A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

Gonadal steroid preservation of central synaptic input to hamster facial motoneurons following peripheral axotomy

In recent work, we have demonstrated that testosterone propionate accelerates recovery from facial nerve injury in the adult male hamster. Central synaptic stripping following peripheral motor neuron damage is a well-established component of the injury response. Gonadal steroids regulate synaptogenesis in the normal nervous system. In this study, we tested the hypothesis that testosterone propionate administration at the time of facial nerve transection alters the synaptic connectivity of injured facial motoneurons. Adult hamsters were subjected to right facial nerve transection at the level of the stylomastoid foramen. Half the animals received subcutaneous implants of testosterone propionate; the other half were sham implanted. At 5 days postoperative, the animals were killed by intracardiac perfusion-fixation, and the control and axotomized facial nuclear groups from the brainstems of nonhormone- and testosterone propionate-treated animals processed for routine transmission electron microscopy. Quantiative analysis of the synaptic ratio (percent somal membrane covered by synaptic profiles) and the average length of axosomatic synapses was accomplished. The results indicate that axotomy alone resulted in an 81% reduction in the synaptic ratio and a 26% decrease in the average synaptic length of axosomatic synapses. Exposure to testosterone propionate from the time of facial nerve transection resulted in only a 48% reduction in the synaptic ratio and a 16% decrease in the average synaptic length of axosomatic synapses following injury. Thus, testosterone propionate significantly attenuated the amount of synaptic stripping that occurred at 5 days postoperative and the decrease in average length of the remaining synapses as well. It is concluded that gonadal steroids modulate central synaptic plasticity following peripheral nerve injury. The results are discussed in light of our recent findings of steroidal effects on the central astrocyctic response to facial nerve injury as well.     

Tibial hypo-/aplasia with preaxial syn- and polydactyly

Summary Tibial hypo-/aplasia with preaxial syn- and polydactyly is a rare autosomal dominant condition. Fewer than 20 cases have so far been described. One is presented here.     

In situ breast carcinomas: A population-based study on frequency,growth pattern,and clinical aspects

This study comprises 78 consecutive women, within situ carcinoma of the breast and no evidence of invasion, who were diagnosed and treated surgically from October, 1979 to June, 1986. Lobular carcinoma in situ (LCIS) was found in 30 patients (38%) and ductal carcinoma in situ (DCIS) was identified in 48 patients (62%). The series is a study based in the county of Funen, which has a total female population of 230,028 inhabitants.Epidemiological calculations were carried out in 5 municipalities in the area of Odense University Hospital with 77,477 female inhabitants 20+ years of age according to a predetermined referral scheme and diagnostic procedures. This sub-study revealed a frequency of 9.0 cases ofin situ carcinomas per 10⁵ woman-years and a cumulated risk of 0.53% of havingin situ carcinoma demonstrated within the age range of 20–75 years.In situ lesions made up about 6% of all newly diagnosed breast carcinomas in the region. Furthermore, in about 3% of all breast biopsies and in about 0.3% of all women having mammography due to breast symptoms, anin situ finding was the only malignant change.Pathoanatomically, a distinction could be made between 3 different growth patterns: microfocal, tumor-forming, and diffuse growths. Microfocal lesions comprised a major part (60%) of in situ carcinomas. With one exception, the microfocal cases were chance findings in an otherwise benign breast biopsy, whereas the more aggressive growth patterns (tumor-forming and diffuse) were predominantly clinical and/or mammographic findings, all belonging to the DCIS type. Excisional biopsy or partial mastectomy was performed in 85% of the women with microfocal cases, while such breast preservation procedures were used in only 27% of patients with tumor-forming or diffuse growths.

---

Resumen El presente estudio comprende 78 mujeres consecutivas con carcinoma mamarioin situ y sin evidencia de invasíon, quienes fueron diagnosticadas y tratadas quirúrgicamente durante el período 1979 a 1986. Se encontró carcinoma lobular in situ (CLIS) en 30 pacientes (38%) y carcinoma ductal in situ (CDIS) en 48 pacientes (62%). La serie proviene de la región de la isla de Funen, Dinamarca, con una población de 230,028 habitantes.Se realizaron determinaciones epidemiológicas en 5 municipalidades correspondientes a la región del Hospital de la Universidad de Odense, con 77,477 habitantes mujeres de acuerdo a un esquema predeterminado de referencia y a procedimientos de diagnóstico estandarizados. Este subanálisis reveló una frecuencia de 9.0 casos de carcinomasin situ por 10⁵ mujer-años y un riesgo de 0.53% de tener carcinomain situ para las mujeres entre los 20 y los 75 años. Las lesionesin situ representaron alrededor del 6% de la totalidad de los nuevos carcinomas mamarios diagnosticados en la región. Además, en alrededor de 3% de todas las biopsias mamarias y en alrededor de 0.3% de todas las mujeres sometidas a mamografía por razón de presentar síntomas mamarios, el hallazgoin situ fue el único hallazgo de malignidad.Se pudo hacer la diferenciación anatomopatológica entre 3 diferentes patrones de crecimiento: microfocal, formación tumoral, y crecimiento difuso. Las lesiones microfocales comprenden la mayor parte (60%) de los carcinomasin situ. Con una excepción, los casos del tipo microfocal fueron hallazgos fortuitos en biopsias mamarias por lo demás benignas, en tanto que los patrones de crecimiento de tipos más agresivos (formación tumoral y crecimiento difuso) fueron predominantemente hallazgos clínicos y/o mamográficos, todos CDIS. Se realizó biopsias excisional o mastectomía parcial en 85% de las mujeres con el tipo microfocal, en tanto que tales procedimientos de conservación mamaria fueron utilizados en solo 27% de las pacientes con los patrones de formación tumoral de crecimiento difuso.

---

Résumé On a étudié les résultats de soixante-dix-huit cancersin situ du sein chez la femme, sans évidence d'envahissement, diagnostiqué et traités chirurgicalement entre octobre 1979 et juin 1986. Il y avait 30 cas (38%) de cancer lobulaire (CL) et 48 cas (62%) de cancer cannalaire (CC). Cette série de patientes provenait du comté de Funen, Danemark, dont la population féminine est de 230,028.L'épidémiologie a été étudiée dans 5 municipalités dans la région de l'Hôpital Universitaire d'Odense où la population féminine est de 77,477 selon une méthode de consultation et de diagnostic standardisée. Cette étude a montré que l'incidence était de 9 cas de cancerin situ pour 10⁵ femmes-années; le risque d'avoir un cancerin situ était de 0.53% entre les âges de 20–75 ans. Six pour cent des cancers diagnostiqués dans la région étaitin situ. Un cancer in situ a été trouvé dans 3% de toutes les biopsies du sein, et 0.3% des femmes ayant une mammographie motivée par une Symptomatologie au niveau du sein.Histologiquement, on pouvait distinguer 3 types de croissance: microfocale, tumorale, et diffuse. Les lésions microfocales étaient responsables de 60% des cancersin situ. A une exception près, les microfoyers de cancer ont tous été découverts par hasard, alors que les formes tumorales et diffuses ont tous été décelés grâce à des signes cliniques et/ou mammographiques. Il s'agissait toujours d'un cancer cannalaire. Une biopsie d'exérèse ou mastectomie partielle a été effectuée chez 85% des femmes ayant un microcancer, mais seulement chez 27% des femmes ayant une forme tumorale ou diffuse.