Miglustat therapy in juvenile Sandhoff disease.

GM(2)-gangliosidosis is a rare and heterogeneous inherited metabolic disorder caused by autosomal recessive mutations in genes encoding the lysosomal enzyme ß-hexosaminidase, resulting in the accumulation of ganglioside GM(2) in various tissues, particularly the central nervous system. It is characterized by progressive neurological deterioration that mainly affects motor and spinocerebellar function. Several forms of GM(2)-gangliosidosis exist, including the Sandhoff variant. Currently there is no treatment for these conditions, except for palliative care. Miglustat (Zavesca) is a reversible inhibitor of glucosylceramide synthase, which catalyses the first committed step in the synthesis of glucose-based glycolipids. Miglustat has pharmacokinetic properties that allow it to cross the blood-brain barrier, and preclinical data suggest that it may benefit neuronopathic lysosomal storage diseases. Here we present a case report of a Norwegian patient with Sandhoff disease treated with miglustat at our centre in Norway. The patient initially presented with ataxia and dysarthria at 2-3 years of age, which progressed slowly during childhood. At age 14, he experienced episodes of depression and apathy, leading to weight loss. He was diagnosed with Sandhoff disease at age 16. Following 2.5 years of treatment with miglustat, his body weight was stabilized and disease progression appeared to have slowed, as evidenced by the lack of progressive brain atrophy. His depressive symptoms were managed using electroconvulsive treatment (ECT), which improved general functioning. These findings suggest that miglustat may provide beneficial effects in patients with juvenile Sandhoff disease, and that ECT may alleviate depressive symptoms.

The antiviral drug docosanol as a treatment for Kaposi's sarcoma lesions in HIV type 1-infected patients: a pilot clinical study.

Docosanol inhibits a broad spectrum of lipid-enveloped viruses in vitro including HSV-1, HSV-2, VZV, CMV, HHV-6, and HIV-1. These observations led us to conduct a pilot clinical study with docosanol 10% cream as a topical treatment for Kaposi's sarcoma (KS) in HIV-1-infected patients. In this open-label study 28 cutaneous KS lesions in 10 HIV-1-infected patients were treated topically five times daily for 4 weeks with evaluation of lesion characteristics of area, edema, and color. All patients elected to enroll in an extended treatment protocol and continued to treat for up to 35 weeks. Within 28 days, 2 of 10 patients exhibited a partial response based on standardized criteria exhibiting 74 to 83% reductions in total target lesion areas. With extended treatment, a partial response was exhibited in two additional patients where total target lesion area was reduced by 52% in one patient and target lesions in another patient that had been large, swollen, and painful at study initiation were no longer visible. No patient experienced disease progression or signs of visceral disease. The average percent decrease in lesion area for all target lesions was 20% (p < 0.01). A patient's response to therapy appeared to be independent of anti-HIV regimen, HIV viral load, or previous KS treatments. These results suggest that docosanol merits further investigation as a potential topical therapy in the treatment of AIDS-associated Kaposi's sarcoma lesions.

Cardiovascular risk determination: discrepancy between total cholesterol evaluation and two compound laboratory indices in Norway.

OBJECTIVE: To compare group classification of cardiovascular risk by two compound laboratory indices with classification according to the serum total cholesterol concentration alone. DESIGN: Healthy employees were defined as low and high cardiovascular risk subjects according to their total cholesterol concentration or two compound indices of blood lipid components-the total cholesterol: high density lipoprotein (HDL) cholesterol ratio and an atherogenic index defined as ([total cholesterol-HDL cholesterol]*[apolipoprotein B])/([HDL cholesterol]*[apolipoprotein A-I]). Cut off values to distinguish between low and high risk subjects were as follows: total cholesterol 6.5 mmol/l, HDL cholesterol 0.9 mmol/l, apolipoprotein A = 1.8 g/l, and apolipoprotein B = 1.3 g/l. These gave total: HDL cholesterol ratio and atherogenic index cut off values of 7.2 and 4.5 respectively. SETTING: An occupational health service in a non-manufacturing company in Norway. PARTICIPANTS: A total of 112 male and 117 female employees. The mean body mass index values were 25.6 and 23.6 kg/m2 and the mean ages 39.8 and 40.1 years in men and women respectively. Those with cardiovascular, diabetic, or renal diseases were excluded. MEAN OUTCOME MEASURES: Serum total cholesterol, HDL cholesterol, apolipoproteins A-I and B, lipid peroxidation, blood pressure, smoking, physical activity, and fruit, vegetables, and salt in the diet were determined. RESULTS: The cut off values allocated 19%, 7%, and 40% as high risk subjects according to total cholesterol, total: HDL cholesterol, and the atherogenic index respectively. The mean age was two to four years higher in the high risk groups. Cardiovascular risk in siblings and no reported physical activity were more prevalent in those high risk groups defined by the compound indices than by total cholesterol alone, as was a high body mass index and a measure of lipid peroxidation. Grouping according to total cholesterol failed to allocate heavy smokers mainly to the high risk group. Diet variables did not demarcate clearly between indices. CONCLUSIONS: There is considerable variability in classification into high and low risk subjects when using the total cholesterol concentration alone compared with compound risk indices. Smoking was more prevalent in the high risk groups defined by the compound indices than by total cholesterol. These findings call for caution when total cholesterol is used to estimate cardiovascular risk in epidemiological studies, and even more so at individual counselling in occupational or primary health care settings.

