24-hour ambulatory dual gastroduodenal pH monitoring. The role of acid in duodenal ulcer disease.

A new system for long-term, 24-hour, ambulatory dual gastroduodenal pH monitoring is described. Eighteen patients with active duodenal ulcers and ten healthy subjects were studied. Simultaneous gastric and duodenal bulb pH were measured during fasting, the ingestion of a solid meal, and for the remainder of the 24-hour period. The gastric pH profile was similar for both groups. There was no significant difference between the fasting duodenal bulb pH of the duodenal ulcer (DU) patients and controls. The daytime and nocturnal duodenal acid exposure was similar for both groups. The meal caused a similar pattern of duodenal acidification in both controls and DU patients, and acid neutralization appeared to be effective in DU patients. The role of acid in the duodenal bulb does not appear to be of primary pathophysiologic importance in duodenal ulcer disease.     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells

Recent studies using human breast cancer cell lines, animal models, and human tissue biopsies have suggested a close correlation between the expression of the peripheral-type benzodiazepine receptor (PBR) and the progression of breast cancer. This study investigates the genetic status of the PBR gene in two human breast cancer cell lines: MDA-MB-231 cells, which are an aggressive breast cancer cell line that contains high levels of PBR, and MCF-7 cells, which are a nonaggressive cell line that contains low levels of PBR. Both DNA (Southern) blot and fluorescence in situ hybridization analyses indicate that the PBR gene is amplified in MDA-MB-231 relative to MCF-7 cells. These data suggest that PBR gene amplification may be an important indicator of breast cancer progression.     

Loss of heterozygosity in normal breast epithelial tissue and benign breast lesions in BRCA1/2 carriers with breast cancer

Loss of heterozygosity (LOH) of the wild-type BRCA1/2 allele is a reproducible event in breast tumors of BRCA1/2 mutation carriers, but it is unknown if this allelic loss occurs only in association with recognizable histopathologic abnormalities. We evaluated the early genomic changes that occur in the mammary glands of patients with increased predisposition to breast cancer due to germline mutations in the BRCA1/2 genes. We tested the hypothesis that these genomic changes may be detected, not only in histologically abnormal and malignant breast tissues, but also in morphologically normal tissues and in areas with pathologically benign changes. Samples were obtained from five breast cancer patients: four BRCA1 carriers and one BRCA2 carrier. In each case, nontumor tissue areas surrounding the tumor or from other locations of the breast were isolated using laser capture microdissection. We evaluated 29 areas showing normal terminal ductal lobular units (TDLUs) or histopathologically benign changes (in particular, sclerosing adenosis), using a panel of polymorphic dinucleotide microsatellite markers for the BRCA1 gene and other chromosome 17 loci, for the BRCA2 gene and other chromosome 13 loci, and for the FHIT gene on 3p14.2. Overall, we analyzed a total of 105 samples of nontumor tissues; LOH was detected in 59 of the 105 (56%). In the normal TDLUs, 15 of 30 samples (50%) showed LOH; in the tissues with benign proliferative changes, such as sclerosing adenosis, 44 of 75 samples showed LOH (59%). Our results suggest that there is a field effect of early genetic events preceding morphologic changes in the mammary glands of BRCA mutation carriers.     

The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD)

We performed genetic analysis for carrier detection for several at-risk females in a four-generation Duchenne muscular dystrophy (DMD) pedigree using deletion analysis. We demonstrated that dosage analysis is a suitable alternative method to determine the carrier status of female relatives of DMD patients shown to have a deletion within the DMD gene. Subsequently, we diagnosed an affected male fetus for an at-risk female shown to be a DMD carrier by deletion analysis. The usefulness of deletion and linkage analysis are compared. In this family, linkage analysis was complicated by the unavailability of key family members, two recombination events and by previously undisclosed nonpaternity. We found that dosage analysis was more efficient than linkage for carrier evaluation in this family.     

Cytogenetic and molecular cytogenetic studies of a case of interstitial deletion of proximal 15q

A 4-month-old child with multiple anomalies was determined to have an interstitial deletion of chromosome 15, i.e., del(15) (q12q14). The deletion appears not to be a typical deletion of 15q12 such as seen in Angelman and Prader-Willi syndromes, but appears to be more distal, involving either loss of all of 15q12 and part of 15q14, or part of 15q12 and most of 15q14. In either case, 15q13 is missing. Fluorescent in situ hybridization with probes for 15 centromere (D15Z), pericentromeric satellite sequences (D15Z1), and chromosome 15 painting probes shows the deleted chromosome to involve only 15 and no other acrocentric chromosome. Hybridization with probes for the AS and PWS loci (D15S11 and GABAB3, Oncor) show both sites to be intact in the deleted 15. The case is compared with two other reports with overlapping interstitial deletions of proximal 15q, neither of which shows typical features of Angelman or Prader-Willi syndromes.     

Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000

BACKGROUND: Meta-analysis and randomized clinical trial results reported in June 1998 indicated a significant reduction in perinatal HIV transmission rates among mothers undergoing a cesarean section (C-section). OBJECTIVE: The objective of this study was to examine recent trends in and factors associated with C-section deliveries among HIV-infected women in the United States. DESIGN: A multisite pediatric medical record review of a cohort of HIV-exposed and HIV-infected infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467) and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was conducted. SETTING/PATIENTS: All infants born between 1994 and 2000 to HIV-positive mothers referred to the PSD study or to a Pediatric HARS hospital or clinic site were enrolled. RESULTS: The proportion of deliveries by C-section was steady at about 20% from 1994 through June 1998. From July 1998 through December 2000, this proportion increased to 44% in the PSD study and to nearly 50% in the Pediatric HARS. On analysis by multiple logistic regression, delivery of infants by C-section was associated with the release of study results (OR = 2.83), delivery in four PSD sites in reference to Texas (OR: 2.02-1.43), having private medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR = 1.43). CONCLUSIONS: The PSD and Pediatric HARS data demonstrate a sharp increase in C-section rates mainly among HIV-infected women in the United States after the release of the meta-analysis and randomized clinical trial results in 1998. This finding highlights the rapid impact of study results on obstetric practice. It underscores the critical role of prenatal care in offering perinatal interventions such as scheduled C-section when indicated to reduce the likelihood of HIV transmission.     

The mammalian testis-specific thioredoxin system

Redox control of cell physiology is one of the most important regulatory mechanisms in all living organisms. The thioredoxin system, composed of thioredoxin and thioredoxin reductase, has emerged as a key player in cellular redox-mediated reactions. For many years, only one thioredoxin system had been described in higher organisms, ubiquitously expressed in the cytoplasm of eukaryotic cells. However, during the last decade, we and others have identified and characterized novel thioredoxin systems with unique properties, such as organelle-specific localization in mitochondria or endoplasmic reticulum, tissue-specific distribution mostly in the testis, and features novel for thioredoxins, such as microtubule-binding properties. In this review, we will focus on the mammalian testis-specific thioredoxin system that comprises three thioredoxins exclusively expressed in spermatids (named Sptrx-1, Sptrx-2, and Sptrx-3) and an additional thioredoxin highly expressed in testis, but also present in lung and other ciliated tissues (Txl-2). The implications of these findings in the context of male fertility and testicular cancer, as well as evolutionary aspects, will be discussed.     

Reporting and grading of complications after mid-urethral sling surgeries: Could the “Clavien-Dindo Classification” be adopted?

Background:To construct a modified model for reporting and grading of postoperative complications after the mid-urethral sling (MUS) procedure based on the Clavien-Dindo classification. In addition, complications of three different types of MUS were compared.Materials and methods:A PubMed search for postoperative complication after MUS was carried out for the period between January 1990 and July 2018. Reported complications were stratified in a plate form designed in accordance with grades of the Clavien-Dindo classification. Then, the proposed model was applied on reported complications in 160 females who underwent three different procedures of MUS (transvaginal tape [TVT], transobturator tape [TOT], and autologous fascial sling) with a minimum follow-up of 24 months.Results:The mean ± SD age at time of surgery was 46 ± 7 years. TVT was carried out in 75 (47%) patients, TOT in 40 (25%), and fascial sling in 45 (28%). The total number of complications was 62 in 43 (26.8%) patients. The vast majority of complications were Grade I and Grade II 19 (12%) and 21 (13%) out of 160 patients, respectively. Transient postoperative voiding difficulty (Grade II) and de novo urgency (Grade II) were the most prevalent complications in the fascial sling method (15.4% for each), whereas transient thigh pain (Grade II) was the most frequently reported complication after TOT (10%). Life-threatening vascular injury (Grade IV-a) was a serious complication in TVT cases.Conclusions:Postoperative complications of the MUS could be graded according to Clavien''s classification. The vast majority of complications were Graded I or II. TVT can cause serious life-threatening complications.