Biomedical subjects
Publications and source records attributed to C Ackerman.
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Trends in the incidence rate of uveal melanoma in Israel during the period 1961-1989 among Jews of various geographical origins and among non-Jews were examined, and found to be stable over time. Based on data of the Israel Cancer Registry, 515 cases were included in the final study population after an independent case-finding ascertainment survey. The average annual incidence rate per million for all Jews was 5.7 for both males and females; the rates for non-Jews were: males 1.6, females 1.3. Incidence rates within the Jewish sub-populations show significant differences. The highest rates by sub-population were for Jews born in Europe or America (7.5 for males and for females), followed by Jews born in Israel (males 6.8, females 6.7); and lowest in Jews born in Africa (males 2.1, females 2.3) and Asia (males 1.6, females 2.8). Jews born in Israel had rates lower than Jews born in Europe and America during the 1960s, but in the 1980s the situation was reversed. Results suggest that rate differences between population groups and over time stem from constitutional factors or from the direct or indirect effect of sunlight radiation, whether early in life or from cumulative exposure.
Moisturizers are known to have occlusive, emollient and humectant properties, all of which help to alleviate the symptoms of skin xerosis. Although the biological mode of action of moisturizers is poorly understood, the recent observation that skin xerosis is associated with incomplete desmosome digestion suggests that moisturizers improve the desquamation process in such conditions. To examine the possibility that certain moisturizers act by facilitating desmosomal digestion, we investigated the ability of glycerol, a common humectant, to influence this process in stratum corneum in vitro. Examining desmosome morphology in isolated stratum corneum by electron microscopy, it was observed that the desmosomes were in more advanced stages of degradation in glycerol-treated tissue compared with control tissue. This enhanced desmosomal degradation in glycerol-treated tissue was confirmed by significant decreases in the levels of immunoreactive desmoglein 1, a marker of desmosome integrity. Desmosomal degradation was also shown to be a humidity-dependent event, being significantly reduced at low relative humidity. The effect of glycerol on desmosome digestion was emphasized further in two in vitro model systems. Firstly, glycerol increased the rate of corneocyte loss from the superficial surface of human skin biopsies in a simple desquamation assay. Secondly, measurement of the mechanical strength of sheets of stratum corneum, using an extensiometer, indicated a dramatic reduction in the intercorneocyte forces following glycerol treatment. These studies demonstrated the ability of glycerol to facilitate desmosome digestion in vitro. Extrapolating from these results, we believe that one of the major actions of moisturizers in vivo is to aid the digestion of desmosomes which are abnormally retained in the superficial layers of xerotic stratum corneum.
Behavioural treatment programmes have been shown repeatedly to be effective in alleviating dental anxiety but few studies have provided long-term follow-ups. In this study, dentally anxious Ss who had completed a 4-session behavioural group programme were followed up for periods between 1 and 4 years after successful completion of treatment. It was hypothesized that dental visit satisfaction would be associated with regular dental attendance. 88% of Ss contacted agreed to cooperate; of these, 70% were still maintaining regular check-ups. There were no differences between regular and irregular attenders in terms of age, gender, education, marital status, degree of pre-treatment avoidance or time elapsed since completion of the programme. However, Ss who did not see their dentists regularly were more likely to have shown higher levels of anxiety immediately after completing the programme, less concordance between the subjective and overt behavioural aspects of anxiety and to have experienced more invasive than non-invasive procedures than the others. It was argued that dentally anxious individuals are not a homogeneous group and that a better understanding of their individual differences would lead to the development of more efficacious treatment procedures.
Fair-skinned individuals have a much higher risk of cutaneous and ocular melanomas than dark-skinned individuals, possibly reflecting a protective effect of melanin against sun exposure. There are some reasons to believe that the effect of sunlight exposure is indirect (i.e., sunlight stimulates growth factor production, which then stimulates melanocytic proliferation, leading to melanoma). Visceral melanomas are extremely rare, and little is known about them. This study used US data on 25,184 melanoma cases to investigate the White-Black ratio for visceral melanoma and did not find a disproportionality similar to that for cutaneous and ocular melanomas. The findings support the hypothesis that the sunlight effect on melanoma is primarily direct.