Street sale of heroin--a profitable way of making a living?

The aim of the study was to give an outline of the financial environment of heroin-sale at street level in Norway and the possibilities of making retail sale of heroin a living. Data were gathered through police records and interviews with informants at street level. Retail sale price has been nominally stable at 300 Nkr (28 pounds, i.e., 1 pound = 11 Nkr) per end-user dose since 1978. This price is coupled to the price of one standard service by street prostitutes. Both the end-users and retailers formally make their living from social welfare payments. The retailer purchases from a wholesaler batches of up to 10 g of heroin at a cost of 50,000 Nkr (4800 pounds). At monthly intervals of delivery this yields 120,000 Nkr (11,500 pounds) as net tax-free income per year, on top of the social welfare payments, even when the retailer and his accomplice consumes a third of the purchased quantity. Crime of gain on the part of the retailer is negligible, due to increased risk of also disclosing his drug trafficking.

Complaints that predict drop-out from a detoxification and counselling unit.

Sixty-one consecutive clients in a multidrug addiction detoxification and counselling unit were interviewed by their medical counsellor about bodily pain, distress, and coherence in their life. Clients who did not complete the 3-week postdetoxification program reported a higher level of fatigue and difficulties with concentration compared with completers. Antonovsky's Sense of Coherence test showed less favourable values in noncompleters than in completers. No significant difference was found on the Hopkins Symptom checklist. Factor analysis showed that both pain and emotional distress belonged to one dimension. Fatigue was the symptom that predicted drop-out when adjusting for other complaints and background factors.

Functional diagnosis as a tool in rehabilitation: a comparison of teachers and other employees.

Work-related stress and burnout has been observed in primary school teachers in many countries. Functional deficits have been related to certain psychosomatic diagnoses and the work environment. We have compared 100 teachers with a matched group of non-teachers according to diagnostic differences, all attending a 4 week resident stay at a vocational rehabilitation centre in 1993-5. Seventy-five percent were women. The use of ICD-9 diagnoses and a five-dimensional functional diagnostic tool were compared. The five dimensions were defined along the following axes: work environment, family relations, health, personal economy and leisure time activity. There were no significant differences between ICD-9 diagnostic groups between teachers and non-teachers. Indefinite diagnostic entities (fatigue, chronic myalgia, fibromyalgia, etc.) were used in more than half of residents in both groups. Definite musculo-skeletal disorders were the second most prominent diagnosis. On the five-dimensional functional diagnostic tool teachers scored significantly worse than non-teachers on the family relations axis, and on a sum score of all axes. The difference was mainly present in women. The study suggests that work-related stress and signs of burnout in teachers may be higher than in other employees, but the factors contributing to this may be found outside the work environment.

Variation in phlebotomy techniques in emergency medicine and the incidence of haemolysed samples.

BACKGROUND: Phlebotomy is a potential cause of preanalytical errors. We have observed phlebotomy in routine practice in a busy Emergency Department, to see how current practice compares with optimal blood sampling. METHODS: Phlebotomy episodes were audited and compared with standard procedures. A computer-based search of the number of haemolysed samples from Emergency Medicine and hospital inpatients was reviewed. RESULTS: Four different ways of taking blood were observed: cannulation and a syringe (38%), cannula with evacuated tube and adaptor (42%), syringe and needle into vein (14%) and evacuated tube system used conventionally (6%). Where a syringe was used, two methods of transfer into the sample tube were observed; needle kept on with cap piercing (77%) and needle and evacuated cap both removed (23%). On 20 out of 50 phlebotomy episodes (40%), the potassium-EDTA tube was filled prior to the biochemistry serum gel tube. A search of the laboratory computer records for ward-based phlebotomy found 30 of 1034 samples were haemolysed (2.9%). In the 50 phlebotomy episodes in the Majors area of the Emergency Department, 24% produced a haemolysed sample (P < 0.0001). For samples taken from all areas of Emergency Medicine over a seven-day period, 52 of 485 were haemolysed (10.7%; P < 0.0001). CONCLUSIONS: This study has shown that phlebotomy techniques in the Emergency Department deviate from standard practice significantly. This may well be a reason for the much higher frequency of haemolysed samples and with the wrong order of collection the possibility of potassium-EDTA-contaminated samples.

