Common founder BRCA2 pathogenic variants and breast cancer characteristics in Ethiopian Jews.

PURPOSE: BRCA1/2 founder pathogenic variants (PVs) occur in various populations, but data on the mutational spectrum in Africans are limited. We examined BRCA1/2 PVs in breast cancer patients of Ethiopian Jewish (EJ) origin. METHODS: We retrospectively analyzed BRCA1/2 test results and clinical features of EJ breast cancer patients from seven medical institutions. We obtained heterozygote carrier rates in affected individuals from the laboratories of the largest Israeli HMO (Clalit). Population carrier frequency was determined in EJ controls. RESULTS: We identified three recurrent BRCA2 PVs in 11 EJ breast cancer patients (9 females, 2 males): c.7579delG, c.5159C > A, and c.9693delA. Only c.5159C > A was previously reported in Africans. In women, mean age at diagnosis was 35.7y; 8/9 were diagnosed with advanced disease. All tumors were invasive, 4/9 were triple negative. Only 3/11 carriers had relevant family history. Carrier rate in high-risk breast cancer patients was 11% (3/28; 95%CI [2.3%, 28.2%]). Combined carrier rate among controls was 1.8% (5/280; 95%CI [0.6%, 4.1%]). CONCLUSION: EJs harbor 3 recurrent BRCA2 PVs presenting with relatively severe breast cancer morbidity. Combined with the high BRCA2 carrier rate in the EJ population, these findings merit increasing awareness in this community and suggest that a culturally adapted population screening approach may be warranted.

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer.

Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory.

Genetic features of Lynch syndrome in the Israeli population.

Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process. Aim of the study is to describe genetic features of LS in the Israeli population and report novel and founder mutations. Patients were studied at high-risk clinics. Diagnostics followed a multi-step process, including tumor testing, gene analysis and testing for founder mutations. LS was defined by positive mutation testing. We diagnosed LS in 242 subjects from 113 families coming from different ethnicities. We identified 54 different mutations; 13 of them are novel. Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2; 27% of the MSH2 mutations were large deletions. Seven founder mutations were detected in 61/113 (54%) families. Constitutional mismatch repair deficiency (CMMR-D) was identified in five families. Gene distribution in the Israeli population is unique, with relatively high incidence of mutations in MSH2 and MSH6. The mutation spectrum is wide; however, 54% of cases are caused by one of seven founder mutations. CMMR-D occurs in the context of founder mutations and consanguinity. These features should guide the diagnostic process, risk estimation, and genetic counseling.

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

BACKGROUND AND STUDY AIMS: The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. METHODS: This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. RESULTS: The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. CONCLUSION: A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?

BACKGROUND: Common reasons for elective screening and surveillance colonoscopy, at predetermined intervals, are family or personal history of colorectal cancer (CRC) or advanced adenoma (AAP). Quantified, human haemoglobin (Hb)-specific, immunochemical faecal occult blood tests (I-FOBT) detect bleeding. AIM: To determine I-FOBT sensitivity for CRC or AAP before elective colonoscopy in patients at high-risk of cancer or advanced adenoma. METHODS: Prospective double-blind study of 1000 ambulatory asymptomatic high-risk patients (555 family history of CRC, 445 surveillance for past neoplasm), who prepared three I-FOBTs before elective colonoscopy. I-FOBTs quantified as ngHb/mL of buffer by OC-MICRO instrument and results >or=50 ngHb/mL considered positive. RESULTS: At colonoscopy, eight patients had CRC, 64 others had AAP. Sensitivity for CRC and/or AAP was the highest, 65.3% (95% CI 54.3, 76.3), when any of the three I-FOBTs was >or=50 ngHb (15.4%), with specificity of 87.5% (95% CI 86.4, 90.5) identifying all CRCs and 62% of AAPs. CONCLUSIONS: All cancers or an AAP were detected every third I-FOBT-positive colonoscopy (47/154), so colonoscopy was potentially not needed at this time in 84.6% (846 patients). I-FOBT screening might provide effective supervision of high-risk patients, delaying unnecessary elective colonoscopies. This favourable evaluation needs confirmation and cost-benefit study by risk-group.

