TP53 gene polymorphisms and breast cancer in Croatian women: a pilot study.

A case-control retrospective association study was conducted to investigate a possible association of the TP53 polymorphisms, Arg72Pro and PIN3 (+16bp), with sporadic breast cancer in Croatian women. Ninety-five women with breast cancer and 108 age-matched healthy women were analyzed. Arg72Pro polymorphism was detected by TaqMan essay. For designation of PIN3 (+16bp) polymorphism DNA amplification was performed by the polymerase chain reaction (PCR) while the PCR products were detected by capillary electrophoresis. Homozygous genotype of minor allele of the PIN3 (+16bp) polymorphism was associated with sporadic breast cancer (OR = 2.15, 95% confidence interval [CI] 1.80-2.56, p = 0.006). For Arg72 polymorphism, the odds ratio for breast cancer of ArgPro versus reference genotype ArgArg was 0.55 (95% CI 0.30-1.02, p = 0.039) suggesting the protective effect. Although different haplotypes did not influence the susceptibility to the disease, the joint occurrence of genotype combination ProPro/A2A2 frequent in cases, was associated with sporadic breast cancer (OR = 2.20, 95% CI 1.89-2.56, p = 0.021). The study provides evidence of the association of the TP53 gene polymorphisms Arg72Pro and PIN3 (+16bp) with sporadic breast cancer in the Croatian population.

Data Sharing, Clinical Trials, and Biomarkers in Precision Oncology: Challenges, Opportunities, and Programs at the Department of Veterans Affairs.

Cancer genomic research reveals that a similar cancer clinical phenotype (e.g., non-small cell lung cancer) can arise from various mutations in tumor DNA. Thus, organ of origin is not a definitive classification. Further, targeted therapy for cancer patients (precision oncology) capitalizes on knowledge of individual patient mutational status to deliver treatment directed against the protein products of these mutations with the goal of reducing toxicity and enhancing efficacy relative to traditional nontargeted chemotherapy.

QIAamp spin columns as a method of DNA isolation for forensic casework.

The Detroit Police Crime Lab has historically used Chelex as a method to isolate DNA for amplification and typing of bloodstains at the HLADQA1, PM and D1S80 loci. However, preliminary validation of several STR systems for casework has demonstrated that the Chelex procedure is not the best method of DNA isolation for STR amplifications for our purposes. Long term storage at -20 degrees C in the presence of unbuffered Chelex beads (approximately 1 year), combined with multiple freeze thaws, resulted in signal loss at a locus for many database samples. Therefore, we have employed the QIAamp spin column as an alternative method of DNA isolation for amplification and typing of STR loci currently being validated for use in the laboratory. Moreover, we determined that QIAamp isolated DNA is also suitable for HLADQA1, PM and D1S80 typing. A matrix study was performed to determine if the QIAamp DNA procedure would give better results on bloodstains deposited on "problem surfaces" such as leather, dirt and various dyed fabrics. Again, QIAamp isolated DNA was more readily typeable than Chelex isolated DNA. We successfully replaced the phenol/chloroform extraction steps utilized in our laboratory for differential extractions, a commonly used method for separating sperm and non-sperm fractions of sexual assault evidence, with the QIAamp spin columns. The QIAamp extracted DNA performed as well in all PCR amplification and typing procedures tested (PM, HLADQA1, D1S80, and STR (PowerPlex)) as the phenol/chloroform Centricon isolated or EtOH precipitated DNAs. Thus we concluded that QIAamp spin columns are a superior method for isolating DNA to be typed for a variety of loci.

Validation of the PowerPlex 1.1 loci for use in human identification.

