Cost-Analysis of Subcutaneous vs Intravenous Administration of Natalizumab Based on Patient Care Pathway in Multiple Sclerosis in Spain.

INTRODUCTION: A subcutaneous (SC) formulation of natalizumab has been recently authorised for multiple sclerosis patients. This study aimed to assess the implications of the new SC formulation, and to compare the annual treatment costs of SC versus intravenous (IV) natalizumab therapy from both the Spanish healthcare system (direct health cost) and the patient (indirect cost) perspectives. METHODS: A patient care pathway map and a cost-minimisation analysis were developed to estimate SC and IV natalizumab annual costs over a 2-year time horizon. Considering the patient care pathway and according to natalizumab experience (IV) or estimation (SC), a national expert panel involving neurologists, pharmacists, and nurses provided information/data regarding resource consumption for drug and patient preparation, administration, and documentation. One hour of observation was applied to the first six (SC) or 12 (IV) doses, and 5 min for successive doses. The Day hospital (infusion suite) facilities at a reference hospital were considered for IV administrations and the first six SC injections. For successive SC injections, either a reference hospital or regional hospital in a consulting room was considered. Productivity time associated with travel (56 min to reference hospital, 24 min to regional hospital) and waiting time pre- and post-treatment (SC 15 min, IV 25 min) were assessed for patients and caregivers (accompanying 20% of SC and 35% of IV administrations). National salaries for healthcare professionals were used for cost estimation (€, year 2021). RESULTS: At years 1 and 2, total time and cost savings (excluding drug acquisition cost) per patient, driven by saving on administration and patient and caregiver productivity for SC at a reference hospital versus IV at a reference hospital, were 116 h (a reduction of 54.6%) and €3682.82 (a reduction of 66.2%). In the case of natalizumab SC at a regional hospital, the total time and cost saving were 129 h (a reduction of 60.6%) and €3883.47 (a reduction of 69.8%). CONCLUSIONS: Besides the potential benefits of convenient administration and improving work-life balance, as suggested by the expert panel, natalizumab SC was associated with cost savings for the healthcare system by avoiding drug preparation, reducing administration time, and freeing up infusion suite capacity. Additional cost savings could be derived with regional hospital administration of natalizumab SC by reducing productivity loss.

Epidemiological behavior and current forecast of syphilis in Mexico: increase in male population.

OBJECTIVES: Even when new cases of syphilis are notifiable since 1944, the Mexican National Epidemiological Surveillance System lacks information on the changes of the rate of case reports considering the geographic and demographic variables. Therefore, it is necessary to have evidence, with particular attention to the study of the epidemiological behavior by the identification of risk factors and groups. The objective of this study was to analyze the epidemiology, geographical distribution, and forecast of syphilis in Mexico. STUDY DESIGN: The design of the study was a secondary research of epidemiological databases. METHODS: A retrospective analysis of the national surveillance data (2007-2017) of acquired and congenital syphilis (CS) issued by the General Directorate of Epidemiology was performed. RESULTS: Of all cases, 34,998 and 1030 cases were reported for acquired syphilis (AS) and CS , respectively, reflecting an increasing trend in the whole country for both diseases. Cases and incidence of AS per year showed that, male gender presented an increase in reproductive age. Distribution of the rate of case reports is mostly commanded by the states in the extreme north (Gulf of California and northern Gulf of Mexico) and south (Gulf of southern Mexico and the Caribbean Sea). Likewise, the Seasonal Autoregressive Integrated Moving Average model was selected as the best-fit model for the forecast analysis. This model was used to forecast AS cases during 2018-2019. AS may have a slight fluctuation (on the rise) during the following 24 months. CONCLUSIONS: These findings underscore the importance of intensifying, as well as expanding screening and treatment in adult population, including men, who are not routinely benefiting from maternal and reproductive service-based syphilis screening and treatment.

Leiomyosarcoma of the breast in a 48-year old male

@#<p style="text-align: justify;">This is a case of a 48-year old male with left-sided 9.0cm x 8.0cm exophytic, foul-smelling, bleeding breast mass. Core needle biopsy revealed a malignant phylloides tumor. He underwent total mastectomy and final histopathology showed a primary breast leiomyosarcoma staining positive for smooth muscle actin. A review of cases of primary breast leiomyosarcoma was done and to date, there are only 70 documented. The treatment of breast sarcomas still follows those strategies for soft tissue sarcomas in other locations. An important prognosticating factor is complete resection on initial treatment. Lymph node metastasis is rare for sarcomas in general.</p><p style="text-align: justify;"> </p>

Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1ß, IL-12p70 and IL-10 in human macrophages.

