Reliability of telemedicine evaluation for EDSS functional systems in multiple sclerosis.

Introduction: There was an increase in telemedicine during the COVID-19 pandemic to follow patients with multiple sclerosis (MS). However, there is scarce data if online evaluations can cover important information assessed during in-clinic appointments, especially the Expanded Disability Status Score (EDSS). This study aims to develop a remote evaluation tool for EDSS functional systems and compare the performance with face-to-face evaluations. Methods: This was a single-center study that included all MS patients followed up at outpatient clinics of Hospital São Lucas Pontifícia Universidade Católica do Rio Grande do Sul, between April and August 2022. Initially, patients were routinely in-clinic evaluated by one trained neurologist for EDSS. After, patients were evaluated remotely without any information about the in-clinic EDSS results. We used a standardized interview with an interactive video platform to evaluate EDSS functional systems by telemedicine. Results: Forty-nine participants completed the two steps. Intra-class coefficient was 0.97 (95% CI: 0.95-0.98), concordance for EDSS below 4.0 was 0.87 (95% CI: 0.77-0.93) and ≥4.0 was 0.97 (95% CI: 0.89-0.99). There was perfect agreement in the final EDSS in 71.4% of the online and in-clinic evaluations. In the multivariate analysis, the visual (beta = 0.453; p = 0.003) and pyramidal (beta = 0.403; p = 0.009) systems contributed significantly to the difference in the final EDSS. Conclusion: The telemedicine tool created in this study can detect changes in functional systems with reliable results compared to in-clinic EDSS assessment. Telemedicine evaluations may reduce the number of in-clinic visits and the disease burden for patients with MS.

Local perceptions do not follow rainfall trends: A case study in traditional Marajo island communities (eastern para state, BR).

The great current challenge for the conservation and use of natural resources refers to global climate change, because of its impacts felt in different intensities at global, regional, and local spatial scales. Within the system of environmental protection areas in Brazil, the extractive reserves ensure the sustainable use of natural resources by traditional populations, thus maintaining the cultural and biological aspects of a region. Such populations, being in close management of the surrounding environments, tend to perceive changes in ecological processes that many need for their livelihoods. The use of this perception of local populations in conjunction with academic research evidence has a high potential to allow a whole and systemic view of possible changes in natural phenomena. This study developed an integrated analysis of scientific evidence and local perceptions to understand the variation of precipitation in a community inserted in an extractive reserve in the eastern Amazon. We used 30 years of precipitation data from the Brazilian National Institute of Meteorology - INMET, the Southern Oscillation Index - SOI, and the Atlantic Meridional Mode Index - AMM. Furthermore, we applied a form to measure the population's perception of possible changes in rainfall cycles in the region. The meteorological data indicate that the region of the community has been presenting a rainfall reduction; however, people in the community do not perceive this trend. Although it is public knowledge that the global climate is undergoing changes, a fact noted after the integrating analysis of scientific evidence with local knowledge in Resexmar Soure is that the perceptions of traditional populations often focus on smaller temporal and spatial scale visions.

Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response.

The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.

Presence of activated T-cells with a T8+ M1+ Leu 7+ surface phenotype in invaded lymph nodes from patients with solid tumors.

The lymphocyte surface phenotype of lymph nodes from patients with larynx or urinary bladder carcinoma was investigated by using a panel of monoclonal antibodies. The phenotype pattern of lymphocytes from lymph nodes invaded by malignant cells (as assessed by histopathology) was different from that of the cells from noninvaded or normal control nodes. Although the proportion of natural killer cells or macrophages was similar in the 3 groups of lymph nodes, invaded lymph nodes contained a higher proportion of T-cells and a lower B-cell percentage. Furthermore, cells from invaded nodes comprised 15-20% of T3+ T8+ cells that coexpressed the M1 marker and, to some extent, also the Leu 7 marker. A large proportion of cells with multiple markers were activated, as shown by the expression of Tac and HLA-DR antigens. In 2 patients activated T8+ cells expressing also M1 and Leu 7 markers infiltrated the tumor site. The presence of these activated cells both in involved nodes and tumor mass may indicate that they originate in response to cancer.

