Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor

To evaluate the effects of the aldose reductase inhibitor Ponalrestat (Statil) on diabetic autonomic neuropathy, a double-blind placebo controlled trial was carried out on a group of 34 diabetic patients with documented cardiac autonomic neuropathy. After a 4-week, placebo run-in period, patients were randomised for treatment with 600 mg Statil or placebo for another 24 weeks. Moreover, the reliability of the autonomic nerve function tests was investigated by comparing the results at onset and at week 4. Fifteen patients treated with Statil and 12 with placebo completed the study. Neither symptom scores nor cardiovascular reflexes, pupil reflexes and skin vasomotor reflexes improved after Statil therapy, which led us to conclude that Statil is not effective in the treatment of diabetic autonomic neuropathy. Reliability coefficients for cardiovascular reflexes and pupil reflex showed high values, ranging from 60% to 80%. Therefore these methods are recommended in future therapy trials.     

Sexually transmitted diseases control in developing countries.

Sexually transmitted diseases (STDs) are a major public health problem now compounded by the advent of AIDS and HIV infection. The size of the problem represented by STDs and HIV is unknown however it is estimated that there are 333 million new cases of STD per annum and currently 15-20 million people infected worldwide with HIV. Control programmes for STDs must prevent the acquisition of STDs, their complications and sequelae and interrupt and reduce transmission. They can also reduce the incidence of HIV infection. Such programmes must place emphasis on health education, condom usage, altering health seeking behaviour and providing case management. The syndromic approach currently offers the most realistic, and cost effective, way in which to treat patients.     

Alteration in the pattern of macrophage subtypes in chronic osteomyelitis compared with acute joint infection

Summary Macrophage subtypes were detected in cryostat sections of biopsies from patients with chronic osteomyelitis, acute joint infections and normal bone marrow, using monoclonal antibodies against different macrophage populations. The resident macrophage subtype 25F9, the glucocorticoid-inducible macrophage RM 3/1 and the inflammatory type 27E10 were found in abundance in acute infections. They were also present in tissue sections of uninflamed bone marrow. By contrast, in about 50% of the biopsies from patients with chronic osteomyelitis a reduced number of macrophage subtypes, or even the lack of one or more macrophage subpopulations was found. The unusual absence of macrophage phenotypes seems to be restricted to the area of osteomyelitis because in the tissues of inflamed sinuses in these patients, the macrophage subtypes were present. These findings suggest a disturbance at the level of the macrophages which may contribute to the persistence of the inflammatory process in osteomyelitis.

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Résumé L'utilisation d'anticorps monoclonaux contre différentes sous-populations de macrophages a permis de mettre en évidence, à l'examen de coupes cryostatiques, des sous-types de macrophages. Ces derniers ont été retrouvés dans les moelles osseuses normales comme dans les biopsies provenant de malades atteints d'ostéomyélite chronique et d'arthrite aiguë. Le sous-type résident 25F9, le macrophage glycocorticoïde inductible RM 3/1 et le sous-type inflammatoire 27E10 ont été trouvés en abondance dans les infections aiguës. Ils étaient également présents dans des coupes de moelle osseuse non inflammatoire. Inversement dans près de 50% des cas le nombre de ces sous-populations était considérablement diminué, et même certaines d'entre elles avaient complétement disparu, sur les pièces biopsiques d'ostéomyélite chronique. L'absence inhabituelle de certains types de macrophages semble être limitée à la zone ostéitique car on les retrouve dans le tissu inflammatoire des fistules. Cette étude semble montrer que l'atteinte de ces sous-populations serait responsable de la chronicité de l'ostéomyélite.

     

Relation between toxicity and carcinogenesis in the kidney: an heuristic hypothesis

Cellular toxicity and cellular carcinogenesis are closely linked. In the kidney, this relationship has been emphasized by the recent discovery of a number of putatively non-mutagenic chemicals that result in acute and chronic toxicity and ultimately in carcinogenesis, especially in the male rat. Many, but not all such compounds, result in renal PTE phagolysosomal overload. At the same time, known metabolites of other carcinogens, e.g., HCBD and FBPA, result in acute renal injury and/or necrosis, followed by chronic tubular disease, interstitial nephritis, and ultimately carcinogenesis. A series of cell mechanisms have been suggested that lead from acute cell injury to altered control of cell division. These mechanisms appear to involve ion deregulation, (especially [Ca2+]i) resulting from a variety of continued injuries, (e.g., oxidative stress from inflammatory cells) and ultimately leading to altered gene expression.     

Modern oxygen carriers: state of art 1990

Three major components of blood with clearly defined functions are: 1) red cells 2) plasma volume 3) coagulation factors At the present time artificial or synthetic coagulation factors are not available. Plasma volume expanders are well known in clinical practice. The main subject of this paper is the complex area of red cell substitutes with particular reference to the oxygen carrying capacity. The history of blood oxygen carrying capacity is briefly presented with particular reference to contributions by G. S. Adair, C. Bohr, M. Perutz and R. R. Benesch. 3 oxygen carrying developments are discussed in detail: 1) perfluorocarbons 2) artificial red cells 3) stroma-free haemoglobin solution Perfluorocarbons were used as carriers of oxygen in experiments and clinical practice. Before their wide clinical application a number of potential problems must be solved. In selected patients (coronary angioplasty, cerebral thrombosis, cardiopulmonary by-pass) perfluorocarbons (Fluosol D-A) could be considered as beneficial. Artificial red cells (neohaemocytes) are available in some centres in which progress of micro-technology appears to lead to encapsulation of purified human haemoglobin. These preparations should receive more attention. Finally stroma-free haemoglobin solution was the subject of our own research for several years. Our preparation met the requirements of the blood substitute, but had the short half-life in the circulation. Recent advances in chemistry in some centres resulted in the modification of hb molecule and linking with P-5-P. The modified poly hb solution is an ideal oxygen delivering fluid.     

A new and highly sensitive method for measuring 3-methoxytyramine using HPLC with electrochemical detection. Studies with drugs which alter dopamine metabolism in the brain

3-Methoxytyramine (3-MT) is a minor metabolite of dopamine which is suggested to reflect the turnover and utilization of dopamine. A novel, isocratic HPLC method has been developed which can be used to analyse 3-MT in homogenates of rat brain without the need for additional purification procedures. Furthermore, the coulometric electrochemical detection system is sensitive enough to measure 3 pg of 3-MT (equivalent to 0.6 ng/g tissue wet weight). 3-Methoxytyramine was measured in the striatum and n. accumbens after decapitation and rapid freezing, using 3-methoxy-4-hydroxybenzylamine as the internal standard. The effects of dopaminergic and other drugs on this metabolite were examined using this method. -Methyl-p-tyrosine (200 mg/kg i.v.) produced parallel linear decreases in dopamine and 3-MT in naive rats, but not those pretreated with tranylcypromine (5 mg/kg i.p.). Methamphetamine (0.3–10 mg/kg i.p.) and amphetamine (0.3–10 mg/kg i.p.) both dose-dependently increased 3-MT in naive and tranylcypromine-pretreated rats. In naive animals, 3-MT was not altered by intraperitoneal injection of the dopamine reuptake inhibitors, bupropion (10 mg/kg) and nomifensine (10 mg/kg) or by sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg) and zimeldine (10 mg/kg). 3-Methoxy-tyramine was decreased by apomorphine (5 mg/kg i.p.) and also by large doses of the selective D₂ antagonist, BRL 34778 (5 mg/kg i.p.) or -DOPA (50 mg/kg i.p.). The selective D₁ antagonist, SCH 23390 (0.1 or 5 mg/kg i.p.) was without effect. In tranylcypromine-pretreated rats, 3-MT was dose-dependently reduced and increased by apomorphine (0.01–5 mg/kg i.p.) and BRL 34778 (0.1–5 mg/kg i.p.), respectively. The drug SCH 23390 (0.1–5 mg/kg i.p.) produced much smaller increases in 3-MT which were probably mediated through the striatonigral pathway. Overall, the data suggest that measurement of 3-MT, after inhibition of monoamine oxidase, is a useful index of the release and utilization of dopamine. However, after substantial and prolonged depletion of dopamine, levels of 3-MT in naive animals are a better index. Also, the formation of 3-MT in naive rats provides a sensitive method for distinguishing between dopamine releasing agents and reuptake inhibitors.     

Deficiencies of Vitamins in CAPD Patients: The Effect of Supplementation

Concentrations of the vitamins B₁, B₂, B₆, B₁₂, C, folic acid,A, E and ß-carotene were determined in blood and 24-hdialysate in 44 CAPD patients. Twenty-five of these patientswere studied during chronic treatment (mean 313 days, range60–1034 days). Nineteen patients were studied during training.In a longitudinal study, 11 patients were analysed again after77–507 (mean 238) days. In both patient groups a considerable portion of patients (11%–64%)had blood concentrations indicative of a deficiency of the vitaminsB₁, B₆, C and folic acid. The average concentrations of thesevitamins were normal in both groups. The only abnormal findingwas the mean EGOT activity being deficient in patients on chronictreatment. Mean concentrations of vitamin A were above normalin both groups. In the longitudinal study a significant increaseof vitamin B₂ and a decrease of vitamin B₆ in blood was found. When compared to 24-h excretion in normal urine, loss with 24-hdialysate was low for vitamin B₁, normal to relatively highfor vitamin B₂ and B₆, but extremely high for vitamin C andfolic acid. The vitamins B₁₂, A, E and carotenoids were hardlydetectable in the dialysate. In ten other patients the effect of daily supplementation with2 mg vitamin B₆, 100mg vitamin C and 400 µg folic acidwas analysed during a 16-week period. In all patients a significantincrease in blood concentrations was obtained. It is concludedthat these dosages were sufficient to maintain a normal statusof these vitamins in CAPD patients.     

Work-related injuries in minors

Since 1938, federal child labor laws have restricted employment of persons under 18 years old, in part to protect them from hazardous occupations. Workers' compensation claims reported to the Supplementary Data System of the Bureau of Labor Statistics were examined to define the current status of occupational injuries among minors. Data tapes from 1980 to 1983 were searched to identify all current claims for injuries and illnesses occurring in 1980 in persons under age 18. Injury rates were calculated using information about employment in 1979 available from the 1980 census. In the 24 states included in this study, 23,823 claims were reported for persons less than 18 years old. Of these claims, approximately 10% were from persons under age 16. Rates of injuries in 16- and 17 year olds were 12.6 per 100 full-time male workers and 6.6 per 100 full-time female workers. Serious injuries included fractures, dislocations, and amputations, accounting for 5.8%, 0.7%, and 0.6% of cases, respectively. California, the only state that coded whether injuries resulted in fatalities, reported 12 deaths in this age group. Machines and vehicles, many of which are restricted under child labor laws, accounted for 8.3% and 5.8% of claims. These data suggest that persons under age 18 years are not adequately protected from occupational injury. Further attention and, possibly, new preventive strategies are needed.