Interconversion algorithm between mechanical and dielectric relaxation measurements for acetate of cis- and trans-2-phenyl-5-hydroxymethyl-1,3-dioxane.

The dielectric and mechanical spectroscopies of acetate of cis- and trans-2-phenyl-5-hydroxymethyl-1,3-dioxane are reported in the frequency domain from 10(-2) to 10(6)Hz. This ester has been selected in this study for its predominant α relaxation with regard to the ß relaxation, which can be neglected. This study consists of determining an interconversion algorithm between dielectric and mechanical measurements, given by using a relation between rotational and translational complex viscosities. These important viscosities were obtained from measures of the dielectric complex permittivity and by dynamic mechanical analysis, respectively. The definitions of rotational and translational viscosities were evaluated by means of fractional calculus, by using the fit parameters of the Havriliak-Negami empirical model obtained in the dielectric and mechanical characterization of the α relaxation. This interconversion algorithm is a generalization of the break of the Stokes-Einstein-Debye relationship. It uses a power law with an exponent defined as the shape factor, which modifies the translational viscosity. Two others factors are introduced for the interconversion, a shift factor, which displaces the translational viscosity in the frequency domain, and a scale factor, which makes equal values of the two viscosities. In this paper, the shape factor has been identified as the relation between the slopes of the moduli of the complex viscosities at higher frequency. This is interpreted as the degree of kinetic coupling between the molecular rotation and translational movements. Alternatively, another interconversion algorithm has been expressed by means of dielectric and mechanical moduli.

Leishmania mexicana lipophosphoglycan activates ERK and p38 MAP kinase and induces production of proinflammatory cytokines in human macrophages through TLR2 and TLR4.

Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. Leishmania promastigotes primarily infect macrophages in the host, where they transform into amastigotes and multiply. Lipophosphoglycan (LPG), the most abundant surface molecule of the parasite, is a virulence determinant that regulates the host immune response. Promastigotes are able to modulate this effect through LPG, creating a favourable environment for parasite survival, although the mechanisms underlying this modulation remain unknown. We analysed the participation of TLR2 and TLR4 in the production of cytokines and explored the possible phosphorylation of ERK and/or p38 MAP kinase signalling cascades in human macrophages stimulated with Leishmania mexicana LPG. The results show that LPG induced the production of TNF-α, IL-1ß, IL-12p40, IL-12p70 and IL-10 and led to phosphorylation of ERK and p38 MAP kinase. Specific inhibitors of ERK or p38 MAP kinases and mAbs against TLR2 and TLR4 reduced cytokine production and phosphorylation of both kinases. Our results suggest that L. mexicana LPG binds TLR2 and TLR4 receptors in human macrophages, leading to ERK and MAP kinase phosphorylation and production of pro-inflammatory cytokines.

Cribado de retinopatía diabética y teleoftalmología / Diabetic retinopathy screening and teleophthalmology

Objetivo: Conocer la prevalencia de retinopatía diabética (RD) y evaluar nuestra experiencia en cribado RD en un estudio llevado a cabo entre el Servicio de Oftalmología del Hospital General Universitario de Alicante y el Departamento 19 de Atención Primaria de Alicante mediante la utilización de retinografías con cámara no midriática y telemedicina. Métodos: Estudio descriptivo transversal de 2.435 pacientes diabéticos desde el 1 de febrero de 2006 hasta el 1 de febrero de 2009, obteniéndose tres retinografías de 45° en ambos ojos de cada pacientes mediante cámara no midriática que son enviadas al Servicio de Oftalmología por la intranet del Hospital, donde son valoradas por dos oftalmólogos expertos en retina que emiten un informe individualizado de cada paciente. Resultados: La prevalencia de retinopatía diabética fue del 17,90%. De ellos un 80,73% presentaban RD no proliferativa leve y moderada, y un 12,16% RD no proliferativa severa y 2,29% RD proliferativa y 4,82% maculopatía diabética asociada a algún grado de retinopatía. En 41 pacientes (1,69%) las retinografías obtenidas no fueron valorables. Conclusiones: Destacamos las ventajas de la teleoftalmología en el cribado de pacientes diabéticos al permitir un diagnóstico y tratamiento precoces, y mejorar el circuito de comunicación entre atención primaria y especializada(AU)

