Moving toward the eradication of syphilis

This study analyzed syphilis incidence among active duty U.S. Sailors and Marines and explored opportunities and strategies for the Department of the Navy to contribute to the achievement of the National Syphilis Elimination Plan. From 1987 through 1999, there were 1,886 cases of syphilis among active duty members reported to the Navy Environmental Health Center. Most were male (90%), younger than 30 years (81%), and black (64%). Most were diagnosed within the continental United States (79%). Incidence rates of primary and secondary syphilis per 100,000 among the active duty force declined steadily, from 37 in 1990 to 3 in 1999. Strategies suggested to further reduce syphilis among active duty members include the following: (1) Navy Medicine adoption and tracking of the national target of < 0.4 cases per 100,000 by 2005; (2) expand training of medical professionals in client-centered prevention counseling; (3) include affected populations in the design of interventions; (4) conduct outcome evaluations of educational interventions; (5) examine condom access policies; and (6) evaluate the current syphilis surveillance system.     

Fear-like biochemical and behavioral responses in rats to the predator odor,TMT, are dependent on the exposure environment

Several laboratories have reported that exposure to predator odor can result in stress-like effects in rodents. While some laboratories have reported fear-like alterations in behavior, other laboratories, including our own, have failed to consistently observe fearful behaviors in rats exposed to the predator odor TMT. One potential contributing factor to this discrepancy is the handling of the rat and its test environment. In the current report, we examine biochemical, endocrinological, and behavioral effects of TMT in two distinct open fields: one small, familiar, and dimly lit, while the other was large, novel, and brightly lit. Only exposure to TMT in the large, novel open field resulted in fearful behavior; however, no increase in dopamine turnover was noted compared to no odor and control odor rats. As expected, the different open fields resulted in some biochemical and behavioral differences, including more horizontal locomotion and less grooming, higher serum corticosterone, and increased dopamine turnover in the ventral prefrontal cortex in the large open field. Finally, compared to the same open field controls, TMT exposure elevated rat serum corticosterone levels in both open fields and dopamine turnover in the dorsal and ventral medial prefrontal cortex and amygdala of rats only in the small, familiar open field. These results indicate that the TMT-induced biochemical activation of may occur without detectable fearful behaviors and may indicate a mechanism that prepares the animal for the expression of a fearful response if additional provocative stimuli are present.     

Ductal lavage and ductoscopy: the opportunities and the limitations

Two related techniques of breast epithelial sampling have emerged in the past several years: ductal lavage, in which fluid-yielding nipple ducts are cannulated at their orifices and lavaged with saline while the breast is intermittently massaged; and ductoscopy, in which discharging or fluid-yielding duct orifices are dilated, intubated with a microendoscope, and the lumen directly visualized. Both of these techniques have significant potential in terms of allowing the repeated sampling of ductal epithelium over time and, as such, have generated considerable enthusiasm. However, data regarding the impact of these techniques on the detection of significant breast disease is very scant. It is important at the outset of the assessment of this new technology that breast cancer clinicians and clinical researchers think carefully about the standards of evidence that need to be met regarding the benefits of these procedures before they are widely adopted. In this review of the rationale and early results of these procedures, we attempt to define some of these evidentiary requirements.     

Divergent effects of putative anxiolytics on stress-induced fos expression in the mesoprefrontal system of the rat

Previously, we reported that R(+)HA-966, a weak partial agonist for the glycine/NMDA receptor, and guanfacine, a noradrenergic alpha2 agonist, have anxiolytic-like actions on the biochemical activation of the mesoprefrontal dopamine neurons and fear-induced behaviors. Here, we examined these two putative anxiolytic agents, both with primary actions independent of GABAergic systems, for their ability to alter stress-induced Fos-like immunoreactivity in the mesoprefrontal cortex and in tyrosine hydroxylase-stained, presumed dopaminergic, neurons in the ventral tegmental area. The benzodiazepine agonist, lorazepam, and partial agonist, bretazenil, were also tested in this footshock paradigm [10 x 0.5 sec, 0.8 mA paired with a 5-sec tone]. In saline-treated rats, footshock resulted in an increase in Fos-li in the prelimbic and infralimbic cortices and tyrosine hydroxylase-labeled cells in the ventral tegmental area. Treatment with lorazepam or bretazenil prevented the stress-induced activation in Fos-li nuclei in all regions of the medial prefrontal cortex and in dopaminergic neurons in the ventral tegmental area. In contrast, the actions of the novel anxiolytic-like agents on stress-induced Fos-li were different than those observed with benzodiazepine agonists. Both putative anxiolytics, R(+)HA-966 and guanfacine, did not reduce, but significantly enhanced the stress-induced Fos-li in the prelimbic region of the medial prefrontal cortex. Additionally, treatment with R(+)HA-966 completely blocked, while guanfacine attenuated, the stress-induced increase in the number of Fos-li, TH-li cells in the ventral tegmental area. These results indicate that the putative anxiolytics, R(+)HA-966 and guanfacine, have actions on the stress-sensitive mesoprefrontal system which appear distinct from those of traditional anxiolytics.     

