Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation.

STUDY QUESTION: What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER: The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY: Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle-Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34-48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26-39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15-26, I2: 0%, fixed-effect) and 33% (95% CI: 25-42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION: The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S): This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER: CRD42021264042.

Patrones de tratamiento con agentes biológicos, eficacia y sobrevida a largo plazo en pacientes con espondiloartritis axial: Impacto de los factores sociodemográficos en Latinoamérica / Patterns of treatment with biological agents, efficacy and long-term survival in patients with axial spondyloarthritis: Impact of sociodemographic factors in Latin America

Objetivos: Evaluar y comparar la eficacia y la sobrevida a largo plazo de las Drogas Modificadoras de la Enfermedad-biológicas (DME-b) en Espondiloartritis Axial (EsPax) mediante el índice LUNDEX y determinar las variables asociadas a la discontinuación de las mismas. Material y métodos: Estudio multicéntrico de corte transversal. Se incluyeron pacientes con EsPax en tratamiento con DME-b. Se registraron variables sociodemográficas, terapéuticas y clínicas. Se consignaron fechas de inicio del tratamiento con DME-b, tratamiento concomitante, suspensión o cambio de tratamiento, y causas de suspensión. La eficacia terapéutica se definió según BASDAI a los 6, 12 meses y luego anualmente a partir del inicio de la DME-b. Se calculó el índice LUNDEX en estos períodos. Análisis estadístico: Estadística descriptiva. Test de Student y test Chi² o test exacto de Fisher. Curvas de Kaplan-Meier y Log-Rank. Análisis de regresión proporcional de Cox. Resultados: Se estudiaron 101 pacientes con EsPax, 80,2% varones, con una edad mediana de 42 años (RIC 35-54,5) y un tiempo mediano de evolución de la enfermedad de 19,3 años (RIC 9,4-28,8). El 26,7% de los pacientes no tenían seguro de salud. Los agentes anti-TNFα utilizados como 1º DME-b en orden de frecuencia fueron: Etanercept (ETN) 44,6%, Adalimumab (ADA) 41,6%, Infliximab 7,9% y Certolizumab 5,9%. En el 32,7% de los casos, la DME-b se administró en combinación con una droga modificadora de enfermedad convencional. La sobrevida media fue de 66,2 meses (IC 95%: 51,8-80,5). Debido a que ETN y ADA se utilizaron en el 85% de los pacientes estudiados, se realizaron comparaciones solamente entre estos agentes. El tiempo medio de supervivencia acumulada fue significaticamente menor para ETN versus ADA (X 53,18±8,8 vs X 74,8±8,9, Log-Rank p=0,02), siendo la causa principal de suspensión, la falta de provisión de la medicación. El tiempo promedio de supervivencia para aquellos que no tenían seguro de salud fue significativamente menor X 31,9 meses (IC 95%: 19-45) con respecto a aquellos pacientes con dicho seguro X 72,3 meses (IC 95%: 55,3-89,3), p=0,03. Luego de ajustar por factores confundidores, la falta de un seguro de salud fue la única variable asociada en forma independiente con menor supervivencia del DME-b (HR 2,54, IC 95%: 1,18-5,75). El LUNDEX global fue del 52,7% a los 6 meses y del 46,9% a los 12 meses. Conclusiones: La sobrevida promedio del 1º DME-b fue de 5,5 años. La falta de cobertura de salud fue la única variable que influyó negativamente en la sobrevida del tratamiento con el 1º DME-b en pacientes con EsPax.

