Is Ramadan fasting safe in type 2 diabetic patients in view of the lack of significant effect of fasting on clinical and biochemical parameters, blood pressure, and glycemic control?

The study objective was to determine if Ramadan fasting was safe in patients with type 2 diabetes mellitus (T2D), based upon a determination of the effect of fasting on a broad range of physiological and clinical parameters, including markers of glycemic control and blood pressure. The study was carried out in Ramadan 1422 (December 2001-January 2002) at the Diabetology Services, Hopital Ibn Sina, Rabat, Morocco. One hundred and twenty T2D Moroccan patients (62 women, 58 men), aged 48-60 yrs with well-controlled diabetes through diet and/or oral hypoglycemic drugs (OHD), received dietary instructions and readjustment of the timing of the dose of OHD (gliclazide modified release) according to the fasting/eating periods. Anthropometric indices and physiological parameters (blood pressure, lipid, hematological, and serum electrolyte profiles, as well as markers of glycemic control, nutrition, renal and hepatic function) were measured on the day before Ramadan and then on the 15(th) and 29(th) day of fasting and thereafter 15 days later. Statistical analysis was done by standard methods. Ramadan fasting had no major effect on energy intake, body weight, body mass index, blood pressure, and liver enzymes. Fasting and post-prandial glucose levels decreased, while insulin levels increased. Diabetes was well controlled, as indicated by HbA1c, fructosamine, C-peptide, HOMA-IR, and IGF-1 values. There were fluctuations in some lipid and hematological parameters, creatinine, urea, uric acid, total protein, bilirubin, and electrolytes; however, all values stayed within the proper physiological range. In conclusion, diabetes was well-controlled in patients with dietary/medical management, without serious complications. With a regimen adjustment of OHD, diet control, and physical activity, most patients with T2D whose diabetes was well-controlled before Ramadan can safely observe Ramadan fasting.

Microhematuria: un enfoque práctico

Existe gran confusión a la hora de definir con precisión la microhematuria, pero el problema es mayor a la hora de considerar las directrices a seguir en la consulta urológica cuando el paciente consulta dicho signo. Esta trabajo presenta una experiencia personal, a la par que plantea un atractiva algoritmo de manejo clínico para estos casos. Dicho algoritmo se basa principalmente en el uso de citometría de flujo por contadores láser para calcular un parámetro hematológico que los autores han definido: la volumetría diferencial del hematíe entre sangre y orina. Esta determinación tiene múltiples ventajas respecto al uso del microscopio de contraste de fases (sedimento especializado) y a la volumetría por citometría automática (contadores Coulter). Dicho estudio, integrado en un contexto clínico apropiado y racional, puede ahorrar cantidad de estudios diagnósticos (muchos de ellos invasivos, caros y laboriosos) en esta patología tan prevalente (AU)

Pulse bifurcations and instabilities in an excitable medium: computations in finite ring domains.

We investigate the instabilities and bifurcations of traveling pulses in a model excitable medium; in particular, we discuss three different scenarios involving either the loss of stability or disappearance of stable pulses. In numerical simulations beyond the instabilities we observe replication of pulses ("backfiring") resulting in complex periodic or spatiotemporally chaotic dynamics as well as modulated traveling pulses. We approximate the linear stability of traveling pulses through computations in a finite albeit large domain with periodic boundary conditions. The critical eigenmodes at the onset of the instabilities are related to the resulting spatiotemporal dynamics and "act" upon the back of the pulses. The first scenario has been analyzed earlier [M. G. Zimmermann et al., Physica D 110, 92 (1997)] for high excitability (low excitation threshold): it involves the collision of a stable pulse branch with an unstable pulse branch in a so-called T point. In the framework of traveling wave ordinary differential equations, pulses correspond to homoclinic orbits and the T point to a double heteroclinic loop. We investigate this transition for a pulse in a domain with finite length and periodic boundary conditions. Numerical evidence of the proximity of the infinite-domain T point in this setup appears in the form of two saddle node bifurcations. Alternatively, for intermediate excitation threshold, an entire cascade of saddle nodes causing a "spiraling" of the pulse branch appears near the parameter values corresponding to the infinite-domain T point. Backfiring appears at the first saddle-node bifurcation, which limits the existence region of stable pulses. The third case found in the model for large excitation threshold is an oscillatory instability giving rise to "breathing," traveling pulses that periodically vary in width and speed.

