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Gene therapy in the world and in Switzerland.

Until the mid-seventies, biology used to be taught as an interesting, yet rather "useless" discipline in our high schools. The advent of molecular biology has drastically changed this image. Now, applied molecular genetics has been shown to have the potential to revolutionize many aspects of our life, including the paradigms of medicine. In a first phase, gene knowledge has allowed medical diagnosis with previously unimaginable precision. In a second wave, gene transfer in micro-organisms has produced a plethora of biopharmaceuticals. This decade has seen the third era of molecular medicine, in which direct gene transfer into humans is being developed. This article comments on the most recent developments and concepts in the field of human gene transfer (also called "gene therapy"). Some essential methods are briefly presented and a great deal of attention is devoted to the technical hurdles still to be overcome in achieving efficient and safe gene therapy protocols. The final paragraph attempts to clear up some myths and misunderstandings that are commonly propagated when people talk or think about gene therapy. The purpose of this article will be fulfilled if at the end the reader is convinced that gene therapy is not necessarily dedicated exclusively to hereditary disorders, that Switzerland undertaken an intensive and competitive experimental effort in this direction, that gene therapy has already proven its efficacy and has great potential, but that it will take a couple of decades before some applications are routinely used in the clinic.

Gene Transfer Techniques↗

[Newcastle disease--seroepidemiologic study of a highly contagious epizootic in poultry and in wild birds in Switzerland].

Newcastle disease (ND) is a highly contagious viral disease particularly of domestic poultry. Switzerland is currently declared free from ND. A serosurvey using an ELISA was performed to investigate infections with ND-Virus (NDV) in 260 Swiss laying hen flocks, 169 backyard poultry flocks and 1576 wild birds. For laying hen flocks, a stochastic model was applied to analyse the results from serological testing. Four laying hen flocks were identified as NDV-seropositive, and the true NDV seroprevalence in this population was most likely between 1.3 and 1.5%. NDV antibodies were also detected in five of the 169 backyard poultry-flocks. ND-antibody positive birds were found in 10% of all wild birds examined, with the highest proportions among cormorants, grebes, birds of prey, owls, and swifts. The study indicated that positive flocks must have been in contact with NDV strains causing sub-clinical infection, since no clinical signs had been observed. Moreover, trade of poultry or poultry eggs was considered to be an important factor associated with seropositivity in backyard poultry flocks. Contact to wild birds did not seem to be of major importance.

Animals↗

[Tuberculosis in Switzerland--a millenium problem?].

In Switzerland a family physician sees a case of tuberculosis only every 4-6 years. While tuberculosis does not seem to be a major medical challenge in western countries, it is a real problem in the developing world. Nevertheless, special situations do arise in the western hemisphere where the standard therapy needs to be changed. HIV-positive patients are at greater risk of contracting tuberculosis after exposure, and therapy must be adjusted to the patient's immunological status. Multidrug-resistant tuberculosis is a major challenge to the attending physician, and takes us back to the time before antitubercular drugs existed. Standard medication is ineffective and we have to fall back on alternative drugs. Compliance of patient and physician are crucial for effective treatment, as in the case of all long-term therapy. Medical staff, and especially hospital personnel in emergency and tuberculosis departments, are at high risk of infection. Younger staff are no longer immunised by vaccination or earlier infection as they were a few decades ago. Multidrug-resistant bacteria pose a real threat for these groups and effective protection against transmission is important. Discovering a new vaccine which provides adequate immunisation is the only way to tackle the problem of tuberculosis worldwide. New drugs must also be developed to treat those already suffering from the disease.

AIDS-Related Opportunistic Infections↗

[A new drug reaches Switzerland: coma after intake of gamma-hydroxybutyrate (GHB)].

The new recreational drug, gamma-hydroxybutyrate (GHB, "liquid ecstasy"), reached Switzerland in 1998. We describe two cases from the city of Zurich. In both of them the subjects were profoundly unconscious and needed hospitalization after intake of a colourless liquid. Both patients recovered after a few hours, rapidly and without after-effects. Gamma-hydoxybutyrate is abused mainly for its euphorigenic and sedative properties by young people in discos, at raves, or on the drug scene. It is also taken as an alleged anabolic agent among bodybuilders. Criminals use it to narcotise potential victims. We summarise its effects, adverse effects, diagnosis, treatment, toxicology, pharmacology, and medical applications.

Adult↗

[Physician workforce and population aging in Switzerland].

The number of physicians in private practice per 100,000 populations will raise to 210 in the year 2005 and to 235-265 in the year 2020, from 187 in 1998. The feeling of manpower surplus is spreading in Switzerland and some commentators are voicy as concerns aggravated oversupply in the future. During the period 1990-2020, the Swiss population will increase +12% but the population aged 65 and over will increase +57%. Even if the elderly in the forthcoming decades will be in better health than their today's counterparts, most probably the demand for health services will increase. Social change, medical technology progress and growth in the population-doctor ratio itself will fuel the process.