Objectives: To evaluate and compare the efficacy and long-term survival of biological disease-modifying drugs (b-DMARDs) in Axial Spondyloarthritis (axSpA) using the LUNDEX index and to determine the variables associated with the discontinuation of these drugs. Material and methods: Cross-sectional multicenter study. Patients with axSpA in treatment with b-DMARDs were included. Sociodemographic, therapeutic and clinical variables were recorded. The dates of initiation of treatment with b-DMARDs, concomitant treatment, suspension or change of treatment, and causes of suspension were recorded. Therapeutic efficacy was defined according to BASDAI at 6, 12 months and then annually from the initiation of b-DMARDs. The LUNDEX index was calculated in these periods. Statistical analysis: Descriptive statistics. Student's test and Chi² test or Fisher's exact test. Curves of Kaplan-Meier and Log-Rank. Proportional regression analysis of Cox. Results: 101 patients with axSpA were studied, 80.2% men, with a median age of 42 years (IQR 35-54.5) and a median disease duration of 19.3 years (IQR 9.4-28.8). 26.7% of patients didn´t have health insurance. The frequency of the anti-TNFα agent used as 1st b-DMARD was: Etanercept (ETA) 44.6%, Adalimumab (ADA) 41.6%, Infliximab 7.9%, and Certolizumab 5.9%. In 32.7% of the cases, the b-DMARD was administered in combination with a c-DMARD (conventional disease-modifying drug). The mean survival was 66.2 months (95% CI: 51.8-80.5). As ETA and ADA were used in 85% of the patients, comparisons were made only between these two agents. The mean survival time was significantly lower for ETA vs ADA (X 53.18 ±8.8 vs X 74.8±8.9, Log-Rank p=0.02), being the main cause of suspension, the lack of drug provision. The average survival time for those who didn´t have health insurance was significantly lower X 31.9 months (95% CI: 19-45) in comparison to those patients who had health insurance X 72.3 months (95% CI: 55.3-89.3), p=0.03. After adjusting for confounding factors, the lack of health insurance was the only variable independently associated with a lower survival of the b-DMARD (HR 2.54, 95% CI: 1.18 to 5.75). The global LUNDEX was 52.7% at 6 months and 46.9% at 12 months. Conclusions: The average survival of the 1st b-DMARD was 5.5 years. The lack of health insurance was the only variable that negatively influenced the survival of the treatment with the 1st b-DMARD in patients with axSpA.

Prevalencia y características de uveítis como manifestación extraarticular en Espondiloartritis Axial / Prevalence and characteristics of uveitis as an extra-articular manifestation in Axial Spondyloarthritis

Introducción: La Uveítis Anterior Aguda (UAA) es la manifestación extraarticular más frecuente en la Espondiloartritis axial (EsPax), con una prevalencia global de 32,7%. El objetivo de este estudio fue determinar la prevalencia de UAA en una cohorte Argentina de pacientes con EsPax, describir sus características clínicas, frecuencia de episodios, respuesta al tratamiento y pronóstico a largo plazo, así como su asociación con características generales de la enfermedad. Material y métodos: Se realizó un estudio de corte transversal. Se incluyeron pacientes con diagnóstico de EsPax (criterios ASAS 2009) de la cohorte ESPAXIA (Estudio de Espondiloartritis Axial IREP Argentina). Se consignaron datos sociodemográficos, características de la enfermedad y tratamientos recibidos; números de episodios de uveítis, año de aparición, características del mismo, tratamiento realizado y complicaciones. Se registró rigidez matinal, medidas de movilidad axial por Bath Ankylosing Spondylitis Metrological Index (BASMI), número de articulaciones tumefactas, sitios de entesitis por medio de Maastricht AS Enthesitis Score (MASES), eritrosedimentación (ERS), proteína C reactiva (PCR) y presencia de HLA-B27. Se empleó Escala Visual Numérica (EVN) para evaluar el dolor, dolor nocturno, actividad de la enfermedad según el paciente y el médico. Se administraron autocuestionarios: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) y Ankylosing Spondylitis Quality of Life (ASQoL). Se calculó Simplified Ankylosing Spondylitis Disease Activity Score con ERS y PCR (SASDAS ERS/PCR). Análisis estadístico: Estadística descriptiva. Test T de Student, test de Chi² y análisis de regresión logística múltiple. Se consideró significativo un valor de p<0,05. Resultados: Se incluyeron 231 pacientes con EsPax, 174 de sexo masculino (75,3%) con una mediana de edad de 46 años (RIC 36-57) y mediana de tiempo de evolución de la enfermedad de 20,5 años (RIC 10,5-30,5). Sesenta pacientes (26%) presentaron al menos un episodio de uveítis, siendo la primera manifestación de la enfermedad en 22 (37,9%) de ellos. La UAA fue la forma más frecuente, observándose en 59 pacientes (98,3%). El promedio de episodios de UAA fue 4,78 (DS 5,64). Las recurrencias fueron unilaterales en 48,8% de los casos. El tratamiento recibido fue local en 42 (79,2%) de los pacientes. Doce pacientes (22,2%) presentaron secuelas luego del primer episodio, siendo la disminución de la agudeza visual y cataratas las más frecuentes (16,7% y 5,6%, respectivamente). Las variables asociadas independientemente con UAA fueron mayor tiempo de evolución de la enfermedad (24,91±14,2 años vs 20,7±13,2 años, p=0,038) y positividad de HLA-B27, (69% vs 47,4%, p=0,006). Conclusión: La prevalencia de uveítis en nuestra cohorte fue del 26%. Fue significativamente más frecuente en pacientes HLA-B27 (+) y con mayor tiempo de evolución de la enfermedad.