Factors associated with radiation exposure in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) patients undergo multiple radiological evaluations. AIM: To estimate total and abdominal radiation exposure from diagnostic X-ray investigations in IBD patients and the associated risk factors. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) treated in the IBD clinic were recruited. Clinical data were extracted from patient files and radiological data were obtained from the central HMO computer data base. RESULTS: A total of 199 CD and 125 UC patients were included. The mean cumulative estimated doses (CED) for CD and UC were 21.1 19.5 and 15.1 20.4 millisieverts (mSv) respectively (P < 0.001). Twenty-three patients (7.1%) had an estimated CED of > or =50 mSv. In multivariate analyses, predictors of increased CED were: surgery (OR 5.68, 95% CI: 2.73-11.8, P < 0.001), CD (OR 2.56, 95% CI: 1.29-5.07, P = 0.007), prednisone use (OR 2.0, 95% CI: 1.11-3.67, P = 0.02), first year of disease (OR 6.4, 95% CI: 1.3-32, P = 0.02) and age in the upper quartile(OR 3.26, 95% CI: 1.68-6.3, P = 0.001). CONCLUSIONS: Diagnosis of CD, IBD-related surgery, prednisone use, first year of diagnosis and age on the upper quartile are independent predictors of increased exposure in IBD patients. Alternative investigations which do not require radiation exposure should be considered for patients at risk for increased radiation exposure.

Identification of colorectal adenomas by a quantitative immunochemical faecal occult blood screening test depends on adenoma characteristics, development threshold used and number of tests performed.

BACKGROUND: Faecal occult blood tests (FOBT) are faulted by low sensitivity for advanced adenomatous polyps (AAP). Quantified, immunochemical, haemoglobin (Hb)-specific immunochemical FOBT (I-FOBT) measurements are now used for colorectal screening. AIMS: To correlate adenoma characteristics to amount of faecal Hb lost and to evaluate sensitivity and specificity for AAP by faecal Hb development threshold used and number of I-FOBTs collected. METHODS: Three daily I-FOBTs were collected and analysed in 1221 patients scheduled for colonoscopy. Faecal Hb was analysed as ngHb/mL of buffer and the highest result related to colonoscopy findings. RESULTS: In 1204 patients without cancer, colonoscopy identified adenomas in 294, 99 with AAPs. Adenoma patients had elevated faecal Hb increasing with advanced histology, size, pedunculated shape and multiplicity (P < 0.001 for all). At 50 ngHb/mL threshold, sensitivity and specificity for AAPs were 54.5% (95%CI 44.7, 64.7) and 88.1% (95%CI 86.2, 90.1) for three tests. At higher thresholds, sensitivity decreased, but was significantly higher with more samples collected. Conversely, specificity increased at higher thresholds, but decreased with more samples. CONCLUSIONS: Faecal Hb loss from adenomas is significantly associated with size, number and advanced features. Sensitivity and specificity for AAPs are determined by test threshold chosen and number of samples collected; these determine the number of colonoscopies needed for positive tests.

Quantitative colonoscopic evaluation of relative efficiencies of an immunochemical faecal occult blood test and a sensitive guaiac test for detecting significant colorectal neoplasms.

BACKGROUND: The guaiac faecal occult blood test (G-FOBT), HemoccultSENSA, is sensitive for significant neoplasms [colorectal cancer (CRC), advanced adenomatous polyps (AAP)], but faulted by non-specificity for human haemoglobin (Hb). Quantified, Hb- specific, immunochemical faecal occult blood tests (I-FOBT) are now used. AIMS: To (i) compare I-FOBT and G-FOBT efficacy in identifying significant neoplasms and colonoscopy needs for positive tests and (ii) examine number of I-FOBTs needed and test threshold to use for equivalent or better sensitivity than G-FOBT and fewest colonoscopies for positive tests. METHODS: Three daily G-FOBTs and I-FOBTs were collected and analysed in 330 patients scheduled for colonoscopy. RESULTS: Colonoscopy found significant neoplasms in 32 patients, 6 CRC, 26 AAP. G-FOBT, sensitivity and specificity were 53.1% (17 neoplasms) and 59.4%, resulting in 8.1 colonoscopies/neoplasm. One I-FOBT having >or=50 ngHb/mL of buffer provided equivalent sensitivity but 94.0% specificity, resulting in 2.1 colonoscopies/neoplasm. By analysing the higher of two I-FOBTs at 50 ngHb/mL threshold, sensitivity increased to 68.8% (22 neoplasms, P = 0.063), specificity fell to 91.9% (P < 0.001), but still required 2.1 colonoscopies/neoplasm. CONCLUSIONS: In this population, quantified I-FOBT had significantly better specificity than G-FOBT for significant neoplasms, reducing the number of colonoscopies needed/neoplasm detected. Results depend on the number of I-FOBTs performed and the chosen development threshold.