Objective: To determine the prevalence of diabetic retinopathy (DR) and evaluate our experience in DR screening in a study carried out between the Ophthalmology Department of the University General Hospital of Alicante and Department 19 Primary Care of Alicante by using a non-retinal mydriatic camera and telemedicine. Material and methods: A descriptive, cross-sectional study was conducted on 2,435 diabetic patients from 1 February 2006 to 1 February 2009. Three 45° retinographies of both eyes of each patient were obtained and sent to the Department of Ophthalmology via the hospital intranet. These were then evaluated by 2 ophthalmologists, experts in the retina, with each issuing an individualized report for each patient. Results: The prevalence of DR was 17.90%, with 80.73% of them having mild-moderate proliferative DR, 12.16% severe non-proliferative DR, 2.29% proliferative DR, and 4.82% with diabetic maculopathy associated with any level of retinopathy. The retinographies were considered low quality in 41 patients (1.69%). Conclusions: We highlight the benefits of the tele-ophthalmology in screening diabetic patients to enable early diagnosis and treatment, and improving the circuit of communication between primary and specialist care(AU)

[Diabetic retinopathy screening and teleophthalmology]. / Cribado de retinopatía diabética y teleoftalmología.

OBJECTIVE: To determine the prevalence of diabetic retinopathy (DR) and evaluate our experience in DR screening in a study carried out between the Ophthalmology Department of the University General Hospital of Alicante and Department 19 Primary Care of Alicante by using a non-retinal mydriatic camera and telemedicine. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted on 2,435 diabetic patients from 1 February 2006 to 1 February 2009. Three 45° retinographies of both eyes of each patient were obtained and sent to the Department of Ophthalmology via the hospital intranet. These were then evaluated by 2 ophthalmologists, experts in the retina, with each issuing an individualized report for each patient. RESULTS: The prevalence of DR was 17.90%, with 80.73% of them having mild-moderate proliferative DR, 12.16% severe non-proliferative DR, 2.29% proliferative DR, and 4.82% with diabetic maculopathy associated with any level of retinopathy. The retinographies were considered low quality in 41 patients (1.69%). CONCLUSIONS: We highlight the benefits of the tele-ophthalmology in screening diabetic patients to enable early diagnosis and treatment, and improving the circuit of communication between primary and specialist care.

Cytokine expression by macrophages in the lung of pigs infected with the porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome (PRRS) is caused by a virus that predominantly replicates in alveolar macrophages. The aim of the present study was to characterize the production of cytokines by subpopulations of pulmonary macrophages in pigs infected by the PRRS virus (PRRSV). Expression of interleukin (IL) 1alpha, IL-6 and tumour necrosis factor (TNF)-alpha correlated with the severity of pulmonary pathology and the numbers of pulmonary macrophages. Significant correlations were observed between PRRSV infection and the expression of IL-10, between the expression of IL-12p40 and interferon (IFN)-gamma, and between the expression of TNF-alpha and IFN-gamma. These findings suggest that PRRSV modulates the immune response by the up-regulation of IL-10, which may in turn reduce expression of cytokines involved in viral clearance (e.g. IFN-alpha, IFN-gamma, IL-12p40 and TNF-alpha). The results also suggest that expression of IFN-gamma is stimulated by IL-12p40 and TNF-alpha, but not by IFN-alpha. All of these cytokines were expressed mainly by septal macrophages with weaker expression by alveolar macrophages, lymphocytes and neutrophils. There appears to be differential activation of septal and alveolar macrophages in PRRSV infection, with septal macrophages being the major source of cytokines.

Expression of steroid receptors and calponin in a cervical leiomyoma in a young pig.

Thickening of the uterine cervix and bilateral ovarian cystic change was identified in a 6-month-old pig during routine abattoir inspection. Microscopically, the cervical lesion comprised a non-encapsulated mass of densely packed, large and monomorphic spindle cells within the myometrium. Immunohistochemically, the majority of these neoplastic cells expressed the cytoplasmic terminal smooth muscle differentiation marker calponin, the nuclear oestrogen receptor alpha and the progesterone receptor. The ovarian cysts were classified as follicular cysts. A diagnosis of leiomyoma of the uterine cervix with bilateral ovarian follicular cysts was made. The expression of calponin as a marker of smooth muscle differentiation in tumours of the genital tract of the pig has not previously been reported. The expression of steroid hormone receptors suggests a role for steroid hormones derived from the ovarian follicular cysts in tumourigenesis.