Recycling probability and dynamical properties of germinal center reactions.

We introduce a new model for the dynamics of centroblasts and centrocytes in a germinal center. The model reduces the germinal center reaction to the elements considered as essential and embeds proliferation of centroblasts, point mutations of the corresponding antibody types represented in a shape space, differentiation to centrocytes, selection with respect to initial antigens, differentiation of positively selected centrocytes to plasma or memory cells and recycling of centrocytes to centroblasts. We use exclusively parameters with a direct biological interpretation such that, once determined by experimental data, the model gains predictive power. Based on the experiment of Han et al. (1995b) we predict that a high rate of recycling of centrocytes to centroblasts is necessary for the germinal center reaction to work reliably. Furthermore, we find a delayed start of the production of plasma and memory cells with respect to the start of point mutations, which turns out to be necessary for the optimization process during the germinal center reaction. The dependence of the germinal center reaction on the recycling probability is analysed.

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: To assess the effect of the age of patients with benign prostatic hyperplasia (BPH) on the clinical uroselectivity of alfuzosin during general medical practice. PATIENTS AND METHODS: The present national, multicentre, open-labelled, observational study involved 4018 Spanish outpatients with BPH, i.e. showing lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction. The patients received sustained release (SR) alfuzosin, 5 mg twice daily, for 2 months. The primary efficacy criteria were symptomatic improvements, as assessed by the International Prostate Symptom Score (IPSS) and quality of life (QoL) index. Safety was assessed by monitoring cardiovascular data and adverse events. RESULTS: The patients were divided into four age groups, i.e. < 56, 56-65, 66-75 and > 75 years. All groups of patients showed a mean IPSS decrease of 11-12 (55.8-65.4% from baseline) at the end of the study, while the QoL decreased by 2-3 points (55.6-63.6% from baseline). There were no relevant effects of age on the efficacy of the treatment. Moreover, alfuzosin was well tolerated independently of the age of the patient; 1.2% of the patients enrolled withdrew because of adverse events. The qualitative distribution of vasodilatory/nonvasodilatory adverse events was similar in all age groups. The incidence of asymptomatic orthostatic hypotension was low (0.58%) and not affected by the age of the patients. CONCLUSION: This study confirms that the clinical uro-selectivity of SR-alfuzosin, already described in ran-domized controlled studies, is not significantly affected in clinical practice by the age of the patients. This is considered particularly relevant to the characteristics of patients with BPH, as they are mostly elderly men.

Dispersion gap and localized spiral waves in a model for intracellular Ca2+ dynamics.

The dispersion relation is the dependence of the velocity of periodic planar wave trains on their wavelength. We study the occurrence of a velocity gap in the dispersion relation in a bistable three component reaction-diffusion system modeling intracellular Ca2+ dynamics. In two spatial dimensions, localized pinned spirals are observed, if their wavelength falls into the dispersion gap. Destruction of free spirals occurs already for conditions where the asymptotic planar wave train exists and the dispersion gap is absent.

Safety and efficacy of sustained-release alfuzosin on lower urinary tract symptoms suggestive of benign prostatic hyperplasia in 3,095 Spanish patients evaluated during general practice.

OBJECTIVES: This general practitioner-run study assess the security as well as the efficacy and impact on health-related quality of life of a sustained-release (SR) form of alfuzosin in Spanish patients suffering from lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: 3,095 patients with symptomatic BPH were enrolled into a national, multicentric, open, phase IV observational study. The period of active treatment studied (5 mg, twice daily) was 60 days. Safety was assessed by monitoring blood pressure and spontaneous adverse events. Symptoms were assessed using a validated Spanish International Prostate Symptom Score (I-PSS). Impact of symptoms on health-related quality of life was assessed using the quality of life index (L). RESULTS: 101 adverse events were reported in 82 patients (2.6%). 28 adverse events (2.6%) were classified as severe. 49 patients (1.6%) dropped out of the study due to adverse events but only 17 of these patients (0.5%) showed adverse events related to vasodilation. Incidence of postural events (vertigo, postural hypotension/hypotension, headache and dizziness) was low (55 patients, 1.8%) and effects on sexual function were found not significant: no retrograde ejaculation was reported and only 1 patient (0.03%) showed impotence. Blood pressure or heart rate showed no clinically significant changes. All the I-PSS scores decreased significantly during the treatment with alfuzosin, improvement being excellent in 60% of the patients. Symptomatic improvement was associated with a significant improvement in health-related quality of life. CONCLUSIONS: This large study conducted during general practice on Spanish BPH patients confirms the efficacy on LUTS and good safety profile of SR alfuzosin, especially its low incidence of postural symptoms and no deleterious effect on sexual function.