Background: Acute Anterior Uveitis (AAU) is the most frequent extra-articular manifestation in axial Spondyloarthritis (axSpA), with an overall prevalence of 32.7%. The aim of this study was to determine the prevalence of AAU in an Argentinian cohort of patients with axSpA and to describe their clinical characteristics, frequency of episodes, response to treatment and long-term prognosis, as well as their association with general disease characteristics. Methods: A cross-sectional study was carried out. We included patients with axSpA according to ASAS 2009 criteria from ESPAXIA cohort (Estudio de Espondiloartritis Axial IREP Argentina). Sociodemographic data, characteristics of the disease, and treatments received; numbers of episodes of uveitis, incidence date, and its characteristics, treatment and complications were consigned. Morning stiffness, axial mobility (BASMI), enthesitis (MASES), ESR, CRP and HLA-B27 were registered. Pain, night pain, patient and physician global assessment were evaluated by Numerical Visual Scale (NVA). BASDAI, BASFI and ASQoL self-questionnaires were administered. Statistical analysis: Descriptive statistics. Student's T-test, Chi² test and multiple logistic regression analysis. A p value <0.05 was considered significant. Results: Two hundred and thirty one patients with axSpA were included, 174 male (75.3%) with a median age of 46 years (IQR 36-57) and median disease duration of 20.5 years (IQR 10.5-30.5). Sixty patients (26%) had at least one episode of uveitis, being the first manifestation of the disease in 22 (37.9%) of them. Acute anterior uveitis was the most frequent form, and it was observed in 59 patients (98.3%). The mean number of episodes was 4.78 (SD 5.64). Recurrences were unilateral in 48.8% of cases. They received local therapy in 42 (79.2%) of the patients. Twelve patients (22.2%) presented a complication after the first episode, being the decrease in visual acuity and cataracts, the most frequent ones (16.7% and 5.6%, respectively). The presence of uveitis was significantly associated with longer disease duration (24.9 years vs 20.7 years, p=0.038) and with the positivity for HLA-B27, (69% vs 47.4%, p=0.006) and these variables were maintained in the multivariate analysis, after adjusting for other variables. Conclusion: The prevalence of uveitis in our cohort was 26%. It was significantly more frequent in patients HLA-B27 (+) and with longer disease duration.

[Immunosuppressive therapy and fertility preservation: Indications and methods]. / Traitements immunosuppresseurs et préservation de la fertilité : indications et modalités pratiques.

Fertility preservation is routinely performed in cancerology but less systematically used in the field of immune diseases, even though the use of gonadotoxic treatments in young patients may be required and even though the disease itself can alter fertility. This review aimed to clarify the indications and methods of fertility preservation in this context. Cyclophosphamide is the only immunosuppressive drug requiring fertility preservation in women. In men, fertility preservation should be proposed before treatment with cyclophosphamide, methotrexate, mycophenolate mofetil or mTOR inhibitors. Other factors inherent to the disease or the patient may alter fertility. Thus, screening for infertility and fertility preservation have to be implemented as much as possible to increase the chances of successful procreation in patients with immune disease. For women, the choice between the different preservation methods depends on the patient's age, disease activity, the time available before the start of treatment, the possibility of future pregnancy and the woman's and even couple's wishes. Before puberty, the only accepted method is cryopreservation of ovarian tissue. After puberty, the first-line method is the cryopreservation of mature oocytes. If the treatment has to be started in an emergency, if ovarian hyperstimulation/oocyte retrieval is contraindicated or if the patient refuses this option, cryopreservation of ovarian tissue or GnRH agonists could be proposed. For men, the accepted method is sperm cryopreservation. For prepubertal boys, the cryopreservation of spermatogonia after testicular biopsy is still experimental.