Actinomicosis maxilar con obstrucción de cavidad nasal en un toro de lidia / Maxilar actinomycosis with obstruction of nasal cavity in bullfight

Se describe el caso de un toro de lidia de 3 años que presentaba un gran abultamiento en el maxilar izquierdo. El animal tenía una manifiesta dificultad respiratoria con leve descarga nasal y sonidos respiratorios anormales cuando realizaba ejercicio. Tras la realización de la necropsia se observó que el abultamiento coincidía con una masa de 25x10x15 cm que afectaba al maxilar. La masa se extendía dorso-rostralmente de forma expansiva, llegando a reducir el interior de la cavidad nasal y ocluyendo parcialmente su luz. Muestras de la masa fueron tomadas para el estudio histopatológico y microbiológico. El diagnóstico definitivo fue de osteomielitis por Actinomyces bovis. En este caso el diagnóstico macroscópico e histopatológico aportan datos suficientes para un diagnóstico de actinomicosis bovina, aunque el diagnóstico definitivo se realizó con el aislamiento del A. bovis. En el toro de lidia ha sido descrita la actinomicosis con anterioridad, considerada como un proceso a diferenciar de actinobacilosis, abscesos inespecíficos, tuberculosis y procesos tumorales. El presente caso describe por primera vez el proceso en un toro de lidia en el maxilar, originando además signos respiratorios. Por tanto, en el toro de lidia hay que considerar que se puede desarrollar la actinomicosis maxilar y hemos de incluirla en el diagnóstico diferencial de procesos que originen patologías de vías respiratorias altas (AU)

The case of a 3-old-year bullfight that presented a mass in the left maxillary bone is described. The animal had severe breathing difficulty, slight nasal discharge and respiratory sounds acentuated after exercising. At necropsy the mass presented dorsal-rostral expansion, penetrating into the nasal cavity and partially reducing the lumen of with site of 25x10x15 cm. Samples of the mass were taken for histopathology and microbiology. The definitive diagnosis was granulomatous osteomyelitis by Actinomyces bovis. In this case, macroscopic and microscopic data were enough for a presuntive diagnosis of bovine actinomycosis and the definitive diagnosis was confirmed by the isolation of A. bovis. Actinomycosis has been previously described in the bullfight and a differential diagnosis with actinobacillosis, unspecific abscesses, tuberculosis and tumoral processes needs to be done. The present case is the first description of maxillary actinomycosis associated with respiratory signs (AU)

Glutamate-dependent translational regulation in cultured Bergmann glia cells: involvement of p70S6K.

Glutamate, the main excitatory amino acid transmitter in the vertebrate brain is involved in the dynamic changes in protein repertoire that underlie synaptic plasticity. Activity-dependent differential expression patterns occur not only in neurons but also in glial cells. In fact, a membrane to nuclei signaling has been described after ionotropic glutamate receptor stimulation in cultured chick cerebellar Bergmann glia cells. In order to characterize other levels of protein expression regulation, we explored the effect of glutamate treatment in [35S]-methionine incorporation into newly synthesized polypeptides. A time-dependent modification in protein synthesis was found. An important component of translational control is the ribosomal S6 protein kinase. Threonine phosphorylation renders the kinase active increasing translation initiation. Glutamate exposure results in ribosomal S6 protein kinase Thr389 phosphorylation in a dose and time-dependent manner that matches perfectly with the overall protein synthesis profile detected upon the excitatory amino acid. Pharmacological characterization of the receptors involved suggests the participation of both ionotropic as well as metabotropic glutamate receptors. The non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase, protein kinase B and the mammalian target of rapamycin are mediators of the glutamate effect. These results not only demonstrate that glutamate receptors activation is critically involved in translational control in glial cells adjacent to synaptic processes like cerebellar Bergmann glia cells, but also further strengthen the notion of an active participation of glial cells in synaptic transmission.