The value of comparative volumetric analysis of urinary and blood erythrocytes to localize the source of hematuria.

PURPOSE: We evaluate comparative volumetric analysis of blood and urinary red blood cells (RBCs) to identify the source of hematuria. Comparative volumetric analysis is defined as the difference between mean corpuscular erythrocyte volume in peripheral blood (MCVB) diluted in urine supernatant after centrifugation and mean corpuscular volume of urinary erythrocytes (MCVU). The potential of MCVB-MCVU to distinguish the origin of hematuria is compared to MCVU alone. The fundamental hypothesis is that RBCs that can go through the glomerulus will be smaller than those from the collecting system or lower urinary tract, thus having a smaller MCVU and larger difference between MCVB and MCVU. MATERIALS AND METHODS: A prospective detailed urological evaluation was performed on 210 patients with glomerular or nonglomerular hematuria detected by urinary sediment, clinical radiological evaluation, endoscopy, cytology and sometimes bladder or renal biopsy. After evaluation 24 cases with an uncertain source of hematuria were excluded from study. Specialized urinalysis, volumetric analysis and clinical investigation were performed in a blind fashion. MCVU and MCVB-MCVU were registered for every patient. The Technicon H-3 system with angle laser scattering dual system allowed measurement of mean corpuscular volume in a minimal number of RBCs, and resuspension of RBC pellets in the same urinary supinate avoided effects of osmolarity and pH on RBC size and shape. Reproducibility in assessing the index was tested in 50 cases in which comparative volumetric analysis was repeated on 2 consecutive days. Unpaired t test was performed, and a threshold value of MCVB-MCVU with maximum sensitivity and specificity to detect glomerular hematuria was identified. The potential of urinary and comparative volumetric analysis to distinguish the source of hematuria was evaluated and compared by receiver operating characteristics curve analysis. RESULTS: Hematuria was nonglomerular in 53 (28.4%) and glomerular in 133 (71.6%) patients. Mean MCVB-MCVU was significantly different for nonglomerular (0.6 fl.) and glomerular (30.5 fl.) sources (p<0.0001). There was a correlation between repeat independent measures of MCVU and MCVB-MCVU. The highest positive predictive value to detect a glomerular origin is desirable so that unnecessary investigation can be obviated without the risk of missing a nonglomerular source. With a limit of 16 fl. specificity and positive predictive value were 98 and 99%, respectively. Receiver operating characteristics curve analysis to localize the source of hematuria revealed significant differences in favor of comparative volumetric analysis versus urinary volumetric analysis alone. CONCLUSIONS: MCVB-MCVU using the Technicon H-3 system is a useful noninvasive and accurate method to locate the source of hematuria. A value of 16 fl. or greater practically rules out a nonglomerular origin and obviates further urological investigation. We have incorporated this investigation in our diagnostic algorithm for hematuria.

Fibrinolytic treatment in primary antiphospholipid syndrome.

We document a 30 y old man with Primary Antiphospholipid Syndrome (PAPS) and thrombosis of the common femoral vein and both the external and common iliac veins, extending to the lower vena cava, which failed to respond to high dose heparin. After three days of fibrinolytic treatment with urokinase there was complete venous recanalization.

[Secondary neoplasm in patients with bladder carcinoma. A case-control study]. / Neoplasia secundaria en pacientes con carcinoma de vejiga. Estudio caso-control.