Characterization of the plasma membrane ATPase of Candida tropicalis.

1) Plasma membrane vesicles from Candida tropicalis were isolated from protoplasts by differential centrifugation and purified in a continuous sucrose gradient. 2) The plasma membrane bound ATPase was characterized. It is highly specific for ATP and requires Mg2+. It is stimulated by K+, Na+ and NH4+. Lineweaver-Burk plots for ATPase activity are linear with a Vmax of 4.2 mumoles of ATP hydrolyzed min-1.mg-1 protein and a Km for ATP of 0.76 mM. The ATPase activity is inhibited competitively by ADP with a Ki of 1.7 mM and non competitively by vanadate with a Ki of 3 microM. The activity is unaffected by oligomycin or azide but is sensitive to DCCD.

Influence of oxygen on the microsomal electron transport system in Saccharomyces cerevisiae.

The influence of oxygen on the level of microsomal electron transport chain components has been studied during the growth of Saccharomyces cerevisiae. Enzyme activities and cytochrome content were assayed in microsomal fractions prepared from a protoplast lysate free from mitochondrial contamination. It was found that the cytochrome P-450 and cytochrome b5 content, to get her with the NADPH-cytochrome (P-450)-reductase and NADH-cytochrome (b5)-reductase activities, were increased in the cells as the pO2 of the medium was decreasing. At the same time an increase in the membrane surface of the endoplasmic reticulum can be observed.

Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia.

Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supernatants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.

Renal effects of prolonged antihypertensive treatment with diltiazem.

The effects of diltiazem (DTZ) treatment on blood pressure, renal function and renal hemodynamics over a six week period of therapy were evaluated in 14 adult patients with mild to moderate hypertension. Their creatinine clearances were 64 to 153 ml/min. After a week of treatment with placebo, DTZ was administered orally at a daily dose of 120 mg b.i.d. Blood pressure decreased from a mean value of 152/99 mm Hg (+/-13/6 SD) up to 144/91 (+/-17/8, P < 0.005) in the supine position and from 149/107 (+/-14/9) to 141/96 (+/-16/9, P < 0.005) in standing position. Heart rate decreased from 74 (+/-9) to 69 (+/-8). Plasma urea, creatinine, uric acid and their clearances as well as GFR and ERPF remained stable throughout the trial. Plasma glucose increased from 81 (+/-15) mg/dl to 98 (+/-30, P < 0.05) and plasma potassium decreased from 4.0 mEq/liter to 3.7 (+/-0.3, P < 0.005). Plasma cholesterol and triglycerides were unmodified. DTZ is an effective antihypertensive agent which does not significantly affect renal function. The effects on plasma glucose and potassium require periodical check-ups of these parameters.

Serum and urinary enzyme activities in renal artery embolism.

Renal artery embolism is not a rare occurrence, especially in patients with valvular heart disease, but the early diagnosis of this condition is infrequently accomplished. We report the clinical and laboratory data of 2 patients with valvular heart disease who presented with unilateral renal artery embolization. The usefulness of the determination of serum and urinary enzymes and renal function tests is discussed. We propose that these parameters support an earlier and more accurate diagnosis of renal artery embolism.

Zidovudine glucuronidation in human liver: interindividual variability.

