[Fatal nutrient deficiencies after gastric bypass]. / Syndrome multicarentiel catastrophique post bypass gastrique.

INTRODUCTION: Bariatric surgery is a very effective treatment for obesity. After gastric bypass, micronutrient deficiencies frequently occur which can have dramatic consequences. CASE REPORT: We report the case of a 55-year-old woman who was admitted for psychomotor retardation, bilateral leg pitting edema and psoriasis-like rash that had been ongoing for 3 months. Pancytopenia, encephalopathy and heart failure rapidly occurred leading to multiorgan dysfunction syndrome and death. We retrospectively identified severe selenium deficiency with possible secondary cardiomyopathy, niacin deficiency resulting in pellagrous encephalopathy with skin lesions and gelatinous transformation of bone marrow. CONCLUSION: Micronutrient deficiency should systematically be assessed when new symptoms occur in a patient with a history of bariatric surgery. Selenium deficiency should be considered in the presence of any heart failure in this context.

[Anorectal manifestations in systemic diseases]. / Manifestations ano-rectales des maladies systémiques.

Numerous systemic diseases (vasculitis, connective tissue disease or sarcoidosis) can display an involvement of the perianal skin, the rectum and/or the anus. Such knowledge is important in order to treat these complications specifically when possible. Lesions of the anorectum arising from systemic diseases can sometimes cause perforations in the peritoneal cavity (if concerning the higher portion of the rectum) and/or fistulization to the anal margin. Differential diagnosis, mostly infectious or inflammatory (Crohn's disease) must be ruled out in every case. Other systemic diseases can display specific manifestations as this is the case in scleroderma which can lead to anal incontinence. Despite the relative rarity of these manifestations, their ignorance would forbid global management of these complex diseases. It should thus be detected in each consultation and a regular follow-up must be provided with a proctologist and/or a gastroenterologist when needed.

[Glassy cell carcinoma of the uterine cervix: An aggressive type of cancer]. / Glassy cell carcinoma du col de l'utérus : une maladie tumorale agressive.

INTRODUCTION: Cervical cancer is the twelfth most frequent cancer in women in France. Glassy cell carcinoma is a rare histological entity, rapidly aggressive, associated with a poor prognosis. CASE REPORT: A 30-year-old woman was admitted in an internal medicine department for polyarthralgia with high grade fever, evolving for 3 weeks. There was an inflammatory syndrome. The 18-FDG-PET-scan showed inflammatory lymph nodes as well as disseminated osteolytic lesions, and a primitive pelvic tumor. A 3cm tumor of the cervix was found during the gynaecologic examination. Histological analysis elicited a high-index mitotic carcinoma, glassy cell carcinoma type. Despite chemotherapy, the outcome was poor, with early death occurring after three months of follow-up. CONCLUSION: The glassy cell carcinoma of the cervix should be considered as an aetiology of bone metastases in young female patients.

Elevated plasma endothelin-1 is associated with reduced weight loss post vertical sleeve gastrectomy.

BACKGROUND: Obesity and insulin resistance are positively correlated with plasma endothelin-1 (ET-1) levels; however, the mechanisms leading to increased ET-1 are not understood. Similarly, the full physiological complexity of ET-1 has yet to be described, especially in obesity. To date, one of the best treatments available for morbid obesity is bariatric surgery to quickly reduce body fat and the factors associated with obesity-related disease; however, the effects of vertical sleeve gastrectomy (SG) on plasma ET-1 have not been described. OBJECTIVES: To determine if SG will reduce plasma ET-1 levels and to determine if plasma ET-1 concentration is associated with weight loss after surgery. SETTING: The studies were undertaken at a University Hospital. METHODS: This was tested by measuring plasma ET-1 levels from 12 obese patients before and after SG. All data were collected from clinic visits before SG, 6 weeks after SG, and 6 months after surgery. RESULTS: At 6 weeks after SG, plasma ET-1 levels increased by 24%; however, after 6 months, there was a 27% decrease compared with presurgery. Average weight loss in this cohort was 11.3% ± 2.4% body weight after 6 weeks and 21.4% ± 5.7% body weight after 6 months. Interestingly, we observed an inverse relationship between baseline plasma ET-1 and percent body weight loss (R2 = .49, P = .01) and change in body mass index 6 months (R2 = .45, P = .011) post bariatric surgery. CONCLUSIONS: Our results indicate that SG reduces plasma ET-1 levels, a possible mechanism for improved metabolic risk in these patients. These data also suggest that ET-1 may serve as a predictor of weight loss after bariatric surgery.