Switching from tacrolimus to sirolimus halts the appearance of new sebaceous neoplasms in Muir-Torre syndrome.

Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.

Can quantification of faecal occult blood predetermine the need for colonoscopy in patients at risk for non-syndromic familial colorectal cancer?

BACKGROUND: Patients at risk for non-syndromic (Lynch or polyposis) familial colorectal neoplasia undergo colonoscopic surveillance at intervals determined by clinically ascertained protocols. The quantitative immunochemical faecal occult blood test for human haemoglobin is specific and sensitive for significant colorectal neoplasia (cancer or advanced adenomatous polyp). AIM: To determine immunochemical faecal occult blood test efficacy for identifying significant neoplasia in at-risk patients undergoing elective colonoscopy. METHODS: We retrospectively identified consecutive at-risk patients who provided three immunochemical faecal occult blood tests before colonoscopy. Quantitative haemoglobin analysis was performed by the OC-MICRO automated instrument using the 100 ng Hb/mL threshold to determine positivity. RESULTS: In 252 at-risk patients undergoing colonoscopy; five had cancer, 14 an advanced adenoma and 46 a non-advanced adenoma. The immunochemical faecal occult blood test was positive in 31 patients (12.3%). Sensitivity, specificity, positive and negative predictive values for cancer were: 100%, 90%, 16% and 100%, and for all significant neoplasia: 74%, 93%, 45% and 98%. With 88% fewer colonoscopies, all colorectal cancers and 74% of all significant neoplasia would have been identified by this one-time immunochemical faecal occult blood test screening. CONCLUSIONS: A sensitive, non-invasive, interval screening test might be useful to predetermine the need for colonoscopy in this at-risk population and minimize unnecessary examinations. This favourable retrospective evaluation will be extended to a prospective study.

A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test.

BACKGROUND: The sensitive guaiac faecal occult blood test, Haemoccult SENSA (HOS; Beckman Coulter, Fullerton, CA, USA), is our standard screening test for significant colorectal neoplasia. We evaluated an automatically-developed, quantified human haemoglobin immunochemical faecal test, OC-MICRO (Eiken Chemical Co., Tokyo, Japan), to improve test specificity and so reduce the colonoscopy burden. AIM: To compare guaiac faecal occult blood test and immunochemical faecal test diagnostic efficacy and costs for identifying significant neoplasia. METHODS: Colonoscopies were performed on patients who prepared three daily guaiac faecal occult blood tests with or without immunochemical faecal tests. RESULTS: Total colonoscopy was performed on 151 subjects who prepared both guaiac and immunochemical faecal tests (group 1) and the positive predictive values (PPV) were also compared to those of 162 subjects undergoing colonoscopy for positive guaiac faecal occult blood tests (group 2). In group 1, comparative sensitivity, specificity, and PPVs for significant neoplasia with guaiac faecal occult blood test were 75%, 34%, and 12% (PPV, 18% for group 2) and with immunochemical faecal test were 75%, 94% and 60% (P < 0.01 for specificity). The number of colonoscopy examinations needed to detect a significant neoplasm because of positive faecal occult blood tests was six to eight with HOS and two with OC-MICRO at 21-31% the cost of evaluating a positive guaiac faecal occult blood test. CONCLUSION: An immunochemical faecal test maintains the high sensitivity of guaiac faecal occult blood test, but significantly reduces the colonoscopy burden and screening costs.

The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled study.

OBJECTIVE: The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension. PATIENTS AND METHODS: Sixty female diabetic patients aged 45-70 years with blood pressure (BP) 140-180/90-110 mmHg, serum creatinine (sCr) < or = 160 micro mol/l, HbA(1c) < or = 10%, and albuminuria were treated by atenolol 12.5-75 mg/d and hydrochlorothiazide 6.25-25 mg/d. Titration-to-target helped to reach BP values < or = 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K(+). sCr and HbA(1c) were assessed at baseline and at weeks 12, 16, 36 and 60. RESULTS: The average BP at week 12 was 128 +/- 4/81 +/- 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124-1571) to 216 (64-875) mg/g (P = 0.001), and on cilazapril to 302 (90-975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 micro mol/l, P = 0.02) on cilazapril. CONCLUSION: At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect.