Presentation of a case-control study on 755 subjects with the purpose of defining whether the development of a neoplasia on any organ and of any histological type, either synchronous or metachronous, occurs more frequently in patients who already have vesical carcinoma (338 cases) versus other populations of similar epidemiological characteristics comprising subjects who do not present that condition (417 controls). The evaluation of the difference between both groups establishes a cause-effect relationship expressed in terms of an odds ratio of 2:11 which allows to claim that presence of a second neoplasia is more frequent in patients with vesical carcinoma (p < 0.001). The paper also includes a discussion on the distribution to organs and systems. Once the cases with urothelial site (renal pelvis, ureter or urethra) are excluded, prostate adenocarcinoma is the most frequent form associated to vesical carcinoma, followed at a distance by renal adenocarcinoma, epidermoid carcinoma of the larynx and bronchopulmonary carcinoma. Cumulative incidence of secondary neoplasias, including tumours diagnosed synchronically is 12% at 54 months.

Total and regional bone mass in metastatic cancer of the prostate.

OBJECTIVES: Given the discrepancies in the findings of regional bone densitometry in patients with osseous metastases of prostate cancer, we decided to evaluate total and regional bone mineral content in 21 patients with stage D cancer of the prostate. These measurements were compared with those of a group of healthy subjects of similar age (n = 21). METHODS: A full body bone densitometry was carried out in all of the men. Dual energy X-ray absorptiometry was used. RESULTS: There were no differences between groups in the anthropometric variables (Student's t test). There were no differences between groups in the bone mass of the skull and arms, but patients had less bone mass in the trunk and legs (p < 0.05) and in the pelvis (p < 0.0001). Total body bone mineral content and total body bone mineral content corrected for weight also were lower in the patients than in the control group (p < 0.005). CONCLUSION: These results show that patients with prostate cancer and bone metastases have decreased bone mass, possibly because of a predominance of osteolytic over osteoblastic metastases.

Association between HLA class II antigens and primary antiphospholipid syndrome from the south of Spain.

Recent studies have suggested an association between primary antiphospholipid syndrome (PAPS), antiphospholipid antibodies and some major histocompatibility complex (MHC) antigens. We have studied the relationship between MHC class II antigens and PAPS in 19 patients from the south of Spain. Univariant analysis showed an association between PAPS and HLA-DQ7 (47% vs 25%l P = 0.3), DR4 (32% vs 16%; P = 0.08) and DQ3 (63% vs 39%; P = 0.04). However, multivariant analysis confirmed the association with DQ7 (RR = 2.5; CI 80%: 1.3-4.7) and DR4 (RR = 2.2; CI 80%: 1.1-4.4) but not with DQ3. When we introduced DRw53 into this analysis, we noticed a DR4 confounding effect, with DQ7 (RR = 3.1; CI 80%: 1.7-5.8) and Drw53 (RR = 2.3; CI 80%: 1.2-4.4) remaining as the most important HLA antigens related to PAPS. In conclusion, in PAPS patients from the South of Spain, HLA-DQ7 antigen showed the highest relative risk for PAPS, followed by DRw53.

[Staging error in bladder carcinoma: anatomo-clinical correlation]. / Error de estadiaje en el carcinoma vesical: correlación anatomo-clínica.

Presentation of clinico-pathological correlation in a series of patients with bladder carcinoma. All of them had a complete pathological and clinical staging following TNM guidelines (UICC 1987). Clinical evaluation consisted of a clinical examination, urography and/or ultrasound, cystoscopy, bimanual palpation under anaesthesia and biopsy. As an option, pelvic CAT, MRI and a bone scan were performed. In all cases a reliable pathological staging was obtained, either from cystectomy or complete TUR. Overall, there is a 66% clinico-pathological correlation (60% for Ta category, 78% for T1, 25% for T2, 57% for T3, and 74% for T4). There is a global error of 34% (40% of cases clinically considered Ta were invasive, 16% T1 were pT2 or more, 42% T2 were pT3 or more, and 10% T3 were pT4; while 6% of those considered T1 were pTa, 33% of T2 were pTa or pT1, 33% of T3 were pT2 or less, and 26% of T4 were pT3 or less). We therefore conclude that when T is lower the risk of being clinically understaged is greater, while higher T values increase the risk of clinical overstaging. From a practical point of view, the most severe errors are in the understaging of T2 and T3 (pT3-pT4) tumours and the overstaging of T2 (pT1) tumours. When cystectomy is performed, the risk of understaging is greater for tumours interpreted as T2-T3 while the risk of overstaging T4 tumours is lower. We conclude that, even when adequate staging of bladder cancer is attempted, pre-treatment tumour classification using the diagnostic methods currently available is far from satisfactory.