Alterations in the Serotonin and Dopamine Pathways by Cystathionine Beta Synthase Overexpression in Murine Brain.

Cystathionine beta synthase (CBS) is one of the 225 genes on chromosome 21 (HSA 21) that are triplicated in persons with trisomy 21 (Down syndrome). Although most triplicate HSA21 genes have their orthologous genes on murine chromosome 16, the murine ortholog of hCBS is on murine chromosome 17 and thus is not present in the well-studied Ts65Dn mouse model of trisomy 21. Persons with trisomy 21 (T21) present deficits in neurotransmission and exhibit early brain aging that can partially be explained by monoamine neurotransmitter alterations. We used transgenic mice for the hCBS gene, which overexpress the CBS protein in various brain regions, to study if CBS overexpression induces modifications in the monoamine neurotransmitters in the hypothalamus, thalamus, hippocampus, and striatum from transgenic and control female and male mice aged 3-4 months and 11-12 months. Sex, age, and brain area each influenced neurotransmitter levels. Briefly, the serotonin pathway was modified by CBS overexpression in various brain areas in female mice but not in male mice. The dopamine pathway was modified in brain regions according to sex and age. These results may allow us to better understand the role of the transsulfuration pathway and especially CBS overexpression in the metabolism of biogenic amines and the catecholamine catabolism in persons with trisomy 21.

Is infrainguinal bypass grafting successful following failed angioplasty?

OBJECTIVES: Angioplasty is often used in the management of lower limb ischaemia and can reduce the need for infrainguinal bypass in some patients. There is an associated failure rate with this technique and bypass surgery is often used in this situation as a secondary limb salvage procedure. We aimed to evaluate the outcome of infrainguinal bypass grafting following failed attempt at angioplasty. METHODS: All cases of infrainguinal bypass at a single centre over a seven year period were identified and notes reviewed. Cases were divided into four groups according to their indication for surgery; acute ischaemia, chronic critical ischaemia, failed angioplasty and an 'other' group including aneurysmal disease and claudicants. The failed angioplasty group was compared with the other three groups. Survival analysis was performed using Kaplan Meier curves and groups compared in terms of long term patency and survival. RESULTS: Primary patency was 61.2% in the failed angioplasty group at 12 months compared with 60.6% in the other groups (P=1.11). There was also no significant difference in primary patency at 60 months (50% vs 40.6%, P=0.26). Survival at 12 months was also comparable between the groups (failed angioplasty group 74.2% compared with 77.3% in the other groups, P=0.662) as was 60 months survival (33.3% and 35.4% respectively, P=0.166). DISCUSSION: In this study, outcome of infrainguinal bypass following failed angioplasty was comparable to outcome of surgery performed for another indication. This paper supports the use of distal bypass surgery for limb salvage in cases where minimal access techniques have failed.

SOD-1 inhibits FAS expression in cortex of APP transgenic mice.

Peptides derived from proteolytic processing of the amyloid precursor protein (APP) are important for the pathogenesis of Alzheimer's disease (AD). In the present study, we found that transgenic mice overexpressing wild-type human APP gene (hAPP/+) displayed a much higher expression of FAS, one of the death receptor subfamily. This FAS overexpression was significantly reduced in the cortex of mice overexpressing both wild-type hAPP gene and wild-type human superoxide dismutase-1 gene (hSOD-1). Moreover hSOD-1 transgenic expression was associated with an increase of Glial fibrillary acidic protein (GFAP) production. This study indicates that SOD-1 overexpression can inhibit FAS expression, which may be beneficial in AD.

Priorities for improving hospital-based trauma care in an African city.

