Efficacy of topical cidofovir on multiple adenoviral serotypes in the New Zealand rabbit ocular model

PURPOSE: The goal of the present study was to determine the efficacy of topical 0.5% cidofovir twice daily for 7 days on the replication of multiple adenovirus (Ad) serotypes of subgroup C (Ad1, Ad5, Ad6) in the New Zealand rabbit ocular model. METHODs: In duplicate experiments for each serotype, a total of 20 rabbits (Ad5) or 16 rabbits each (Ad1 and Ad6) were inoculated topically in both eyes, with 1.5 X 10(6) pfu/eye of the appropriate virus. Twenty-four hours later, the rabbits in each serotype group were randomly divided into two topical treatment groups: I, 0.5% cidofovir; II, control vehicle. Treatment was twice daily for 7 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. RESULTS: Compared to the control, treatment with 0.5% cidofovir reduced the following: mean Ad titer (days 1 to 7) for Ad1 (6.3 +/- 20 x 10(1) versus 2.5 +/- 3.9 X 102 pfu/ml; P < 0.0003), Ad5 (3.4 +/-5.8 x 102 versus 1.6 +/- 2.0 x 10(3) pfu/ml; P < 0.000001), and Ad6 (1.2 +/- 5.1 x 10(2) versus 5.5 +/-14 x 10(2) pfu/ml; P = 0.015); reduced Ad-positive eyes/total for Adl [45/128 (35%) versus 84/128 (66%); P = 0.000002], Ad5 [84/160 (53%) versus 131/152 (86%); P < 0.000001], and Ad6 [36/128 (28%) versus 82/128 (64%); P < 0.000001]: and reduced the duration of Ad shedding forAdl (4.9 +/-1.9 versus 9.3 +/- 3.3 days; P < 0.00007), Ad5 (6.4 +/- 2.8 versus 11.5 +/- 2.3 days; P < 0.0001), and Ad6 (4.4 +/- 2.1 versus 8.4 +/- 2.5 days; P < 0.00004). CONCLUSIONS: Topical 0.5% cidofovir twice daily for 7 days demonstrated significant antiviral activity against multiple adenoviral serotypes (Ad1, Ad5, and Ad6) in the New Zealand rabbit ocular model. These in vivo data expand in vitro studies indicating the efficacy of cidofovir against different adenovirus serotypes and support its use in clinical trials.     

Factors associated with corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the factors associated with corneal scarring at baseline. METHODS: We defined corneal scarring as scars that had been detected both by the clinician examining the patient with the slit-lamp biomicroscope and by masked readers of corneal photographs at the CLEK Photography Reading Center. We investigated associations between corneal scarring and patient variables including gender, ethnicity, a family history of keratoconus, a history of ocular trauma, eye rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal findings (such as curvature, Vogt's striae, Fleischer's ring, and central/apical staining). Multiple logistic regression analysis using generalized estimating equations to adjust for the correlation between eyes was used for analysis. RESULTS: The following factors were found to increase the odds of corneal scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) = 3.40, 95% confidence interval 2.53-4.59), contact lens wear (OR = 3.51, 95% confidence interval 2.27-5.45), Fleischer's ring (OR = 1.63, 95% confidence interval 1.11-2.40), steeper first definite apical clearance lens base curve radius (per diopter, OR = 1.29, 95% confidence interval 1.25-1.33), and age (per decade, OR = 1.54, 95% confidence interval 1.35-1.75). CONCLUSIONS: These baseline data suggest that corneal scarring in keratoconus is associated with corneal staining, contact lens wear, Fleischer's ring, a steeper cornea, and increasing age. The factors that imply added risk for corneal scarring that may be affected by practitioner intervention are staining of the cornea, contact lens wear, and the contact lens fitting relationship.     

Corneal scarring and vision in keratoconus: a baseline report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study

PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the correlation of corneal scarring with clinical and patient-reported variables at the baseline visit. METHODS: Patients completed a questionnaire on their vision, effect of glare, contact lens wear, and work-related issues. Clinical examination included high- and low-contrast visual acuity, refraction, assessment of corneal scarring by the clinician and by photography, and measurement of corneal curvature. The correlation of central corneal scarring with visual acuity and patient-reported variables was analyzed using multiple regression analysis and generalized estimating equations. RESULTS: High- and low-contrast visual acuity with habitual and optimal correction is reduced in scarred eyes. Multiple regression analyses controlling for age, contact lens wear, and disease severity show that central scarring is associated with poorer visual acuity and increased patient-reported symptoms of glare. Restrictions on day-to-day activities do not appear to be associated with corneal scarring above and beyond the effects of keratoconus alone. CONCLUSIONS: Corneal scarring in keratoconus is significantly associated with decreased high- and low-contrast visual acuity.     