Adolescent↗

[Ehrlichiosis in Switzerland--significance for veterinary medicine].

Ehrlichiosis is a rickettsial disease of animals and humans caused by various species of Ehrlichia. These obligate intracellular microorganisms infect granulocytes or monocytes of mammalian hosts and are transmitted mostly by ticks. The febrile disease is often undiagnosed and characterized by leukopenia, anemia and thrombocytopenia. The diagnosis of ehrlichiosis is based on clinical findings, tick infestation, direct or indirect detection of the agent, and serology. The role of native and imported ehrlichiae of animals in Switzerland is discussed.

Animals↗

[Start of an adult living donor liver transplantation program in Switzerland].

The shortage of cadaver organs has prompted transplant centres to seek new sources of grafts. While living-donor left lobe transplantation (segments II and III) is an established procedure for children, living donor right liver transplantation (segments V, VI, VII, VIII), which can provide adequate liver mass for an average-sized adult patient, is technically more demanding and potentially associated with higher risks for the donor. In view of the permanent shortage of organs in Switzerland, we started an adult living donor liver transplantation programme in 1999 with the approval of the Clinical Ethics Committee of Geneva University Hospitals. Donor evaluation was performed only after the recipient had been officially registered for transplantation in the national waiting list. Preoperative evaluation consisted of a preliminary information phase with blood tests and Doppler ultrasonography, a second phase with radiological non invasive investigations (CT scan with volume measurements, magnetic resonance cholangiography) and a third phase including liver biopsy and angiography. A formal psychiatric evaluation was performed in all cases and detailed consent was required. Eight potential donors were investigated, 5 were not retained because of too small right liver or steatosis, and 3 were accepted (wife, son, sister). Living-donor hepatectomy was performed without interrupting the vascular blood flow. The liver graft was perfused ex-situ with University of Wisconsin solution. The grafts were anastomosed to the preserved vena cava of the recipient and the portal and arterial anastomoses were performed without interposition grafts, with short cold ischaemic times in the 3 cases. The graft-to-recipient weight ratio ranged from 1.04 to 1.12%. The grafts worked immediately; the post-operative course in the 3 recipients was unremarkable and no rejection episode occurred. Significant complications were observed in one donor (percutaneously drained bilioma and spontaneously resolved popliteal sensory palsy). Living-donor right liver transplantation is a potentially valuable solution to the increasing shortage of donor organs. The procedure can be performed safely provided stringent criteria for donor selection, for donor-recipient coupling (> 1% graft to body weight ratio) and for centre selection (experience in liver surgery, reduced and split liver transplantation) are applied.

Adenosine↗

[Endemic and imported severe leptospirosis (Weil's disease) in southern Switzerland].

We report on 4 cases of severe icteric leptospirosis. Three patients developed renal failure requiring haemodialysis and one required mechanic ventilation for 10 days. On entry all patients presented with severe myalgia, particularly in the calves, jaundice, oligo-anuria and severe thrombocytopenia. In one case an acute abdomen-like presentation led to exploratory laparotomy. We believe that the abdominal pain was mainly due to rhabdomyolysis of the abdominal wall. The outcome was favorable in all cases and recovery of renal function was observed after a few days to several weeks. Three out of 4 patients were infected in southern Switzerland. This observation underscores the importance of wild and domestic animals as a leptospira reservoir. Patients presenting with acute renal failure and jaundice, but only mild-to-moderate elevation of transaminases, are suspect for leptospirosis regardless of travel to a tropical or subtropical country.

Acute Kidney Injury↗

Health and safety at work in Switzerland: impact of European Union directives.

Switzerland, surrounded by European Union (EU) member states, rejected a 1992 referendum to join the European Economic Communities (EEC), which currently includes 15 member states. As a result, the country has had difficulties resolving economic issues with health and safety interests. This study analyzed the consequences of selected EU Directives of Health and Safety at Work in a country that chose not to join the EU. The Directives went into effect throughout the entire EU in 1993. Executive directors and safety advisors from the Swiss company "Migros" participated in a two round Delphi survey focused on timing, feelings, and preference of the legal system in relation to the EU, prioritizing selected EU directives, and implementing health and safety concepts. The results showed the effects of the Directives (although not legally required) demand careful consideration particularly in terms of the timing of the implementation and the priorities of the Swiss health and safety legal system. The two professional groups involved showed congruent opinions on several questions, presenting a solid foundation for planning common action. In conclusion, the growing awareness of occupational health and safety aspects observed during the survey should be pursued among all Migros key staff in decision making positions in occupational safety and health. In this way, Migros could serve as a role model in the occupational health and safety field, much as it has long been recognized as a pioneer in funding social causes throughout Swiss society.