Lesiones asociadas a una toxoplasmosis aguda en perdices rojas (Alectoris rufa) infectadas experimentalmente / Lesions associated with acute toxoplasmosis in experimentally infected partridges (Alectoris rufa)

En el presente trabajo se describen las lesiones asociadas a una toxoplasmosis aguda en perdices rojas(Alectoris rufa) infectadas experimentalmente con ooquistes de Toxoplasma gondii. Para ello, treinta perdicesrojas de cinco meses de edad fueron infectadas por vía oral con ooquistes de la cepa OV-51/95 de T. gondii.Las aves fueron distribuidas en cinco lotes, que recibieron unas dosis infectantes de 10, 50, 100, 1000 y 10000ooquistes, respectivamente. Sólo dos aves, inoculadas con 50 y 10000 ooquistes, murieron por toxoplasmosisaguda al cabo de 7 días postinoculación. Macroscópicamente se apreció hepatomegalia, esplenomegalia ycongestión vascular del intestino delgado. Las lesiones microscópicas más características consistieron en unaenteritis y focos de necrosis en el bazo y el hígado. Se observaron taquizoítos en los cortes histológicos de estostejidos, y además en pancreas, pulmón, riñón, tejido muscular esquelético y cardíaco, proventrículo, molleja ybolsa de Fabricio

The present study describes lesions associated with acute toxoplasmosis in red-legged partridges (Alectorisrufa). Thirty red-legged partridges, 5-month-old, were orally inoculated with oocysts of the OV-51/95 strain ofToxoplasma gondii. Birds were distributed into five groups, and received respectively 10, 50, 102, 103 and 104oocysts. Only two partridges that received 50 and 10000 oocysts, respectively, died suddenly of acute toxoplasmosisat 7 day after inoculation. Partridges had splenomegaly, hepatomegaly and gastrointestinal congestion.The main microscopic lesions were seen only in small intestine, spleen and liver sections, associated with numerous tachyzoites of T. gondii. Tachyzoites were also seen in pancreas, lung, kidney, heart and esqueletalmuscle, proventriculus, gizzard and bursa of Fabricius histological sections

Interconversion of mechanical and dielectrical relaxation measurements for dicyclohexylmethyl-2-methyl succinate.

A comparison between results of dielectrical relaxation and dynamic mechanical spectroscopies is carried out for the alpha-relaxation of the ester dicyclohexyl methyl-2-methyl succinate (DCMMS). The results for the dielectric permittivity and the shear modulus measurements are presented according to the empirical Havriliak-Negami (HN) equation. By using the time-temperature principle a master curve in each case was obtained for several temperatures. The comparative analysis presented here is based on the assumption of a relationship between rotational and shear viscosities. The former one is associated to the dielectrical relaxation, whereas the latter is associated to mechanical relaxation. Both viscosities are not necessarily equal in general, and we assume that the difference between them is an important factor to appropriately compare the dielectrical and mechanical results.

Experimental toxoplasmosis in red-legged partridges (Alectoris rufa) fed Toxoplasma gondii oocysts.

Thirty red-legged partridges (Alectoris rufa), 5-month-old, were orally inoculated with oocysts of the OV-51/95 strain of Toxoplasma gondii. Birds were distributed into five groups and received, respectively, 10 (group A, 4 birds), 50 (group B, 14 birds), 10(2) (group C, 4 birds), 10(3) (group D, 4 birds) and 10(4) (group E, 4 birds) oocysts. One partridge from group B and one from group E died suddenly of acute toxoplasmosis at 7 day after inoculation (DAI) with demonstrable T. gondii in several tissues. The rest of birds remained clinically normal until killed at 44, 58, 65, 72, 79 or 100 DAI. Brain, heart, liver and skeletal muscle from these partridges were bioassayed individually in mice; T. gondii was demonstrated in all these tissues, except in heart of three birds inoculated, respectively, with 10, 50 and 10(2) oocysts. Lesions were not seen in histologic sections of tissues from surviving partridges. These results suggest that red-legged partridges are resistant to clinical toxoplasmosis.

Presentación clínica del síndrome dermatitis nefropática porcino en animales de cebo en un sistema de producción en tres fases / Clinical presentation of porcine dermatitis and nephropathy syndrome in fattening pigs in a three sites production system

Se ha estudiado la incidencia de aparición de casos de síndrome dermatitis nefropatía porcino (PDNS)en animales de cebo criados en un sistema de producción en tres fases. Los animales afectados presentabanlesiones en piel y riñón características del proceso. El porcentaje de cerdos afectados fue del 0,52% y la edadmedia de presentación de 15 semanas de vida. El porcentaje de animales afectados que murieron fue del 58,9% y la principal causa de muerte fue la úlcera gástrica

The incidence of cases of porcine dermatitis and nephropathy syndrome (PDNS) in fattening pigs in a threesites production system was studied. Affected animals presented the typical lesions of the syndrome in skinand kidney. The percentage of affected pigs was 0.52% and the mean age of presentation was 15 weeks. Thepercentage of affected animals that died was 58.9% and the main cause of death was gastric ulcer

Serologic response of red-legged partridges (Alectoris rufa) after oral inoculation with Toxoplasma gondii oocysts.

