Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA)

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Attempted experimental infection of domestic goats with Ehrlichia chaffeensis

Although white-tailed deer (WTD; Odocoileus virginianus ) are considered the primary natural reservoir host for Ehrlichia chaffeensis, the causative agent of human monocytotropic ehrlichiosis, the potential role of other vertebrates as reservoir hosts has not been fully explored. Because domestic goats are naturally infected in areas where E. chaffeensis is endemic in deer, we evaluated the susceptibility of domestic goats to experimental infection with E. chaffeensis. A total of 12 goats were inoculated with E. chaffeensis (15B-WTD-GA or Ark strain)-infected DH82 cells by one of three routes: intravenously, subcutaneously, or intradermally. White-tailed deer simultaneously inoculated with the same dose, route, and inoculum served as positive controls; additional goats and WTD were included as negative controls. Evidence of E. chaffeensis infection was evaluated in all animals by indirect fluorescent antibody assay, PCR, and cell culture isolation techniques. All goats exposed to E. chaffeensis seroconverted by 14 days post-infection (DPI), and E. chaffeensis was isolated from one goat on 3 DPI; however, molecular or cell culture evidence of active infection was not detected in goats later than 3 DPI. White-tailed deer exhibited serologic and molecular evidence of E. chaffeensis infection throughout both trials, and E. chaffeensis was reisolated in cell culture from all infected WTD on numerous days post-infection. Our results suggest that despite the occurrence of natural infection in goats, this animal may not be susceptible to experimental infection and thus may not serve as a suitable model of E. chaffeensis reservoir host infection.     

Effects of electroacupuncture on gastric mucosal blood flow and transmucosal potential difference in stress rats

ＥｆｅｃｔｓｏｆｅｌｅｃｔｒｏａｃｕｐｕｎｃｔｕｒｅｏｎｇａｓｔｒｉｃｍｕｃｏｓａｌｂｌｏｏｄｆｌｏｗａｎｄｔｒａｎｓｍｕｃｏｓａｌｐｏｔｅｎｔｉａｌｄｉｆｅｒｅｎｃｅｉｎｓｔｒｅｓｓｒａｔｓＸＵＧｕａｎＳｕｎ１，ＳＵＮＹｏｎｇ１，ＷＡＮＧＺｈｅ...     

Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice

Hypothalamic feeding circuits have been identified as having innate synaptic plasticity, mediating adaption to the changing metabolic milieu by controlling responses to feeding and obesity. However, less is known about the regulatory principles underlying the dynamic changes in agouti-related protein (AgRP) perikarya, a region crucial for gating of neural excitation and, hence, feeding. Here we show that AgRP neurons activated by food deprivation, ghrelin administration, or chemogenetics decreased their own inhibitory tone while triggering mitochondrial adaptations in neighboring astrocytes. We found that it was the inhibitory neurotransmitter GABA released by AgRP neurons that evoked this astrocytic response; this in turn resulted in increased glial ensheetment of AgRP perikarya by glial processes and increased excitability of AgRP neurons. We also identified astrocyte-derived prostaglandin E₂, which directly activated — via EP2 receptors — AgRP neurons. Taken together, these observations unmasked a feed-forward, self-exciting loop in AgRP neuronal control mediated by astrocytes, a mechanism directly relevant for hunger, feeding, and overfeeding.     

Consanguinity in the Bishopric of Ourense (Galicia,Spain) from 1900 to 1979

Background : Knowledge of the levels of inbreeding in the human population is interesting because it is one of the characteristics that conditions its genetic structure and has important genetic-medical repercussions in the descendants of marriages between close relatives. Galicia (north-west Spain) is a region with very special geographic, historic and social characteristics that makes it particularly interesting for consanguinity studies. Primary objective : The object of this investigation is the study of the levels of inbreeding and the structure of consanguinity in rural area of the Dioceses of Ourense (Galicia) during the period 1900-1979. Subjects and methods : In the study, data corresponding to 437 parishes, integrated in 80 municipalities of the rural area of the Dioceses of Ourense were analysed. In the period studied, of a total of 110 128 marriages, 9010 took place between biologically related individuals up to the level of second cousins. The rate of consanguinity and the average coefficient of inbreeding of the population, as well as the percentage of the different types of consanguineous marriages, were calculated. Main outcomes and results : The rate of consanguinity for the period 1900-1979 is 8.18% and the average coefficient of inbreeding is 3.0662 &#50 10 &#109 3. The most frequent type of consanguineous marriage is between second cousins (4.00% of all marriages). There is a notably high frequency of marriages of multiple relationships (0.52%) and the frequency of uncle-niece or aunt-nephew marriages is 0.16%. The average value of the M22/M33 ratio is 0.66 and during the 80 years studied, with regard to the temporal variation of the average coefficient of inbreeding, the annual values followed a polynomial curve with an inflection point in 1921. Conclusions : The highest values of consanguinity detected in Galicia, for the same period, were registered in the Dioceses of Ourense and the high rate of uncle-niece or aunt-nephew marriages habitual in this region was confirmed. The latter is explained by the important incidence in the Galician population of the migration to America at the end of the 19th and beginning of the 20th century. However, when the relative frequency of this type of marriage with respect to the total number of consanguineous marriages is calculated, it has relatively low values due to the high proportion of marriages between second cousins and marriages of multiple relationships, the highest in Galicia for an equal period of time. The rate of marriages between first cousins is also the highest in Galicia, confirming a phenomenon that appears to be common in the rural areas of the northern area of the Iberian Peninsula.