Zidovudine 3'-azido-3'-deoxythymidine is the drug chosen for the treatment of patients suffering from AIDS; zidovudine being a potent inhibitor of HIV replication. The drug is extensively metabolized by conjugation with glucuronic acid into an inactive compound, and 30-40% of the dose is eliminated presystemically. We studied the variability and characterized the frequency distribution of the activity of zidovudine glucuronosyl transferase in 93 specimens of human liver. A rapid and reproducible radiometric assay for the glucuronidation of 14C-zidovudine is reported. The method is based on the extraction of the unreacted zidovudine into organic solvents and the radioactivity of the unextractable zidovudine glucuronide was measured in the aqueous phase residue. The rate of zidovudine glucuronidation was neither sex- nor age-dependent, ranged over 1 order of magnitude, and was positively skewed. The possibility that endogenous bilirubin should interact with glucuronidation of zidovudine was explored and the endogenous concentration of bilirubin was measured in the microsomal preparations of 59 liver samples. The final concentration of bilirubin in the assay mixture for zidovudine glucuronidation ranged between 2.2 and 13.2 microM and did not interact with the rate of zidovudine glucuronidation. The kinetics of glucuronosyl transferase towards zidovudine was studied in 20 livers, Michaelis-Menten kinetics were observed and the K(m) estimate ranged over 2-fold with an average of 2.89 mM. These in vitro results are consistent with the view that the rate of glucuronidation varies over 1 order of magnitude in the human liver and its distribution is positively skewed. This variability may modulate the patient's exposition to zidovudine and thereby the efficacy of therapy.

Cystatin C, beta 2-microglobulin, and retinol-binding protein as indicators of glomerular filtration rate: comparison with plasma creatinine.

BACKGROUND: The aim of this study was to assess the diagnostic accuracy of plasma levels of three low-molecular weight proteins cystatin C, beta 2-microglobulin, and retinol-binding protein, as indicators of impairment of glomerular filtration rate in comparison with plasma creatinine. METHODS: Glomerular filtration rate (GFR) was measured in 110 patients (51 M and 59 F, aged 18--79 years); creatinine (Creat), cystatin C (Cys), beta 2-microglobulin (beta 2M), and retinol-binding protein (RBP) were determined on the same day. The correlation coefficients between the different markers and GFR were determined. Receiver-operating characteristics (ROC) analysis was performed to assess their diagnostic accuracy. Furthermore, the relationship between plasma levels of the examined markers of GFR and body weight, height, fat-free mass (FFM) and body cell mass (BCM) was determined. FFM and BCM were calculated by means of total body electrical impedance measurement. RESULTS: Serum concentrations of Cys, beta 2M and RBP increase progressively with the reduction of GFR. The magnitude of the increase in blood levels of Creat and beta 2M was higher than the increase of Cys, and much more than that of RBP, in particular in patients with GFR<20 ml/min/1.73 m(2). The correlation coefficients between GFR and 1/plasma concentrations were 0.647 for Creat, 0.651 for Cys, 0.731 for beta 2M, and 0.406 for RBP. ROC analysis indicated that the accuracy of beta 2M and Cys, as indicators of different degrees of GFR impairment (<80, <60, and <40 ml/min per 1.73 m(2)), was similar to that of Creat, while the diagnostic accuracy of RBP resulted significantly lower than that of Creat for any level of GFR. In patients without renal failure (GFR>40 ml/min per 1.73 m(2)), plasma concentrations of Creat were positively correlated with body weight (P<0.01), height (P<0.01), FFM (P<0.001) and BCM (P<0.001). Serum concentrations of RBP resulted correlated with FFM (P<0.05) and BCM (P<0.05), while no correlation was found between anthropometric data and Cys and beta 2M. CONCLUSION: Cystatin C and beta 2-microglobulin have a diagnostic accuracy very similar to that of creatinine, while retinol-binding protein is not an adequate marker of glomerular filtration.

Therapeutic efficacy and renal effects of cefonicid in the treatment of difficult urinary tract infections.

UNLABELLED: EFFICACY, renal effects and nephrotoxicity of the cephalosporin cefonicid (CEF) were evaluated in 11 adult patients with urinary tract infection and varying renal function (creatinine cl 19-161 ml/min, mean 75). CEF was administered i.m. for 7 days at a daily dose adjusted to renal function of the patients. EFFICACY: At the 4th day and at the end of the treatment urine cultures were negative in all cases; a recurrence of the infection was observed in 4 patients 10 days after completion of therapy. Renal effects and nephrotoxicity: CEF neither modified plasma creatinine, urea, uric acid and their renal clearances nor glomerular filtration rate. Only the urinary enzyme activity of alanine aminopeptidase increased slightly at the end of the therapy. It returned to basal values in the post-treatment period. Urinary enzyme activities of gamma-glutamyltransferase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and lysozyme were unmodified during and after treatment with CEF. These results indicate that CEF is an effective antimicrobial agent which does not influence renal function, nor cause nephrotoxic effects.