Asociación de los antígenos HLA-DR10,DR4 y DR1 con artritis reumatoidea / The association of the HLA-DR10,DR4 and DR1 antigens with rheumatoid arthritis

Objetivo:Establecer la relación entre los antígenos HLA de clase I y II y artritis reumatoidea. Material y métodos: Mediante un diseño de casos y controles se ha evaluado una muestra de conveniencia de 39 pacientes con artritis reumatoidea,que cumplían al menos cuatro criterios del American College of Rheumatology (ACR).Como grupo de comparación se utilizaron 264 controles sanos de la población.La tipificación de HLA se determinó serológicamente.Resultados:En el análisis se determinó por regresión logística,se detectó asociación de la enfermedad con DR10 (RR:7,7;IC 95 por ciento ,28,9-2,1),DR4 (RR:5,3;IC 95 por ciento,11,7-2,4)y DR1 (RR:3,6;IC 95 por ciento,8,0-1,6).La presencia de más de uno de estos antígenos no significaba mayor riesgo de padecer la enfermedad.No hemos observado asociación entre la presencia de estos antígenos y la gravedad de la enfermedad,manifestada por la seropositividad o afectación sistémica del proceso.Conclusiones:Nuestros resultados confirman que los antígenos HLA de clase II,DR10,DR4 y DR1, que comparten secuencias de aminoácidos en la región que contacta con el receptor del antígeno de los linfocitos T, son un factor de riesgo para el desarrollo de la artritis reumatoidea.

Asociación de los antígenos HLA-DR10,DR4 y DR1 con artritis reumatoidea / The association of the HLA-DR10,DR4 and DR1 antigens with rheumatoid arthritis

Objetivo:Establecer la relación entre los antígenos HLA de clase I y II y artritis reumatoidea. Material y métodos: Mediante un diseño de casos y controles se ha evaluado una muestra de conveniencia de 39 pacientes con artritis reumatoidea,que cumplían al menos cuatro criterios del American College of Rheumatology (ACR).Como grupo de comparación se utilizaron 264 controles sanos de la población.La tipificación de HLA se determinó serológicamente.Resultados:En el análisis se determinó por regresión logística,se detectó asociación de la enfermedad con DR10 (RR:7,7;IC 95 por ciento ,28,9-2,1),DR4 (RR:5,3;IC 95 por ciento,11,7-2,4)y DR1 (RR:3,6;IC 95 por ciento,8,0-1,6).La presencia de más de uno de estos antígenos no significaba mayor riesgo de padecer la enfermedad.No hemos observado asociación entre la presencia de estos antígenos y la gravedad de la enfermedad,manifestada por la seropositividad o afectación sistémica del proceso.Conclusiones:Nuestros resultados confirman que los antígenos HLA de clase II,DR10,DR4 y DR1, que comparten secuencias de aminoácidos en la región que contacta con el receptor del antígeno de los linfocitos T, son un factor de riesgo para el desarrollo de la artritis reumatoidea.

[Brucellar orchitis with abscess]. / Orquitis brucelosa abscesificada.

A clinical case of orchitis with brucellosis etiology is presented. Testicular symptomatology appeared from the beginning of the brucellosis's general clinical picture. It envolved painfully and increased the testicular size, with no mictional symptoms, expanding progressively in spite of specific brucellosis therapy given from the beginning, towards formation of an intratesticular abscess which required orchiectomy, a way of progression we have not found in the related literature. The main differential diagnosis must be done with tuberculosis orchitis. Since our country had the largest incidence of brucellosis in Europe, and it is possible that in many cases a orchiepididymarial condition can become apparent in the initial phases, this is an etiology that should be taken into account among specific orchiepididymitis.