Changing patterns of referral into a family history clinic and detection of ovarian cancer: a retrospective 10-year review.

This study examines whether a change in the criteria for genetic testing for ovarian cancer risk changed the nature of referrals into our Familial Cancer service. This is a retrospective review of 273 women who underwent risk reducing surgery (RRS). The primary outcome was to establish whether there was an increase in women having RRS with a confirmed genetic mutation. Secondary outcomes included the incidence of occult cancer and of subsequent primary peritoneal cancer. The results showed an increase in women being offered RRS based on genetic diagnosis; 91% versus 32% before the criteria change. Four occult malignancies (1.5%) and two peritoneal cancers (0.7%) were noted.We have demonstrated a change in the nature of referrals to the familial cancer service from perceived risk to genetic diagnosis. We can now counsel women more accurately. With a defined risk we are enabling them to make an informed decision regarding risk reduction.

Low Prevalence of Screen-Detected Colorectal Cancer in an Average-Risk Population: The New Normal.

Prior studies have reported the prevalence of colorectal cancer (CRC) in average-risk screening population ages 50-75 to be 0.7%-1.0%.1,2 However, no estimates from studies enrolling individuals undergoing screening colonoscopy have been reported. The experience of ongoing studies enrolling average-risk individuals is that the prevalence rates are substantially lower. A 2020 study from a community-based cohort undergoing CRC screening with fecal immunochemical testing followed by diagnostic colonoscopy reported a CRC prevalence rate of 1.46 per 1000, or 0.15%.3 The aim of our study is to report the screen-detected prevalence of CRC and advanced neoplasia in average-risk asymptomatic individuals from selected academic and community medical centers in the United States, Canada, and Germany and describe associated risk factors.

Emergency care of esophageal foreign body impactions: timing, treatment modalities, and resource utilization.

Esophageal foreign body impaction (EFBI) often requires urgent evaluation and treatment, but characteristics of emergency department (ED) care such as timing of presentation and therapeutic procedures and costs of care are unknown. We aimed to study health-care utilization for patients with EFBI presenting to the ED. Cases of EFBI from 2002 to 2009 were identified by querying three different databases from the University of North Carolina Hospitals for all records with ICD-9 CM code 935.1: 'foreign body in the esophagus.' Charts were reviewed to confirm EFBI and extract pertinent data related to the ED visit, including time of presentation, length of ED stay, medications administered, type of procedure performed, characteristics of procedures, and time to therapeutic procedure. Hospital charges for EFBI encounters and consult fees were determined from the Physicians' Fee Reference 2010, and were compiled to estimate costs. Of the 548 cases of EFBI identified, 351 subjects (64%) presented to the ED. A total of 118 (34%) patients received a medication to treat EFBI, which was only effective in 8% of those patients. Two hundred ninety (83%) subjects underwent a procedure including esophagogastroduodenoscopy (EGD) (n=206) or ear, nose, and throat surgery (ENT)-performed laryngoscopy/esophagoscopy (n=138). Admission to the hospital occurred in 162 (46%) of cases. There was no relationship between ED arrival time and time-to-procedure or total time in ED. There was also no significant relationship between delivery of ED medications and likelihood of undergoing a procedure, or between ED arrival time and delivery of medications. The charges associated with a typical EFBI episode ranged from $2284-$6218. In conclusion, the majority of patients with EFBI at our institution presented to the ED. Medical management was largely ineffective. A therapeutic procedure was required to clear the EFBI in most patients. Time of ED arrival made no difference in time-to-procedure, indicating that gastroenterology and ENT specialists recognize the urgency of treating EFBI regardless of time of day.

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study.

BACKGROUND: Cough may be a manifestation of gastro-oesophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. AIM: To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. METHODS: Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24-h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. RESULTS: Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. CONCLUSION: In subjects with chronic cough and rare or no heartburn, high-dose proton pump inhibitor does not improve cough-related quality of life or symptoms.

The Ex Situ Comparison of Two Improved St. John's wort (Hypericum perforatum) Cultivars with an Iranian Wild Population.