Clinical differences between immigrants voluntarily and involuntarily admitted to acute psychiatric units: a 3-year prospective study.

Involuntary psychiatric admissions are widespread among patients with an immigrant background. According to a study in Norway, involuntary admissions are about 75% of admissions among immigrants compared to roughly 50% among ethnic Norwegians. The aim of the present study was to compare clinical and demographic characteristics of immigrant patients with involuntary or voluntary admissions to two acute psychiatric units. A 3-year prospective study of 94 immigrant patients involuntarily and voluntarily admitted to acute psychiatric units was carried out. Sixty-two patients (66.0%) were voluntarily and 30 (31.9%) involuntarily admitted. Involuntary admissions were significantly higher among men (22, 73.3%) compared to women (8, 26.7%; χ(2) = 4.507, d.f. = 1, P= 0.03). The mean length of stay for voluntary and involuntary patients were 7.8 (SD = 6.6) and 21.6 (SD = 27.3; t=-2.7, d.f. = 88, P= 0.01). Patients diagnosed with schizophrenia and psychotic disorder were more often admitted involuntarily (63.0%; χ(2) = 17.83, P= 0.001). This study confirms that immigrant patients diagnosed with psychotic disorders are more often involuntarily than voluntarily admitted. Comparing the clinical and demographic characteristics of immigrants helps identify the reasons behind involuntary admissions and might improve efforts towards reducing such admissions in the future.

[Unemployment and ill health. What is the relationship between occupational ability and employees' resources?]. / Arbeidsledighet og uhelse. Hva betyr forholdet mellom jobbkrav og arbeidstakerens ressurser?

The relationship between vocational ability and job requirements is postulated to be of importance for the development of health defects from being unemployed. A simple model of three groups of employees is presented. Two earlier studies are reestimated within the model, giving opposite conclusions as to the effect of unemployment on health.

Screening for cardiovascular risk: cost-benefit considerations in a comparison of total cholesterol measurements and two compound blood lipid indices.

BACKGROUND: Serum total cholesterol measurements have been shown to differentiate between patients with angiographically confirmed coronary artery disease and controls less well than compound indices of cardiovascular risk. Details of employees (n = 229) nominated by an occupational health service in a non-manufacturing firm were used as a starting point for calculations to compare the costs and benefits of using compound indices of cardiovascular risk with those of total cholesterol measurements alone. METHODS: Healthy employees were defined as having a low or a high risk of cardiovascular disease according to either total cholesterol level or two compound indices of blood lipid components. The compound indices were the ratio of total to high-density lipoprotein (HDL) cholesterol (the TC: HDLC ratio) and an 'atherogenic index' defined as ([total cholesterol-HDL cholesterol] x [apolipoprotein B])/([HDL cholesterol] x [apolipoprotein A]). If compound indices discriminate better between people at low and high risk, both the number of people given unnecessary advice on lifestyle changes or urged to take cholesterol-reducing medication and the number of people not treated because of their 'normal' cholesterol levels would be reduced. In our calculations, we assumed as 'gains' that (1) the disclosure that a total cholesterol test result is false-positive is equal to treatment costs, consultation fee and consumption foregone (i.e. resources already used on medication, services etc.) (8909 Nkr [US $1 = 7 Nkr]), and (2) the disclosure that a test result is false-negative is equal to consultation fee plus loss of 2 h wages (288 Nkr). RESULTS: The screening of 100,000 men and 100,000 women would incur a cost of 99 and 710 Nkr, respectively, per person assumed to benefit from extended screening using two different compound indices. Net gain would be 438 and 192 million Nkr, respectively, for the two compound indices. However, the lack of prospective data on compound indices suggests the need for cautious interpretation. CONCLUSION: Although prospective studies are needed to confirm our findings, the changes in number of false-positive and false-negative values achievable using different indices suggests a need for greater caution when using single lipid measurements as predictors of risk. The calculations of this non-prospective study indicated an increased benefit-cost ratio in assessing cardiovascular risk by using compound indices of cardiovascular risk compared with total cholesterol measurements alone.

A comparison of cardiovascular risk as measured by compound blood lipid indices and two indices including lifestyle factors in occupational health service.