Using the 51Cr-EDTA resorption test, gut permeability was measured in 129 patients with inflammatory joint diseases and in 97 control patients (42 patients with no inflammatory rheumatic disorders taking antiinflammatory medication and 55 healthy controls). Thirty-two patients (30 arthritis and 2 control patients) taking nonsteroidal antiinflammatory drugs (NSAID) as well as corticosteroids were excluded from statistical analysis. The intake of NSAID significantly increased gut permeability in controls but not in the arthritis groups. The same applied to corticosteroid intake. This could be due to the restricted number of arthritis patients who had never taken antiinflammatory drugs or to a disease related increased permeability. There was no statistically significant difference in altered gut permeability between patients taking NSAID and patients taking corticosteroids. Our findings suggest that drug induced alteration of gut permeability may not only be accounted for by an inhibition of mucosal cyclooxygenase activity, but that other enzymatic pathways in the arachidonic cascade might be implicated.
Gut permeability as measured by the 51Cr-EDTA resorption test was determined in 56 patients with rheumatoid arthritis (RA), 73 patients with spondyloarthropathies (SpA), 18 patients with inflammatory bowel disease (IBD) and 97 controls (42 patients with no inflammatory rheumatic diseases and 55 healthy controls). Gut permeability was found to be increased in the 3 patient groups, partially due to the intake of antiinflammatory drugs. When only patients not taking these drugs were considered, an increased gut permeability was found in patients with SpA and IBD. In patients with RA gut permeability could not be evaluated as they were all taking antiinflammatory medication. Ileocolonoscopy with biopsies of the gut was performed in 62 of the 73 patients with SpA and disclosed subclinical gut inflammation in 21. No difference in gut permeability was found between patients with or without gut inflammation. However, when the type of gut inflammation was considered, a significant increase of gut permeability was found in patients with chronic gut inflammation compared with patients presenting acute lesions. Our findings again suggest that the chronic gut inflammation seen in SpA is fundamentally different from acute gut inflammation and possibly related to the gut inflammation of IBD.
Ninety-two patients with intractable rheumatoid arthritis (RA) participated in an open prospective study of the longterm efficacy and toxicity of methotrexate (MTX), administered orally at a constant dosage of 7.5 mg/week. Twenty-four patients (25%) had to be withdrawn from the study within the first 12 months because of inefficacy or adverse reactions with a fatal outcome in 2 patients. In the remaining 68 patients, the mean duration of therapy was 19 months. Sixty-three of 92 patients (68%) experienced significant clinical improvement after one year, 23 (25%) were in clinical remission. Twenty-three of these patients initially responded well but relapsed after a median of 15 months of therapy. In 5 patients (5%) the disease activity remained status quo. Toxicity was noted at some time in 51 patients (54%), consisting of clinical side effects in 37 patients (40%) and biological abnormalities in 36 patients (39%), including 9 patients (10%) with blood and bone marrow toxicity, in whom renal function at start was normal. Two of these latter 9 patients had a fatal outcome because of an unexpected renal deterioration due to intercurrent disease. Thus, MTX at this constant low dose appears to be a temporarily valuable therapy for intractable RA. Careful monitoring is necessary in view of the potentially dangerous side effects.
Between 1977 and 1988 twenty-five patients with rheumatoid arthritis involving the cervical spine were treated by an occipito-cervical fusion. Twenty-two patients are included in this study. The main indications for surgery were intractable pain and progressive neural impairment. The operative procedure consisted of an H-bone graft fixed with steel wire in 19 cases, fusion of occiput-C2 six times and of occiput-C3 thirteen times. A Hartshill-Ransford (5, 12) loop was used in three cases: occiput-C3 twice and occiput-C7 once. The mean duration of follow-up was 3 years 8 months in 17 patients. Improvement of symptoms and signs was achieved in 88%. There were 2 post-operative deaths. The high rate of pseudarthrosis in our series was confirmed by several authors. The loop technique provides a more stable fixation and will be our technique of choice in the future.
We conducted a double-blind placebo-controlled clinical trial on 98 subjects to assess the efficacy of two strengths of topical human leukocyte alpha-interferon, 10(4) and 10(6) IU/g in a 1% nonoxynol-9 base, in the treatment of recurrent genital herpes simplex virus (HSV). The study medication was applied during the prodromal phase or at the first sign of recurrence of the infection. The high-dose alpha-interferon was found to be significantly more effective than the low-dose interferon and placebo with respect to the duration of viral shedding as well as in reducing the time to the end of all subjective symptoms, including pain, burning and itching. No difference between the three groups was found in times to crusting or healing. Further studies of topical interferon in the treatment of HSV and other viral infections are merited.
In a population of 564 patients with rheumatoid arthritis (RA), the onset of symptoms has been studied in relation to age, sex and last menstrual period for women. Median age of menopause was 49 years (3rd percentile: 32 years and 97th percentile: 56 years). Median age of first symptoms was 45 years in women and 50 in men. The individual interval between menopause and first symptoms has a Gaussian distribution with mean at time 0, implying that the average woman develops the first symptoms at the time of her menopause. The F:M ratio of all patients was 2.3; with increasing age the F:M ratio decreased from 3.7 before 30 years of age to 1 after the 6th decade of life, with a peak at the age of 40-44 years. A possible effect of age related changes in sex hormone levels on the pathogenesis of RA is suggested.
Previous surveys have indicated that there is a substantial proportion of dentally anxious individuals in the general population. Many of these individuals avoid contact with dentistry as much as possible, while fearful individuals who present themselves for treatment are probably too uncomfortable or too afraid to make their views known. Consequently, a study of the feelings and attitudes of a group of dental phobics was carried out as part of a larger study of the efficacy of psychological treatments for excessive dental anxiety. The subjects were recruited by means of a newspaper advertisement and asked to complete a questionnaire designed to obtain information regarding their dental experiences and attitudes. Twenty-three individuals provided enough data for analysis. They were distributed widely in terms of age, education, income levels, and general fearfulness. They reported less satisfaction with the level of understanding or acceptance found in the last dentist they had seen than with the dentist's level of technical competence and the diagnostic information they received. Dental phobics who had been to a dentist in the past year were generally more satisfied with their dentist than those who had not. It is suggested that a good dentist-patient relationship based on understanding and acceptance is an important factor in overcoming the avoidance of fearful patients.
In the seronegative spondyloarthropathies the hip lesions can be subdivided into a concentric type progressing to ankylosis and an eccentric type leading to joint destruction. Radiologic examination of the hips was performed in 177 of 211 patients suffering from seronegative spondyloarthropathies on whom ileocolonoscopy with biopsies of ileum and colon was performed; in 27 of these 177 patients, hip lesions were demonstrated. The concentric form seems to be radiologically, clinically and genetically more related to axial involvement; moreover, the frequency of subclinical gut inflammation was the same as in the group of patients with ankylosing spondylitis (AS) without peripheral arthritis, and thus significantly lower than in patients with AS with peripheral arthritis. Eccentric, destructive hip lesions seem to be unrelated to axial involvement, but they are associated with the presence of HLA-Bw62 and gut inflammation (100%), mainly of the chronic, Crohn disease-like type.
Prednisolone intake causes a drop in the absolute numbers of circulating T-cell populations. OKT4+ (helper-inducer) cells are more susceptible to this. Higher doses are needed to depress OKT8+ (suppressor-cytotoxic) cell numbers. Administration of up to 10 mg prednisolone affects the suppressor-cytotoxic (OKT8+) absolute cell numbers only in patients with initially low OKT4+/OKT8+ ratios and not the values of OKT8+ cells in patients with high OKT4+/OKT8+ ratios, since these patients already have low OKT8+ cell counts.
The introduction of an automated flow cytofluorograph has facilitated the detection of T lymphocyte subsets because it enables a larger number of cells to be analyzed. Many authors have reported a decrease of cytotoxic/suppressor T lymphocytes in rheumatoid arthritis (RA), in contrast to the results of other workers. We believe that the discrepancy between the various studies is due to the fact that different methods and different criteria for patient selection were used. Our study comprised a larger number of patients which makes the results suitable for statistical inference. Disease activity is clearly defined and all drugs that could alter the results were excluded. The use of a flow cytometer enhances the reliability of T lymphocyte subset determination by monoclonal antibodies (OKT series). Our study confirms the reports, which suggested that the number of suppressor/cytotoxic T lymphocytes (OKT8+ cells/mm3) is decreased in patients with active RA, resulting in a high T helper/inducer lymphocyte/T suppressor/cytotoxic lymphocyte ratio (OKT4+:OKT8+). This immune balance represents an interesting feature of the disease, since several active antirheumatic drugs share a common immunomodulatory action, which normalizes the OKT4+:OKT8+ ratio. Finally, we found a good correlation between the OKT4+ cells and OKT8+ cells in the normal control population. This observation enabled us to isolate a subgroup of active patients with RA not responding to slow acting antirheumatic drugs and characterized by a low OKT4+:OKT8+ ratio.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.