STR typing is now the favored method of DNA analysis for the purposes of human identification in the forensic community. The Forensic Services Division of the Detroit Police Department has completed its validation of the PowerPlex 1.1 loci (CSF1PO, TPOX, THO1, vWA, D16S539, D7S820, D13S317, and D5S818) for use in forensic casework. Detroit Metro Area Red Cross samples were typed from each of five racial/ethnic groups--the Hispanic, Caucasian, African American, Asian, and American Indian populations--and allele and genotype frequencies were calculated. A rare off-ladder variant (9.1 allele at D7S820) was identified among the database samples. A number of validation studies were performed. DNA was extracted from different substrates and typed as expected, except for the DNA extracted from leather (signal absent from the D16S539, D7S820, D13S317, CSF1PO, and TPOX loci) and from dirt (no PCR product generated). The minor contributor in the mixture study (250 pg input DNA) was facile to discern. The Concordance study, the variety of fluids from the same individual, and NIST standards studies all produced the expected results. Finally, STR data confirmed previous DNA typing results from adjudicated casework samples.

Dermatoglyphic analysis in borderline personality disorder and schizophrenia--results of a Croatian study.

Dermatoglyphic features of 52 male patients with borderline personality disorder (BPD) were compared with those of 200 male controls (control group-CG) and 195 males with schizophrenia (SCH). Quantitative analysis showed statistically significant differences between BPD-CG and between BPD-SCH, mainly regarding the palmar traits, but also the 5th, the 4th and the 1st finger of the right hand as well as the 5th and the 4th finger of the left hand between BPD and SCH patients. The canonical discriminant analysis permitted correct classification with 69.84% probability between the BPD and CG and with 76.11% probability between the BPD and the SCH group. Qualitative finger and palmar traits analysis showed differences between the BPD and SCH groups on the 3rd finger of the left hand, total frequency for all fingers and in the III interdigital space. Significant differences between the BPD and CG were found on the 3rd finger of the left hand. Our results show that the dermatoglyphic features of BPD differ from those of schizophrenia and from those of control subjects. The possible significance of these findings is discussed.

Apolipoprotein E genotypes and metabolic risk factors for coronary heart disease in middle-aged women.

Apo E genotypes and plasma metabolic risk factors (total cholesterol, triglycerides, HDL and LDL cholesterol, total/HDL cholesterol ratio, lipoprotein Lp (a), apolipoprotein A-I, A-II, apo B, and apo E) were determined in 134 healthy middle-aged (X +/- SD 49.62 +/- 4.83) women. The aim of this study was to investigate metabolic risk markers according to various apo E genotypes, and to evaluate a possible risk for coronary heart disease. The results revealed that the frequencies of apo E3/3 are the most frequent (46%), followed by E4/4 (2%), E3/4 (14%), E2/3 (14%), and E2/4 (2%) in the middle-aged women. Higher mean triglycerides, LDL-C and apo B levels were found with apo E3/4, and lower mean levels of HDL-C i.e. apo A-I than in other analyzed genotypes. Greater mean of total/HDL ratio and lower levels of apo A-II were seen with E2/4. Serum lipoprotein Lp (a) concentration was higher in women with genotypes E3/3. Apo E concentration was the lowest with genotypes E4/4, i.e. the highest with E2/3. Serum total cholesterol tended to be higher in women with genotypes E4/4. Genotype E3/4 is connected with the highest concentrations of (X +/- SD) triglycerides (1.74 +/- 0.78), LDL (4.28 +/- 1.88), apo B (1.03 +/- 0.32) and with the lowest concentrations of HDL cholesterol (1.11 +/- 0.21) in the relation to the other analyzed genotypes. This group of women could possibly represent high risk women for CHD. Genotype E3/3 is associated with the highest concentration of independent genetic risk marker for CHD, lipoprotein Lp (a) (0.19 +/- 0.27). The genotype E4/4 has the highest concentration of total cholesterol (5.93 +/- 1.01), and has to be taken in account for risk evaluation in women. High level of apo E (0.11 +/- 0.05) and low level of apo A-I (1.80 +/- 0.44) were associated with E2/3 genotypes. The significance of E3/4 with the high total/HDL ratio (5.52 +/- 2.21) and low apo A-II (0.53 +/- 0.09) is important indicator, because total/HDL cholesterol ratio represents independent Established Risk Factor (ERF) for CHD. Apolipoprotein E genotypes as genetic markers and investigation of serum metabolic risk markers appear to be important in view for further evaluation of high risk women for CHD in our population.

The usefulness of biochemical bone markers in predicting the response of hormone replacement therapy in perimenopausal cigarette smoking healthy women.

The purpose of our study was to evaluate the effects of orally administered combined sequential estradiol (2 mg 17 beta estradiol) with progestin (1 mg norethisteron acetate) daily during ( +/- SD) 15.34 +/- 13.89 months on bone markers in perimenopausal cigarette smoking women. The control group consisted of cigarette smoking perimenopausal women without hormone replacement therapy (HRT). The following biochemical bone markers were analyzed in hormone replacement users (N = 35) and non-users (N = 28): serum total calcium (Ca), total alkaline phosphatase (ALP), procollagen I C-terminal propeptide (PICP), cros-linked carboxyterminal collagen I telopeptide (ICTP) and osteocalcin (OC). When we compared the results of bone markers in the cigarette smoking current users and non cigarette smoking non-users, we found statistically significant lower levels of bone formation markers, ALP and OC, and lower level of bone resorption marker; ICTP in users than in non-users. In perimenopausal cigarette smoking women on HRT lower levels of new biological markers reflected less intensive bone remodelling and probable decrease in bone loss than in non-users. These results indicate that the measurement of biological bone markers are useful to identify risk women for osteoporosis who may have special benefit from the treatment with hormone replacement therapy, even when they smoke.

Dermatoglyphic analysis in bipolar affective disorder and schizophrenia--"continuum of psychosis" hypothesis corroborated?

Dermatoglyphic features are thought to be indicators of events in the early embryonal stages. They might also be associated with the developmental disorders of the central nervous system (CNS) including schizophrenia. Dermatoglyphic features of 92 male patients with bipolar affective disorder (BPAD) (unipolar depression and schizoaffective psychosis were excluded from the study) were compared with those of 195 males with schizophrenia (SCH) and both with those of 200 male controls (control group-CG). DSM-III-R criteria were used for the diagnostic evaluation. Quantitative analysis showed only one statistically significant difference between BPAD and SCH patients groups, regarding the c-d ridge count of the left hand. The canonical discriminant analysis did not permit correct classification (only 59.23% of cases were correctly classified) between BPAD and SCH. Numerous quantitative dermatoglyphic features of both BPAD and SCH differed significantly from those of the control subjects. Finger ridge counts as well as palmar ridge counts were markedly lower in BPAD and SCH as compared to the controls. These findings are not in contradiction with the hypothesis claiming that psychoses are a set of diverse expressions (due also to noninherited factors) of a single underlying entity.

The corrected Q-T interval in the elderly with urban hypothermia.

During winter time in the period from 1993 to 1998, 18 elderly patients: 11 female and 7 male aged 65-88 years, were treated because of hypothermia. Rectal temperature on admission was 20-34.5 degrees C. Ten patients suffered from moderate hypothermia (35-32 degrees C), and eight suffered of severe hypothermia (< 32 degrees C). Arterial hypotension was recorded in 7, and shock in 11 patients. In all of them, and in 18 controls, an electrocardiogram was analyzed with the special reference to the corrected Q-T interval. Decompensated metabolic acidosis was observed in 7/8 patients with severe hypothermia and in 4/10 with moderate hypothermia. Among patients with moderate hypothermia, sinus tachycardia was present in 2, sinus bradycardia in 2, idioventricular rhythm in 2 and atrial fibrillation in 4/10 patients. In patients with severe hypothermia, sinus tachycardia was present in 2, sinus bradycardia in 3, idioventricular rhythm in one, and atrial fibrillation in 2/8 patients. In moderate hypothermia Osborn's or Tomaszewski's J wave was present in 7/10, and it only appeared in 3/10 patients; in severe hypothermia it was present in 6/8 and only appeared in 2/8 patients. The corrected Q-T interval in the group with hypothermia ranged 0.450-0.688 s, in the control group 0.343-0.444 s. The X minimum (s) in the group with hypothermia was 0.508 +/- 0.079, in the control group it was 0.371-0-139 s, and the difference was statistically significant (p < 0.001). The X maximum (s) in the group with hypothermia was 0.576 +/- 0.067 s, in the control group 0.390 +/- 0.019 s, and the difference was also statistically significant (p < 0.0001). In both groups the most significant prolongation of the corrected Q-T interval in the majority of patients was found in anteroseptal leads. The dispersion of the corrected Q-T interval in the group with hypothermia was 87.19 +/- 28.44 ms, in the control group it was 32.06 +/- 8.94 ms, and the difference was statistically significant (p < 0.001).

Hypothermia and acute renal failure in the elderly.

During 1993-1998, in winter time 14 elderly patients: 8 female and 6 male aged 65-88, were treated because of hypothermia. Rectal temperature on admission was 20-34.9 degrees C. Sopor was present in 2 and various grades of coma were present in 10 patients. Arterial hypotension was recorded in 5, and shock in 9 patients. Increased serum creatinine level was found in 8 patients. The mean rectal temperature in the whole group was 31.3 degrees C +/- 4.7, ranging from 20.0 to 34.9 degrees C, and the mean serum creatinine level was 172.2 +/- 93.5, in range of 66.0 to 360.0 mumol/L. Negative correlation between those two parameters was found: r = -0.572. In 2 of them parameters of renal failure were analyzed: urine sodium concentration, creatinine urine/plasma ratio, urine osmolality, urine/plasma osmolality ratio, renal failure index and fractional excretion of filtered sodium. In one of the patients all parameters were within the range of functional oliguria, in an other the urine sodium concentration serum showed acute renal failure, but all other findings showed borderline values between functional oliguria and acute renal failure. Twelve out of 14 patients died within 1-216 hours from admission.

A large cross-sectional study of health attitudes, knowledge, behaviour and risks in the post-war Croatian population (the First Croatian Health Project).

As the liberation of occupied Croatian territories ended the war in the country in 1995, the Ministry of Health and Croatian Health Insurance Institute have agreed to create the new framework for developing a long-term strategy of public health planning, prevention and intervention. They provided financial resources to develop the First Croatian Health Project, the rest of the support coming from the World Bank loan and the National Institute of Public Health. A large cross-sectional study was designed aiming to assess health attitudes, knowledge, behaviour and risks in the post-war Croatian population. The large field study was carried out by the Institute for Anthropological Research with technical support from the National Institute of Public Health. The field study was completed between 1995-1997. It included about 10,000 adult volunteers from all 21 Croatian counties. The geographic distribution of the sample covered both coastal and continental areas of Croatia and included rural and urban environments. The specific measurements included antropometry (body mass index and blood pressure). From each examinee a blood sample was collected from which the levels of total plasma cholesterol (TC), triglycerides (TG), HDL-cholesterol (High Density Lipoprotein), LDL-cholesterol (Low Density Lipoprotein), lipoprotein Lp(a), and haemostatic risk factor fibrinogen (F) were determined. The detailed data were collected on the general knowledge and attitudes on health issues, followed by specific investigation of smoking history, alcohol consumption, nutrition habits, physical activity, family history of chronic non-communicable diseases and occupational exposures. From the initial database a targeted sample of 5,840 persons of both sexes, aged 18-65, was created corresponding by age, sex and geographic distribution to the general Croatian population. This paper summarises and discusses the main findings of the project within this representative sample of Croatian population.

[Fundamentals of quality control systems in medical-biochemical laboratories--the role of marketing]. / Osnove sustava kakvoce u medicinsko-biokemijskom laboratoriju--doprinos marketinga.

The basic criterion for the overall quality system in medical biochemistry laboratories concerning equipment, premises and laboratory staff in primary health care (PHC) (Regulations on quality systems and good laboratory practice of the Croatian Medical Biochemists Chamber, 1995, Regulations on categorization of medical biochemistry laboratories of the Croatian Medical Biochemists Chamber, 1996, EC4: Essential criteria for quality systems in medical laboratories. Eur J Clin Chem Clin Biochem 1997 in medical biochemical laboratories included in the First Croatia health project, Primary health care subproject, has been met by the marketing approach to the project. The equipment ensuring implementation of the complete laboratory program (NN/96), more accurate and precise analytical procedures, and higher reliability of laboratory test results compared with previous equipment, has been purchased by an international tender. Uniform technology and methods of analysis have ensured high standards of good laboratory services, yielding test results than can be transferred from primary to secondary health care level. The new equipment has improved organization between central and detached medical biochemistry laboratory units, while the high quality requirement has led to improvement in the staff structure, e.g., medical biochemists have been employed in laboratories that had previously worked without such a professional. Equipment renewal has been accompanied by proper education for all levels of PHC professionals.