Potential Prognostic Value of Handgrip Strength in Older Hospitalized Patients.

OBJECTIVES: Objective measures of physical function are useful prognostic tools also for hospitalized elders. Low handgrip strength is predictive of poor outcomes and it can be assessed also in a sitting position, representing a potential alternative measure in bedridden patients. We evaluated grip strength prognostic value in hospitalized older patients. DESIGN: Prospective cohort study. SETTING: Geriatric, medical ward of an academic medical center in Ferrara, Italy. PARTICIPANTS: Patients aged 65 and older (N = 88) admitted to the hospital for an acute medical condition. MEASUREMENTS: Patients were evaluated for grip strength at hospital admission and were re-evaluated at discharge. After discharge, they were followed every 3 months for 1 year by telephone interviews to assess new hospitalizations and vital status. RESULTS: The mean age of the sample was 77.3 years, 47% were women. At admission, mean height standardized handgrip strength was 15.7±5 kg/m; men had greater strength (p<0.001). There was a direct relationship of admission grip strength with BMI (p<0.05), serum albumin (p=0.07), and Short Physical Performance Battery score (p<0.05), and an inverse relationship with age (gender-adjusted p value <0.01). In multiple regression analysis, after adjustment for possible confounders, patients in third tertile of grip strength had a shorter hospital stay compared to those in the first tertile (ß -2.8; p<0.05). Patients with higher grip strength at discharge also had a lower risk of rehospitalization or death over the follow-up, although the result was not statistically significant (OR: 0.68; 95% CI: 0.30-1.52). CONCLUSION: In older hospitalized medical patients, grip strength assessment might provide useful prognostic information.

Relationship between low levels of high-density lipoprotein cholesterol and dementia in the elderly. The InChianti study.

BACKGROUND: To evaluate the association between plasma lipid fractions and the prevalence of dementia in a large sample of Italian older individuals. METHODS: A total of 1051 older community-dwelling individuals (age >/=65 years), enrolled in the InChianti study, were included. Diagnosis of dementia was established at baseline and at the 3-year follow-up using Diagnostic and Statistical Manual of Mental Disorder (Fourth Edition) criteria. Plasma lipids were measured by standardized methods at baseline and after 3 years. RESULTS: At baseline, 61 individuals (5.8%) were affected by dementia. Demented individuals showed significantly lower total cholesterol (TC), nonhigh-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels compared with controls; no differences were found in triglycerides (TG) and lipoprotein (a) levels. Of the 819 subjects reevaluated at the 3-year follow-up, 81 (9.9%) received a new diagnosis of dementia. Again, demented subjects were characterized by significantly lower TC, non-HDL-C, and HDL-C levels compared with controls, thus confirming the baseline findings. At multivariate logistic regression analysis, HDL-C levels (odds ratio: 0.96, 95% confidence interval: 0.93-0.99), but not TG and non-HDL-C, were associated with dementia independent of important confounders including age, gender, apo E phenotype, stroke, weight loss, interleukin 6 levels, and ankle-brachial index. CONCLUSIONS: Among community-dwelling older people, individuals affected by dementia showed significantly lower TC, non-HDL-C, and HDL-C levels; however, at multivariate analysis, only HDL-C was associated with dementia. Our results suggest the existence of an independent relationship between dementia and low HDL-C levels.

The role of polyunsaturated fatty acids (PUFA) in the treatment of dyslipidemias.