Healthy employees in a non-manufacturing firm (n = 252) were divided into low and high cardiovascular risk subjects in order to compare different indices of cardiovascular risk for use in occupational health service. The levels of total cholesterol (TC), a compound index of blood lipid components, the 'atherogenic index' (ATH-index) defined as ([TC-HDLc] x [apoB])/([HDLc] x [apoA]), and two other compound indices, one Norwegian (Westlund) and one Scottish (Dundee score) were compared. Information on smoking habits and blood pressure were part of the two last indices. Cut-off values to separate between low and high risk subjects were defined with TC = 6.5 mmol/l, HDLc = 0.9 mmol/l, apoA = 1.8 g/l and apoB = 1.3 g/l, all values based on clinical guidelines in Norway. No smoking and a systolic blood pressure < 150 mmHg was included as cut-off of the combined indices. According to the three indices (ATH, Westlund and Dundee) 102, 25 and 116 employees were allocated to the increased risk group. Persons allocated to the increased risk group by the combined indices and not by the compound index were practically all smokers. Systolic blood pressure differed between indices only for persons with extreme pressures. A compound blood lipid index of CV risk, which may be drawn easily in an occupational health setting in an unfasting state and sent by post to a laboratory, mimics the allocation of persons to an increased risk group using combined indices. Smokers with normal lipid values would be allocated to increased risk by the combined indices, but not necessarily by the compound index. The use of the compound index together with advice to stop smoking is suggested as a time-saving strategy.

Normal cholesterol measurements in white collar workers still at cardiovascular risk?

Low serum total cholesterol (TC) in workers has been taken to indicate absence of cardiovascular (CV) risk. In angiographically confirmed coronary artery disease TC has been shown to be less poignant than compound indices of cardiovascular risk in separating patients from controls. The implications for prevention in an industrial medical setting of relying on TC measurements are discussed. Employees (n = 229) tested by an occupational health service in a non-manufacturing firm were dichotomized as low and high cardiovascular risk subjects either by the level of total cholesterol, or by two compound indices of blood lipid components. The compound indices were: the TC/HDLc-ratio, and an 'atherogenic index' (ATH-index) defined as ([TC-HDLc] x [apo B]) + ([HDLc] x [apo A]). (apo A = apolipoprotein A-I, apo B = apolipoprotein B). Cut-off values to separate between low- and high-risk subjects were defined as TC = 6.0 mmol/l, HDLc = 0.9 mmol/l, apo A = 1.8 milligrams and apo B = 1.3 milligrams, based on clinical guidelines in Norway. These individual cut-off values gave TC/HDLc and ATH-index cut-off values of 6.7 and 4.1, respectively. Assuming a more correct discrimination between persons at low- and high-risk, using compound lipid indices, both the number of persons given unnecessary advice on lifestyle changes or urged to take TC reducing medication, and the number of persons not treated on the basis of normal TC levels, would be reduced. Percentages of persons classified as TC-level-low risk, were adjusted using empirical data on sensitivity and specificity of the compound indices. Among employees with TC < 6.0mmol/l, 15% and 23% of women, and 12% and 19% of men would be classified as high-risk persons using the TC/HDLc-ratio or the ATH-index, respectively. Lack of prospective data on compound indices suggests cautious interpretation. TC values in spurious testing, as often applied in occupational health service without due regard to other lipid fractions, would increase the probability of unnecessarily treating persons not at CV risk and withholding people at probable CV risk from treatment. Although prospective studies are needed to confirm findings, the changes observed suggest avoiding measurements of some single lipid factors.

Workload and cardiovascular risk factors in executives and non-executives of the same company.

The lifestyle of executives purportedly differs from that of their employees who are not in an executive position, with respect to workload, amount of travelling, and eating habits. These aspects of lifestyle and cardiovascular (CV) risk factors in blood were compared in 22 executives and a matched sample of non-executives in an insurance company in Norway. The mean age was 42.8 years in both groups and the mean body mass index was 25.5 and 24.8 kg/m2 in executives and non-executives, respectively. Executives travelled more and worked more hours than non-executives, but smoking habits, levels of physical activity, diet habits and blood pressure were comparable in the two groups. The blood lipoprotein estimates of total cholesterol, high density lipoprotein cholesterol, apolipoproteins and two compound lipoprotein indices of CV risk, as well as liver enzymes, were also of the same magnitude in both groups. The executive lifestyle as such, compared to that of non-executives, does not imply an elevated CV risk in this study, as judged from CV risk factors in blood. The efforts of the occupational health service to improve health, including the opportunity for executives to choose their workload, may have contributed to this 'negative' finding. This may indicate that preventive health programmes in the company could have been acting as intended for all groups of employees. However, somewhat high mean levels of total cholesterol (> 6.0 mmol/l) and of a compound atherogenic index in both groups suggest that continued action by the occupational health service is required.

