Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain).

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population. OBJECTIVE: We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing. MATERIAL AND METHODS: Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307 651, of whom 96 544 (31.4%) were aged ≥ 65 years. RESULTS: We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases. CONCLUSION: The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.

Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain). / Epidemiología de la miastenia gravis en la provincia de Ourense (Galicia, noroeste de España).

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population. OBJECTIVE: We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing. MATERIAL AND METHODS: Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307,651, of whom 96,544 (31.4%) were aged ≥ 65 years. RESULTS: We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases. CONCLUSION: The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.

Ventilación diferencial en patología pulmonar bilateral con distinta fisiopatología / Differential ventilation in bilateral pulmonary pathology with different physiopathology

En este caso clínico presentamos un paciente con diagnóstico de Enfermedad Pulmonar Obstructiva Crónica internado en paro respiratorio secundario a neumotórax derecho espontáneo hipertensivo. Ante hipoxemia refractaria por persistencia de neumotórax derecho, con fístula broncopleural, eventos repetidos de atelectasia izquierda con dificultades para resolver mediante ventilación convencional, fibroncoscopia y kinesioterapia, se decide aplicar ventilación pulmonar diferencial (VPD). La VPD fue aplicada con dos ventiladores no sincronizados y PEEP diferencial. El destete fue progresivo, volviendo a modos convencionales con tubo un lumen y traqueostomia. Se realizó extubación exitosa, egresando de la Terapia Intensiva al día 33 del ingreso y del hospital al día 48. En el seguimiento a 7 meses recuperó su capacidad funcional previa y se reintegró a sus tareas laborales habituales. La VPD puede ser útil en pacientes seleccionados cuando la ventilación convencional no obtiene una respuesta adecuada en el adecuado sostenimiento de la ventilación pulmonar.(AU)

Could ivermectin have a synergic effect with albendazole in hydatidosis therapy?

The efficacy of a combination of ivermectin (IVM) and albendazole (ABZ) used as a chemoprophylactic treatment and as treatment of secondary hydatidosis is described for the first time. IVM treatment alone was not effective against Echinococcus granulosus, either when the protoscolices were recently inoculated or when they had developed to the metacestode stage. However, the efficacy of IVM and ABZ when used in combination as a prophylactic treatment was 95.72% and 87% with respect to the number and the wet weight of cysts, respectively. These results were higher than in the treatment of secondary hydatidosis, which were 44.8% and 45.26%, respectively. The ultrastructural changes in the germinal layer of the cysts after the treatments are also described.

Could ivermectin have a synergic effect with albendazole in hydatidosis therapy?

The efficacy of ivermectin (IVM) alone, albendazole (ABZ) alone and a combination of both (IVM + ABZ) against Echinococcus granulosus protoscolices was studied by means of in vitro incubation. The maximum protoscolicidal effect was detected when we used IVM+ABZ in combination. In this case, protoscolex viability dropped to 35% in comparison with 50% for IVM alone and 82.5% with ABZ alone 18 days post-incubation. Only the protoscolices incubated with IVM + ABZ did not develop into cysts following their inoculation into mice. The changes in ultrastructure induced in the protoscolices after the different drug incubations are also described. The incubation of cysts with IVM and IVM + ABZ shows that IVM + ABZ in combination is more effective than IVM alone as only when we incubated the cysts with IVM + ABZ did they completely lose their infectivity to mice. This occurred after only 10 days post-incubation. Cellular alterations were also more marked with IVM+ABZ incubations with: (1) the presence of residual bodies, (2) numerous lipids droplets and (3) vacuoles in the cytoplasm of cytons. However, the truncated microtriches and the nuclei remained unaltered after 10 days.

Relationship between the efficacy of praziquantel treatment and the cystic differentiation in vivo of Echinococcus granulosus metacestode.