Polyunsaturated fatty acids (PUFA) are a family of lipids including some subgroups identified by the position of the last double bond in their structure. PUFA n-3 include alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), while PUFA n-6 include linoleic acid (LA) and arachidonic acid (AA). Since PUFA n-3 consumption has been shown to be inversely correlated with coronary heart diseases (CHD) incidence, clinical trials have been principally conducted by administering fish oil supplements or purified PUFA n-3. The relationship between dietary PUFA n-3 and CHD is believed to be only partially mediated by their effects on plasma lipoprotein profile. PUFA n-3 have shown to reduce only slightly total and LDL cholesterol, probably as they crowd saturated fatty acids out of diet. Data on HDL cholesterol suggest that PUFA n-3 produce only a small increase in this fraction. The effect of PUFA n-3 supplementation on plasma triglycerides (TG) is much more important, with a reduction of about 25% in normolipidemic subjects and about 50% in hypertriglyceridemic patients. This effect seems to be mediated by an inhibition of hormone-sensitive lipase, and VLDL secretion, and an increase in apo B liver degradation. They also increase lipoprotein lipase activity resulting in a reduction of post-prandial TG. PUFA n-3 might be used as second line therapy, additional or alternative to fibrates and nicotinic acid, in the treatment of severe hypertriglyceridemia. Furthermore, the addition of PUFA n-3 to statin therapy might contribute to normalize TG levels in patients with combined hyperlipidemia.

Markers of endothelial dysfunction in older subjects with late onset Alzheimer's disease or vascular dementia.

A consistent amount of evidence suggests that vascular factors might be involved in the pathogenesis of late onset Alzheimer's disease (LOAD). We evaluated the presence of endothelial dysfunction by measuring the plasma levels of soluble E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in a sample of patients affected by LOAD (n. 60) or vascular dementia (VD: n. 80). They were compared with a sample of older patients with cerebrovascular disease but not-dementia (CDND: n. 40), and with a sample of healthy older controls (n. 30). sVCAM-1 plasma levels were higher in LOAD and VD compared with controls. Among patients (LOAD, VD, and CDND), sE-selectin levels were higher in individuals with most severe cerebrovascular disease on CT scan. At multivariate regression analysis, fasting glucose (p<0.05) and TNF-alpha levels (p<0.02) were positively correlated with sE-selectin levels (adjusted r(2): 20%), while sVCAM-1 was positively correlated with age (p<0.01), and alcohol consumption (p: 0.03), and negatively associated with HDL-C levels (p: 0.005), (p<0.01; adjusted r(2): 44%), independent of possible confounders. Increased sVCAM-1 plasma levels in LOAD and VD suggest the existence of endothelial dysfunction in both types of dementia. The possible role of E-selectin in the pathogenesis of cerebrovascular disease is also supported by our data.

Ki-67 expression in anal intraepithelial neoplasia in AIDS.

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of histological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 +/- 10.99; in group 2 (area A) it was 46.73 +/- 10.409; and in area B it was 36.43 +/- 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

High-density epicardial mapping during current injection and ventricular activation in rat hearts.

The purpose of this study is to report new methods for manufacturing precision electrode arrays for recording high-resolution potential distributions from epicardial surfaces of small-animal hearts. Electrode arrays of 64 leads (8 x 8) and 121 leads (11 x 11) were constructed with a tulle substrate to which insulated, fine silver wires (60-micrometer diameter) were attached by knots at mesh node intervals of 540 x 720 micrometers. Insulation was removed at the tips of the knots. Potential distributions and waveforms were recorded from saline solutions and rat heart epicardium during ventricular paced beats and during passive current injection in the diastolic interval. Electrical responses obtained from rat epicardium compared favorably with those observed in studies of larger-animal hearts, which used arrays having greater electrode spacing, and revealed the effects of myocardial anisotropy. Epicardial potentials measured early after stimulation in the region surrounding the pacing site were interpreted in terms of potentials generated by an equivalent quadrupolar source. We conclude that electrode arrays for epicardial mapping of small hearts can be constructed with sufficient ease and precision to allow detailed study of fiber structure and electrophysiology in these hearts in normal and pathological conditions.

