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Biomedical subjects

M Zak

Publications and source records attributed to M Zak.

At least 19 recordsLinked to original sources

Refraction in juvenile chronic arthritis: a long-term follow-up study, with emphasis on myopia.

OBJECTIVE: Assessment of refraction anomalies in juvenile chronic arthritis (JCA) on a long-term follow-up basis. MATERIAL AND METHODS: Sixty-five adults, 52 females and 13 males, with a history of active JCA had a complete ophthalmic evaluation including subjective refractioning on average 26.4 years after JCA onset. The age range was 22-49 years. RESULTS: The refraction ranged from -8.12 D to +6.5 D with a mean (SD) of -0.64 (2.16) D. The mean refraction in the JCA group was significantly more towards myopia than that of a coeval adult hospital-based sample used as controls (p = 0.008). Twenty-eight out of the 65 (43%) had a negative refractive value of at least 0.37 D. Myopia onset age ranged from 8 to 31 years. In those able to specify their myopia onset by first purchase of spectacles (n = 25) the JCA onset had preceded the myopia, with a mean (SD) interval of 10.1 (5.4) years. CONCLUSION: The elevated myopia figure of 43% among JCA patients suggests an association between myopia and JCA. In lack of more precise indicators and in accordance with older literature, an explanation might be a weakening effect of chronic inflammation on scleral connective tissue.

Adolescent↗

Orofacial pain, jaw function, and temporomandibular disorders in women with a history of juvenile chronic arthritis or persistent juvenile chronic arthritis.

OBJECTIVES: We sought to study the long-term outcome of juvenile chronic arthritis (JCA) in the temporomandibular joint (TMJ). STUDY DESIGN: Temporomandibular disorders, including TMJ involvement, were assessed in 42 women with pauciarticular or polyarticular JCA--on average 25.8 years from disease onset--and compared with those found in matched control subjects. Disease-related parameters associated with temporomandibular disorders were identified. RESULTS: The TMJ was involved in 66.7% of the patients, most severely in extended pauciarticular JCA. Temporomandibular disorders were more frequent in the patients than in the control subjects, especially in those with persistent disease. The TMJ involvement was positively correlated with disease duration and negatively correlated with jaw opening and occlusal support. Duration of active JCA and history of functional pain were identified as predictors of present TMJ involvement. CONCLUSION: In a long-term follow-up, TMJ involvement proved frequent in the studied patients and was associated with long disease duration and previous pain on jaw opening. The findings suggest that patients with JCA should undergo orofacial evaluation on a regular basis.

Adult↗

Clinical intestinal transplantation: a decade of experience at a single center.

OBJECTIVE: To assess the long-term efficacy of intestinal transplantation under tacrolimus-based immunosuppression and the therapeutic benefit of newly developed adjunct immunosuppressants and management strategies. SUMMARY BACKGROUND DATA: With the advent of tacrolimus in 1990, transplantation of the intestine began to emerge as therapy for intestinal failure. However, a high risk of rejection, with the consequent need for acute and chronic high-dose immunosuppression, has inhibited its widespread application. METHODS: During an 11-year period, divided into two segments by a 1-year moratorium in 1994, 155 patients received 165 intestinal allografts under immunosuppression based on tacrolimus and prednisone: 65 intestine alone, 75 liver and intestine, and 25 multivisceral. For the transplantations since the moratorium (n = 99), an adjunct immunosuppressant (cyclophosphamide or daclizumab) was used for 74 transplantations, adjunct donor bone marrow was given in 39, and the intestine of 11 allografts was irradiated with a single dose of 750 cGy. RESULTS: The actuarial survival rate for the total population was 75% at 1 year, 54% at 5 years, and 42% at 10 years. Recipients of liver plus intestine had the best long-term prognosis and the lowest risk of graft loss from rejection (P =.001). Since 1994, survival rates have improved. Techniques for early detection of Epstein-Barr and cytomegaloviral infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, and most recently allograft irradiation may have contributed to the better results. CONCLUSION: The survival rates after intestinal transplantation have cumulatively improved during the past decade. With the management strategies currently under evaluation, intestinal transplant procedures have the potential to become the standard of care for patients with end-stage intestinal failure.

Adult↗

Erythrocyte-methotrexate and disease activity in children treated with oral methotrexate for juvenile chronic arthritis.

