Association between the A1166C polymorphism of the angiotensin II receptor type 1 and progression of chronic renal insufficiency

BACKGROUND: In some studies genetic variation in the renin-angiotensin-aldosterone system (RAAS) has been associated with hypertension and rapid progression of renal insufficiency to end-stage renal disease (ESRD). Most of these studies do not take into account covariables influencing progression. We studied retrospectively the role of angiotensinogen (AGT) M235T, angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensin II type 1 receptor (AT1R) A1166C, aldosterone syntase (CYP11B2) -344C/T and intron 2 W/C polymorphisms in conjunction with clinical and biochemical covariables on the rate of progression of renal insufficiency in a group of patients with ESRD of various etiologies. METHODS: Genotyping was performed by polymerase chain reaction (PCR) in 104 ESRD patients (62 males and 42 females), aged 64 +/- 14 years (mean +/- SD) with mean initial serum creatinine of 2.6 +/- 1.1 mg/dL and a mean time to reach ESRD of 52 +/- 38 months. RESULTS: The univariate analysis showed that there was a significant difference in the values of the slopes among the AT1R A1166C polymorphism genotypes: AA -4.87 +/- 0.22, AC -5.09 +/- 0.65 and CC -5.52 +/- 0.66 (p<0.05). None of the remainder polymorphisms showed significant association with progression. Stepwise multiple regression analysis including all the clinical, biochemical and genetic variables showed that only systolic blood pressure (SBP), serum PTHi and AT1R genotype were independently associated with the rate of progression, excluding the other variables from the model. CONCLUSIONS: These results indicate that susceptibility to faster progression to ESRD is associated with the AT1R A1166C polymorphism. This association remains significant after adjustment for relevant covariates, highlighting the importance of analyzing genetic risk factors in the context of clinical and biochemical variables.     

Report of a case: non-Hodgkin's lymphoma of the hypopharynx in a patient with HIV infection. Remission without lymphoma-specific treatment

Non-Hodgkin's lymphomas (NHL) are common in HIV patients, although it is rare for primary lymphomas to develop in the larynx or hypopharynx. We present the case of a patient that was diagnosed of a high degree NHL, following a biopsy of the piriform sinus' lesion, taker by direct laryngoscopy. Simultaneously he was diagnosed as HIV. The interest of this paper is the total remission of the lymphoma seen after specific HIV treatment only.     

Feed restriction significantly alters lipogenic gene expression in broiler breeder chickens

Broiler breeder pullets were divided into two groups at 21 wk of age. One group was given free access to feed (ad libitum) and the other fed a limited amount of feed (restricted). At 22 wk, all birds were photostimulated and maintained throughout an egg-laying cycle ending at 36 wk. Samples of liver and abdominal fat pad were collected just before photostimulation (prelight), after photostimulation at first egg and at peak egg production (plateau). Hepatic expression of sterol regulatory element binding protein-1, ATP-citrate lyase, fatty acid synthase, malic enzyme, acetyl-CoA carboxylase and stearoyl-CoA (Delta9) desaturase 1 genes in ad libitum birds declined from their highest levels just before photostimulation as the birds came into and maintained egg production. In contrast, the restricted birds had significant (P < 0.05) increases in the expression of these genes after photostimulation at first egg with a subsequent decline as they reached peak egg production. Hepatic expression of fatty acid binding protein, VLDL apolipoprotein (apoVLDL-II) and apoB genes increased significantly (P < 0.05) in both ad libitum and restricted breeders after photostimulation, whereas apoA1 gene expression declined during this time. Abdominal fat pad weights were significantly (P < 0.05) higher in the ad libitum compared with restricted birds after photostimulation. Lipoprotein lipase in this tissue showed a pattern of expression similar to that observed for the hepatic lipogenic enzyme genes. In conclusion, feed restriction during the pullet-to-breeder transition period significantly (P < 0.05) altered hepatic lipogenic gene expression in broiler breeders.     

Stomal recurrence after laryngectomy. An inevitable late complication

Postlaryngectomy tumoral recurrence on the stoma is a terrible late complication that has a fatal outcome. In spite of advances in laryngeal surgery and modern reconstructive techniques, it is still a major cause of death in patients with laryngeal cancer. In a review of 500 patients who underwent surgery for laryngeal cancer in 1981-86 and 1995-97, we found no changes in the frequency of stomal recurrence between periods (4% in both periods). Stomal recurrence was associated in our study with subglottic extension and with transglottic lesions. Previous tracheotomy was not a decisive factor in the appearance of stomal recurrence in our patients.     

Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants

Flavin-containing monooxygenases (FMOs) are important for the disposition of many therapeutics, environmental toxicants, and nutrients. FMO3, the major adult hepatic FMO enzyme, exhibits significant interindividual variation. Eighteen FMO3 single-nucleotide polymorphism (SNP) frequencies were determined in 202 Hispanics (Mexican descent), 201 African Americans, and 200 non-Latino whites. Using expressed recombinant enzyme with methimazole, trimethylamine, sulindac, and ethylenethiourea, the novel structural variants FMO3 E24D and K416N were shown to cause modest changes in catalytic efficiency, whereas a third novel variant, FMO3 N61K, was essentially devoid of activity. The latter variant was present at an allelic frequency of 5.2% in non-Latino whites and 3.5% in African Americans, but it was absent in Hispanics. Inferring haplotypes using PHASE, version 2.1, the greatest haplotype diversity was observed in African Americans followed by non-Latino whites and Hispanics. Haplotype 2A and 2B, consisting of a hypermorphic promoter SNP cluster (-2650C>G, -2543T>A, and -2177G>C) in linkage with synonymous structural variants was inferred at a frequency of 27% in the Hispanic population, but only 5% in non-Latino whites and African Americans. This same promoter SNP cluster in linkage with one or more hypomorphic structural variant also was inferred in multiple haplotypes at a total frequency of 5.6% in the African-American study group but less than 1% in the other two groups. The sum frequencies of the hypomorphic haplotypes H3 [15,167G>A (E158K)], H5B [-2650C>G, 15,167G>A (E158K), 21,375C>T (N285N), 21,443A>G (E308G)], and H6 [15,167G>A (E158K), 21,375C>T (N285N)] was 28% in Hispanics, 23% in non-Latino whites, and 24% in African Americans.     

Chirurgische Versorgung von Leberrupturen

Zusammenfassung. Von Januar 1979 bis August 1996 wurden an der Chirurgischen Universit?tsklinik Ulm 178 Patienten aufgrund eines Lebertraumas chirurgisch versorgt. Es handelte sich dabei zu 91,6 % um stumpfe und nur zu 8,4 % um penetrierende Traumen. Bei 110 F?llen (62 %) handelte es sich um leichte Verletzungen der Schweregrade I und II, w?hrend sich bei 68 Patienten (38 %) schwere Traumen der Grade III, IV und V fanden. Die Letalit?tsrate wird vom Schweregrad der Leberruptur und der Begleitverletzung bestimmt. Die Gesamtletalit?t lag bei 32 % (57 Patienten). Davon sind 28 Patienten an den Folgen der Leberverletzung verstorben. Dies bedeutet, die reine Sterblichkeit aufgrund der Leber betrug 15,7 %. Keiner der Patienten mit einer penetrierenden Verletzung ist verstorben. Die Komplikationsrate lag bei 55 %, wobei die H?matombildung die am h?ufigsten beobachtete Komplikation darstellte (12,9 %), an zweiter Stelle folgte die Nachblutung mit 9,6 %. Die Absce?rate lag bei 2,8 %. Bei einem kreislaufstabilen Patienten sollte grunds?tzlich die konservative Therapie angestrebt werden, sofern er die gegebenen Voraussetzungen erfüllt. Bei kreislaufinstabilen Patienten ist ein operatives Vorgehen unumg?nglich. Das chirurgische Vorgehen h?ngt vom Schweregrad der Leberverletzung ab. Bei leichter Blutung steht die „einfache“ Versorgung durch Coagulation oder Naht im Vordergrund. Liegt eine schwere Blutung vor, so empfiehlt sich die Hepatotomie, die gezielte Blutstillung und Débridement (Pachters Vorgehen). Ist die Blutung nicht unter Kontrolle zu bringen, ist die perihepatische Bauchtuchtamponade das Mittel der Wahl.      

IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression

1. Download : Download high-res image (246KB)
2. Download : Download full-size image

     

The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer

BACKGROUND/AIMS: Recently we have shown that NSC-631570 (Ukrain) is a safe and effective drug in the treatment of unresectable pancreatic cancer. The aim of this study was to determine the effectiveness of the combined treatment with Gemcitabine and NSC-631570 in the adjuvant treatment of resected advanced pancreatic cancer. METHODOLOGY: 30 patients received adjuvant chemotherapy following surgical resection for pancreatic cancer. Chemotherapy consisted of Gemcitabine according to the Burris-protocol with weekly infusions of 1000 mg/sqm. Immediately following Gemcitabine infusion 20mg of NSC-631570 were administered intravenously over 15 minutes. RESULTS: WHO grade II toxicities were observed in 53%, no WHO grade III or IV toxicities occurred. In 80% of the patients recurrence of the disease was observed. The relapse-free survival time was 21.7 months. The actuarial survival rates were 86.7% after one year, 76.6% after two years, 46.7% after three years and 23.3% after five years. The median survival time according to Kaplan-Meier regression analysis was 33.8 months. CONCLUSIONS: Adjuvant chemotherapy in advanced stages of pancreatic cancer using the combination of Gemcitabine and NSC-631570 is a safe treatment and seems to lead to a prolonged survival. Although further investigation is needed to confirm these results, the combined treatment of Gemcitabine and NSC-631570 is a promising therapy for the adjuvant treatment of resectable advanced pancreatic cancer.