Enhanced antifungal activity of ketoconazole by Euphorbia characias latex against Candida albicans.

The in vitro suseptibility of Candida albicans to ketoconazole and Euphorbia characias latex alone or in combination was tested using the macrobroth dilution method. The MIC 80% of crude latex and ketoconazole are respectively 159 microg protein/ml and 0.3901 microg/ml. This method permits us to determine an affinity constant K(aff) for crude latex (0.015 microg(-1) protein ml) and ketoconazole (23.828 microg(-1) ml). The utilization of a mixture of latex at several concentrations (7.8-15.62-31.25-62.5 and 125 microg protein/ml) and ketoconazole indicates a synergistic effect between latex and ketoconazole. For latex concentrations of 31.25 and 62.5 microg protein/ml the MIC 80% of ketoconazole were inferior (0.194 and 0.183 microg/ml respectively) to that obtained with ketoconazole alone (0.390 microg/ml). A synergistic effect is therefore obtained between ketoconazole on the one hand and two concentrations of Euphorbia characias latex.

Platelet aggregation behaviour in patients treated with ticlopidine.

Thirty patients (18 women, 12 men) with permanent or paroxysmal atrial fibrillation were treated with a new antiplatelet drug, ticlopidine, in order to study platelet aggregation behaviour, to see whether the drug prevents thromboembolisms and to observe side-effects over a period of 6 months. A further comparative study of the effects of ticlopidine and dipyridamole + aspirin on platelet aggregation was carried out in 20 patients. All appropriate haematological parameters were tested every 3 months, while platelet aggregation curves with ADP were examined also after 15 days. At the end of the period an echocardiogram was performed to check for any sign of thrombosis. The reduction in the aggregation curves was statistically significant for all the ADP stimuli, except at low doses. In the comparison with dipyridamole + aspirin, ticlopidine gave better results; with the former there was no significant reduction in platelet aggregation. A more significant reduction was seen in patients who had showed hyperaggregation at the outset. Bleeding time was increased and platelet adhesivity was reduced. During the 6-month period a slight reduction in white blood cells and a slight increase in creatinine were observed, both remaining within the normal range. Some 33.3% of the patients experienced side-effects. No embolic event or thrombosis in the left atrium was seen. Ticlopidine seems to be an effective antiplatelet drug, especially for patients with hyperaggregation.

Azthreonam in the treatment of urinary tract infection: evaluation of efficacy, renal effects and nephrotoxicity.

The efficacy, renal effects and nephrotoxicity of a short course of treatment with azthreonam were evaluated in 11 adult patients with urinary tract infection. Azthreonam was administered for 5 days at a daily dose adjusted to the residual renal function of the patients. In the pre-treatment period, during treatment and 10 days after completion of therapy, urine cultures, urinalysis and routine renal function tests (clearance of creatinine, urea and uric acid) were performed and urinary enzymes (alanine-aminopeptidase, gamma-glutamyl-transpeptidase, N-acetyl-beta-D-glucosaminidase, lysozyme) were determined. Renal haemodynamics (glomerular filtration rate and effective renal plasma flow) were measured in the pretreatment period and on the 5th day of therapy. The results confirm the efficacy of azthreonam for treatment of urinary tract infection. Results of renal function tests and measurements of urinary enzymes remained unchanged during and after treatment with azthreonam. These data support the conclusion that azthreonam is an effective antimicrobial agent which does not influence renal function or cause nephrotoxic effects.

Coagulation activation in extracorporeal hemodialysis.

The authors evaluated the behavior of protein C activity, factor X and factor VII coagulant activity and serum lipoprotein(a) before and after dialytic treatment in patients on maintenance hemodialysis. They observed depressed protein C activity that significantly (p < 0.005) increased and became normal immediately after hemodialysis while factor X and factor VII increased (p < 0.01; p < 0.05) despite heparinization together with amount of serum lipoprotein(a). In vitro incubation (30' at 37 degrees C) of uremic and healthy blood showed a decrease in serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and physiopathological implications of these results are discussed.