The cyst differentiation of protoscolices inoculated in NMRI mice was studied in detail. Although the laminated layer began its formation at 21 days post-infection (p.i.), we could not identify this structure in all parasites until 34 days p.i.. At 34 days p.i., all protoscolices were transformed into the metacestode stage. Subsequently, the efficacy of praziquantel (PZ) was studied in different stages of development of the parasite. We have found a different PZ susceptibility in both earlier stages and well-developed cyst. PZ treatment exhibited a high efficacy at the beginning of cyst differentiation and a zero efficacy in the mature metacestode when the cystic layers were totally developed. The relationship between the tegumental ultrastructural changes occurring during the vesicular evolution of protoscolices in NMRI mice and the efficacy of PZ treatment is discussed in the present study.

Combined praziquantel and albendazole chemoprophylaxis in experimental hydatidosis.

The results of the chemoprophylaxis of experimental hydatidosis with a combination of praziquantel and albendazole are presented. In vivo studies were performed on NMRI mice injected with protoscolices of Echinococcus granulosus. The treatment was the same as that previously used by us, but reducing the treatment period to only 1 month. Four months after injection , the mice were killed and autopsied. Developed hydatid cysts were counted, weighed and processed for observation by transmission electron microscopy. The efficacy of the present treatment was 97.7% and 97.15%, in number and weight of the cysts respectively, only slightly lower than that obtained by us after 4 months of treatment. Moreover, the few cysts that had developed in the treated mice showed severe damage to their ultrastructure.

Chemoprophylactic praziquantel treatment in experimental hydatidosis.

In the present study, new data on the chemoprophylactic treatment of experimental hydatid disease with praziquantel are presented. In vivo studies have been performed reducing the treatment to 1 and 2 months. NMRI female mice inoculated with protoscolices of Echinococcus granulosus were treated with praziquantel 48 h p.i. at a dose of 600 mg/kg, 5 days a week for 1 or 2 months. After 4 months p.i. the animals were killed, and the cysts obtained were counted, weighed and processed for observations by means of transmission electron microscopy. Both wet weight and number of hyaline cysts found in treated mice were significantly lower than those found in control groups in both experiments (1 and 2 months of treatment), obtaining a high efficacy in all cases. Moreover, severe ultrastructural damage in the treated cysts was seen compared to the control cysts. The reduction in treatment time lays the basis for an important advance in the control and prevention of hydatidosis.

Praziquantel and albendazole in the combined treatment of experimental hydatid disease.

The combination of praziquantel and albendazole (PZ + ABZ) used in the present study demonstrated an efficacy of 100% when used as chemoprophylactic treatment because no viable hydatid cysts developed after mice had been injected with protoscolices. However, when the PZ + ABZ combination was used for the treatment of 4-month secondary experimental hydatidosis, no significant difference was found between the control and treated mice, although severe damage to the cyst ultrastructure of the treated mice was observed.

In vitro effect of praziquantel and albendazole combination therapy on the larval stage of Echinococcus granulosus.

Protoscolices of Echinococcus granulosus were incubated in vitro with praziquantel (PZ), albendazole (ABZ), or a combination of both (PZ + ABZ). PZ and ABZ displayed slower protoscolicidal activity when applied separately than when used in combination. Despite the low PZ + ABZ concentrations used, protoscolex viability dropped rapidly (within 15 days). At this time, cysts did not develop following their inoculation into mice. The ultrastructural changes induced in the protoscolices by PZ + ABZ were (a) the loss of sucker concavity, (b tegumental contraction of the soma region, (c) the formation of digitiform tegumental extensions, (d) destruction of the tegument, and (e) the degeneration of parenchyma cells as reflected by the presence of numerous lamellar bodies. The PZ + ABZ treatment was effective only against small cysts, which had collapsed at 10 days postinoculation (p.i.). This treatment caused the following alterations: (a) loss of cyst turgidity at 6 days p.i.; (b) separation of the laminated and germinal layers; (c) loss of microtriches; (d) the appearance of numerous lipid droplets in the inner region of the germinal layer, (e) vacuolation of the cyton cytoplasm; and (f) the formation of abundant autophagosomes, which finally led to loss of the integrity of the germinal layer.

