Acute and nongenomic effects of testosterone on isolated and perfused rat heart

Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.     

Unique brain anomalies in an infant of a diabetic mother

An offspring of a class F diabetic primigravida with marginal control during the first 8 weeks of the gestation had a level II sonogram at 23 weeks. It showed polyhydramnios and "hydrocephaly." Macrosomia, right hydroureter, megacystis and premature birth corroborated the diagnostic impression of diabetic embryopathy. At age 3 years, the child functions within the moderate range of mental retardation. Angiography, choanogram, CT and MRI scans showed unique CNS abnormalities that appeared secondary to a hamartomatous growth within the left cerebral hemisphere. Such anomaly, most likely a part of the phenotype of the diabetic embryopathy, implies a growth disturbance secondary to dysregulated paracrine growth factors (somatomedins, nerve growth factor, panregulin and/or their receptors in this case). It also indicates a possibility of interaction between two dysregulated major growth mechanisms; the endocrine in the mother considered responsible for the overall phenotype of the diabetic embryopathy/fetopathy and the paracrine fine tuning mechanism in the embryo incriminated by the hamartomatous over/undergrowth.     

Primary intracranial arachnoidal cysts

Sixty-seven cases (41 males and 26 females) of arachnoidal cysts in children under 11 years are reported. About 53% of cases were diagnosed before 1 year of life. Thirty-one (42.2%) were supratentorial (interhemispheric 9, temporal fossa 10, convexity 5, sylvian fissure 3, supra- and/or retrosellar 4); 31 (46.2%) infratentorial (supra- and/or retrocerebellar 22, foramen of Magendie 3, quadrigeminal cistern 5, pontocerebellar 1); 5 (7.5%) supra-and infratentorial. Macrocephaly was the presenting symptom in 48 cases (71.5%). Associated features were frequent: cranial asymmetry in 24; aqueductal stenosis in 10; agenesis of corpus callosum in 8; deficient cerebellar lobullation in 4; Chiari I malformation in 2; neurofibromatosis type 1 with dysgenetic zones of the brain in 1; arteriovenous malformation in 1. Diagnosis was made at autopsy in six cases in the days before computed tomography and magnetic resonance: three patients had a cyst in the supra-and retrocerebellar midline; two had a cyst in the quadrigeminal cistern and the sixth was a rare case with the cyst passing from the posterior fossa to the left lateral ventricle through a hole in the basal surface of the brain. Small and some middle-sized cysts were not treated. Big and some middle-sized cysts were usually treated by cysto- and/or ventriculoperitoneal shunts. Arachnoidal cysts of the quadrigeminal cistern usually present with aqueductal stenosis and have to be treated with ventriculoperitoneal shunt. Craniotomy and fenestration of the cysts were performed in some cases with good results. The average mental level of these children is usually moderately low.     

Unusual fractures and dislocations of the axis vertebra

Seven percent of 400 patients with cervical spine fractures and/or dislocations had unusual lesions of the axis. The authors have analyzed axis injuries by review of radiographs and clinical data and have derived a classification of traumatic conditions. Uncommon traumatic axis abnormalities are discussed with reference to incidence, causes, clinical findings, mechanism of injury, and roentgen characteristics.Picker Scholar, James Picker Foundation     

Presence of receptors for bombesin/gastrin-releasing peptide and mRNA for three receptor subtypes in human prostate cancers

BACKGROUND: Bombesin-like peptides can function as autocrine or paracrine growth factors and stimulate the growth of some cancer cells, including human prostate cancer. Three bombesin receptor subtypes, termed gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMBR), and bombesin receptor subtype 3 (BRS-3), have been identified in rodents and humans. METHODS: We investigated the presence and characteristics of the functional receptors for bombesin/GRP in human prostate adenocarcinoma specimens by radio-receptor assay and the mRNA expression of the three bombesin receptor subtypes by RT-PCR. RESULTS: Of the 80 specimens of primary prostate cancer examined by receptor binding assays, 50 ( approximately 63%) showed high-affinity, low-capacity binding sites for bombesin/GRP, and 12 of these 50 receptor-positive specimens also showed a second binding site. Of the 22 prostate cancer specimens analyzed by RT-PCR, 20 (91%) expressed GRPR mRNA, 3 (14%) showed NMBR mRNA, and 2 ( approximately 9%) revealed BRS-3 mRNA. No correlation was observed between receptor expression and patients' age or pathological data. CONCLUSIONS: The detection of a wide distribution of bombesin/GRP receptors in human prostate carcinomas supports the view that they may be involved in modulation of tumor progression and suggests that approaches based on binding of bombesin receptor antagonists or new targeted cytotoxic bombesin analogs to prostate cancers could be considered for the therapy.     

Smoking exposure as a risk factor for prevalent and recurrent colorectal adenomas.

Colorectal adenomatous polyps are considered to be the precursor lesion of colorectal cancer (1-3). Greater understanding of the association between smoking and adenoma development enable better detection and prevention of colorectal cancer. This study was conducted in men and women, ages 40-80, participating in a randomized trial testing the effects of wheat bran fiber supplement on adenoma recurrence. First, we investigated smoking exposure (status, cigarettes/day, and years of smoking) and colorectal adenoma characteristics (location, histology, size, and multiplicity) at baseline colonoscopy (n = 1429). Second, we evaluated smoking exposure and adenoma recurrence (n = 1304). The prevalence of distal versus proximal adenomas was greater for < or =30 cigarettes/day [odds ratio (OR), 1.48; 95% CI, 1.02-2.16] and 15 to <25 years of smoking (OR, 1.95; 95% CI, 1.23-3.09) compared with never smokers. Tubular versus villous histology prevalence was increased for > or =30 cigarettes and > or =35 years of smoking (OR, 1.74; 95% CI, 1.21-2.49 and OR, 1.74; 95% CI, 1.24-2.45, respectively) compared with never-smokers. Years of smoking increased prevalence of multiple versus single adenomas, whereas cigarettes/day and years of smoking were associated with large adenomas (> or =1 cm) prevalence as compared with small lesions (< or =0.5 cm). Greater than 35 years of smoking was significantly associated with an increased risk of adenoma recurrence (OR, 1.42; 95% CI, 1.01-1.98). These results suggest that the association between smoking and adenoma prevalence varies by the characteristic of the lesion. Furthermore, the association between smoking and adenoma recurrence is modest and was only significant after a long duration of exposure. Additional investigations that characterize the genetic changes in specific subgroups of prevalent and recurrent adenomas associated with smoking exposure are needed.     

Free flaps for head and neck reconstruction in non-oncological patients: experience of 200 cases

Two hundred free flaps for reconstructing the head and neck regions in 192 patients with non-oncological pathology were studied. Pathological entities included Romberg's disease, hemifacial microsomia, acquired facial palsy, trauma, and burn sequelae. Indications for selecting a specific free flap for reconstructing each case, details of anastomoses, reexploration, flap success, operative time, length of hospitalization, and complications were studied. The long-term results of cosmetic and function were also obtained. Patient age ranged from 6 to 40 years. The most common diagnosis was Romberg's disease 39% (n = 75), followed by hemifacial microsomia 20% (n = 40). The free flap most frequently used was the scapular 32% (n = 64), followed by the groin free flap 21% (n = 42). A total of 190 flaps (95%) were successful, whereas only 10 (5%) were lost. The mean operative time was 5:30 h and the average hospital stay was only 6 days. There were no major complications and no deaths in the study group. The patients were followed for at least 1 year in all cases. It is concluded that free flaps are safe and reliable procedures for reconstructing complex head and neck non-oncological defects.