[A new test for monitoring heparin therapy]. / Un nuovo test per il monitoraggio della terapia eparinica.

A simple and easy assay for plasma heparin measurement (international units/ml) is described. The method is based upon the heparin neutralization and titration by polybrene. Heparin biological activity is measured first by activated partial thromboplastin time prolongment and then by means of polybrene titration: plasma heparin concentration was evaluated in international units/ml (IU/ml). The design and properties of this method are reported. Application in clinical practice of monitoring heparinization during hemodialysis is evaluated.

[Comparative analysis of 2 thromboplastins]. / Analisi comparativa di due tromboplastine.

BACKGROUND: This study was performed to evaluate the prothrombin time in normal healthy people (102 subjects) by means of two thromboplastins. METHODS: Dade Thromboplastin IS (rabbit brain thromboplastin) and Dade Innovin (recombinant tissue factor) were used. Derived fibrinogen, Claus fibrinogen and in vitro sensibility of these thromboplastins to known amount of heparin were also measured. RESULTS: A different behaviour of prothrombin time measurement linked to different thromboplastin sensibility connected to the age was observed. A different fibrinogen (Claus and derived) behaviour connected to the age that may help to explain thromboplastin sensibility difference with the age was also observed. Finally different sensibility of these two thromboplastins to heparin in vitro was observed. CONCLUSIONS: This result should be considered when anticoagulation is started with oral anti coagulant drug and heparin together.

[An increase in bile acids in the serum of patients with chronic kidney failure]. / Incremento degli acidi biliari nel siero dei pazienti affetti da insufficienza renale cronica.

Measurement of serum bile acids was performed in 86 uremic patients without any liver or bile tract diseases. Thirty-six patients (23 males and 13 females, aged 21-60 years) were on conservative dietary treatment, whereas 50 uremics (31 males and 19 females, aged 23-82 years) were on maintenance hemodialysis. The assays were made by means of enzymatic procedure and confirmed by RIA method too. Elevated serum concentrations of bile acids (> 6 mumol/L) were found in 24 out of the 86 uremics (27.9%), and the prevalence was similar in patients on conservative (10/36, 27.7%) and on dialysis treatment (14/50, 28%). Then, abnormally elevated concentrations of circulating bile acids are present in a quite high percentage of uremics both on hemodialysis and on conservative dietary therapy. The existence of a subclinical liver disease or an abnormal entero-hepatic cycle of bile acids might explain these findings.

Blood reduced glutathione (GSH) concentrations in healthy and ill subjects.

BACKGROUND: Recently blood reduced glutathione (GSH), an important cellular antioxidant, has been proposed as an indicator of health, particularly in the elderly. To date, a gold standard unit for the expression of GSH concentrations is not known. The aim of the study is to define the most sensitive laboratory expression of GSH. EXPERIMENTAL DESIGN: a comparative study among some laboratory expressions of GSH. SETTING: Geriatric and Internal Medicine Units; General Community. PATIENTS AND PARTICIPANTS: forty-eight inpatients from Geriatric and Internal Medicine Units and 82 healthy subjects recruited among medical students and residents, people from preventive medicine services and from local senior centres. EXCLUSION CRITERIA FOR HEALTHY SUBJECTS: use of drugs in the year prior to the study. INTERVENTIONS: neither treatment nor interventions. MEASURES: the laboratory expression of GSH, compared in this study, were mg/dl, packed cell volume (PCV), mg/1010 RBC, mM/gHb. RESULTS: We noted statistically significant differences only if GSH was calculated as mg/1010 RBC; higher values were found in healthy subjects than in inpatients, apart from age. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb. Instead, the ratio GSH mg/1010 RBC expresses the true GSH concentrations inside each erythrocyte. This modality of expression is minimally affected by haematological parameters; the low sensibility of the other modalities may be due to variations of MCV and Hb.