Echinococcus granulosus: praziquantel treatment against the metacestode stage.

The efficacy of praziquantel against the metacestode of Echinococcus granulosus was studied by means of in vitro incubations or in vivo experiments. The results of in vitro incubations indicated that the effectiveness of praziquantel was higher when the parasite material comprised cysts from cyst masses than in the case of intact cysts that retained their adventitial layer. Ultrastructural alterations in the germinal layer of collapsed cysts incubated in vitro were detected. The results obtained in mice after 4 months of treatment demonstrated no significant difference between the control and treated groups with regard to the number and wet weight of developed cysts. However, ultrastructural alterations were detected in the cyst tissue that were similar to those described in the in vitro experiment. In contrast, the effect of chemoprophylaxis on the number and the wet weight of developed cysts was extremely significant as compared with the control value, the efficacy being 99.41% and 98.32%, respectively. Moreover, ultrastructural observations of the cyst tissue revealed loss of its integrity, and no intact cyton was observed in the germinal layer of the developed cyst.

[Post-operative care for heart transplant patients. Review of the last 2 years]. / Atención postoperatoria en UCI al paciente con trasplante cardíaco. Revisión de los dos últimos años.

The quality of the nursing care affects greatly the success of the heart transplant. This is the reason why we considered of great interest to review the care planning established in the ICU of the University Clinic for these patients and to assess the incidence of complications detected during the immediate post-operatory. On the whole, the care planning is similar to the one used with patients who undergo heart surgery under extracorporal circulation, emphasizing the surveillance and maintainance of heart function, administering of immunosuppression drugs, prophylaxis of the infection and psychological care. 29 patients with an average age of 58.6 years who underwent heart transplant were studied retrospectively. The collection of data was performed using nursing and clinical records, which allowed us to analyse the evolution of the different corporal functions such as respiratory, cardiovascular, etc., and those aspects related to rejection, infection, welfare and comfort. Observing the results obtained, the incidence of complications was low. Evolution of heart function was correct in 96% of cases, there were no clinical signs of pulmonar, urinal, or vascular catheters infection in any cases. Psychic alterations and sleeping disorders were recorded in 24% of patients. We conclude that the care planning, although it could be improved, can be considered adequate.

In vivo effect of oral albendazole and albendazole sulphoxide on development of secondary echinococcosis in mice.

This paper describes the effectiveness of ABZ, ABZ.SO and ABZ + ABZ.SO treatment in mice infected with Echinococcus granulosus protoscoleces. The results were evaluated in two ways: measuring the number and wet weight of developed cysts and by transmission electron microscopy (TEM) of tissue cyss. ABZ and ABZ + ABZ.SO had an important effect upon larval growth in E. granulosus. The ultrastructural changes noted were: vacuolation of tegumentary cells of the germinal membrane; increased number of mitochondria; increased number of autophagosomes and an increase in lipid deposits.

Development of chemotherapeutic model for the in vitro screening of drugs against Echinoccus granulosus cysts: the effects of an albendazole-albendazole sulphoxide combination.

This paper describes a novel experimental model for the screening of putative drugs against the metacestode stage of E. granulosus using hydatid cysts derived from in vitro culture of protoscoleces. The effects of an ABZ+ABZ.SO combination against cultured and murine cysts were studied with this in vitro model system. This treatment produced loss of turgidity of the cultured cysts in less time than in the murine cysts but the ultrastructural tissue damage observed in both cultured and murine cysts was similar. The ultrastructural changes induced by ABZ+ABZ.SO were: (i) vacuolation of the distal cytoplasm that extended to the tegumentary cells of the germinal membrane; (ii) increased number of mitochondria; (iii) partial loss of microtriches; (iv) increased number of autophagosomes; and (v) an increase in lipid deposits.

