ONCOPROTEIN EXPRESSION IN HUMAN SYNOVIAL TISSUE: AN IMMUNOHISTOCHEMICAL STUDY OF DIFFERENT TYPES OF ARTHRITIS

Based on the fact that synovial lining cells have some propertiesof transformed-appearing cells, we have examined the expressionof Myc, Myb, Fos, Jun and Ras oncoproteins in synovial tissuesfrom patients with different types of arthritis. Formalin-fixedand paraffin-embedded sections of synovial tissue from 12 patientswith rheumatoid arthritis (RA), 14 with reactive arthritis (ReA),nine with other seronegative arthritis (OSA), seven with bacterialarthritis (BA), eight with probable bacterial arthritis (PBA)and eight with osteoarthritis (OA) were studied using the immunoperoxidasestaining technique. The oncoproteins studied were expressedboth in the synovial lining layer and in the sublining layer,consisting of lymphocytes, other inflammatory cells and bloodvessels. Among the six disease entities, RA and OA appearedto be the most distinct, whereas the results obtained for ReAand OSA, and on the other hand for BA and PBA, closely resembledeach other. The expression of Myc, Myb, Fos and Jun was significantlycorrelated both to the degree of synovial hypercellularity andthe synovial lymphocytic infiltration. For Ras, such a correlationcould not be seen. We conclude that we find no evidence of acell lineage-specific or a disease-specific abnormality of proto-oncogeneproducts in RA, and the expression of these oncoproteins isconsistent with inflammation rather than with any primary abnormalityof cell growth. KEY WORDS: Oncoproteins, Rheumatoid arthritis, Reactive arthritis, Osteoarthritis, Synovial tissue     

Phrenic Nerve Stimulation for Central Ventilatory Failure with Bipolar and Four-Pole Electrode Systems

A multi-channel phrenic nerve stimulator developed in Tampere has been implanted into seven patients with C2-tetraplegia and into three patients with central sleep apneas. Six bipolar cuff electrodes were implanted bilaterally into the neck. Two four-pole cuff and 14 four-pole noncuff electrodes were used in seven patients and to replace one bipolar electrode. Four-pole electrodes were implanted within the thorax. Seven patients achieved total independence from conventional ventilators within 4 months of implantation, and one for 18 hours each day. Two patients died 12 days and 3 months after implantation and two patients after having achieved independence from mechanical ventilators from causes unrelated to the stimulators. Reoperations were necessary because of dislocation of receivers, electrodes, electrode lesions, nerve injuries, and technical failures in seven patients. Most of the problems appeared in two patients with obesity and in three patients with very thin phrenic nerves. Single unit prototypes failed technically more frequently than units of prototype serial fabrication. New electrode design, progress in the manufacture of receivers, and improved implantation technique should help to diminish failures in future.     

Influence of apolipoprotein A-1 promoter polymorphism on lipid levels and responses to dietary change in Finnish adults

Objectives. To analyse the association between the G/A polymorphism in the apolipoprotein A-1 (apo A-1) promoter region and plasma lipid levels, as well as their responses to dietary change, in Finnish adults.
Subjects and design. Blood samples from 86 subjects (42 men, 44 women) who attended a dietary intervention study carried out in North Karelia in 1993 were available for the current analysis. The diet study consisted of a 2-week baseline period, followed by an 8-week intervention period, and an 8-week switchback period.
Intervention. Diet was modified to a low-fat, low-cholesterol diet during the dietary intervention.
Main outcome measures. Fasting plasma lipid, lipoprotein and apolipoprotein levels were determined.
Results. At baseline, the high-density lipoprotein (HDL) cholesterol and apo A-1 levels were higher ( P <0.01) and the triglyceride levels were lower ( P <0.05) in men, but not in women, with the A allele. The differences in HDL cholesterol and apo A-1 levels between genotypes remained during the low-fat, low-cholesterol diet and switchback periods. Apart from the difference between responses in apo A-1 during switchback to the original diet, lipid responses to dietary change did not differ significantly between genotypes.
Conclusion. Our findings indicate a significant association between the apo A-1 promoter polymorphism and plasma apo A-1 and HDL-cholesterol in men. In theory, the higher plasma HDL-cholesterol and apo A-1 levels in the GA/AA group may confer some protection against coronary artery disease. The differences in HDL-cholesterol and apo A-1 levels between genotypes persisted during different diets suggesting that the possible benefit is independent of fat and cholesterol intake.     

