response towards Th1 immunity. A similar shift from Th2 to Th1 immunity was observed when the skin area used for gene-gun-mediated DNA transfer was conditioned by injection of recombinant IL-12. DNA vaccination can thus prime polarized immunity to HBsAg. The polarization of immunity is determined by the technique of plasmid DNA delivery as well as by conditions of the tissue into which DNA is inoculated. Th1 immunity to HBsAg (primed by injection of naked pCI/S DNA) dominated Th2 immunity (primed by gene-gun-mediated pCI/S DNA). In contrast, an established HBsAg-specific Th2 immunity was readily shifted towards Th1 immunity (including specific CTL priming) by an intramuscular boost injection of pCI/S DNA. These data contribute to the rational design of DNA vaccination strategies to efficiently prime anti-viral Th1 immune effector specificities using the gene gun.     

Mitochondrial dysfunction in myofibrillar myopathy

'Myofibrillar myopathy' defines a myopathic condition with focal myofibrillar destruction and accumulation of degraded myofibrillar elements. Despite the fact that a number of mutations in different genes as well as cytotoxic agents lead to the disease, abnormal accumulation of desmin is a typical, common feature. Pathological changes of mitochondrial morphology and function have been observed in animal models with intermediate filament pathology. Therefore, in the present study we tested for mitochondrial pathology in skeletal muscle of five patients with the pathohistological diagnosis of myofibrillar myopathy. Screening for large-scale mtDNA deletions and the frequent MERRF (myoclonic epilepsy; ragged red fibres) and MELAS (mitochondrial encephalomyopathy; lactic acidosis; stroke) point mutations was negative in all patients. Histologically, all muscle biopsies showed nonspecific abnormalities of the oxidative/mitochondrial enzyme stainings (histochemistry for reduced nicotinamide adenine dinucleotide, succinic dehydrogenase, cytochrome c oxidase), only one of them had ragged red fibres and a significant number of cytochrome c oxidase-negative fibres. Upon biochemical investigation, four of our patients showed pathologically low respiratory chain complex I activities. Only one of our patients had a pathologically low complex IV activity, while the measurements of the others were within low normal range. The single patient with pathological values for both complex I and IV was the one with the clear histological hallmarks (ragged red and cytochrome c oxidase-negative fibres) of mitochondrial pathology. She also was the only patient with clinical signs hinting at a mitochondrial disorder. Together with data from observations in desmin- and plectin-deficient mice, our results support the view that desmin intermediate filament pathology in these cases is closely linked to mitochondrial dysfunction in skeletal muscle.