Behavioral medicine in medical education: report of a survey

Behavioral medicine has become increasingly important in medical education over the past two decades, but adoption of its principles and methods has been slow. Behavioral medicine stresses the effects of human behavior on health and illness using a biopsychosocial approach. It also focuses on the use of the doctor-patient relationship, which, if developed using appropriate communication skills, can result in greater patient satisfaction and increased compliance. The authors surveyed all 124 American medical schools to assess both national trends and specific efforts in the teaching of behavioral medicine principles and methods. A review of the types of behavioral medicine programs offered reveals that eight percent of U.S. medical schools had integrated programs of behavioral medicine. Several successful and effective programs were identified, as were a number of specific curricular components. There are several options available to medical schools to integrate behavioral medicine into medical education. The authors conclude that medical education must include behavioral medicine in order to improve the health of the public and to meet the demands of a changing health care system.     

Extreme virilization in patients with congenital adrenal hyperplasia fails to induce descent of the ovary

The commonly held hypothesis that androgens cause testicular descent in the male [9] predicts that excess endogeous androgens in the female fetus might cause descent of the ovary. To re-evaluate this prediction from a clinical perspective, a retrospective review was made of genotypic females with congenital adrenal hyperplasia and severe virilization. Patients with maximal virilization were included, since this is the group with the earlies and highest production of adrenal androgens during fetal development. Records were reviewed of five children in whom the external genitalia were completely or almost completely masculinized, who had been regarded as males with undescended testes at birth. The position of the ovaries was determined where possible from operative or pathological reports. In four patients the ovaries had been identified at operation, and were found to be in their normal position. In none were the ovaries in or adjacent to the inguinal canal. In the most recent patient, who presented in 1979, laparotomy was not performed because of the belief that the female internal genitalia were normal. In addition, review of the literature revealed two other similar female children with maximal virilization but documented normal ovarian position. The significance of these well-known findings has been ignored in recent studies of testicular descent. Failure of endogenous androgens to affect ovarian position supports the view that initiation of gonadal descent is independent of androgens. Since Müllerian inhibiting substance is the other recognizable hormone in the fetal testis apart from testosterone, it is suggested that it may be responsible for initiating gonadal descent.     

Detection of human papillomavirus DNA in advanced epithelial ovarian carcinoma

Tissue specimens from 10 out of 12 patients with advanced epithelial ovarian adenocarcinoma contained DNA of human papillomavirus type 6 (HPV-6). HPV DNA was identified by in situ hybridization at high stringency using biotin-labeled DNA probes. Nonneoplastic tissue specimens from other pelvic sites of the same patients were also examined. None showed evidence of HPV DNA. The meaning of these findings in relation to epithelial ovarian carcinoma is discussed.     

Safety and immunogenicity of Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children 15 to 24 months of age

To evaluate the safety and immunogenicity of the Haemophilus influenzae type b polysaccharide vaccine, PRP, and a new polysaccharide-diphtheria toxoid conjugate vaccine, PRP-D, a collaborative study was carried out in six centers in five states. Subjects were 585 infants 15 to 24 months of age. They were randomly assigned to receive a single dose of PRP or PRP-D vaccine. There were no significant differences in the rate of adverse reactions between the two vaccine groups. Minor local reactions occurred in 10.3% of PRP and 12.5% of PRP-D recipients, and fever in 27.4% of PRP and 23.8% of PRP-D recipients. All reactions resolved within 48 hours. Serum samples were obtained just before vaccination and after 1 month. Prevaccination antibody levels were similar for the PRP (0.035 micrograms/mL) and PRP-D (0.027 micrograms/mL) groups, with no differences in levels by age, sex, race, vaccine lot, or study site. Both groups had significant rises in geometric mean levels, but this difference was significantly greater for PRP-D (2.166 micrograms/mL) than for PRP (0.154 micrograms/mL). In addition, the percentage of responders as determined by three definitions (twofold titer rise, greater than 0.15 micrograms/mL, and greater than 1.0 micrograms/mL) was also significantly greater for PRP-D than PRP. In contrast to a marked age-related immunogenicity to PRP (P less than 0.001), there was no significant variation in immune response to PRP-D by age. PRP-D conjugate vaccine appears to be as safe and significantly more immunogenic than PRP vaccine for children vaccinated at 15 to 24 months of age.     

Successful treatment of leptomeningeal relapse of epithelial ovarian cancer

A case of isolated leptomeningeal recurrence of an epithelial ovarian cancer was recently diagnosed and treated successfully with methotrexate placed via an Ommaya reservoir in combination with radiation therapy. A review of the literature revealed no other cases of epithelial ovarian leptomeningeal malignancy similarly treated.