Modern Methods for Reliable Preoperative Localization of Insulinoma

A case of insulinoma is reported in which the correct localization of tumor was made with PTP and immunoreactive insulin values from the portal venous system and in which pancreas angiography indicated a false positive tumor localization. PTP should be done to every patient to confirm the preoperative location of the insulinoma(s).     

Disease-related distress among insulin-treated diabetic patients: Associations with health status, psychosocial factors and self-care practices

Background: Diabetes is a chronic illness that affects manydomains of life. This cross-sectional study examined disease-relateddistress and its associations with health and psychosocial factorsamong insulin-treated diabetic persons. Method: The sample (n=423)was drawn from the Social Insurance Institution's drug registry.Health indicators were duration of diabetes, complications,and glycaemlc control. Psychosocial measures included generaland diabetes-specific social support, diabetes locus of control(DLC), self-efficacy, diabetes health beliefs and self-carepractices and subjective health. Results: Most respondents reportedmoderate diabetes-related distress. In multi-variate analysis,severe diabetes distress was related to lower net benefits ofregimen (ß = –0.29, and p<0.001), poorerperceived health (ß = –0.25, and p<0.001),higher perceived threat of complications (ß = 0.19,and p<0.001), less adequate social support (ß =–0.16, and p<0.01), stronger beliefs in chance (ß= 0.15, and p<0.01) and internal DLC (ß = 0.11,and p<0.05) and more frequent exercising (ß = 0.10,and p<0.05). Conclusions: The results suggest that emotionaladjustment to diabetes is predominantly determined by diabetes-relatedcognitions and subjective health and to a lesser degree by objectivediabetes indlcators, which underlines the Importance of assistingthe patient with adjustment with the disease in health carecentres.     

COMMENTS

Glial-cell-line-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor superfamily. It binds to and activates a receptor complex consisting of GFR-α1 and Ret receptor tyrosine kinase. In testis, GDNF is expressed by Sertoli cells. We have shown by transgenic loss- and gain-of-function mouse models that GDNF regulates the cell fate decision of undifferentiated spermatogonia. In the GDNF +/− mice, the spermatogonia differentiate in excess leading to the depletion of germ cells. In the mice overexpressing GDNF in testes, undifferentiated spermatogonia accumulate in the tubules, no sperm is produced, and the mice are infertile. After a year, the GDNF overexpressing mice frequently (89%) develop testicular tumours, and most of them are bilateral (56%). All these tumours show the same histological pattern. They are composed of round spermatogonial/gonocytic cells with only a scant cytoplasm. The tumours are locally invasive but do not metastasise. They express germ line markers, are positive for alkaline phosphatase, and aneuploid with a triploid peak. Thus, by several histological, molecular, and histochemical characteristics, the GDNF-induced tumours mimic classical seminomas in men, but the precursor lesions are apparently different in mouse and man.     

Effects of 2-Ethylhexanoic Acid on Reproduction and Postnatal Development in Wistar Rats

Reproductive toxicity of 2-ethylhexanoic acid (2-EHA) was studiedin Wistar rats. The animals (24 animals per sex per group) weregiven 2-EHA as a sodium salt in drinking water at daily dosesof 100, 300, or 600 mg/kg. Control animals received plain water.Male rats were exposed to 2-EHA for 10 weeks and females for2 weeks prior to mating, both sexes during the mating periodand females during the entire gestation and lactation period.2-EHA caused a slight but dose-dependent decrease in fertility;time to mating increased at 300 and 600 mg/kg and even totalinfertility ensued. 2-EHA slightly decreased sperm quality inmales. The spermatozoa were significantly less motile at 100and 600 mg/kg and abnormal sperm occurred more frequently atthe two highest dose levels. The average litter size was reducedby 16% in the dose group receiving 600 mg/kg. The birth weightsof the pups were unaffected but the body weight gain was transientlyslower during lactation at 600 mg/kg. Several pups appearedabnormal (kinky tail, lethargic, slightly paralyzed legs) andthe physical development assessed by several landmarks (openingof eyes, eruption of teeth, hair growth) and reflexes (gripreflex, cliff avoidance) was delayed at 300 and 600 mg/kg. Inanother experiment, a single dose of 600 mg/kg 2-EHA was givento pregnant females by gavage on Gestational Day 4, 5, 6, or7 and the number of implantations were counted on GestationalDay 10. Administration on Day 6 decreased the number of implantationsand caused resorptions. In conclusion, 2-ethylhexanoic acidcaused impaired fertility in Wistar rats and delayed postnataldevelopment of pups. The reduced fertility might result fromdisturbed implantation in uterus and the retarded developmentof pups from teratogenicity and pre- and postnatal toxic effectsof 2-EHA.     

Mental disorders and suicide prevention

Abstract In the research phase of the National Suicide Prevention Project, all suicides ( n = 1397) in Finland between March 1987 and April 1988 were examined retrospectively using the psychological autopsy method. Careful retrospective diagnostic evaluation of the victims according to DSM-III-R criteria was done by weighing and integrating all available information. A series of studies addressing the mental disorders among suicide victims, the treatment received before death and the life events is now reviewed.
Among a random sample of suicide victims from the nationwide suicide population, at least one psychiatric diagnosis was made for 93% of the victims. The most prevalent disorders were depressive syndromes (66%) and alcohol dependence/abuse (43%). The prevalence of major depression was higher among women than among men. Major depression as the principal diagnosis was more common among the elderly suicides. Among adolescent victims, depressive syndromes were also the most prevalent disorders. Adjustment disorders were common (25%) among male adolescent suicides. The majority of suicide victims of all ages suffered from comorbid mental disorders.
Among suicide victims who had had contact with a health carer before death, inadequacy of treatment for mental disorders seems to have been common. Of the major depressive victims only 3% were found to have received adequate psychopharmacological treatment, and only 7% received weekly psychotherapy by a trained therapist.
The analysis of the massive database collected in the research phase of the National Suicide Prevention Project in Finland is still ongoing, and the implications of the findings for suicide prevention will be refined during the research process. The necessity to improve recognition and treatment for comorbid depressive disorders in all age groups seems evident already.     

Morbid Obesity,Gastric Plication and a Severe Neurological Deficit

ABSTRACT. SomerH, BergstrÖm L, Mustajoki P, Rovamo L. (Department of Neurology, Third Department of Internal Medicine and Children's Hospital, University of Helsinki, Helsinki, Finland.) Morbid obesity, gastric plication and a severe neurological deficit. A 39-year-old man had protracted vomiting after gastric plication for morbid obesity. Within three months he lost 53 kg in weight and developed neuromuscular weakness, especially in the lower extremities. Clinical and laboratory studies suggested both radicular and peripheral neuropathy. One year later the condition was only marginally improved: he took only few steps unsupported. The apparent etiology is malnutrition but the primary cause remained unknown.     

Reversal of Atrial Remodeling after Cardioversion of Persistent Atrial Fibrillation Measured with Magnetocardiography

Background : Atrial fibrillation (AF) causes electrical, functional, and structural changes in the atria. We examined electrophysiologic remodeling caused by AF and its reversal noninvasively by applying a new atrial signal analysis based on magnetocardiography (MCG).
Methods : In 26 patients with persistent AF, MCG, signal-averaged electrocardiography (SAECG), and echocardiography were performed immediately after electrical cardioversion (CV), and repeated after 1 month in 15 patients who remained in sinus rhythm (SR). Twenty-four matched subjects without history of AF served as controls. P-wave duration (Pd) and dispersion (standard deviation of Pd values in individual channels) and root mean square amplitudes of the P wave over the last 40 ms portions (RMS40) were determined.
Results : In MCG Pd was longer (122.8 ± 18.2 ms vs 101.5 ± 14.6 ms, P < 0.01) and RMS40 was higher (60.4 ± 28.2 vs 46.9 ± 19.1 fT) in AF patients immediately after CV as compared to the controls. In SAECG Pd dispersion was increased in AF patients. Mitral A-wave velocity and left atrial (LA) contraction were decreased and LA diameter was increased (all P < 0.01). After 1 month, Pd in MCG still remained longer and LA diameter greater (both P < 0.05), while RMS40 in MCG, Pd dispersion in SAECG, mitral A-wave velocity, and LA contraction were recovered.
Conclusions : Magnetocardiographically detected atrial electrophysiologic alterations in persistent AF diminish rapidly although incompletely during maintained SR after CV. This might be related to the known early high and late lower, but still existent tendency to AF relapses.