Mitochondrial DNA depletion in children

The first girl of an unrelated couple was noted to have failure to thrive since age 3 months, generalized hypotonia and weakness, hepatomegaly, hypoglycemia, and lactic acidosis at 4 months. She was found to have severe mitochondrial DNA (mtDNA) depletion and respiratory chain complex IV deficiency in both skeletal muscle and liver but without other common mtDNA mutations. Her younger brother developed vomiting at age 3 weeks and was diagnosed as having pyloric stenosis. His skeletal muscle and liver also showed severe mtDNA depletion. He developed generalized weakness and hypotonia, hepatomegaly, and lactic acidosis at age 3 months. Both siblings died of hepatic failure and hemorrhagic complication before 6 months of age. The brother also had chemical pancreatitis, which had not been reported before in mtDNA depletion in children. Severe mtDNA depletion may present with nonspecific symptoms such as vomiting, failure to thrive, and developmental delay; multiorgan involvement such as hepatomegaly, pancreatitis, and myopathy occurs later. Mitochondrial DNA depletion should be considered in the differential diagnosis in children with developmental delay or failure to thrive of unknown etiology.     

Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients.

PURPOSE: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. RESULTS: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)-pulmonary embolus, 1 (4%)-febrile neutropenia, and 1 (4%)-infection; grade 3 toxicities were 4 (15%)-neutropenia, 4 (15%)-fatigue, 2 (7%)-neuropathy, 2 (7%)-athralgias, 2 (7%)-stomatitis, 1 (7%)-pleural effusion, and 1 (4%)-hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. CONCLUSION: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.     

Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers.

Free radicals in cigarette smoke (CS) cause oxidative damage to proteins, DNA, and lipids, contributing to the pathobiology of atherosclerosis, heart disease, and cancer. In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS. It is hypothesized that a combination of antioxidants is more effective than a single antioxidant, due to their interactions. To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination, we conducted an intervention study in smokers. In a randomized double-blind placebo-controlled trial, we investigated whether vitamin C or an antioxidant mixture containing vitamin C, alpha-lipoic acid, and vitamin E decreases plasma F(2)-isoprostane levels, an index of oxidant stress, in smokers. Plasma of 126 smokers (mean age, 46 years; age range, 20-78 years) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo. In smokers with a body mass index (BMI) above the median, 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group (P = 0.001); levels in the mixture group were 7.45 pmol/liter lower after treatment, but this difference was not statistically significant (P = 0.14). There was no treatment effect in smokers with a low BMI. BMI was significantly positively associated with plasma F(2)-isoprostane levels (trend P = 0.001). Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI. Our results do not indicate that an antioxidant combination is more effective than vitamin C alone. The intake of antioxidants may help prevent smoking-related diseases. Smoking cessation should still be considered the most effective way to prevent smoking-related diseases.     

A population-based study of geriatric trauma in a rural state

BACKGROUND: Urban geriatric trauma patients are known to die more often than their younger counterparts. Little is known of the fate of geriatric trauma patients in a rural environment where delays to definitive treatment are frequent. We hypothesized that rural trauma patients would do worse than their urban counterparts because of prolonged delays to definitive care. METHODS: Five-year retrospective analysis of all trauma deaths occurring within a rural state and retrospective outcome analysis of trauma patients admitted to a tertiary care facility who were less than 55 years old (defined as young) and 55 or more years old (defined as old). Outcome analysis was performed comparing old and young rural hospitalized patients to the Major Trauma Outcome Study data set collected in major urban trauma centers. RESULTS: Of the total trauma deaths in the state, 32.5% were old. Old patients were less likely to die at the scene of the injury than were their younger counterparts (R2 = 0.84, p < 0.001). Hospitalized old patients had a significantly higher mean Revised Trauma Score and a significantly lower Injury Severity Score, a higher complication rate, and a higher mortality rate than did hospitalized young patients. The young group had a significantly better survival (W = 0.59, Z = -3.49, p = 0.0001) than the MTOS data set, but the old group had a significantly worse survival (W = -1.8, Z = -3.49, p = 0.001). CONCLUSION: In a rural environment, old trauma patients die more commonly in the hospital than their younger counterparts, who die more commonly at the scene. Old trauma patients who die in the hospital were less severely injured than their younger counterparts who died in the hospital. Old patients admitted to this rural trauma center have a significantly worse survival than their urban counterparts despite the fact that young rural trauma patients do significantly better than their urban counterparts. Understanding the demographics of rural geriatric trauma may be useful in allocating resources in rural trauma system design. It must be understood that despite relatively low injury severity and physiologic stability, there is a significant potential for rural geriatric trauma patients to do poorly.