Microsphere antioxidant and sustained erythropoietin-R76E release functions cooperate to reduce traumatic optic neuropathy.

Wild-type erythropoietin (EPO) is promising for neuroprotection, but its therapeutic use is limited because it causes a systemic rise in hematocrit. We have developed an EPO-R76E derivative that maintains neuroprotective function without effects on hematocrit, but this protein has a short half-life in vivo. Here, we compare the efficacy and carrier-induced inflammatory response of two polymeric microparticle (MP) EPO-R76E sustained release formulations based on conventional hydrolytically degradable poly(lactic-co-glycolic acid) (PLGA) and reactive oxygen species (ROS)-degradable poly(propylene sulfide) (PPS). Both MP types effectively loaded EPO-R76E and achieved sustained release, providing detectable levels of EPO-R76E at the injection site in the eye in vivo for at least 28 days. Testing in an in vitro oxidative stress assay and a mouse model of blast-induced indirect traumatic optic neuropathy (bITON) showed that PPS and PLGA MP-mediated delivery of EPO-R76E provided therapeutic protection. While unloaded PLGA MPs inherently increase levels of pro-inflammatory cytokines in the bITON model, drug-free PPS MPs have innate antioxidant properties that provide therapeutic benefit both in vitro and in vivo. Both PLGA and PPS MPs enabled sustained release of EPO-R76E, providing therapeutic benefits including reduction in inflammation and axon degeneration, and preservation of visual function as measured by electroretinogram. The PPS-based MP platform is especially promising for further development, as the delivery system provides inherent antioxidant benefits that can be harnessed to work in complement with EPO-R76E or other drugs for neuroprotection in the setting of traumatic eye injury.

Treatment of congenital melanocytic naevi with CO2 laser.

This study assesses the effectiveness of CO2 laser in treating congenital melanocytic naevi (CMN). A retrospective review of 12 patients with CMN treated with CO2 laser was carried out. In all cases, there was minimal visible naevus after treatment. Six patients developed hypertrophic scarring; this was significantly more likely following CO2 laser treatment on the anterior torso, flanks, or arms than on the back or buttocks (P = 0.01, 1-tailed Fisher exact test). We conclude that CO2 laser is an effective treatment for reducing visible pigmentation of CMN. However, it can cause hypertrophic scarring, which has not been reported before. This risk can be reduced by limited use in areas of the body where the dermis is thinner or there is a known risk of hypertrophic scarring. In addition, the cautious use of paint mode and prophylactic use of pressure or silicon dressings may also reduce the risk of hypertrophic scarring.

Association of influenza vaccination and reduced risk of recurrent myocardial infarction.

BACKGROUND: Numerous studies have suggested that microbial agents may promote atherosclerosis. A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infarction (MI). We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease (CHD). METHODS AND RESULTS: A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998. Patients who experienced new MI were included in the case group, and those who did not experience new MI or unstable angina were assigned to the control group. Data were collected by structured review of patients' charts and through a subsequent telephone survey. Adjusted for history of influenza vaccination in previous years, multivariate logistic regression revealed risk of MI to be associated with current hypertension (OR 4.96, 95% CI 2.06 to 11.96, P<0.0001), hypercholesterolemia (OR 4.08, 95% CI 1.67 to 9.99, P=0.002), smoking (OR 3.75, 95% CI 1.76 to 7.98, P=0.001), and influenza vaccination (OR 0.33, 95% CI 0.13 to 0.82, P=0.017). Despite significant association in univariate analysis, multivitamin therapy and physical exercise were not associated with risk of reinfarction in multivariate analysis. CONCLUSIONS: In this study in patients with chronic CHD, vaccination against influenza was negatively associated with the development of new MI during the same influenza season. However, to address causal inference, examination of prospective data sets will be needed.

Endobronchial intubation causes an immediate increase in peak inflation pressure in pediatric patients.