The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured twice with three months interval in 21 children suffering from juvenile chronic arthritis (JCA). At the same time joint score, visual analogue scale (VAS), and laboratory parameters (CRP, WBC, PMNs, and ALAT) were obtained. There was only a weak insignificant correlation between the dose of MTX/m2 and E-MTX (r=0.24, p=0.11). No significant relations between the clinical or laboratory parameters and E-MTX was found. However, ALAT above normal range was associated with a lower dose of MTX (p=0.02) and lower VAS (p=0.02), indicating that toxicity may be associated with less articular discomfort. At present we consider routine determination of E-MTX in children with JCA of limited value.

Administration, Oral↗

Juvenile chronic arthritis into adulthood: a long-term follow-up study.

OBJECTIVE: To evaluate a group of 65 adults with a history of or persistent juvenile chronic arthritis (JCA), on average, 26.4 yr after disease onset. METHODS: Disease status at the time of the study included an evaluation of disease-related parameters assessed by the patient and the investigator. RESULTS: Active disease was present in 37% of the study participants, of which 80% had either extended pauciarticular or polyarticular JCA. Eleven per cent of the study subjects were in Steinbrocker functional classes III and IV and 22% had undergone JCA-related major surgery. The pain visual analogue scale, health assessment questionnaire, erythrocyte sedimentation rate and C-reactive protein (CRP) were significantly increased in those participants who had active JCA at the time of the study. Disease duration proved to be the parameter most strongly associated with an unfavourable disease outcome. CONCLUSIONS: Although the study group was biased towards the more severe cases, the data suggest that the long-term functional outcome in JCA is, in more than one-third, associated with active disease persisting into adulthood, increasing residua and the need for surgery.

Adult↗

Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: a cross-sectional long-term followup study.

OBJECTIVE: To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD. METHODS: Sixty-five white patients (mean age 32.2 years) with a history of JCA and 65 age-, sex-, height-, and weight-matched healthy control subjects participated in the study. Densitometry of the left hip and the lumbar spine was performed, and osteocalcin (bone formation marker) and crosslinks (bone resorption marker) were measured. In addition, bone-related clinical parameters were assessed in the JCA group. RESULTS: BMD in the hip and lumbar spine was significantly lower in the JCA group than in the controls. Levels of osteocalcin and crosslinks were significantly increased in the JCA group. According to WHO definitions, significantly more subjects in the JCA group had "osteopenia" and "osteoporosis" than would be expected in a normal population sample. Active disease at the time of the study (1996-1997), baseline erosions evaluated in 1979, Steinbrocker functional class in 1996-1997, polyarticular course of JCA, and history of systemic steroid treatment for more than 1 year were significantly associated with reduced BMD. In linear regression analysis including both the JCA and control groups, presence of JCA proved to be the factor most strongly associated with reduced BMD, explaining approximately 20% of its variation. CONCLUSION: Reduced BMD and evidence of increased bone turnover suggest that JCA patients may be at risk of developing premature osteoporosis and associated fractures later in life. The data are consistent with the concept that BMD in JCA is determined by many factors.

Adult↗

A mathematical model of aerosol holding chambers.

A mathematical model of aerosol delivery from holding chambers (spacers) was developed incorporating tidal volume (VT), chamber volume (Vch), apparatus dead space (VD), effect of valve insufficiency and other leaks, loss of aerosol by immediate impact on the chamber wall, and fallout of aerosol in the chamber with time. Four different spacers were connected via filters to a mechanical lung model, and aerosol delivery during "breathing" was determined from drug recovery from the filters. The formula correctly predicted the delivery of budesonide aerosol from the AeroChamber (Trudell Medical, London, Ontario, Canada), NebuChamber (Astra, Södirtälje, Sweden) and Nebuhaler (Astra) adapted for babies. The dose of fluticasone proportionate delivered by the Babyhaler (Glaxco Wellcome, Oxbridge, Middlesex, UK) was 80% of that predicted, probably because of incomplete priming of this spacer. Of the above-mentioned factors, initial loss of aerosol by impact on the chamber wall is most important for the efficiency of a spacer. With a VT of 195 mL, the AeroChamber and Babyhaler were emptied in two breaths, the NebuChamber in four breaths, and the Nebuhaler in six breaths. Insufficiencies of the expiratory valves were demonstrated by comparison of pressure flow curves during "inspiratory" flow with and without occluded expiratory openings. Insufficient inspiratory valves were demonstrated by comparison of "expiratory" pressure flow curves with and without occluded inspiratory openings. With children breathing through the spacers, mask pressure variations were generally on the same order as that seen with the mechanical respiratory, supporting the clinical relevance of the in vitro findings.

Aerosols↗

Final height, armspan, subischial leg length and body proportions in juvenile chronic arthritis. A long-term follow-up study.

OBJECTIVE: Assessment of growth disturbances in adults with a history of juvenile chronic arthritis (JCA). MATERIAL AND METHODS: Sixty-five subjects, 52 premenopausal females and 13 males with a mean age (range) of 32.2 years (22.3-49.4) participated. Mean age at disease onset was 5.7 years (0.8-15.8) and mean disease duration was 12.4 years (0.4-32). The follow-up time ranged from 18.7 to 46.9 years with a mean of 26.4 years. For each participant standard deviation scores (z-scores) for final height, delta-height (the difference between observed and expected height), armspan, subischial leg length and sitting height ratio, were calculated. RESULTS: The study group as a whole did not exhibit linear growth impairment. The categorical distribution of heights differed significantly from a expected distribution in a healthy population (p < 0.001). A height z-score < -2 SD was present in 10.7% of the study group, of whom all had polyarticular course of JCA. Polyarticular and systemic course of JCA (versus pauciarticular) (p = 0.022), systemic steroid treatment (p = 0.006) and Steinbrocker functional class II-IV (vs. I) in 1979 (p = 0.043) were variables associated with reduced delta-height. In linear regression analyses, disease severity defining variables were statistically significant predictors of reduced final height and armspan. 27% of the study subjects had significantly reduced arm span (p < 0.001). Subischial leg length and body proportions (sitting height ratio) were normal. CONCLUSION: Our findings suggest that functionally impaired polyarticular and systemic JCA patients treated with systemic steroids may be at an increased risk of developing reduced final height and armspan. Disease control achieved by an aggressive therapeutic approach, if possible with a minimal use of systemic steroids, may reduce growth impairment in JCA.

Adult↗

Comparative incidence of de novo nonlymphoid malignancies after liver transplantation under tacrolimus using surveillance epidemiologic end result data.

BACKGROUND: An increased incidence of de novo nonlymphoid malignancies has been shown in immunocompromised patients. However, the true risk over time compared to the general population has not been determined. METHODS: One thousand consecutive patients were carefully followed for an average of 77.8+/-11.1 (range, 56.3-96.3) months after primary liver transplantation at a single center. All de novo nonlymphoid malignancies were recorded. Each malignancy was compared with a standard Occupational Cohort Mortality Analysis Program population matched for age, sex, and length of follow-up using modified life table technique and surveillance epidemiology end result (SEER) data. RESULTS: Fifty-seven patients accounted for de novo malignancies and contributed 4795.3 total person years, a mean+/-SD of 36+/-21 (median, 36; range, 6-74) months after liver transplantation. Twenty-two of these malignancies were skin malignancies including two melanomas. Oropharyngeal cancers (n=7) were found to be 7.6 times higher (P<0.05) and respiratory malignancies (n=8) were 1.7 times higher (P>0.05) compared to the SEER incidence rate. Female reproductive system malignancies including breast cancer (n=3) were 1.9 times lower (P>0.05) and genitourinary malignancies were (n=5) 1.5 times lower (P>0.05) than their matched cohorts. No differences was observed in gastrointestinal malignancies (n=5). There was a significant difference in survival of the patients after diagnosis of malignancy depending on the type of cancer. There were two Kaposi's sarcomas, two metastatic unknown primaries, one thyroid, one brain, and one ophthalmic malignancies in the series. Mortality for Kaposi's and metastatic disease of unknown primary was 100% within 5 months, while the 1-year mortality for oropharyngeal cancer was 57.1% and that for lung cancers was 62.5%. Long-term survival for skin cancer was highest: 86.4% at 3 years (P=0.015 by log-rank test). CONCLUSION: An increased incidence of de novo cancers in the chronically immunocompromised patient demands careful long-term screening protocols which will help to facilitate the diagnosis at an early stage of the disease. This is particularly true for oropharyngeal cancers where the risk is more than 7 times higher compared to SEER incidence data matched for age, sex, and length of follow-up.

Adult↗

A Markovian formalization of heart rate dynamics evinces a quantum-like hypothesis.

Most investigations into heart rate dynamics have emphasized continuous functions, whereas the heart beat itself is a discrete event. We present experimental evidence that by considering this quality, the dynamics may be appreciated as a result of singular dynamics arising out of non-Lipschitz formalisms. Markov process analysis demonstrates that heart beats may then be considered in terms of quantum-like constraints.

Animals↗

A terminal dynamics model of the heartbeat.

It is widely assumed that heartbeat dynamics are chaotic, although there has been no evidence confirming such an opinion, and some evidence to the contrary. Additionally, the deterministic assumptions of such dynamics cannot be demonstrated. An alternative model is presented based upon the notion of terminal dynamics, which can more faithfully represent key features of the heartbeat: namely, piecewise determinism, and singular points between beats, which allow for adaptability while maintaining stability.

Adaptation, Physiological↗

In vitro cytokine production and phenotype expression by blood mononuclear cells from umbilical cords, children and adults.

Age related differences in immunological reactions include variations in the in vitro functions of blood mononuclear cells (MNC). In an attempt to understand the mechanism behind these differences we examined age related differences in the phenotype profiles of MNC in parallel with the in vitro production of interleukin IL-6, tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFNg) in neonates, children and adults. In cultures without added polyclonal activators IL-6 and TNF alpha levels in children were 3-6 times higher than those of umbilical cords and adults. However, using optimal in vitro stimulation (E. coli lipopolysaccharide (LPS), phytohaemmagglutinin or pokeweed mitogen (PWM)) no significant differences in the levels of these cytokines were observed. The levels of IFNg in PWM driven cultures followed a different pattern with comparable levels in children and adults, and unmeasurable levels in cord blood MNC. Flow cytometry analysis of the phenotypic distribution of MNC revealed age related differences in the expression of CD3, CD4, CD8, CD14, CD19, CD45RA, CD45R0, CD2, LFA-1, ICAM-1 and LFA-3. Correlation studies did not indicate that the observed differences in cytokine production could be ascribed to differences in the frequency of monocytes, T cells or B cells. The TNF alpha levels in suboptimally stimulated cultures correlated negatively with the expression of LFA-3 and positively with CD45RA, while IFNg correlated positively with CD2, LFA-1, CD45R0 and CD8. In conclusion, the study provides evidence of age related differences in the production of TNF alpha, IL-6 and IFNg among neonates, children and adults. These differences may to some extent be caused by differences in the expression of cell surface molecules involved in cellular interactions and signalling.

Adult↗

Autoantibodies to IL-1 alpha in sera from umbilical cords, children, and adults, and from patients with juvenile chronic arthritis.

Antibodies against interleukin-1 alpha (aAb-IL-1 alpha) have previously been demonstrated in sera of healthy adults and in patients with inflammatory diseases. In the present investigation the occurrence of aAb-IL-1 alpha was examined by second antibody precipitation technique in sera from umbilical cords (n = 11), children (n = 45), and adults (n = 20), as well as in 51 patients with juvenile chronic arthritis (JCA) of pauciarticular (n = 34), polyarticular (n = 8), or systemic onset type (n = 9). RESULTS. The frequency of positive sera was significantly lower in children than in cord blood and adults as were the levels of aAb-IL-1 alpha (p < 0.0001). In the non-neonatal group of individuals the levels of aAb-IL-1 alpha correlated positively with age (r = 0.394, p = 0.0015). The frequency of sera positive for aAb-IL-1 alpha was higher in the JCA patients, as were the levels (p < 0.005), and correlated positively with disease activity as evaluated by joint score and visual analogue score.

Adult↗

Terminal chaos for information processing in neurodynamics.

New nonlinear phenomenon-terminal chaos caused by failure of the Lipschitz condition at equilibrium points of dynamical systems is introduced. It is shown that terminal chaos has a well organized probabilistic structure which can be predicted and controlled. This gives an opportunity to exploit this phenomenon for information processing. It appears that chaotic states of neurons activity are associated with higher level of cognitive processes such as generalization and abstraction.

Animals↗

Neurodynamics with spatial self-organizations.

A neural network architecture with self-organization in phase and actual space is proposed and discussed. Special type of differential local interconnections simulating diffusion, dispersion, and convection were investigated. It is shown that these interconnections are responsible for biological pattern formation in a homogeneous neural structure. The model suggests a phenomenological explanation of the mechanisms of edge detection in vision process.

Models, Neurological↗