Adult↗

[Ant venoms: a rare cause of allergic reactions in Switzerland].

In Switzerland, unlike other countries, allergic reactions to ants are a rare phenomenon when compared to the well known allergies to bee and wasp venom. In this report we present a series of case reports and a review of the different types of allergy to ants. Due to increased travel and heterogeneity of the population, we have observed several patients with sensitisation or allergy to the venom of imported fire ants (Solenopsis), a species of ant found in the Americas. Furthermore, allergic reactions to bites of the mound-building wood ant (Formica rufa), whose habitat is Central and Northern Europe, have been documented. Whereas reactions to fire ants can be life-threatening, reactions to mound-building wood ants have led to marked local reactions and in 2 cases to dyspnoea and wheezing. These reactions could be due either to primary sensitisation to ant venom or cross-reactivity in the presence of an allergy to wasp venom. Evaluation of patients presenting with a potential ant venom allergy includes a detailed personal history, skin testing and determination of specific IgE. However, to date only extracts from fire ants are commercially available for diagnostic tests. In the light of our observations we assume cross-reactivity between the venoms of fire ants and mound-building wood ants, and it therefore seems appropriate to use fire ant diagnostics in determining sensitisation to mound-building wood ants. In patients with severe fire ant-venom allergy we recommend desensitisation by immunotherapy, whereas in patients presenting with minor allergic reactions, e.g. after bites by mound-building wood ants, we provide the patients with emergency medication. Since current knowledge of ant allergies in Europe is limited, further studies are warranted.

Animals↗

Farm and slaughter survey of bovine tuberculosis in captive deer in Switzerland.

In 1998, a survey was conducted by postal questionnaire to gather basic knowledge about the management, health and productivity of captive deer in Switzerland. In addition, lymph nodes were collected from slaughtered deer from 124 of the 262 holdings surveyed, and tested for Mycobacterium bovis and Mycobacterium tuberculosis. The total farmed deer population was 8389 animals kept on 485 holdings; 87 per cent were fallow deer, 8 per cent red deer, 4 per cent sika deer, and there were small numbers of other species. The median herd sizes were 12 for fallow deer and eight for red deer. Few owners had handling facilities or crushes. In none of the lymph nodes examined were lesions typical of bovine tuberculosis observed, and neither M bovis nor M tuberculosis was cultivated from any of the samples.

Animal Husbandry↗

Veterinary epidemiology--a key to sustainable pig production in Switzerland.

Sustainable animal production requires a healthy production system including healthy animals producing wholesome products. Epidemiology as a discipline is concerned with the occurrence of disease or disease indicators in populations as well as with factors influencing disease occurrence. By providing this information, epidemiology contributes significantly to the development and maintenance of healthy livestock. This is illustrated with the example of the enzootic pneumonia (EP) eradication programme of Switzerland. A series of observational studies were conducted in order to obtain the necessary knowledge to implement an area-wide EP eradication programme. The issues of economical eradication strategies at the herd level and the risk of re-infections were addressed. Simulation modelling and economical analysis were also applied. These research projects led to the successful start of a national eradication programme. The example of the EP eradication programme illustrates that applied epidemiological research provides critical information for the planning, implementation and evaluation of disease control programmes and is thus a key tool in developing sustainable animal production.

Animal Husbandry↗

[Intestinal microecology of the adult population of Mongolia, Switzerland, and Russia].

The study of intestinal microflora was made in clinically healthy young adults living in rural areas of Mongolia, in Russia (Moscow) and in Switzerland, as well as in Swiss citizens of elderly age groups (55-68 and 87-94 years). Essential differences in the quantitative and qualitative characteristics of intestinal microflora both in the inhabitants of different countries as well as in people belonging to different age groups in the same country were established. The results of the study demonstrated the expediency of working out the criteria of the norm for intestinal microflora both for the population of different countries and for people living in the same country, but belonging to different age groups.

Adult↗

[Incidence of thalassemia in Switzerland].