UNLABELLED: Our purpose was to determine whether endobronchial intubation always causes an immediate increase in peak inflation pressure and, if so, the magnitude of the increase. Fourteen children scheduled for central line placement for prolonged antibiotic administration comprised the study group. After routine premedication and induction of anesthesia (halothane in oxygen), an endotracheal tube was inserted, and its position was verified by auscultation and fluoroscopy. Children were mechanically ventilated using a preset volume pressure-limited ventilator with a 5-L fresh gas flow. All children received a constant tidal volume using a similar circuit, similar tubing, and a similar compression volume. The lowest peak inflation pressure to deliver a tidal volume of 15 mL/kg was used. After adjusting the respiratory rate (end-tidal CO2 30 mm Hg) and anesthetic level (halothane end-tidal 1.2%), the peak inflation pressure at this endotracheal position was recorded. The endotracheal tube was advanced into a bronchus, the position was verified as above, and peak inflation pressure was recorded. The endobronchial tube was then pulled back into the trachea, and placement of the central line proceeded. The peak inflation pressure at the endobronchial position was significantly greater than the peak inflation pressure at the endotracheal position (P < 0.0001). The increase was instantaneous at the endobronchial position. Monitoring peak inflation pressure while inserting an endotracheal tube and during anesthesia can help to diagnose endobronchial intubation. IMPLICATIONS: Monitoring peak inflation pressure while inserting an endotracheal tube and during anesthesia can help to diagnose endobronchial intubation.

Presumed primary malignant melanoma of the gallbladder. Report of a case and a review of literature.

Primary malignant melanomas of the gallbladder are rare lesions that have been the subject of debate. Only 11 such cases have been reported. The debate is reviewed and conflicting opinions of workers in the field are discussed. Attention is drawn to some of the features that are said to characterize the lesions presumed to be primary melanomas of the gallbladder, such as polypoid growth, "junctional" changes in the normal mucosa, and, above all, absence of other demonstrable primary foci of malignant melanomas. What at first appeared to be the 12th case of this rare entity, and in the youngest patient at that, is now described by light and electron microscopy, but a more likely possibility, supported by biopsy of the skin, is that an undiagnosed malignant melanoma in the skin had undergone complete regression after it had metastasized to the gallbladder.

Relation of various epidemiologic factors to cervical cancer as determined by a screening program.

PIP: This study attempted to elucidate the etiology of cervical cancer by examining its association with a number of factors in a relatively unselected group of women. In 1963, a cytologic screening program was undertaken in Washington County, Maryland. The irrigation smear method was used. The final study group of 4341 was 46% of all white women aged 30-45 years enumerated in the census. Of the 4290 satisfactory smears, 46 were positive or suspicious. Subsequent investigation confirmed 31 cases of which 28 were at Stage 0 and 3 were invasive carcinoma of the cervix. Of 15 with suspicious cytologic findings 6 had confirmed findings, all of which were at Stage 0. Women who were never married had no confirmed cases. Currently-married women had lower rates than women whose marriages had been disrupted. Those who were married at age 16 or earlier had higher rates of cervical cancer as did those from lower socioeconomic levels. Having had multiple sex partners was associated with an increased risk of developing cervical cancer. Smokers had slightly higher rates than nonsmokers. Trichomonas vaginali s infestation was associated with higher rates. Findings indicate that trichomoniasis and cervical cancer are both associated with sexual activity.^ieng

Epidemiologic study of trichomoniasis in normal women.

PIP: The prevalence of trichomonas vaginalis in a relatively unselected group of 4341 30-45 year old white women from Washington County, Maryland, was examined in Papanicolaou stained smears prepared by the self-administered irrigation smear method. 14.5% of the 4290 satisfactory smears were classified as positive for T. vaginalis. This may have been underestimated since over 1/2 of the group showed few parasites. 2.7% of the total (20% of the positive group) had heavy infestations. There was an insignificant increase between 30-34 and 40-45 year old women (13.6%-15.2%). There was a negative association between the amount of schooling and incidence of infection. Married women had 1/2 the infection incidence of widowed or never married women and one-third the incidence of divorced or separated women, a a pattern which differs from other reports. However, symptomatic unmarried women may have responded to the survey in greater numbers than symptomatic unmarried women, biasing the results. There was a significantly higher incidence of trichomoniasis among women married several times than among women married only once. There was a correlation between age at first marriage and infection incidence. The use of intravaginal contraceptive agents may have an effect on the trichomonads. There was no correlation with religion or size of household. Inverse correlations were noted between income, occupation of husband, crowding and sanitary facilities and trichomoniasis infection with an exception being the low frequency among farm women. Moderate and heavy cigarette smokers had higher infection rates than light and nonsmokers, and there was a high association of trichomoniasis with abnormal cytologic findings. These were all consistent with a venereal mode of transmission.^ieng