The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study.

AIM: Acarbose, a glucose oxidase inhibitor, delays the absorption of glucose thus reducing post-prandial blood glucose level, haemoglobin A1c (HbA1c) and insulin resistance in patients with diabetes mellitus and in subjects with impaired glucose tolerance. The effect of acarbose in subjects with normal glucose tolerance (NGT) has hitherto not been examined. The aim of the present study was to examine the effect of acarbose in obese hypertensive subjects with NGT. METHODS: A double-blinded, parallel group study was performed on 56 male subjects with hypertension, body mass index (BMI) 27-35 kg/m2, fasting blood glucose < or =6 mmol/l and a normal oral glucose tolerance test. Blood pressure, HbA1c, lipid profile and insulin resistance [homeostasis model assessment (HOMA) index] were determined initially and following 24 weeks of acarbose, 150 mg/day or placebo. The primary end point was the change in insulin resistance. Anti-hypertensive treatment and diet were kept constant during the study. RESULTS: Insulin resistance decreased in acarbose users but not on placebo. HOMA index declined from 5.36 +/- 1.7 to 4.10 +/- 1.6 (p=0.001) on acarbose, the corresponding values on placebo were 5.44 +/- 1.9 and 5.53 +/- 1.7. A decrease in serum triglyceride values (2.16 +/- 0.16 mmol/l to 1.76 +/- 0.15 mmol/l, p=0.02) took place on acarbose with no change on placebo. There was no change in BMI, low-density lipoprotein or high-density lipoprotein values in either group. Blood pressure declined equally in both the groups, probably due to better patient compliance. CONCLUSIONS: Acarbose may reduce insulin resistance and triglycerides also in obese hypertensive subjects with normal glucose tolerance.

Rosiglitazone (PPARgamma-agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes-atherosclerosis mouse model.

BACKGROUND: The administration of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists to low-density lipoprotein (LDL)-receptor-deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARgamma agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)-deficient mice rendered diabetic by low-dose streptozotocin (STZ). METHODS: Male, apoE-deficient mice (n = 48) were randomly divided into four groups. To induce diabetes, two groups received low-dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARgamma agonist) was administered by oral gavage to one of the diabetic and one of the non-diabetic groups. RESULTS: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non-diabetic apoE-deficient mice: 340 +/- 54 vs. 201 +/- 27 micromol2 (p = 0.001) in diabetic mice; 243 +/- 22 vs. 158 +/- 27 micromol2 (p = 0.001) in non-diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone-treated mice, both diabetic and non-diabetic, had higher lipid levels. CONCLUSIONS: Rosiglitazone-treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti-atherogenic effect of rosiglitazone on the arterial wall.

Teaching patients to monitor their risk factors retards the progression of vascular complications in high-risk patients with Type 2 diabetes mellitus--a randomized prospective study.

AIMS: Intensive management of risk parameters in diabetic patients may retard the progression of both micro- and macrovascular complications. Intensified care requires expert staff and is expensive. The aim of the present study was to examine whether sharing the therapeutic responsibility with the patients will improve the outcome. METHODS: A randomized prospective study of 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL-C > 120 mg/dl). Patients were randomly allocated to standard annual consultation (SC) or to a patient participation programme (PP). The medical care for both groups was administered by primary care physicians, who were unaware of the nature of the intervention. RESULTS: At 4 years the mean blood pressure was 148/88 (+/- 6.1/1.7) mmHg in the SC patients vs. 142/84 (+/- 5.8/1.8) mmHg in the PP group (P = 0.02). The mean LDL-C was 124 +/- 8 and 114 +/- 6 mg/dl (P = 0.01) and the mean HbA1c was 8.9 +/- 1.2% and 8.2 +/- 1.5% (P = 0.04) in the SC and PP groups, respectively. The average annual fall in estimated glomerular filtration rate was 3.5 ml/min per year in the SC group vs. 2.25 in the PP group (P < 0.05). Albumin/creatinine ratio > 300 mg/g developed in four SC patients vs. none of the PP patients. There was a total of 36 cardiovascular events in the SC group vs. 23 in the PP group (P = 0.04). All patients in the PP group received ACE inhibitors (or AII blockers) and statins vs. 52% and 43%, respectively, in the SC group. Glucose-lowering regimens were similar. CONCLUSIONS: Well-informed and motivated patients were more insistent to reach and maintain target values of the main risk factors of diabetic complications. The differences between the PP and SC groups were of the same order of magnitude as those between intensive and standard care groups in other studies albeit with, comparatively, a very modest cost.

