Evaluation of an extremely flatulent patient: case report and proposed diagnostic and therapeutic approach

We recently encountered a patient with severe flatulence who previously had been subjected to innumerable diagnostic tests and ineffective therapies based on the belief that his rectal gas was produced in the colon. Analysis of three flatus samples demonstrated that nitrogen (N2) was the predominant flatus gas whereas the three gases produced in the gut (CO2, H2 [hydrogen], and CH4 [methane]) comprised <16% of rectal gas. This result plus a series of other diagnostic tests clearly indicated that the patient's flatus was derived almost entirely from swallowed air. Based on this case, the present report summarizes available data on excessive flatulence and suggests a rational approach to the patient complaining of this problem. Particular emphasis is placed upon a sequential strategy consisting of: 1) a count of flatus passages to determine if the subject truly is abnormal (normal: <20 passages/day); 2) an analysis of flatus to determine if the flatus originates from swallowed air (predominantly nitrogen) or intraluminal production (predominantly CO2, H2, and CH4); and 3) treatment based upon the origin of the rectal gas.     

Differentiating keratinocytes express a novel cytochrome P450 enzyme, CYP2B19, having arachidonate monooxygenase activity

The novel cytochrome P450, CYP2B19, is a specific cellular marker of late differentiation in skin keratinocytes. CYP2B19 was discovered in fetal mouse skin where its onset of expression coincides spatially (upper cell layer) and temporally (day 15.5) with the appearance of loricrin-expressing keratinocytes during the stratification stage of fetal epidermis. CYP2B19 is also present postnatally in the differentiated keratinocytes of the epidermis, sebaceous glands, and hair follicles. CYP2B19 mRNA is tightly coupled to the differentiated (granular cell) keratinocyte phenotype in vivo and in vitro. In primary mouse epidermal keratinocytes, it is specifically up-regulated and correlated temporally with calcium-induced differentiation and expression of the late differentiation genes loricrin and profilaggrin. Recombinant CYP2B19 metabolizes arachidonic acid and generates 14,15- and 11, 12-epoxyeicosatrienoic (EET) acids, and 11-, 12-, and 15-hydroxyeicosatetraenoic (HETE) acids (20, 35, 18, 7, and 7% of total metabolites, respectively). Arachidonic acid metabolism was stereoselective for 11S,12R- and 14S,15R-EET, and 11S-, 12R-, and 15R-HETE. The CYP2B19 metabolites 11,12- and 14,15-EET are endogenous constituents of murine epidermis and are present in similar proportions to that generated by the enzyme in vitro, suggesting that CYP2B19 might be the primary enzymatic source of these EETs in murine epidermis.     

Presence of the Apert canonical S252W FGFR2 mutation in a patient without severe syndactyly

We describe a case of acute myocarditis subsequent to varicella virus infection. We comment on the rarity of the clinical entity together with the nonspecificity of the routine diagnostic technique (EKG, X-ray, echocardiography study, routine laboratory, etc.) linked with the excellent gain of antibodies cardiac gammagraphy joined with viral serology, after the primary suspicion factor prior to the presence of skin lesions, fever and thoracic pain.     

Antigen-specific cytolysis by neutrophils and NK cells expressing chimeric immune receptors bearing zeta or gamma signaling domains

TCR- and IgG-binding Fc receptors (Fc gamma R) mediate a variety of critical biologic activities including cytolysis via the structurally related zeta- and gamma-chains. In previous studies, we have described chimeric immune receptors (CIR) in which the ligand-binding domain of a heterologous receptor or Ab is fused directly to the cytoplasmic domain of the TCR zeta-chain. Such zeta-CIRs efficiently trigger cytotoxic function of both T and NK cells in a target-specific manner. In this report, we compared the ability of both zeta- and gamma-CIRs to activate the cytolytic function of two distinct classes of Fc gamma R-bearing effectors, NK cells and neutrophils. Mature neutrophils expressing zeta- and gamma-CIR were generated in vivo from murine hemopoietic stem cells following transplantation of syngeneic mice with retrovirally transduced bone marrow or in vitro from transduced human CD34+ progenitors following differentiation. Both zeta- and gamma-based CIRs were capable of activating target-specific cytolysis by both NK cells and neutrophils, although the zeta-CIR was consistently more efficient. The experimental approach described is a powerful one with which to study the role of nonlymphoid effector cells in the host immune system and permits the rational design of immunotherapeutic strategies that rely on harnessing multiple immune cell functions via CIR-modified hemopoietic stem cells or progenitors.     