The effects of albendazole and albendazole sulphoxide combination-therapy on Echinococcus granulosus in vitro.

Protoscoleces of Echinococcus granulosus were incubated in vitro with decreasing concentrations of either albendazole (ABZ) or albendazole sulphoxide (ABZ.SO) (50, 10, 1 and 0.1 micrograms ml-1), and in combination. Viability was assessed by the methylene blue exclusion test and establishment of infection in mice. Protoscolex ultrastructure was determined by means of transmission and scanning electron microscopy. ABZ and ABZ.SO, when used separately had protoscolicidal activity after a longer incubation period (30 days) than when used as combined compounds. When incubated in the presence of ABZ + ABZ.SO, protoscolex viability dropped rapidly. That is, protoscoleces were all non-viable at 12 days of exposure, with no cyst developing following their inoculation into mice. The ultrastructural changes induced by ABZ or ABZ.SO alone, were: (a) rostellar disorganization, (b) formation of numerous blebs on the tegument, (c) loss of the microtriches, (d) increased vesiculation within the tegumentary cytons together, (e) an increase in lipid deposits and (f) depletion of glycogen reserves. After incubation with combined ABZ and ABZ.SO the tegument contained numerous blebs which became detached, leaving debris only, some intact nuclei being discernible in the protoscolex parenchyma.

Development of truncated microtriches in Echinococcus granulosus protoscolices.

The development of truncated microtriches in the somatic region of both (a) protoscolices incubated in vitro with two different drugs, i.e. ivermectin or a combination of albendazole and albendazole sulphoxide, and (b) protoscolices removed from hydatid cysts in humans treated with albendazole for 1.5 months is described. Our findings seem to indicate that the development of microtriches is either an indirect effect of treatment with anthelmintics or a possible response to other, as yet unidentified, adverse conditions.

Randomised controlled trial of efficacy of albendazole in intra-abdominal hydatid disease.

The efficacy of albendazole in hydatid disease is still unclear, because there has been no study that assessed the status of the parasite after treatment. The significance of albendazole-induced echographic changes in the cyst therefore cannot be judged. We did a prospective, controlled, randomised, open study of albendazole in patients with liver hydatid disease, and assessed parasite viability after treatment. 18 patients received no albendazole treatment (controls), 18 received albendazole (10 mg/kg daily) for 1 month (group A), and 19 received the drug for about 3 months (group B). Echography was done before and during treatment; all patients underwent surgery on completion. Parasite (protoscolex viability and development of cysts in mice) and ultrastructure studies were done for all cysts removed. 8 (50%) of cysts in the control group, 13 (72%) in group A, and 16 (94%) in group B were non-viable (p = 0.015). Protoscolex and cyst viability were significantly (p = 0.039 and p = 0.018, respectively) lower in treated patients than in controls. Treatment was also significantly associated with total cyst membrane disintegration. 68% of cysts treated for 3 months showed echographic changes, and only 1 of 20 cysts showing echographic changes during treatment was judged viable. The efficacy of albendazole at a dose of 10 mg/kg daily for 3 months suggests that it is a suitable alternative to surgery in uncomplicated hydatid liver disease, as initial treatment.

Viability of Echinococcus granulosus cysts in mice following cultivation in vitro.

The viability of hydatid cysts developed in vitro for 90 days was assessed by implantation into mice. Cysts removed from mice at 270 days post-infection (p.i.) increased their size 13.5-fold and contained several brood capsules containing protoscoleces. Thus, cysts remain viable after prolonged in vitro culture. The implantation in mice of 15 cysts developed in vitro yielded an average of 10 cysts per mouse, which is indicative of a high survival rate in these experimental infections. The ultrastructural study of cysts recovered from mice 270 days p.i. showed that the germinal membrane was more compact than before implantation and several layers of tegumental cells had developed. Observations of cysts removed from mice indicated that the plasma membrane surrounding microtriches had prolongations opening into the laminated layer.