A total of 2672 cases with thalassemia syndromes observed in the period from 1 January 1968 to 30 April 1974 are classified according to type of thalassemia and the patient's country of origin. During the past 15 years some 10 patients annually with classical heterozygous beta-thalassaemia have been found to be of purely Swiss origin. Due to increased immigration from Mediterranean countries the Swiss patients represent only 2.6 percent of all cases at the present time, a marked decrease from the earlier 30 percent. Since 1968 2260 cases of thalassemia syndrome have been found in Italian patients. Smaller groups of patients originate from Greece, Spain and Turkey. Homozygous beta-thalassemia was observed in 56 cases. Ranking third among thalassemia syndromes is the Hb Lepore trait found in 16 cases. The increase in thalassemia syndromes due to population migration over the past 10 years has resulted in the finding of rare types in Switzerland: 8 patients with HbS-beta-thalassemia, 2 with HbC-beta-thalassemia, 3 cases of HbH-alpha-thalassemia and 2 cases of Hb Bart's-alpha-thalassemia are reported. The difficulty of diagnosing deltabeta-thalassemia and alpha-thalassemia is emphasized.

Diagnosis, Differential↗

[Status of scalp hair and therapy of alopecia in men in Switzerland].

A community-based interview and a questionnaire of men visiting the dermatologist for treatment of hair loss were conducted in Switzerland, to characterize the significance of scalp hair and self-perception of hair loss in Swiss men, and to evaluate current treatment of hair loss. 508 men, aged 15-74 years, regardless of the degree of hair loss, were interviewed by telephone, and 308 patient questionnaires were completed by 19 dermatologists. The questions addressed by the interview were: degree of self-rated hair loss, time invested for hair care, use or reasons for rejecting hair growing agents, relevant criteria for scalp hair, self-assessment with respect to different "hair communication types". The questionnaire analysed the causes of hair loss, prior and current treatment modalities, and follow-up at the dermatologist. Respondents rated their hair loss on a 5-point, textual scale that ranged from 'no hair loss' to 'bald areas'. 43% reported hair loss to some extent. For 42% a full head of hair was very important, especially for men under 29 years, who invested more time for hair care and had not lost hair. Of men with hair loss, 26% previously applied hair growing agents. Of men consulting the dermatologist for hair loss, 90% had androgenetic alopecia. 37% were previously treated: prior treatment was in 59% minoxidil, in 4% finasteride (Propecia), in 7% Aminexil, in 7% dietary supplements, and in 6% conducted by the hair dresser. In 79% treatment was switched to Propecia: of these, 73% adhered to the follow-up consultations at the dermatologist.

Adolescent↗

[Three cases of postweaning multisystemic wasting syndrome (PMWS) due to porcine circovirus type 2 (PCV 2) in Switzerland].

Porcine circovirus type 2 (PCV 2) was found in three five- and nine-week-old pigs from two feeder pig producer farms. Clinical signs were persistent diarrhea and wasting. The animals showed histomorphologic changes characteristic for "Postweaning Multisystemic Syndrome" (PMWS). One animal had the typical basophilic intracytoplasmatic circoviral inclusion bodies in the Peyer's patches of the ileum. Circoviral DNA was detected in the lymphatic organs as well as in the liver. This case report is the first description of PCV 2 in Switzerland.

Animals↗

Memory Clinics in Switzerland. Collaborative Group of Swiss Memory Clinics.

Currently, eleven Memory Clinics (MC) in Switzerland offer their services to patients, caregivers and family doctors. Their primary goal is the early diagnosis and management of dementia in elderly outpatients. Special emphasis is put on the detection of reversible causes of dementing disorders. Diagnoses and medical, pharmacological, neuropsychological and social treatment recommendations are established in a multidisciplinary consensus conference and communicated back to the referring physicians. The psychosocial therapies and supportive activities include counseling, memory training for patients, neuropsychological rehabilitation, caregiver groups, relaxation and biofeedback training, day care centers, Alzheimer's Tanzcafé, and special vacations for dementia patients. These activities vary from MC to MC according to the availability of resources. Research activities are an integral part of all MCs and range from the attempt to identify preclinical markers of Alzheimer's disease to studies of neuropathological correlates of cognitive disturbances. Moreover, patients are encouraged to participate in studies investigating new medications. MCs play an important role in the education and training of health care professionals and in raising awareness and support in the general population.

Aged↗

[Avian leukosis subgroup J in broiler breeders in Switzerland].

Since a new envelope subgroup (J) of the avian leukosis-sarcomatosis-complex was isolated for the first time from broiler breeders in the United Kingdom in 1989 and was characterized and associated with myeloid leukosis (syn. myelocytomatosis) the emergence of this subgroup was reported from all over the world. Thus the first known case of subgroup J avian leukosis in Switzerland in four imported broiler breeder flocks will be described. A total of 53 broiler breeder birds from four flocks showing reduced performance and increased mortality were submitted for postmortem examination. Approximately 20 blood samples from each flock were monitored serologically for antibodies against avian leukosis virus subgroup J (ALV-J). On necropsy myeloid leukosis (ML) was diagnosed in all four flocks. Furthermore the blood samples of three flocks showed significant ELISA-titres for ALV-J.

Animals↗