Thirty 5-month-old red-legged partridges (Alectoris rufa) reared in battery were divided into five groups: 4 birds in group A, 14 birds in group B, 4 birds in group C, 4 birds in group D and 4 birds in group E, and were inoculated orally with 10, 50, 10(2), 10(3) and 10(4) oocysts of the OV-51/95 strain of Toxoplasma gondii, respectively. During the experiment, blood samples from all birds were drawn every 3-7 days and at necropsy. Serologic response was measured by the modified agglutination test (MAT) and the latex agglutination test (LAT). One bird from each group was killed at 44, 58, 65 and 72 days after inoculation (DAI). From 72 DAI to the end of the experiment, surviving partridges from group B were killed at weekly intervals. The last partridges were sacrified 100 DAI. MAT was the most sensitive and specific test for detecting T. gondii antibodies in the birds. First positive titers were detected by MAT in all sera on 7 DAI, but titers by LAT did not appear until 13 DAI. Antibody titers detected by MAT on 7 DAI were higher in the partridges with the largest inocula (10(3) or 10(4) oocysts) than those inoculated with 10, 50 or 10(2) oocysts. All surviving birds developed a serologic response to T. gondii, with maximum titers of 512-32,768 in the MAT on 13-17 DAI, and positive titers persisted at least until 100 DAI. To the contrary, LAT reveals only very low antibody titers even in partridges inoculated with the highest dose of T. gondii.

Oral lacidipine in the treatment of anal fissure.

The aim of this prospective study was to assess the effectiveness in healing anal fissure (AF) of lacidipine, a calcium channel blocker with a better tolerability in comparison to other calcium antagonists. Twenty-one consecutive patients (16 women, 76.2%) with AF (16 chronic, situated posteriorly in 17 patients (81.0%), anteriorly in 4) with a mean age of 37.1 years (SD, 13.6, range, 20-6) were treated with oral lacidipine (6 mg daily) and warm sitz baths for 28 days, adding only stool softeners for patients with constipation. Blood pressure, pain scores (assessed from 0 to 10 on a visual analogue scale) and fissure healing were monitored at 14 days, 28 days and 2 months. At the 14-day and 28-day follow-ups, the mean systolic and diastolic pressures were not significantly different from pre-treatment levels. Seven patients (33.3%) developed side effects, but only one, who developed dyplopia, withdrew from the study at the 14-day control (non-compliance rate with treatment, 4.8%). Pain scores were significantly reduced after 14 days and continued to show a significant reduction throughout the treatment period. Three fissures (14.3%) healed by 14 days and a total of 19 (90.4%) after 28 days: among the healed AF no recurrences were seen at the 2-month control. Among the two treatment failures, one was the patient who withdrew from the study at the 14-day control due to dyplopia and the other was a patient who failed to heal up to the 2-month follow-up, although completely asymptomatic. Both patients underwent left lateral sphincterotomy and healed. In conclusion, oral lacedipine is quite well tolerated and may offer a promising alternative treatment for AF.

Immunocytochemical light- and electron-microscopic studies of growth hormone, prolactin and somatomammotroph cells in female goat.

We have studied the structural and ultrastructural changes that occur in growth hormone (GH), prolactin (PRL) and somatomammotroph (SMT) cells of female goats of the Murciano-Granadina breed during different physiological stages: prepuberty, anestrus, pregnancy and lactation. Serial sections were stained with double immunolabeling, alkaline phosphatase and avidin-biotin complex for light microscopy, and immunogold labeling was used for electron microscopy. These techniques allowed the identification of GH, PRL and SMT cells, which were evenly distributed throughout the whole pars distalis. PRL cells were the most frequent. Both PRL and GH cells showed morphological changes that may be related to a given physiological stage. These changes include the number of cells and the number and size of the secretory granules. SMT cells were clearly identified by having two types of monohormonal secretory granule showing single labeling, in spite of their similar ultrastructural characteristics to the other adenohypophysary cells. They are found in low percentages (0.6%). We postulate that cell aggregates which look like SMT syncytia may be artifacts caused by interdigitation of PRL and GH cells, and that cells which are normally taken to be SMT cells are not an interconversion stage between monohormonal cells.