The phenotypic overlap of syndromes associated with hereditary gingival fibromatosis: follow-up of a family for five years.

Hereditary gingival fibromatosis (HGF) is characterized by the slowly progressive fibrous enlargement of gingival tissue. It usually develops as an isolated disorder but can also be one feature of various syndromes. The currently preferred terminology of these syndromes mainly describes the clinical features of the disorder without identifying the cause. In this report, we present the 5-year follow up of a family with HGF and features of 3 previously described syndromes: Jones syndrome, Zimmerman-Laband syndrome, and HGF-hypertrichosis syndrome. The 45-year-old father had HGF, hypertrichosis, hearing loss, and short stubby fingers and toes with hypoplasia of the terminal phalanges and hypoplasia of the nails on the thumbs. The features of 13-year-old son were almost identical to those of his father except for hypertrichosis, but in addition he was mentally retarded. Although the 10-day-old son had HGF and defective fingers, the mother and 7-year-old daughter were unaffected. Owing to the overlap of these syndromes, we argue that the identification of the genetic pathways and mechanisms will be the most important factor in classifying these disorders, with the phenotype playing a minor role.     

Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations

A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP. It will continue to be important to use complementary methods for mutational analysis.     

p53 alterations in oesophageal cancer: association with clinicopathological features, risk factors, and survival.

AIM: To characterise the spectrum of p53 alterations (gene mutations and protein accumulation) in a consecutive series of surgically resected oesophageal cancers, and to evaluate associations with clinicopathological findings (age, sex, tumour histology, grade, and stage), potential risk factors (alcohol, tobacco, hot beverage consumption, history of gastrooesophageal reflux disease and antacid use), and survival. METHODS: The case series comprised 61 sequentially accrued patients with primary oesophageal carcinomas. Genomic DNA was extracted from banked (frozen) tumours and matched normal mucosal tissue; p53 mutations (exons 4-10) were studied by means of polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) analysis and DNA sequencing. Immunohistochemistry (DO7, CM1) was used to assess cell nuclear p53 protein accumulation. Risk factor data, overall and disease free survival were measured prospectively, and analysis was carried out at the univariate level using Kaplan-Meier survival curves with log rank tests, and in multivariate analysis using Cox's proportional hazards models (parsimonious and fully adjusted). RESULTS: p53 mutations were found in 59% (36 of 61) and p53 protein accumulation was detected in 39% (24 of 61) of oesophageal cancers. Eighty eight per cent (23 of 26) of poorly differentiated tumours had p53 alterations compared with 57% (20 of 35) of moderate/well differentiated tumours (odds ratio (OR) = 5.575; p = 0.013). p53 mutations increased significantly with increasing consumption of hot beverages (measured by the average temperature of beverage, number consumed daily, and an index made by multiplying the two variables together) using both univariate (OR = 18.6; p = 0.0025) and multivariate (OR = 24.5; p = 0.0025) analysis. p53 alterations were associated with reduced disease free and overall survival (p = 0.051, log rank), with a univariate (unadjusted) hazard ratio (HR) of 2.241 (95% confidence limits (CL) = 0.973, 5.159; p = 0.058) for overall survival. By multivariate analysis adjusted for other relevant variables, the HR for tumours with p53 alterations was estimated at 2.913 (95% CL = 1.069, 7.936; p = 0.036) for overall survival. CONCLUSIONS: This study reports novel p53 mutations (exon 10), and an association between increasing consumption of hot beverages as a risk factor for p53 mediated oesophageal cancer. p53 is a potentially useful prognostic marker in this disease.     

The role of Casoni’s skin test and indirect haemagglutination test in the diagnosis of hydatid disease

Casonis skin test and indirect haemagglutination test (IHA) are still used in Turkey. The preoperative IHA test or Casonis skin test results of 120 patients with surgically confirmed hydatidosis were retrospectively studied during 1997–2004. At the same period, 306 patients with non-hydatid disease had serologic results for echinococcosis. The sensitivity of immediate intradermal reaction, delayed intradermal reaction, and IHA were 70, 62, and 56%, respectively. Casonis skin test components had higher sensitivity than IHA (P<0.01). The specificity of immediate intradermal reaction, delayed intradermal reaction, and IHA were 87, 85, and 84%, respectively. Cystic lesions in non-hydatid patients were localised commonly in the lungs. The occurrence of hydatid disease for pulmonary, hepatic, and renal cysts was 19, 54, and 5%, respectively. An immediate skin reaction to crude hydatid antigens is more useful than IHA.     

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

The effect of pneumoperitoneum on bacterial clearance and RES functions in a model of E. coli peritonitis

The use of laparoscopic surgery in peritonitis has increased rapidly. The present study examined the effects of pneumoperitoneum on bacterial clearance. Spraque-Dawley rats were divided into six groups of seven animals. In groups 1 and 4, laparotomy with a midline incision was performed and 10(9) E. coli in a volume of 1 ml inserted into the peritoneal cavity. Groups 2, 3, 5, 6 received an identical quantity of E. coli by intraperitoneal injection. Groups 3 and 6 received carbon dioxide pneumoperitoneum at a constant pressure of 5 mmHg for 60 minutes after intraperitoneal injection of E. coli. In one hour groups; the mean bacterial counts per lung from the E. coli injection with laparotomy group was significantly higher than for the E. coli injection with pneumoperitoneum group (p < 0.05). The mean bacterial counts per kidney in the E. coli injection with laparotomy group was higher compared with the E. coli injection and E. coli injection with pneumoperitoneum groups (p < 0.0001). There was statistically significant difference in quantitative bacteraemia between the E. coli injection with laparotomy group and the E. coli injection or E. coli injection with pneumoperitoneum groups (p < 0.05). In four-hour groups; the mean bacterial counts of lungs and liver-spleen were significantly higher in the E. coli injection with laparotomy group than in the E. coli injection and E. coli injection with pneumoperitoneum groups (p < 0.05 and p < 0.001 respectively). The quantitative bacteria was significantly higher in the E. coli injection with laparotomy group than in the E. coli injection and E. coli injection with pneumoperitoneum groups (p < 0.05). This study demonstrates that pneumoperitoneum impairs the clearance of bacteria from the peritoneal cavity in an experimental model of peritonitis. However, we could not detect the deleterious effects of pneumoperitoneum compared with laparotomy.     

传染性肺结核患者家庭中儿童结核感染发病及预防的研究

目的　分析传染性肺结核患者家庭中的儿童结核感染和发病情况 ,探讨预防儿童发病的有效方案。方法　对与传染性肺结核患者密切接触的儿童进行X线胸透和做结核菌素试验 ;对结核菌素强阳性者给予预防性治疗。结果　与传染性肺结核患者密切接触的儿童感染率为 88 2 %。规则预防治疗组、不规则预防治疗组和不接受预防治疗组的患病率分别为 :8 3%、4 7 6 %、5 8 8%。结论　与传染性肺结核患者密切接触的儿童属于高危人群 ,给予预防性治疗可减少发病。     

Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry.

There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04-2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer.