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Reproductive health and blurred professional boundaries.

We recognize that many of the issues raised are not simple. Our proposal calls for the same thoughtful deliberation applied in other settings to be brought to bear on reproductive health care. Some have already tried alternative approaches. In Albuquerque, New Mexico, a university hospital neonatologist and the district attorney have collaborated to create an alternative to sentencing program for women who are arrested for drug-related crimes and found to be both pregnant and drug addicted. Rather than proceed with criminal sanctions, these women are offered entry into a drug treatment program that is geared to families with young children and run by the pediatrics department. Here, the physician and the district attorney collaboratively responded in ways congruent with the professional integrity of each. In another example in Portland, Oregon, physicians, drug treatment providers, and child protective social service representatives cooperatively defeated a legislative proposal to mandatorily test and report pregnant women for illicit drug use and, instead, formed a task force to jointly develop state policy regarding the issue. Drug use, HIV infection, child abuse, and poverty are all cause for alarm. Yet it is critical that our frustration about these difficult problems not be translated into blaming individuals for "deviance," or into short-term inadequate responses. In developing policy we should consider the impact on the legal and ethical rights and obligations of both patient and physician. For every course, we should evaluate both immediate and long-term efficacy, the consequences for the doctor-patient relationship, and the consequences for medical integrity. In the midst of the present regulatory and fiscal turmoil affecting health care, we urge physicians to be careful and deliberate in the policies they embrace and the actions they take.

Confidentiality↗

Periodic health examination, 1994 update: 3. Primary and secondary prevention of neural tube defects. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To make recommendations on nutritional interventions and screening manoeuvres to prevent the birth of infants with neural tube defects (NTDs). OPTIONS: Folic acid consumption through diet or supplementation in women at low risk and at high risk of having a fetus with an NTD, and maternal serum alpha-fetoprotein (MSAFP) screening in low-risk pregnancies. OUTCOMES: A reduction in the incidence rate of NTDs and potentially harmful effects of false-positive results of screening tests (i.e., abortion of a normal fetus). EVIDENCE: A MEDLINE search with the use of medical subject headings "neural tube defects," "prenatal diagnosis" and "prevention and control" identified 103 original articles published between January 1979 and March 1993. Two reviewers extracted the data by applying the rules of evidence developed by the Canadian Task Force on the Periodic Health Examination. VALUES: The task force's evidence-based methods and values were used; high value was placed on prevention of NTDs and on limitation of the harmful effects of a pregnancy involving a fetus with an NTD. BENEFITS, HARMS AND COSTS: Evidence suggests that folic acid supplementation can decrease the incidence rate of NTDs in low-risk pregnancies by 40% to 60% with no adverse effects. MSAFP screening between the 16th and 18th weeks of gestation can reach a sensitivity of 83% and a specificity of 98% when it is used as part of an organized program. The effect of screening on the incidence rate of NTDs depends on whether affected fetuses are aborted. RECOMMENDATIONS: All women of childbearing age should be advised to increase their consumption of folic acid through diet or supplementation to 0.4 mg/d beginning 1 month before pregnancy and ending at the start of the second trimester. MSAFP screening is recommended in low-risk pregnancies only when it is part of a screening program that includes access to all necessary diagnostic services. High-risk women should be referred to genetic counselling before they plan a pregnancy. VALIDATION: These recommendations are comparable to the current recommendations of the US Centers for Disease Control and Prevention, the Society of Obstetricians and Gynaecologists of Canada, the Canadian Laboratory Centre for Disease Control and the Canadian College of Medical Geneticists, and they were validated through external review. SPONSOR: These guidelines were developed and endorsed by the Canadian task force, which funded by Health Canada.

Canada↗

[Possibilities and risks of genetic diagnosis].

In the recent past, cytogenetic and molecular genetic methods led to an enormous increase in knowledge on genetic information. It reveals a correlation between the genetic information and the phenotype of an individual. Therefore, new starting points concerning the origin of diseases arise. A new nosology will develop. It will force researchers to emphasize more and more on the contribution of the--disturbed--genetic information system to the development of diseases. They will routinely carry out genome analyses on the following four already established levels: 1. phenotype level, 2. biochemical level, 3. chromosomal level, 4. molecular genetic level. Practicians mustn't close their mind to these new possibilities and methods: The three classical tasks of medicine--diagnosis, prevention and therapy--will be supplemented considerably by an earlier (presymptomatic) and more precise diagnosis that is furthermore independent of the organ. Moreover, there is the increasing possibility to predict the risk to develop a disease for descendants in certain partnerships more precisely and, if necessary, to diagnose prenatally. From the medical point of view, these advances are predominantly positive and to the patient's benefit. But it is pointed out that the diagnostic progress also raises new problems which were previously unknown. The answers will have to be given by society as a whole.

Chromosome Mapping↗

ICH-harmonised guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact.

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has convened an expert working group which consisted of the authors of this paper and their respective committees, consulting groups and task forces. Two ICH guidances regarding genotoxicity testing have been issued: S2A, 'Guidance on Specific Aspects of Regulatory Genotoxicity Tests' and S2B, 'Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals.' Together, these guidance documents now form the regulatory backbone for genotoxicity testing and assessment of pharmaceuticals in the European Union, Japan, and the USA. These guidances do not constitute a revolutionary new approach to genotoxicity testing and assessment, instead they are an evolution from preexisting regional guidelines, guidances and technical approaches. Both guidances describe a number of specific criteria as well as a general test philosophy in genotoxicity testing. Although these guidances were previously released within the participating regions in their respective regulatory communiqués, to ensure their wider distribution and better understanding, the texts of the guidances are reproduced here in their entirety (see Appendix A) and the background for the recommendations are described. The establishment of a standard battery for genotoxicity testing of pharmaceuticals was one of the most important issues of the harmonisation effort. This battery currently consists of: (i) a test for gene mutation in bacteria, (ii) an in vitro test with cytogenetic evaluation of chromosomal damage with mammalian cells or an in vitro mouse lymphoma tk assay, (iii) an in vivo test for chromosomal damage using rodent hematopoietic cells. A major change in testing philosophy is the acceptance of the interchangeability of testing for chromosomal aberrations in mammalian cells and the mouse lymphoma tk assay. This agreement was reached on the basis of the extensive review of databases and newly generated experimental data which are in part described in this publication. The authors are fully aware of the fact that some of the recommendations given in these ICH guidances are transient in nature and that the dynamic qualities and ongoing evolution of genetic toxicology makes necessary a continuous maintenance process that would serve to update the guidance as necessary.

Animals↗

The centralized prenatal genetics screening program of New York City: I. Developmental phase.

The increasing demand in New York City for prenatal diagnosis of genetic disorders has necessitated the development of a large-scale, centralized prenatal genetic screening program. The objective of this program is eventually to serve 3,000 to 4,000 at-risk New York City pregnant women annually. Through the teamwork of a task force comprising representatives from the New York Scientists' Committee for Public Information (SCPI), the Medical and Health Research Association of New York City Departments of Health, and five different advisory committees, the centralized Prenatal Diagnosis Laboratory of New York City (PDL) was designed and established. While this program aims to provide high quality, centralized laboratory service for the prenatal detection of chromosome abnormalities and open neural tube defects, it also emphasizes quality-controlled services in genetic counseling, aminocentesis, ultrasound monitoring, obstetric care, and patient follow-up. Genetic counseling by PDL-employed counselors is made available to patients whenever the participating hospital lacks such service or cannot handle their patient load. In addition, PDL has launched a vigorous public health education program. A detailed guideline for the program was prepared describing the highest standards of quality for each component. The initial step was th developmental phase that included establishing the advisory committees, searching for sponsors, preparing guidelines, developing the health education program, renovating the laboratory site, purchasing and installing equipment, and recruiting of staff. The experience gained from this endeavor will be of value in the development of similar large-scale prenatal diagnosis programs.

Amniocentesis↗

Effects of transgenic overproduction of CRH on anxiety-like behaviour.

Central administration of corticotropin-releasing hormone increases anxiety-like behaviour and arousal in rodents, and increased anxiety-like behaviour has been shown in mice overproducing corticotropin-releasing hormone on an elevated plus maze and in a dark-light emergence task. However, evidence is accumulating that measures obtained from different anxiety tasks may reflect different aspects of anxiety-like behaviour in animals. We therefore tested mice overproducing corticotropin-releasing hormone in a battery of paradigms, studying spontaneous behaviour after a mild stressor, tasks of innate anxiety-like behaviour (light-dark box), lick suppression (Vogel conflict), conditioned fear, and forced swimming. Exploratory behaviour was studied in a 16-hole board task. Furthermore, pain threshold, water intake, locomotor activity and sensorimotor learning/co-ordination were tested to control for confounding factors. In line with previous findings, increased anxiety-like behaviour of transgenic mice was observed in the light-dark box paradigm. However, no differences were seen in the conflict paradigm. Conditioned fear was decreased 1 h but not 24 h after conditioning in transgenic mice, and immobility was decreased [corrected] in forced swimming in corticotropin-releasing hormone overexpressors. Locomotor activity in a novel open field and on the hole board was reduced in transgenics. Exploratory behaviour (hole pokes) was reduced during initial exploration of an unfamiliar hole board. Moreover, sensorimotor performance on a rotorod was impaired, and water intake was reduced in corticotropin-releasing hormone overproducing mice, while no changes were seen in nociception. No differences in locomotor activity were seen in a second group of mice, tested in a familiar open field. When these animals were challenged with diazepam, transgenic mice were less susceptible to the sedative effects of the drug on locomotor activity. These data suggest that corticotropin-releasing hormone overproduction leads to specific effects in a subset of anxiety paradigms, and that these transgenic mice suffer from a motor deficit in addition to altered anxiety-like behaviour/arousal.

Animals↗

A reassortant bunyavirus isolated from acute hemorrhagic fever cases in Kenya and Somalia.

In late 1997 and early 1998, a large outbreak of hemorrhagic fever occurred in East Africa. Clinical samples were collected in Kenya and southern Somalia, and 27 of 115 (23%) hemorrhagic fever patients tested showed evidence of acute infection with Rift Valley fever (RVF) virus as determined by IgM detection, virus isolation, detection of virus RNA by reverse transcription-polymerase chain reaction (RT-PCR), or immunohistochemistry. However, two patients (one from Kenya and the other from Somalia) whose illness met the hemorrhagic fever case definition yielded virus isolates that were not RVF. Electron microscopy suggested these two virus isolates were members of the family Bunyaviridae. RT-PCR primers were designed to detect bunyavirus RNA in these samples. Regions of the S and L segments of the two isolates were successfully amplified, and their nucleotide sequences exhibited nearly complete identity with Bunyamwera virus, a mosquito-borne virus not previously associated with severe human disease. Unexpectedly, the virus M segment appeared to be reassorted, as the sequences detected exhibited 32-33% nucleotide and 28% amino acid differences relative to the corresponding M segment sequence of Bunyamwera virus. The association of this reassortant bunyavirus, proposed name Garissa virus, with severe disease is supported by the detection of the virus RNA in acute-phase sera taken from 12 additional hemorrhagic fever cases in the region.

Animals↗

[Polish Multicenter Study on Diabetes Epidemiology (PMSDE)--1998-2000].

Diabetes mellitus is a growing health problem at all ages in all countries. The Saint Vincent Declaration signed by the representatives of all European countries--among them by Poland--indicated the main goals to reduce this burden. This may be achieved by elaboration and initiation of the nation-wide programme for early detection and control of diabetes on the population level. The Polish Task Force for Diabetes Management worked out and put into operation in 1998 the project commissioned by the Ministry of Health funded by the Polish State Committee for Research (PBZ-018-11). The urgent need for the implementation of this programme was a result of the increasing number of diabetic patients on the primary health care level, diabetic complications and hospitalisations. The programme was based on the assumption that primary and secondary prevention of NIDDM may eliminate or reduce its risk factors and therefore decrease its prevalence and morbidity and should integrate epidemiology, identification of risk factors, education, intervention models and economics of diabetes. This issue of the Polish Archives of Internal Medicine contains the main results of the programme and reflects an actual situation of diabetes in Poland creating a rational basis for intervention on the population level. Evaluation of the incidence rate of the diabetes type 1 in 10 selected areas (population basis 30% of age group 0-29) revealed values from 8.4 to 14.7/100,000 in the age group 1-14 and from 4.4 to 11.2/100,000 in the age group 15-29. It accounts for the 2-3 fold increase in comparison with the results achieved in 1986 (Z. Szybinski). However an ascertainment of the register in the age group 15-29 dropped down during the last 10 years and additional sources of data must be involved in the survey. Prevalence of diabetes type 2 in 3 selected areas Krakow 10.77% (M. Szurkowska), Lublin 15.6% (J. Łopatynski) and Łódź 15.7% (J. Drzewoski) based on the population random sample over 35 years of age, constitutes over 90% of all patients with diabetes. When standardized to the Polish population the prevalence of diabetes type 2 accounts for 5.37% and reflects a true endemic state. With comparison to a similar survey carried out in 1986 in Wrocław the prevalence 3.71% of the diabetes type 2 increased 2-3 times. It allowed to calculate an actual number of patients with diabetes type 2--over 2 million and around 50% of them represents "unknown" diabetes. Such high contribution of the unknown non-diagnosed diabetes has been confirmed in the survey carried out in Poznań on the non-randomized professional group of persons (B. Wierusz-Wysocka) in investigation on the first-degree relatives of patients with known diabetes in Warsaw (T. Kasperska-Czyzyk) and in Wroclaw (R. Wasikowa). This raises the question about the criteria of diagnosis for unknown diabetes. Comparative analysis carried out in Krakow revealed that fasting glycemia 7.0 mmol/L allowed to diagnose diabetes with 50% with respect to the 2 hours oral glucose tolerance test (WHO 1985) and shouldn't be use as a tool for early diagnosis of diabetes type 2 (Z. Szybinski, M. Szurkowska) Identification of the risk factors in PMSDE for diabetes type 2 allowed to introduce the term "global risk factors", divided into two groups primary (obesity, age, pregnancy and genetic background) and secondary (hyperinsulinemia, hyperglycemia, dyslipidemia and hypertension). In the multifactor analysis obesity and hyperinsulinemia are the strongest predictors and modifiable risk factors of the development of diabetes type 2 and late complications. Especially hyperinsulinemia as an independent secondary risk factor for hypertension, dyslipidemia--in consequences late diabetic complications and perhaps carcinogenesis may play an important role as a predictor of diabetes type 2 and biochemical marker of effectiveness of non-pharmacological and pharmacological approach in the global concept of diabetes type 2 treatment (Z. Szybinski). Analysis of the late complications of diabetes were focussed on visual disability and lower extremity amputation due to diabetic foot development. Analysis of prevalence (PR) of visual disability due to diabetes in Krakow (J. Pantoflinski) and Olsztyn (E. Bandurska-Stankiewicz) revealed similar values, in the both areas around 6% of general visual disability in population. Monitoring of the visual disability in diabetic patients seems to be a good indicator of the quality level of the diabetic care. Analysis of the lower extremity amputation carried out in Krakow district (A. Nazim) revealed that incidence rate of amputation in diabetics was 15 times higher than in non-diabetics and in 10.8% of cases amputation was performed in unknown diabetes type 2. The preventive measures and non-pharmacological and pharmacological management approximately in diabetes should be solved with education based on the separate post of a diabetic educator within a diabetic team and on the primary health care level. The articles presenting elaborated educational model in diabetes are published in "Diabetologia Polska" (A. Czyzyk). Intervention model was tested in Krakow in the groups of obese patients with newly diagnosed "unknown" diabetes and was based on the 12 weeks supervised dietician education with standardized physical activity programme. In obese diabetic patients the weight loss less than 10% of the initial body weight can markedly improve biochemical parameters like hyperglycemia dyslipidemia and hyperinsulinemia without pharmacological therapy and 45% of patients has been transferred to the group of Impaired Glucose Tolerance (A. Gilis-Januszewska). Another model of intervention may be applied in menopausal women (J. Nadel, K. Cypryk) treated with hormonal replacement therapy as a complementary factor to education and if necessary to anti-diabetic drugs. Increase number of diabetic patients especially of the "unknown" type 2 has serious economic aspect by increasing a burden of patients, theirs families, society and health care system. Within PMSDE programme elaboration of the model for calculation the direct costs about of diabetes and burden in terms of years of life lost using DALY measure was performed (K. Kissimova-Skarbek). Average diabetes type 1 patients costs 7 times and type 2 over 3 times higher than average health care cost and 95% of total time lost due to disability is caused by diabetes type 2. Therefor primary and secondary prevention of diabetes typ 2 have highest priority among strategic preventive targets. The Review Conference held in Warsaw at 24-25 February 2001 in the presence of WHO Experts formulated the recommendations focused on: 1. Elaboration of high risk strategy for early diagnosis of unknown diabetes type 2 based on the 2-hours OGTT (WHO 1985) 2. Continuation of the epidemiologic study in diabetes 3. Instituting the professional post for diabetes educator on the specialized and primary health care levels. 4. Further research are recommended for evaluation of the role of fasting glycemia and hyperinsulinemia as predictors and risk factors of diabetes type 2, for development of preventive models in diabetes type 2 and for development of the economical models to asses the costs of diabetes (Recommendations).

Adult↗