This research is part of an ongoing selection and breeding effort to target Iranian genotypes of Hypericum perforatum with the potential to produce higher amounts of desired secondary metabolites and greater resistance to fungal pathogens. There is a significant interest in the development of such cultivars to supply materials to the local pharmaceutical industries. For this reason, two improved cultivars of H. perforatum ("Gold" and "Veperikon") were compared with a wild Iranian population (Ardabile population) under common garden conditions in Iran. Plants were cultivated from seed in a greenhouse and seedlings were transplanted after one month to the field plots. The statistical design of this study was a Randomized Complete Block Design with three replications. During the period of full flowering, selected phenological (number of days to flowering), morphological (plant height, mean leaf area, number of black glands/leaf) and chemical (hypericin and pseudohypericin content) characteristics were assessed. Our observations were that the "Veperikon" cultivar is very sensitive to soil-borne diseases. All transplanted seedlings were infected by the plant pathogenic fungus Colletotrichum gloeosporioides, which caused necrosis of the whole plant. Both the "Gold" cultivar and plants from the wild population persisted despite mild infections with C. gloeosporioides and produced flowering shoots at both the first and second years after cultivation. The "Gold" cultivar was superior to the Ardabile population in terms of phenological and morphological characteristics. The average naphthodianthrone content (% dry weight of tissue) for the wild Iranian population was 0.04(±0.01)%, but for the "Gold" cultivar, 0.33(±0.43)%. These data indicate that selection and directed cultivation of Iranian H. perforatum plants can result in plants with improved morphological, phenological and chemical characteristics.

Authentication of medicinal plants using molecular biology techniques to compliment conventional methods.

Medicinal plants have become extremely popular in the United States as botanical supplements, herbal medicines and sources of lead compounds for pharmaceutical development. It is estimated that in 1997 Americans used or consumed 5.1 billion US dollars worth of herbal medicines. For the protection of consumers, authentication of medicinal plants is a critical issue. Ideally, authentication should occur from the harvesting of the plant material to the final product. Unfortunately there is no single or superior method to assure 100 percent authentication during the entire process, but the goal can be achieved through the application of a variety of different methodologies. The whole process starts with good voucher specimens that act as reference material and to prove chain of custody. Macroscopic and microscopic examinations can be used as rapid and inexpensive identification techniques. Chemical analysis is by far the best method for the detection of contaminants and can be an excellent method for plant identification. Each of these methodologies has limitations and more analytical methods are needed to assist in the authentication process. Molecular biology offers an assortment of techniques that can be very useful for authentication of medicinal plants. This review covers various aspects of authentication methods, with special emphasis on molecular biology techniques.

Aberrant monocyte prostaglandin synthase 2 (PGS2) expression in type 1 diabetes before and after disease onset.

METHODS: We examined monocyte prostaglandin synthase 2 (PGS2/COX2) expression in individuals at risk for or with type 1 diabetes including: (i) 58 established type 1 and 2 diabetic patients; (ii) 34 autoantibody positive (AA+) children and adults; (iii) 164 infants and young children with insulin-dependent diabetes mellitus (IDDM) susceptibility human leukocyte antigen (HLA) alleles; and (iv) 37 healthy control individuals, over a 5-yr period. RESULTS: Established type 1 diabetic patients (1 month to 30+ yr post-disease onset) had significantly higher PGS2 expression than healthy controls; by contrast, insulin-treated type 2 diabetic patients had significantly lower PGS2 expression than healthy controls. Longitudinal studies of AA+ subjects at risk for type 1 diabetes indicated that 73% (11/15) of individuals who developed this disease during the study period expressed high levels of PGS2 prior to or after onset. We also found high level PGS2 expression in genetically at-risk infants and young children that correlated with having a first-degree relative with type 1 diabetes, but not with age, gender, or HLA genotype. In this population, high level PGS2 expression coincided with or preceded autoantibody detection in 30% (3/10) of subjects. CONCLUSIONS: These findings suggest that high level monocyte PGS2 expression, although subject to fluctuation, is present in at-risk subjects at an early age and is maintained during progression to and after type 1 diabetes onset.

Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: results from a multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Benzydamine was evaluated in patients with head and neck carcinoma for treatment of radiation-induced oral mucositis, a frequent complication of radiation therapy (RT) for which there is no predictable therapy or preventive treatment currently available. METHODS: The safety and efficacy of 0.15% benzydamine oral rinse in preventing or decreasing erythema, ulceration, and pain associated with oral mucositis during RT were evaluated in a randomized, placebo-controlled trial conducted in patients with head and neck carcinoma. Subjects were to rinse with 15 mL for 2 minutes, 4-8 times daily before and during RT, and for 2 weeks after completion of RT; study evaluations were conducted before RT and routinely thereafter up to 3 weeks after RT. RESULTS: During conventional RT, regimens up to cumulative doses of 5000 centigrays (cGy) benzydamine (n = 69) significantly (P = 0.006) reduced erythema and ulceration by approximately 30% compared with the placebo (n = 76); greater than 33% of benzydamine subjects remained ulcer free compared with 18% of placebo subjects (P = 0.037), and benzydamine significantly delayed the use of systemic analgesics compared with placebo (P < 0.05). Benzydamine was not effective in subjects (n = 20) receiving accelerated RT doses (> or = 220 cGy/day). The incidence of adverse events between treatment groups was comparable without significant differences. Early discontinuation because of adverse events occurred in 6% of benzydamine subjects and 5% of placebo subjects, and there was 1 death (related to the primary diagnosis) in a placebo subject. CONCLUSIONS: Benzydamine oral rinse was effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis.

Ambulatory diagnoses-cluster statistics of patient visits at a clinic in the Amazon Region of Ecuador.

INTRODUCTION: Mondana Clinic is a small rural clinic located in the Napo river region of the Amazon basin in Ecuador. Since its opening in 1997 the clinic has grown to be the primary health care facility for approximately 3000 individuals. METHODS: A retrospective study was performed tabulating the ambulatory diagnosis, age, sex, and domicile of patients over a 9 month period in 1999. RESULTS: During the study period there were 765 patient visits that resulted in at least one diagnosis. Of the patient visits, 175 (22.8%) resulted in multiple diagnoses. Women accounted for 58% of the patient visits, which is similar to the 60% of ambulatory patient visits made in the USA by women. The age distribution showed 66% of patients were under 25 years of age. When comparing diagnoses of males with females, several differences were noted. As expected, urinary tract infections were approximately four-fold more common in females than in males. Gastritis and headaches were also more common reasons for patient visits in the female population than in the male. Conversely, lacerations, abrasions, and contusions ranked higher in the male than in the female population for patient visits. CONCLUSION: This study is the first to provide public health information for this region that will prove useful to the health professionals and funding agencies working in the region. Furthermore, it provides a baseline for comparison with other regions in Ecuador and South America in general, as well as comparisons with data-rich countries such as the USA.

Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives.

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study.

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.

Mutation analysis of the c-mos proto-oncogene in human ovarian teratomas.

Female transgenic mice lacking a functional c-mos proto-oncogene develop ovarian teratomas, indicating that c-mos may behave as a tumour-suppressor gene for this type of tumour. We have analysed the entire coding region of the c-MOS gene in a series of human ovarian teratomas to determine whether there are any cancer-causing alterations. DNA from twenty teratomas was analysed by single-strand conformational analysis (SSCA) and heteroduplex analysis (HA) to screen for somatic and germline mutations. In nine of these tumours the entire gene was also sequenced. A previously reported polymorphism and a single new sequence variant were identified, neither of which we would predict to be disease-causing alterations. These results suggest that mutations in the coding region of the c-MOS gene do not play a significant role in the genesis of human ovarian teratomas.

Although DR3-DQB1*0201 may be associated with multiple component diseases of the autoimmune polyglandular syndromes, the human leukocyte antigen DR4-DQB1*0302 haplotype is implicated only in beta-cell autoimmunity.

