Arterial reactivity is enhanced in genetic males taking high dose estrogens

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.     

Predation of livestock ticks by chickens as a tick-control method in a resource-poor urban environment

The increasing prevalence of streptococci as causes of potentially fatal nosocomial bacteremia requires that antimicrobial agents used for empiric therapy in hospitalized patients include both pneumococci and viridans group streptococci as well as beta-hemolytic streptococci in their activity profile. In this study, the in vitro activity of cefepime, a new fourth-generation cephalosporin, was compared with other cephalosporins versus 197 nosocomial blood stream isolates of streptococci (20 Streptococcus pneumoniae, 104 viridans group, and 73 beta-hemolytic) isolated from patients at more than 30 medial centers from 1995 to 1997. Additional agents tested included penicillin, erythromycin, and vancomycin. Overall, cefepime inhibited 83% of the isolates at concentrations < or = 0.5 microgram/mL and 100% at < or = 8 micrograms/mL. By comparison, ceftazidime inhibited 35 and 88% of isolates at the same concentrations. Cefepime was approximately eightfold more potent than ceftazidime against S. pneumoniae, viridans group streptococci, and beta-hemolytic streptococci. Among the 42 isolates with penicillin MICs > 0.12 microgram/mL, 100% were inhibited by cefepime and only 48% by ceftazidime at < or = 8 micrograms/mL. The rank order of activity for all six agents against the 197 isolates was vancomycin > ceftriaxone > cefepime > penicillin > erythromycin > ceftazidime. Based on the results of the present study, cefepime and ceftriaxone were the superior cephalosporins in potency and spectrum for empiric coverage of patients at risk for streptococcal blood stream infections.     

Peripheral nerve stimulation in a whole-body echo-planar imaging system

Echo-planar techniques in MRI use a rapidly oscillating frequency-encoding gradient with the potential to produce peripheral nerve stimulation. To evaluate the incidence, type, and location of stimulation in a commercial whole-body scanner, we studied two groups: (a) 173 consecutive individuals scanned by echo-planar imaging for other purposes and (b) seven subjects who were scanned with an extensive set of 36 echo-planar sequences (with prompting after each scan to report any peripheral nerve stimulation) to test the effects of various parameters. Although only 5% of group A reported symptoms of peripheral nerve stimulation, all in group B experienced some type of stimulation, dependent primarily on direction of the oscillating gradient and location of the body within the gradient coil. Maximum stimulation typically occurred 30 to 40 cm from isocenter in the region of maximum dB/dt. Generally, y gradients produced truncal stimulation, and x gradients produced stimulation in the head. When hands were clasped over the abdomen, a tingling in the hands occasionally was felt. Patients should be instructed to keep their hands apart.     

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.     

Long-term observation of subcutaneous tissue reaction to synthetic auditory ossicle (Apaceram) in rats

The present study evaluates histological characteristics of the soft tissue response to long-term implantation of Apaceram discs composed of dense hydroxyapatite in rats. Discs were implanted into the subcutaneous tissue of 76 rats for six to 20 months. Decalcified histological sections stained with haematoxylin and eosin (H & E) and Mallory's azan were examined. Different cell types surrounding implants were counted. The greatest proportion of macrophages was found at six months (13.5 per cent). This proportion gradually decreased to four per cent at 20 months. Small numbers of lymphocytes and foreign body giant cells were observed in every group, but neither neutrophils nor osteogenesis were observed in any specimens. Results of the present study and previous related studies indicate that despite reappearance of a small number of macrophages six months after implantation, Apaceram is useful for reconstructive surgery.     

Nuciruptor rubricae, a new pitheciin seed predator from the Miocene of Colombia

A new genus and species of platyrrhine primate, Nuciruptor rubricae, are added to the increasingly diverse primate fauna from the middle Miocene of La Venta, Columbia. This species displays a number of dental and gnathic features indicating that it is related to living and extinct Pitheciinae (extant Callicebus, Pithecia, Chiropotes, Cacajao, and the Colombian middle Miocene Cebupithecia sarmientoi). Nuciruptor is markedly more derived than Callicebus but possesses a less derived mandibular form and incisor-canine complex than extant and extinct pitheciins (Cebupithecia, Pithecia, Chiropotes, and Cacajao), suggesting that it is a primitive member of the tribe Pitheciini within the larger monophyletic Pitheciinae. Nuciruptor has procumbent and moderately elongate lower incisors and low-crowned molars, suggesting that is was a seed predator, as are living pitheciins. Its estimated body size of approximately 2.0 kg places it within the size range of extant pitheciines. The dental and gnathic morphology of Nuciruptor clarifies several aspects of dental character evolution in Pitheciinae and makes it less likely that the enigmatic Mohanamico hershkovitzi (m. Miocene, Columbia) is a pitheciin.     

HLA-DR mismatching correlates with early cardiac allograft rejection, incidence, and graft survival when high-confidence-level serological DR typing is used

To determine if cardiac allograft outcome is improved among patients with fewer HLA-DR mismatches with their donors, we studied 132 recipients of a primary cardiac allograft who were transplanted between December 1985 and December 1991. These recipients and their donors all had high-confidence-level serological HLA-DR typing, previously shown to correlate highly with DNA DR typing. Patients were divided in two groups based on the HLA-DR mismatch with their donors. Group I consisted of 78 patients with 1 or zero DR mismatch and group II of 54 patients with 2 DR mismatches. Allograft outcome measurements included incidence of moderate rejection, incidence of allograft vasculopathy at 12 months, cardiac function measured as left ventricular ejection fraction (LVEF) and cardiac index (CI), and actuarial graft survival up to 7 years. Groups I and group II were not different with regard to recipient age, donor age, ischemia time, pulmonary vascular resistance, sex, or PRA greater than 0%. Group II had a higher incidence of moderate rejection on the first-week biopsy (47% vs. 25%, P = 0.019), and during the first month (84% vs. 58%, P = 0.006), but no difference was found in frequency of rejection from months 2 to 12. LVEF was not different in the groups at any point. CI was better in group I at 12 months (2.76 vs. 2.5, P = 0.03). No statistically significant difference was found in incidence of allograft vasculopathy (17% vs. 26%, P = 0.204). Actual graft survival at 1 year was better for group I (91% vs. 74%, P = 0.008), and actuarial graft survival at 6 years also favored group I (76% vs. 56%, P = 0.04). Using high-confidence-level serological HLA-DR typing assignments we demonstrated that HLA-DR mismatching correlates highly with cardiac allograft outcome. Implications are that heart transplant survival could be improved if prospective matching were feasible and prioritized or if immunosuppression were tailored to the HLA-DR match.     

Biological rhythms as organization and information

The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures.     

The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3

We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy.