Do disease specific characteristics add to the explanation of mobility limitations in patients with different chronic diseases? A study in The Netherlands

STUDY OBJECTIVES: To determine whether disease specific characteristics, reflecting clinical disease severity, add to the explanation of mobility limitations in patients with specific chronic diseases. DESIGN AND SETTING: Cross sectional study of survey data from community dwelling elderly people, aged 55-85 years, in the Netherlands. PARTICIPANTS AND METHODS: The additional explanation of mobility limitations by disease specific characteristics was examined by logistic regression analyses on data from 2830 community dwelling elderly people. MAIN RESULTS: In the total sample, chronic non-specific lung disease, cardiac disease, peripheral atherosclerosis, diabetes mellitus, stroke, arthritis and cancer (the index diseases), were all independently associated with mobility limitations. Adjusted for age, sex, comorbidity, and medical treatment disease specific characteristics that explain the association between disease and mobility mostly reflect decreased endurance capacity (shortness of breath and disturbed night rest in chronic non-specific lung disease, angina pectoris and congestive heart failure in cardiac disease), or are directly related to mobility function (stiffness and lower body complaints in arthritis). For atherosclerosis and diabetes mellitus, disease specific characteristics did not add to the explanation of mobility limitations. CONCLUSIONS: The results provide evidence that, to obtain more detailed information about the differential impact of chronic diseases on mobility, disease specific characteristics are important to take into account.     

Suppression and long latency excitation of single spinal motoneurons by transcranial magnetic stimulation in health, multiple sclerosis, and stroke

Our objective was to identify risk factors for development of immunologically mediated respiratory disease in workers exposed to hexahydrophthalic anhydride. We performed a medical and immunologic survey study of 57 workers in a workplace molding operation utilizing hexahydrophthalic anhydride. The main outcome measurements were the development of a respiratory disease due to specific IgE antibody (asthma and/or rhinitis) or specific IgG antibody (hypersensitivity pneumonitis or hemorrhagic rhinitis). Of the 57 workers, 7 had both IgE- and IgG-mediated disease, whereas 9 had only IgE-mediated disease. Although neither smoking, age, nor race were risk factors for development of immunologically mediated disease, exposure level and specific antibody were. In conclusion, development of immunologically mediated respiratory disease due to hexahydrophthalic anhydride is most closely associated with exposure level and development of specific IgE or IgG antibodies.     

Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate

BACKGROUND: The accumulation of chromogranin A (Chr A) and cathepsin D (Cath D) gene products may be important in prostate carcinoma progression. This study assessed whether the levels of immunoreactivity for Chr A and Cath D are better predictors of disease specific survival than conventional pathologic parameters of the primary tumor such as Gleason score, capsular penetration, seminal vesicle invasion, and percent tumor in the specimen for patients with clinically localized prostate carcinoma managed by radical prostatectomy. METHODS: Seventy-one patients with modified Jewett clinical stages A1 to B2 adenocarcinoma of the prostate underwent a radical prostatectomy after a negative metastatic workup. No neoadjuvant or adjuvant treatments were given and all disease recurrences and causes of death were recorded. Analysis of prostatectomy specimens was undertaken to determine the conventional pathologic parameters of the primary tumor and Chr A and Cath D immunohistochemical staining. Univariate and multivariate analyses were performed to determine the independent contributions of Chr A and Cath D in predicting survival. RESULTS: On univariate analysis Chr A was the only variable that reached statistical significance for disease specific survival (P = 0.035). Cath D nearly reached significance with a P value of 0.079 for disease specific survival. On multivariate analysis, the only independent factor predicting disease specific survival was the Chr A staining score (P < 0.05). In patients with unequivocal foci of Chr A immunoreactivity, the 14-year disease specific survival was 50% compared with 68% for patients lacking such foci. CONCLUSIONS: The level of Chr A immunohistochemical staining is a strong predictor of disease specific survival and is superior to standard pathologic prognostic factors. Such findings lay the groundwork for future prospective study of the utility of such markers on biopsy specimens to predict patient outcome.     

Molecular biology analysis: hereditary hemochromatosis, Wilson disease, alpha 1-antitrypsin deficiency and Dubin-Johnson syndrome

The molecular pathology of hereditary hemochromatosis, Wilson's disease, alpha 1-antitrypsin-deficiency and Dubin-Johnson syndrome could be well characterised during the last years. Diagnosis of hereditary hemochromatosis is reliably confirmed by PCR-augmentation and restriction-analysis. Wilson's disease is a monogenetic disease, which is characterised by over 50 mutations. Molecular diagnosis is complicated by the lack of a single specific mutation. Diagnosis of Dubin-Johnson syndrome and alpha 1-antitrypsin-deficiency is possible by PCR-analysis and hybridisation with specific oligonucleotides.     

Regional myocardial blood flow during hyperemia induced by contrast agent in patients with coronary artery disease

Regional myocardial specific blood flow (regional specific flow) was measured at rest and during contrast hyperemia after the intracoronary injection of xenon-133. The changes in regional specific flow were transient, resulting in some compromise in one of the underlying restraints of the inert gas washout method, namely, the presence of a steady state. Therefore, to determine the clinical utility of this technique, regional specific flow values obtained with this method were correlated with the presence and severity of coronary artery disease as assessed from the coronary arteriogram and left ventriculogram. Regional specific flow during contrast hyperemia was 186+/- 11 (mean +/- 1 standard error of the mean) ml/min per 100 g in control patients and 115+/-5 in patients with coronary artery disease. There was an inverse relation between regional specific flow during contrast hyperemia and the percent coronary stenosis when the stenosis was 40 percent or greater (r = 0.70, P less than 0.001). Regional specific flow was significantly less in patients with asynergy (77 +/- 10 ml/min per 100 g) than in patients with normal ventricular function (105 +/- 5) distal to coronary stenoses of greater than 75 percent. Thus regional specific flow measured during contrast hyperemia using the xenon washout technique and the Anger camera differentiated patients with normal coronary arteriograms from those with coronary artery disease. With this technique, good correlation was shown between regional specific flow and the percent coronary stenosis and presence of ventricular wall abnormalities. The information obtained with this method may provide prognostic information concerning suitability for surgical intervention.     

The neuroregulatory properties of L-DOPA. A review of the evidence and potential role in the treatment of Parkinson's disease

Accumulating evidence suggests that L-dihydroxyphenylalanine (L-DOPA) has neurotransmitter-like and/or neuromodulatory properties in the CNS. Such evidence is based on a wide range of findings including the existence of specific L-DOPAergic neurons in several regions of the CNS, neurotransmitter-like characteristics and specific pharmacological effects. This review attempts to outline the main evidence for this conception and to relate such findings to L-DOPA treatment effects in Parkinson's disease. In this context L-DOPA in itself has been shown to potentiate D2 receptor-mediated effects, inhibit acetylcholine release and increase the release of L-glutamate, neuropharmacological effects which can be linked to treatment side-effects in advanced Parkinson's disease. It is suggested that supersensitive L-DOPA-mediated effects contribute to the pathogenesis underlying L-DOPA-induced motor complications in advanced Parkinson's disease. However, since specific L-DOPA receptors have yet to be identified, the assessment of the relative importance of L-DOPA-mediated effects in this clinical context must be regarded as incomplete.     

Cardiovascular disease among firefighters

The author reviews the literature of the past 20 years on heart disease among firefighters, covering the specific aspects of firefighting that may be related to potential cardiovascular disease. The author then outlines steps that can be taken to reduce the risks of developing cardiovascular disease.     

Biplane computed cerebral angiotomography of moyamoya disease (author's transl)

In this paper, the authors report biplane computed cerebral angiotomographic findings in 5 cases of Moyamoya disease. The specific features of Moyamoya disease on the CT image were as follows: On the axial plane, the linear structures of the anterior half of the circle of Willis and the proximal portion of the middle cerebral arteries disappeared, and instead of these normal structures, irregular, tortuous or patchy high-density areas just like a "caterpillar" were shown in the basal cistern and medial Sylvian fissures. On the modified coronal plane, the supraclinoid internal carotid arteries and the carotid fork could be identified only with a difficulty, and abnormal, "nebular" high-density areas consisting of irregular, tortuous or patchy high-density vascular components became visible in the basal cistern extending to the basal ganglia. A modified coronal plane and intravenous minimum dose bolus injection method seemed to be more useful for the visualization of these specific features on the CT image. Even before carotid angiography, we can suspect Moyamoya disease for finding these specific features on the CT image. Carotid angiography has been the only method of diagnosing Moyamoya disease. Instead of this invasive examination, computed cerebral angiotomography is useful in detecting Moyamoya disease conveniently and non-invasively. Therefore, we may conclude that computed cerebral angiotomography is very useful method for screening and follow up study of Moyamoya disease.     

The arena test and cortisol response of sheep as indirect selection criteria for the improvement of lamb survival

Manias, and particularly depressions, are syndromes not disease. Considerable data support the fact that depressions, though similar clinically, are of heterogeneous etiologies. We can separate depressions generally into those that are endogenous/psychotic and those that occur in the context of marked emotional instability. Familial pure depressive disease is a specific example of the former, depression spectrum diseases a specific example of the latter. These are separable on the basis of personality, clinical, follow-up, familial and treatment variables.     

Pushing the envelope: VA''s mail-service operation

A western blot assay was performed for the detection of Fasciola hepatica specific antigens for the diagnostic of fasciolasis; 72 sera were tested, 28 coming from patients with the parasitic disease and 44 from persons either healthy or presenting other diseases; 11 different antigenic bands were detected using sera from patients with fasciolasis. The 57 and 29 kDa specific antigens are considered like major, their specificity is about 100% and their respective sensibility, 79 and 93%. Band of 9-12 kDa is also appeared specific but is revealed only in 47% of the cases; 27 out of the 28 sera from patients with fasciolasis were able to recognize at least one of the 57, 29 or 9-12 kDa specific antigens. The present results suggest that western blot could be useful for the diagnosis of this parasitic disease as far as the criteria of positivity is based on the recognition of at least one of the major specific antigens.     

Use of the thrombocyte aggregation test for detecting immune complexes circulating in the serum of cholera patients

It was shown that the blood sera of patients suffering from cholera and of persons who had sustained the disease contained specific antibodies in titres below the diagnostic level (according to the indirect hemagglutination test) caused platelet aggregation, most pronounced during the first week of the infectious process. In the presence of a specific cholera antigen the phenomenon of platelet aggregation was considerably enhanced; the indices reached the maximum when the experiment was conducted with the blood sera of those who had sustained the disease.     

Immune response profile in patients with active tuberculosis in a BCG vaccinated area

Tuberculosis patients with pulmonary (N = 95) or lymph node disease (N = 23) were assessed for Th1 responses (PPD skin test and lymphocyte blastogenic and interferon gamma) and Th2 responses (polyclonal and antigen specific IgE). Skin test responses to PPD and lymphocyte proliferative responses to crude mycobacterial antigens (PPD, culture filtrate and sonicate) and recall antigens (tetanus toxoid and streptolysin O) were significantly suppressed (p < 0.001) in patients with pulmonary disease compared to endemic controls. However, mitogen (phytohemagglutinin)-stimulated responses were comparable in patients and controls. Polyclonal and antigen specific (M. tuberculosis culture filtrate) IgE responses which are considered to be surrogate markers for Th2 responses were significantly higher in patients with pulmonary disease compared to healthy endemic controls (Mann Whitney analysis p < 0.01). Patients with lymph node disease showed strong Th1 responses but did not show significant responses for either polyclonal or antigen specific IgE. Thus overall suppression of T cell memory response was observed only in patients with pulmonary disease but not in patients with lymph node disease suggesting that sequestration of antigen in different compartments leads to differential activation of Th1 and Th2 responses. PPD skin test responses were highly positive in endemic controls (47% positive) and household contacts (86% positive). Furthermore, PPD positivity decreased with disease severity. Therefore PPD positivity in a BCG vaccinated TB endemic area cannot be used as a diagnostic marker for active tuberculosis particularly in advanced disease.     

Absent mesosternum in congenital heart disease

The association of developmental abnormalities of the sternum with congenital heart disease is well known. These abnormalities include hypoplasia, multiple centers, and premature fusion. The absence of the sternal bodies in patients with congenital heart disease unrelated to a specific syndrome complex has not been previously described. Possible association with congenital pulmonary vascular disease was noted.     

Cardiac disease in chronic uremia: management

Heart disease is a common cause of morbidity in end-stage renal disease (ESRD) patients. The management of heart disease in these patients requires a multidimensional approach to the management of heart failure, coronary disease, and arrhythmias, and to risk factors such as hypertension, anemia, secondary hyperparathyroidism, and electrolyte/acid-base disturbances. Coronary artery disease management includes use of antianginal drugs and revascularization of coronary arteries with angioplasty +/- stent placement or coronary artery bypass grafting. The long-term outcomes of these procedures need to be assessed and improved. Hypertension occupies a major role in the pathogenesis of heart disease in ESRD, and early and adequate control of hypertension is likely to have a major impact on the progression of cardiac disease. This entails the achievement of optimal volume status, combined with the appropriate use of antihypertensive agents such as calcium channel blockers, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, vasodilators, alpha-blockers, and central sympatholytic drugs. In ESRD patients, specific dialysis-related complications such as intradialytic hypotension and pericardial effusion may have additional effects on cardiac function and require attention. The choice of dialysate composition and membrane may influence clinical outcomes with specific effects on cardiac performance.     

Markers of melanogenesis in malignant melanoma

Biochemical specifity of malignant melanoma is represented in part by the formation of specific cytoplasmatic particles of the pigment cell--melanosomes--in which the synthesis of pigment eumelanin and pheomelanin takes place and in part by the presence of a specific enzyme--tyrosinase--which catalyzes the formation of pigment eumelanin and pheomelanin and even the formation of specific metabolites (so called melanogens) which are excreted in increased amounts in the course of the disease. Tyrosinase and melanogens are specific for pigment cell and therefore can be used for monitoring of melanogenesis in malignant melanoma. When comparing our results and the results of other authors we can conclude that following of specific markers of melanogenesis in malignant melanoma should serve for the evaluation of prognosis of the disease. The study of melanoma markers is by far not finished. We do hope that nearly future will be able to give a sufficient answer to the question, whether melanogenuria is actually an expression of expected different biochemical or metabolic types of malignant melanoma on the one hand and/or biochemically or immunologically conditioned responses of the host organism on the other.     

Antiviral treatment of diseases in pediatric dermatology

Pediatric dermatologic disease that have specific therapies and/or specific prophylactic measures are reviewed. Herpes simplex virus and varicella-zoster virus infections, human papillomavirus infections, and molluscum contagiosum infections are discussed with special emphasis on recent advances of therapy and prophylaxis.     

Management of cardiac complications in neuromuscular disease

Cardiovascular complications are common and varied in neuromuscular diseases. Knowledge of the complications specific to each disease is essential for appropriate screening for cardiovascular disease. Appropriate treatment of complications varies between neuromuscular diseases and draws primarily on experience from patients without neuromuscular disease. This article details the known cardiovascular complications and treatments for some of the major neuromuscular diseases.     

Angiographic studies in fluoroscopically detected coronary calcification (author's transl)

We performed coronary angiography in eighty subjects with radiographically diagnosed coronary calcification. Radiographically proven coronary calcification is highly specific for coronary heart disease. Within certain limitations it helps in locating stenoses and is present more frequently in multiple vessel disease. It sometimes detects coronary artery disease missed by other non-invasive methods.     

Benefits of direct glomerular filtration rate (GFR) determination versus creatinine-based tests for evaluating renal function

To diagnose renal disease earlier and thereby reduce the number of patients with endstage renal disease, accurate, specific diagnostic tests are necessary. The author explains the benefits of using tests that rely on the glomerular filtration rate measurement rather than on traditional creatinine-based diagnostic tests.