Imunidade anti-rábica contra amostras de vírus de rua / Immunity against rabies street virus isolates

Avaliou-se a imunidade anti-rábica em camundongos e cobaias imunizados com vacina inativada tipo Fuenzalida & Palacios e modificada, amostra SAD (Street Alabama Dufferin). A imunidade foi testada pelo emprego de seis amostras de vírus isoladas de procedência humana, canina, bovina, eqüina, suína, e do morcego hematófago Desmodus rotundus (E. Geoffroy, 1810) em Minas Gerais de 1993 a 1995. A multiplicaçäo e titulaçäo dos vírus de rua e dos fixos CVS-24 (Challenge Vírus Standard) e DR-19 (Desmodus rotundus) foram realizados em camundongos de 21 dias de idade. Utilizaram-se os testes de Habel e Koprowski, recomendados pela OMS, para testar o grau de proteçäo conferido pelas vacinas, diante do desafio com as amostras de vírus rábico de rua e fixo. As vacinas avaliadas conferiram proteçäo de 70 por cento e 100 por cento de acordo com as amostras de vírus empregadas no desafio

Immunocytological localization by monoclonal antibodies of alpha-latrotoxin in the venom gland of the spider Latrodectus tredecimguttatus.

Monoclonal antibodies, raised against alpha-latrotoxin, have been used on serial sections of the venom glands with localization by indirect immunofluorescence. Colloidal gold immunovisualization and electron microscopy were used in order to localize the structure of the cells that synthesize and store the toxin. The antibodies were able to recognize the native toxin revealing its presence mainly in the 'replacement cell' layer, a layer of cells close to the muscular sheath of the gland. These cells apparently replace the disintegrated epithelial cells at the end of the holocrine cycle. Gold grains were predominantly observed around the free ribosomes and the secretion droplets of the 'replacement cells'.

Characterization and some properties of the venom gland extract of a theridiid spider (Steatoda paykulliana) frequently mistaken for black widow spider (Latrodectus tredecimguttatus).

The simplified purification protocol established for the isolation of alpha-latrotoxin from the venom of the spider Latrodectus tredecimguttatus, has been employed for the purification of toxic components present in the venom of the spider Steatoda paykulliana. The venom of this spider, frequently mistaken for L. tredecimguttatus, is by tradition considered to cause an envenomation potentially dangerous to man. The venom of S. paykulliana has little toxic effect on guinea-pigs but is extremely toxic to houseflies (Musca domestica). No proteolytic activity was detectable. Interaction of microgram/ml amounts of the venom extract with artificial lipid membranes produces an increase of membrane conductance through the formation of stable ion-permeable channels modulated by the direction and size of the electric potential differences across the membrane. Higher concentrations of this venom are able to stimulate the release of transmitters from neurosecretory cells in a fashion reminiscent of black widow spider venom. Antibodies against the whole L. tredecimguttatus venom gave a few positive cross-reactions in the immunodiffusion test with S. paykulliana venom gland extract indicating the presence of common molecular sequences in the two venoms. Polyclonal antibodies against alpha-latrotoxin did not cross-react in the immunodiffusion test with S. paykulliana venom extracts, nor in the immunofluorescence assay with its cephalothorax sections, thus suggesting that the venom glands do not contain alpha-latrotoxin. A partial characterization of S. paykulliana venom has been performed and a high molecular weight protein toxic to houseflies has been partially purified.

Miopatia miotubular: estudo clinico, etrophysiological and histological study so. / Myotubular myopathy: clinical,elecof a case

Sao apresentados os resultados dos exames clinicos, eletrofisiologicos e do estudo do ponto motor, da imunofluorescencia, da histoquimica e da ultramicroscopia da biopsia muscular de um caso de miopatia miotubular. Sao discutidos estes resultados em relacao aos achados de 56 casos desta molestia consignados na literatura ate 1978, sendo cada enfase a etiopatogenia

[McArdle's disease: a case report]. / Doença de McArdle: registro de caso.

This disease was described by McArdle as an inherited autosomal recessive affection characterized by glycogen storage with normal chain in the skeletal muscles, due to absence of myophosphorylase activity. Under a clinical aspect, excessive fatigability, cramps and myoglobinuria appear following physical exercise. A case of this disease in a 36-year-old male patient is reported. Failure of elevation of venous blood lactate after physical effort under anaerobic conditions, as well as muscle histochemistry, made diagnosis confirmation possible. The authors comment on the differential diagnosis between McArdle's disease and the other causes of myoglobinuria, specially phosphofructokinase and carnitine-palmityl-transferase deficiency.