Technetium-99m-tetrofosmin uptake in brain tumors by SPECT: comparison with thallium-201 imaging

BACKGROUND/AIMS: There is growing interest worldwide in primary liver cancer. The aim of this study was to describe the incidence of this cancer over a 20-year period in a well-defined French population. METHODS: Time trends by 4-year period were studied by sex, age group, place of residence, histological type and associated cirrhosis. Trends were also analysed using the age-period-cohort model. RESULTS: Primary liver cancer incidence in men increased from 7.5/100000 for the period 1976-79 to 10.2/100000 for the period 1992-95. The mean annual variation was +2.2%, (p<0.05). The increase in incidence was seen mainly in the 55-64 and 65-74 age groups and concerned hepatocellular carcinomas. In men, the increase in incidence rates with time was observed mainly in rural areas, whereas incidence rates in urban areas remained stable. The rise in incidence was due mostly to an increase in primary liver cancer with cirrhosis, in relation to a progressive increase in post-hepatitic cirrhosis and a recent increase in alcoholic cirrhosis. The estimated cumulative risk for the life span 30-74 years increased from 0.8% for the 1904-1908 cohort to 2.1% for the 1934-1938 cohort. There was no significant trend in female rates. CONCLUSIONS: In France, incidence rates for primary liver cancer are increasing in men, whilst they are remaining stable in women. Our data confirm the primary importance of alcohol in the aetiology of this cancer. Further studies are necessary to unravel the respective roles of alcohol and hepatitis C virus in the increasing incidence of primary liver cancer.     

Seroprevalence of selected disease agents from free-ranging black bears in Florida

Streptococcus pneumoniae is a common cause of meningitis. Nitric oxide (NO) has been implicated in causing cerebral edema. Modulating NO production in cerebrospinal fluid (CSF) may have a role in the treatment of bacterial meningitis. Experimental S. pneumoniae meningitis was induced in a rabbit model to determine CSF parameters and NO concentrations. An electrochemical probe in the CSF throughout the 7-hour experiment monitored NO concentrations. The animals had S. pneumoniae (10(5)) injected intracisternally and incubated for 1 hour. Cerebrospinal fluid 200-300 microl was obtained by intracisternal puncture at zero, 2, 4, and 7 hours after drug administration to measure glucose, protein, and lactic acid by standard chemical methods. White blood cell count was measured by hemocytometry. Three groups of five animals were used-control (C), ceftriaxone (CTX), and ceftriaxone plus dexamethasone (CTX+D). Ceftriaxone concentrations in CSF were obtained by microdialysis and analyzed by high-performance liquid chromatography. Mean (+/- SEM) CSF white blood cell count was significantly higher at 2 hours in the C group than in the other two groups (C 7307 +/- 1302, CTX 605 +/- 345, CTX+D 730 +/- 43/mm3, p<0.002). Ceftriaxone induced a significant rise in protein at 4 hours compared with the other groups (C 364 +/- 107, CTX 1158 +/- 797, CTX+D 365 +/- 100 mg/dl, p<0.02). Cerebrospinal fluid lactic acid was significantly different at 4 and 7 hours between C and CTX+D groups (4-hr C 8.0 +/- 2.2, CTX+D 2.0 +/- 0.4 mmol/L, p<0.05; 7-hr C 10.2 +/- 2.4, CTX+D 2.8 +/- 0.8 mmol/L, p<0.01). Median NO concentrations were significantly elevated in the control group compared with the other two groups (C 11.7, CTX 6.8, CTX+D 6.5 micro, p<0.02 C vs CTX, p<0.01 C vs CTX+D). Average (+/- SEM) NO concentrations were significantly higher in the C group at 4 hours (18.1 +/- 0.4, CTX 5.8 +/- 1.8 microM, p<0.05; CTX+D 11.5 +/- 4.0 microM, p>0.05), whereas they did not rise significantly until 7 hours in the CTX group (CTX 18.7 +/- 0.7, C 8.9 +/- 0.4 microM, p=0.055; CTX+D 8.1 +/- 2.2 microM, p<0.05). These results indicate that ceftriaxone with or without dexamethasone significantly decreases lactic acid concentrations and white cell penetration into the CSF in an experimental model of S. pneumoniae meningitis. In addition, ceftriaxone induced a significant elevation in CSF protein. Median NO production in the CSF was significantly attenuated by ceftriaxone.     

Sensitive radioimmunoassay for digoxin in plasma and urine

A reproducible and sensitive radioimmunoassay for digoxin in either serum, plasma or urine is described. Using 0.5 ml of serum or plasma, the assay sensitivity is 0.05 ng of digoxin/ml. The antiserum and tracer solutions employed are available in a kit sold in the United States. All other reagents were prepared in the laboratory. The assay allows measurement of digoxin in plasma or serum for 96 hours after single 0.5 mg doses of digoxin; this is necessary in human bioavailability studies to accurately estimate the total area under the digoxin concentration, time curve from zero to infinite time. In contrast, with the kit assay, employing 0.2 ml of plasma or serum, it has been reported that the 12 hr serum digoxin levels, after single 0.5 mg doses, are, in most subjects, below the sensitivity limit (about 0.5 ng/ml) of the assay.