[The age of diagnostic radiologic equipment in Croatia]. / Starost radioloske dijagnosticke opreme u Republici Hrvatskoj.

The quality of health care also depends partly on technological equipment. Among the devices which diminish the quality of services if they are old, increasing at the same time the danger when used, are certainly those in radiodiagnostics. Besides, their age controls the dose of radiation to which patients and professional staff are exposed. The knowledge of the age of this equipment is the basis of the plans for further development. The aim of the study is to determine the age of each individual radiodiagnostic device in Croatian institutions. The assessment of each device was made by a qualified professional. The method of data collection was based on the uniform questionnaire which comprised radiodiagnostic devices older than ten years, classified according to type and location (primary health care center or hospital, in total 655 devices). Determination of the age index of generators and x-ray tubes older than seven years (according to the World Bank recommendation), included also mobile units (55 for fluoroscopy and 68 for radiography), devices for dental radiography, devices in private sector (118) and devices which are out of use but not officially blocked (88), which means in total 859 generators and 1111 x-ray tubes. In addition, the availability of image intensifiers for fluoroscopy and manufactures of all devices were determined. The results of the study reveal that in primary health care centers, out of 248 radiodiagnostic devices, 193 are older than ten years (77.8%), while 4 are of unknown age. In hospitals, out of 407 devices, there are 261 older than ten years (64.1%), while 46 are of unknown age (11.3%). Among devices for fluoroscopy, 97 out of totally 206 have no image intensifier (32%). These devices should be immediately excluded from utilization. The index of age above seven years, which is according to the recommendation of the World Bank the lifetime of devices, reveals that 859 generators out of totally 984 (91%) are too old to be used, while there are 1111 x-ray tubes out of totally 1206 (92%) which are in the same condition. Regarding the manufacturers, the ratio is also unfavourable, since 49.3% of devices have been manufactured by comparies whose technology and spare parts are now inaccessible (Elektronska industrija). Such unacceptable obsoleteness of the radiological equipment requires urgent renewal.

Reform of health insurance in Croatia.

After democratic changes in 1990 and the declaration of independence in 1991, Croatia inherited an archaic system of economy, similar to all the other post-communist countries, which had especially negative effects on the health system. Health services were divided into 113 independent offices with their own local rules; they could not truly support the health care system, which gradually stagnated, both organizationally and technologically. Such an administrative system devoured 17.5% of the total funds, and primary care used only 10.3% of this. Despite the costly hospital medicine the entire system was financed with US$300 per citizen. The system was functioning only because of professionalism and enthusiasm of well-educated medical personnel. Such health policy had a negative effect on all levels of the system, with long-term consequences. The new health insurance system instituted a standard of 1,700 insureds per family medicine team, reducing hospital capacities to 3.8 beds per 1,000 citizens for acute illnesses. Computerization of the system makes possible the transparency of accounting income and expenses. In a relatively short period, in spite of the war, and in a complex, socially and ethically delicate area, Croatian Health Insurance Institute has successfully carried out the rationalization and control of spending, without lowering the level of health care or negatively influencing the vital statistics data.

Identification of synthetic /bdg/ by hearing-impaired listeners under monotic and dichotic formant presentation.

Individuals with sensorineural hearing losses of both flat and sloping configuration evidence difficulty in identifying stop consonant place of articulation. To assess whether upward spread of masking is responsible for this difficulty, we presented hearing-impaired listeners with stimuli from a /ba da ga/ continuum in both monotic and dichotic (F1 to one ear; F2/F3 to the other ear) listening conditions. In the monotic conditions, listeners with similar audiograms evidence great variability in identification performance. In the dichotic conditions performance did not generally improve. For a few listeners, however, the improvement was striking. At moderate levels of signal presentation, upward spread of masking does not appear to be responsible for the poor identification of place by the majority of listeners with moderate hearing losses.