BACKGROUND: This study sought to identify potential cost-effective methods to improve trauma care in hospitals in the developing world. METHODS: Injured patients admitted to an urban hospital in Ghana over a 1-year period were analyzed prospectively for mechanism of injury, mode of transport to the hospital, injury severity, region of principal injury, operations performed, and mortality. In addition, time from injury until arrival at the hospital and time from arrival at the hospital until emergency surgery were evaluated. RESULTS: Mortality was 9.4%. Most deaths (65%) occurred within 24 hours of admission. Sixty percent of emergency operations were performed over 6 hours after arrival. Tube thoracostomy was performed on only 13 patients (0.6%). Only 58% of patients received intravenous crystalloid and only 3.6% received 1 or more units of blood. CONCLUSION: We identified several specific interventions as potential low-cost measures to improve hospital-based trauma care in this setting, including shorter times to emergency surgery and improvements in initial resuscitation. In addition to addressing each of these aspects of trauma care individually, quality improvement programs may represent a feasible and sustainable method to improve trauma care in hospitals in the developing world.

Ultrastructural study of the FVB/N mouse thymus: presence of an immature epithelial cell in the medulla and premature involution.

FVB/N inbred mice have been widely used to generate a variety of transgenic lines, but their physiology and especially their immunological characteristics are poorly documented. We therefore studied the ultrastructure of the thymus and the distribution of thymocyte subpopulations in FVB/N mice at several ages. In young FVB/N mice the stromal microenvironment exhibits the three types of epithelial cells and the two types of bone-marrow derived cells (macrophages and interdigitated cells) previously described in other strains of mice. Moreover, in the thymic medulla of young FVB/N mice, a fourth cell type with the morphological characteristics of an immature epithelial cell was present in relatively high number. Furthermore, thymocyte subpopulations distribution shows an earlier thymocyte maturation than in other strains. Finally, changes associated with thymic involution were observed about 5 months earlier than in many other mouse strains. Our results demonstrated that the FVB/N strain has a specific immunological status.

Overview of the Internet and prostate cancer resources.

The hallmark of the age of personal computers is the ability to obtain information and communicate with others on nearly any subject using a computer connected to the global network known as the Internet. Information on many diseases is available on the World Wide Web. Information on prostate cancer, including its characteristics, diagnosis, and treatment, is abundantly present on the Internet. This article provides an overview of Internet prostate cancer resources, presenting a brief history of the Internet and its ubiquitous application, the World Wide Web, with a discussion of search engines, the utilization of web resources by physicians (including evaluating web sites, and a highly selected list of noteworthy sites), and the growing use of electronic mail (e-mail) in the patient-physician relationship.

Transgenic murine cortical neurons expressing human Bcl-2 exhibit increased resistance to amyloid beta-peptide neurotoxicity.

The generation of reactive oxygen species has been implicated in the neurotoxicity of amyloid beta-peptide, the main constituent of the senile plaques that accumulates in the brain of Alzheimer's disease victims. In this study, we have compared the toxicity of amyloid beta-peptide on cultured cortical neurons from control mice and transgenic mice expressing either human copper-zinc superoxide dismutase or human Bcl-2, two proteins that protect cells against oxidative damage. Copper-zinc superoxide dismutase overexpression failed to protect cortical neurons against the toxicity of amyloid beta-peptide(25-35) [the minimal cytotoxic fragment of amyloid beta-peptide(1-42)] as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction and an enzyme-linked immunoabsorbent assay using an antibody directed against microtubule-associated protein-2 (a specific neuronal protein), ruling out a role for superoxide anion and peroxynitrite in amyloid beta-peptide-evoked neurotoxicity. On the contrary, cortical neurons expressing human copper-zinc superoxide dismutase exhibited increased apoptotic nuclei in both untreated and amyloid beta-peptide(25-35)-exposed neurons. Transgenic neurons expressing human Bcl-2 were partially protected against amyloid beta-peptide-induced neuronal death. This neuroprotection appears to be related to the complete inhibition of apoptosis induced by both amyloid beta-peptide(25-35) and amyloid beta-peptide(1-42). This study may be relevant for developing neuroprotective gene therapy to inhibit neuronal apoptosis in Alzheimer's disease.

Prophylactic antibiotics for elective laparoscopic cholecystectomy: are they necessary?