[Unemployment among long-term sick-listed persons. From the project Evaluation of Follow-up of Long-term Sick-listed Persons]. / Arbeidsledighet blant langtidssykmeldte. Fra prosjeket Evaluering av oppfølging av langtidssykmeldte.

The aim of the study was to compare two subgroups of patients with long-term sickness certificate, i.e. a group who were unemployed after eight weeks of incapacity for work and a group who still had a paid job at the end of the eight weeks. 712 patients who received a medical certificate II after eight weeks of incapacity for work in 1988 were followed up for another 12-15 months by means of information collected as a routine at the local National Insurance Offices in five municipalities in Norway. Of our total sample of patients, the sub-group of unemployed persons differed in a number of ways from the group who still had a job. Among the unemployed the duration of sickness certificate was longer and there were higher frequencies of mental disorders and diseases of the nervous system/sense organs. Admission to hospital was less frequent, however, among the unemployed group than among the group who still had a job. The rate of return-to-work observed after one year of sickness certificate was lower among the unemployed.

Cardiovascular risk factors in young drug addicts.

Since the type of life-style often encountered in drug addicts is purported to influence their risk of cardiovascular disease, it seemed of interest to carry out a descriptive study on risk factors in young addicts. Twenty-four young intravenous drug addicts, mean age 29 years and mean body mass index (BMI) 22.5 (kg/m(-2)), were compared with 24 healthy people matched for age, gender and BMI. Both groups responded to a questionnaire on life-style risk factors. In addition, fasting blood samples were investigated for several coronary risk factors. Drug addicts had smoked more cigarettes (17 vs. 3 cigarettes/day) for a longer time period (15 vs. 5 years) than control subjects. They also had higher serum activities of liver enzymes related to alcohol abuse than controls. Level of physical activity and indicators of dietary intake of fruit, vegetables and salt were not significantly different between the groups. Blood lipid values, total cholesterol (5.1 vs. 5.6 mmol/l), and HDL-cholesterol (1.2 mmol/l), apolipoproteins, and an atherogenic index reflecting the balance between the atherogenic low density lipoproteins (LDL) and the antiatherogenic fraction (HDL), as well as the smoking-related factors fibrinogen and TBARS, were all similar in both groups. The study indicates that the prevalence of many known cardiovascular risk factors was similar in drug addicts and matched controls.

[How is it going with the Sick-listing II patients? From the project Evaluation of Follow-up of Long-term Sick-listed Persons]. / Hvordan går det med Sykmelding II-pasientene? Fra prosjektet Evaluering av oppfølging av langtidssykmeldte.

The aim of the study was to follow up 712 persons with respect to social insurance and labour market status one year after the start of a period of long-term sickness certificate. The study is based on information from the local National Insurance Offices in five municipalities in Norway. Mean duration of the long-term sickness certificate was 185 calendar days, slightly longer for males than females. 44.9% returned to work during the first year, another 2.9% attended vocational rehabilitation programmes, 11.7% were still receiving medical treatment, 12.2% had qualified for a disability pension, 5.6% were in receipt of an old age pension and 5.6% were unemployed. The remaining 17.1% had either died or had moved from the municipality. The few patients attending vocational rehabilitation programmes, compared with the increasing number of persons granted a disability pension in Norway since 1985 indicate insufficient effort to provide vocational rehabilitation.

[Working in basic groups. From the Project Evaluation of Follow-up of Long-term Sick-listed Persons]. / Arbeidet i basisgrupper. Fra prosjektet Evaluering av oppfølging av langtidssykmeldte.

By 1988, all Norwegian municipalities were to have established "basic groups", i.e. interprofessional groups to guide patients in their vocational rehabilitation process. The work of these "basic groups" has been evaluated, both in terms of patients admitted for group discussions, type of actions taken and the work status of the patients one year later. The material consists of all patients admitted for basic group discussions in eight municipalities over a three months' period in the autumn 1988 (n = 261). In general the educational level of the patients was found to be low and their most common complaint was musculoskeletal/connective tissue diseases. The most frequent action suggested by the basic groups was continued medical attention. Only 11% of the patients actually attended the meeting where their situation was discussed. After a follow-up period of one year one fifth of the patients were back at their normal job, and one fourth were receiving a disability pension. Good motivation was regarded as the most important factor influencing whether the patients returned to work.