Human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles were analyzed using a PCR-based sequence-specific priming technique in 16 patients with autoimmune polyglandular syndrome type I (APS-I), 31 patients with APS-II, and 110 patients with component diseases of APS-II, including 9 patients with isolated Addison's disease, 43 patients with Hashimoto's thyroiditis, 22 patients with Graves' disease, and 36 patients with vitiligo. No significant associations was observed between HLA and APS-I patients in our data set, nor was sharing of HLA haplotypes by sibling pairs affected by APS I significantly different from the random expectation. Thus, HLA-DRB1 and -DQB1 genes are probably not involved in APS-I. To delineate the associations between HLA-DRB1, DQB1, and APS-II, we analyzed APS-II patients with or without beta-cell autoimmunity [i.e. insulin-dependent diabetes (IDD) and/or islet cell or glutamic acid decarboxylase autoantibodies]. Our results suggest that the association between DR4-DQB1*0302 and APS-II was entirely due to the presence of pancreatic beta-cell autoimmunity, since this haplotype was otherwise not significantly associated with APS-II or with any other of its component diseases. In contrast, the DR3-DQB1*0201 haplotype was associated not only with IDD, but also with APS-II in the absence of pancreatic beta-cell autoimmunity, as were several its component diseases, including isolated Addison's disease, Graves' disease, and Hashimoto's thyroiditis. Interestingly, the frequency of DQB1*0602, a dominantly protective allele against IDD, was not significantly decreased in the APS-II patients with IDD or beta-cell autoimmunity, albeit the patient numbers were small. This phenomenon may suggest that the development of autoimmunity to nonpancreatic endocrine glands may predispose autoimmunity to the pancreatic beta-cells and involve genes other than those of the MHC.

Validation of a self-reported shelf inventory to measure food purchase behavior.

A mailed, self-reported shelf inventory was validated for use as a tool in assessing the impact of a community nutrition intervention that included a point-of-purchase component. The self-reported inventory was evaluated for overall accuracy as well as for the effects of gender, age, and shopping responsibility on accuracy. In addition, the food-shelf inventory was compared with a specific food frequency questionnaire. Specificity and sensitivity were calculated for self-reported inventories using an interviewer-completed, same-day inventory as the gold standard. Overall sensitivity was 86% and 87%, and overall specificity was 92% and 90% in two validation studies. Results show that the mailed, self-reported shelf inventory is a valid measure of the presence or absence of particular foods in households. As such, it may be a useful tool for assessing the impact of point-of-purchase nutrition interventions.

Nutrition knowledge, attitudes, and practices of older and younger elderly in rural areas.

Using a mailed survey, we gathered data to examine selected aspects of nutrition attitudes, knowledge, and practices of two groups of randomly selected older individuals living in rural areas. In one group respondents were 75 through 85 years old, and in the other group respondents were 60 through 70 years old. A senior nutrition survey and a shelf inventory were used to obtain information from the 698 respondents. The 60- through 70-year-old group expressed significantly more (P less than .001) positive attitudes for efficacy, intention, and outcome expectation than the older group. In addition, the younger group had a higher level (P less than .01) of knowledge about fat and salt. They also tended to make more healthful food selections in 7 of 11 categories of the shelf inventory. Our study suggests that 75- through 85-year-old individuals have different nutrition attitudes, knowledge, and practices. Nutrition education should focus on positive messages that are age appropriate, practical, and achievable. Specific topics should include information about beneficial outcomes of healthful eating behaviors.

Pethidine (meperidine) inhibition of oxytocin secretion and action in parturient rats.

Pethidine (also known as meperidine and as Demerol) injected subcutaneously at 10 mg/kg into parturient rats on the birth of the second pup resulted in a marked slowing of the progress of parturition, associated with reduced plasma oxytocin concentrations. Injection of the opiate antagonist naloxone counteracted the inhibition of oxytocin secretion and largely prevented the slowing of parturition. In vitro, pethidine inhibited spontaneous, oxytocin-induced and acetylcholine-induced contractions of uteri from rats immediately post partum, and these effects were not reversed by naloxone. In anesthetized lactating rats, pethidine inhibited the suckling-induced milk-ejection reflex and attenuated oxytocin-induced contractions of mammary myoepithelium. Finally, pethidine depressed plasma oxytocin concentrations in rats given 2% saline to drink for 24 h to stimulate oxytocin secretion. Thus pethidine inhibits oxytocin secretion in all three conditions; this inhibition is probably mediated by central opioid receptors. In addition, however, pethidine depresses the oxytocin responsiveness both of mammary myoepithelium and of myometrium. The latter effect at least is not opioid mediated.