HYPOTHESIS: Prophylactic antibiotic treatment in elective laparoscopic cholecystectomy does not lower the already low infection rate associated with this procedure. DESIGN AND SETTING: Prospective double-blind randomized trial at a community-based training hospital. PATIENTS: Four hundred fifty patients undergoing elective laparoscopic cholecystectomy were randomized into 1 of 3 treatment arms: (1) preoperative cefotetan disodium, 1g intravenously; (2) preoperative cefazolin, 1g intravenously; and (3) intravenous placebo. There were no demographic differences between groups in age, smoking history, American Society of Anesthesiologists score, infection risk class, time of antibiotic administration prior to surgery, and type of skin preparation. INTERVENTIONS: Laparoscopic cholecystectomy was attempted in all cases; however, 10 patients required conversion to an open cholecystectomy and they were included in the statistical analysis. Preoperatively, all patients were randomized in a blinded manner and received cefotetan, cefazolin, or placebo intravenously. RESULTS: There were 10 postoperative infections. In the cefotetan group, there were 3 cases of superficial surgical site infections. In the cefazolin group, there were 2 superficial surgical site infections-1 pneumonia and 1 rhinosinusitis. In the placebo group, there were 2 superficial surgical site infections and 1 urinary tract infection. The overall infection rate in this series was 2.4%. Follow-up was performed at routine postoperative visits and by telephone contact. Data were evaluated using the chi2 test and analysis of variance with Duncan post hoc test (P<.05). CONCLUSION: Based on our data, use of prophylactic antibiotics does not decrease the rate of wound infections in elective laparoscopic cholecystectomy.

Spatial and temporal expression of the cystathionine beta-synthase gene during early human development.

We report the cystathionine-beta synthase (CBS) gene expression pattern during early human embryogenesis (3 to 6 weeks post conception) by in situ hybridization and in fetal and adult tissue by Northern Blot analysis. Probes were chosen to recognize either the common sequence to all known CBS mRNAs or the sequences of two different major exons 1 issued of we have previously identified. We demonstrate by in situ hybridization that CBS is continuously expressed from the earliest stages studied (22 days post conception) during embryogenesis in the tissues of developing embryos which will after birth present clinical abnormalities in homocystinuria patients. It is expressed at an especially high level in the neural and cardiac systems until the liver primordium appears. In embryonic central nervous system, the whole neural tube and primary brain vesicles are labeled. Secondary brain vesicles labeling are dependent on the neuroepithelium differentiation. The ventricular layer of the rhombencephalon, cranial nerve nuclei and then after cerebellar cortex derived from rhombencephalon ventricular layer are strongly labeled. Thalamus and other derivatives of the diencephalon plate, the neuroblastic layer of the retina, lens and dorsal root ganglia are labeled. After 35 days post conception, CBS mRNAs was detected in endocardial cells and in cells derived from the neural crest of the heart and in particular developing mesodermic regions such as the primitive hepatocytes of the liver, mesonephros vesicles, various endocrine glands and developing bones. We could not detect tissue specificity of different probes at this embryonic stage. Northern blot analysis consistently detected mRNA species in fetal 25 weeks post conception brain, liver and kidney. The common cDNA probe revealed the 2.5 and 3.7 kb mRNA species from brain, liver and kidney. The exon 1b probe detected only the 2.5 kb mRNA and the exon 1c probe the 3.7 kb mRNA in these three tissues. In adult tissue, the 1b probe detected only the 2.5 kb mRNA and the 1c probe only the 3.7 kb mRNA in the liver.

Results of surgery and angioplasty for the treatment of chronic severe lower limb ischaemia.

OBJECTIVE: To aims of this study was to assess and compare the efficacy of PTA and surgery in the treatment of severe lower limb ischaemia. DESIGN: Prospective 12-month study of 180 consecutive patients with severe chronic lower limb ischaemia. METHODS: PTA was used as first line therapy whenever possible and appropriate. Surgical revascularisation, primary amputation and conservative therapy were used in eh remaining patients. Patient survival and limb salvage were derived using life table analysis. RESULTS: Revascularisation was attempted in 135 (75%) patients, with PTA in 82 (46%), surgery in 19 (27%) and a combination of both in four (2%). Overall 12-month survival and limb salvage was 75% and 71%, respectively. Surgery and PTA had significantly higher survival rates (91% and 78%) than primary amputation or conservative therapy (57% and 52%) (p < 0.0001 log rank test). Revascularisation with either surgery or PTA achieved the same limb salvage rate of 76%. CONCLUSION: A large proportion of patients with severe chronic lower limb ischaemia can be managed by PTA. THis management strategy produces a clinically effective outcome at 1-year.

Linkage disequilibrium at the cystathionine beta synthase (CBS) locus and the association between genetic variation at the CBS locus and plasma levels of homocysteine. The Ears II Group. European Atherosclerosis Research Study.

Cystathionine beta synthase (CBS) is a key enzyme in homocysteine metabolism. We have examined four apparently non-functional polymorphisms in the CBS gene and have determined their frequency, degree of linkage disequilibrium and association with plasma homocysteine levels. The polymorphisms are a 68 bp insertion in exon 8, C699T in exon 8, C1080T in exon 11 and C1985T in the 3' untranslated region. 785 individuals participating in the European Atherosclerosis Research Study II (EARSII), from 11 countries across Europe were genotyped for these polymorphisms. The 68bp insertion had the highest frequency in the UK and in the Middle region, with a lower frequency in the Baltic and the South (p = 0.01), and the exon 11 polymorphism had the highest frequencies of the rare allele in the Baltic (p < 0.05). There was a high degree of linkage disequilibrium between the polymorphisms (p < 0.001 overall), except between C699T and the C1985T, with three common haplotypes accounting for nearly 80% of chromosomes. Examination of the association between these polymorphisms and plasma homocysteine levels revealed that the carriers of the rare alleles of the C699T, C1080T and C1985T polymorphisms had lower plasma homocysteine concentrations than those homozygous for the common alleles, although these differences were not statistically significant. The thermolabile valine variant caused by a substitution of a C for a T at nucleotide 677 in the methylenetetrahydrofolate reductase (MTHFR) has previously been shown to have profound effects on plasma levels of homocysteine in this sample, but the homocysteine-raising effect associated with this thermolabile variant was not seen in carriers of the 68 bp insertion, with this interaction being statistically significant (p < 0.001). These data demonstrate that variation in the CBS gene as detected with these four polymorphisms, had no statistically significant effect on plasma homocysteine levels in these healthy young men. However, the presence of the 68 bp insertion, which is found in approximately 7.5% of individuals in the populations of Europe sampled, abolishes the raising effect of thermolabile MTHFR Val/Val genotype, and may be of importance in the situation of high homocysteine.

Human cystathionine beta-synthase: gene organization and expression of different 5' alternative splicing.

The human cystathionine beta-synthase (CBS) gene spans in excess of 30 kb and consists of 19 exons, with three different 5' untranslated regions including three different exons 1 (exons 1 a, b, and c). Exon 1a and 1b are 390 bp apart from each other and are linked to exon 2 in cDNA << a >> and cDNA << b >>. Exon 1c, which linked to exon 5 in cDNA << c >>, is 7 kb apart from exon 1b. All splice sites conform to the GT/AG rule, including those from exon 1a or 1b to exon 2 and from exon 1c to exon 5. Upstream of exons 1a and 1b, we found two putative promoter sequences with high C + G nucleotide content, one CAAT box at -70 nucleotides (for exon 1b), no TATA box, several Spl binding regulatory consensus sequences, and some other regulatory sequences. Human adult and fetal Northern blots hybridized with total cDNA containing exon 1b, or specific probes from exons 1 (b and c) showed mRNAs of 2.5 kb, 2.7 kb, and 3.7 kb. These results suggest that the mRNAs containing the different exons 1 are under the control of different promoters.

The implementation of telemedicine within a community cancer network.

Telemedicine is being used by physicians at the member hospitals of the Jefferson Cancer Network (JCN) for consultations regarding the diagnosis and management of cancer patients. The technology employed for this telemedicine system was chosen to meet three related specifications: low capital and operating cost, internal maintainability by community hospital data processing staffs, and compatibility with the existing technologic infrastructure. The solution selected is the ubiquitous desktop personal computer and associated software, and Integrated Services Digital Network (ISDN) communications links. The overall performance of this technology has been very satisfactory; ISDN communications has sufficient bandwidth for the transfer of patient data, including text reports, radiographs, and pathology slide images. The presence of the radiologist's interpretation along with the radiographic images allows the presentation of the images on these systems to be acceptable for review purposes. The video frame rates of these systems (12 to 15 frames per second) is adequate, particularly given the "talking heads" nature of the video presentations. Furthermore, the quality of the video image (resolution, size, frame rate) is secondary to the quality of the presentation of the medical information displayed and the capability for mutual annotation of the patient data during the consultation.