Size-dependent absorption and defect states in CdSe nanocrystals in various multilayer structures.

GeS2-CdSe superlattices and composite films are prepared by consecutive thermal evaporation of CdSe and GeS2 in vacuum. CdSe layer thickness varies between 1 and 10 nm, while the thickness of GeS2 layers is either equal (in superlattices) to or 20 times greater (in composite films) than that of CdSe layers. Standard spectral photocurrent measurements and various constant photocurrent methods are used to study optical absorption of all samples. An overall blueshift is observed with decreasing CdSe layer thickness of superlattices. This shift is related to a size-induced increase of the optical band gap of CdSe due to one-dimensional carrier confinement in the continuous nanocrystalline CdSe layers. A number of features are observed in the absorption spectra of composite films containing CdSe nanocrystals with average radii of approximately 2.5 and approximately 3.3 nm. They are discussed in terms of three-dimensional carrier confinement and are considered a manifestation of excited electron states in CdSe nanocrystals embedded in GeS2 thin film matrix. In addition to these discrete features, the exponential dependence of the optical absorption (Urbach) edge indicates a distribution of "valence band" tail states associated with disorder. Transient photoconductivity measurements made on similarly prepared SiOx-CdSe superlattices exhibit a rapid fall in photocurrent by a power law decay over several orders of magnitude of time, which is consistent with multi-pletrapping transport via an extensive distribution of deep defects.

Frequency of sister-chromatid exchange among greenhouse farmers exposed to pesticides.

Sister-chromatid exchange (SCE) was measured in peripheral lymphocytes of 104 greenhouse farmers exposed to pesticides and 44 unexposed workers. The results of SCEs are expressed in two variables: (a) mean number of SCEs per chromosome and, (b) proportion of high frequency cells (cells with more than eight SCEs). A high correlation was found between these two variables. The adjusted means of both SCEs variables were significantly higher among the farmers compared with the unexposed group (P < 0.01). Adjustment was made for smoking, age, education, and origin. The adjusted means of both SCE variables, were significantly elevated (P < 0.05) among the farmers who prepared and applied more than 70% of the pesticides by themselves compared with those who prepared and applied less than 70% of the pesticides by themselves. Both SCEs variables were also significantly elevated (P < 0.05) among farmers who were involved in more than 7.4 sprays per year compared with those with 7.4 or less sprays per year (P < 0.05). We found a tendency towards elevation of the two variables of SCEs among those who did not use protective measures while preparing the pesticides. Evaluation of the influence of years of exposure on the frequency of SCEs showed that the two variables of SCEs were higher among those farmers who were exposed to pesticides for more than 21 years than among those with less than 21 years of exposure. The variables that had the most influence on the elevation of SCEs were self-preparation of the pesticide mixtures and the number of sprayings per year. Because the farmers used a mixture of almost 24 different chemical classes it was impossible to attribute exposure to a specific pesticide or group of pesticides to single farmers. Our finding of a significant increase of SCEs frequency in peripheral lymphocytes in greenhouse farmers indicates a potential cytogenetic hazard due to pesticides exposure.

Therapeutic drug monitoring of once daily gentamicin in serum and saliva of children.

UNLABELLED: Gentamicin is widely used in paediatric medicine and therapeutic monitoring is mandatory due to the narrow margin of safety. Saliva sampling may be of potential interest, especially in children in whom blood sampling is often difficult. Experience with once daily intravenous administration of aminoglycosides has grown in recent years. Gentamicin levels were measured in serum and saliva of 55 children treated with the drug (5 mg/kg per day), administered intravenously in three different regimens: thrice (n = 19), twice (n = 18), and once daily (n = 18). No correlation was found between serum gentamicin concentrations and saliva levels when the drug was administered twice or thrice daily, however, there was good correlation when the drug was administered once daily (r2 = 0.96, P < 0.0001). CONCLUSION: In children with uncomplicated infections treated with once daily gentamicin, trough concentrations of the drug can be monitored in saliva.