Prenatal exposure, maternal sensitization, and sensitization in utero to indoor allergens in an inner-city cohort.

Primary sensitization to antigens may occur prenatally. We hypothesized that high prenatal exposure to indoor antigens increases the risk for sensitization in newborns in New York City populations with increased risk for asthma. We also investigated whether maternal sensitization is required for in utero sensitization to occur. One hundred sixty-seven pregnant African American or Dominican women residing in northern Manhattan were recruited and antigen was measured from home dust. After delivery, newborn cord and maternal blood were assayed for IgE and mononuclear cell proliferation and cytokine production in response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell proliferation occurred in 54% of newborns in response to cockroach, 25% in response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced mononuclear cell proliferation occurred in cord blood even in the absence of antigen-induced mononuclear cell proliferation in the mother. Proliferation in response to antigens did not correlate with IgE levels, but proliferation in response to dust mite extracts correlated with interluekin-5 (IL-5) production in cord blood. These results suggest that (1) high prenatal exposures to cockroach and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor antigens is common, occurs to a different degree than maternal sensitization, and may involve IL-5 upregulation.

Standards for assessment of lung function and respiratory health in minority populations: some challenges linger into the new millennium.

Results of pulmonary function tests (as an indicator of respiratory health) are from 11 to 13 percent lower in African Americans and other racial ethnic populations than in Caucasians when controlled for gender, age, and height. Environmental factors influencing these indices are circadian variation, altitude, air pollutants, technology, state of nutrition, smoking history, and other indicators of lifestyle. A combination of subtle, genetically determined anthropometric variants may also be operative, the extent of which is controversial. Population-based, population-specific standards are required to avoid erroneous diagnosis of cardiorespiratory disease, erroneous assessment of operative risk, unfair hiring practices when lung function tests are used for preemployment evaluation in dusty occupations, and unfair labeling when workers apply for disability compensation. Tailoring of statistical prediction standards from simple linear to more complex polynomial regression models will increase the accuracy of population prediction standards for pulmonary function variables into the 21st century.

5-Fluorouracil for the treatment of intraepithelial neoplasia of the conjunctiva and cornea.

OBJECTIVE: To evaluate the efficacy of pulse dosing of topical 5-fluorouracil (5-FU) in the treatment of conjunctival and corneal intraepithelial neoplasia. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Seven patients with histologic evidence of intraepithelial neoplasia were identified by conjunctival biopsy or tumor excision. METHODS: Seven patients with a minimum of 7 months of follow-up were treated with pulsed dosing of 1% 5-FU. Topical 1% 5-FU was administered four times daily for 2 to 4 days for each cycle. The number of initial treatment cycles was two to six, with the time between cycles being 30 to 45 days. MAIN OUTCOME MEASURES: The presence or absence of clinically evident intraepithelial neoplasia was evaluated after each treatment interval. Patients were also monitored for adverse reactions to the use of topical 5-FU. RESULTS: Four patients remain disease free with a mean follow-up of 18.5 months (range, 7-36 months) with no additional treatment after the initial treatment cycles (mean, 3.75 cycles; range, 2-5 cycles). Three patients had recurrence of disease after the initial treatment cycles. Two patients were treated with additional cycles for recurrent disease (six cycles in one patient and five cycles in the other patient) and are free of disease at 20 and 21 months after treatment, respectively. One patient had persistent disease despite treatment with topical 5-FU and was treated with topical mitomycin C with resolution of the disease without recurrence for 16.5 months. No adverse reactions to pulse dose treatment with topical 5-FU were noted. CONCLUSIONS: Pulsed dosing with 1% topical 5-FU for the treatment of conjunctival and corneal intraepithelial neoplasia, alone or as an adjunct to excision of bulky disease, is a well-tolerated and effective method of treatment.

Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans.

Glutathione S:-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case-control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31. 6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09-8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81-4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31-29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P: = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.

Combined intraepithelial squamous neoplasia and atypical fibroxanthoma of the cornea and limbus.

PURPOSE: To investigate a case of an unusual neoplasm of the cornea and limbus. METHODS: A 59-year-old man presented with a highly vascularized, nodular mass involving the left cornea and limbus. An excisional biopsy and, subsequently, a superficial lamellar keratectomy and multiple conjunctival biopsies were performed. At the 6-month follow-up examination, repeat conjunctival biopsies were performed. RESULTS: Histopathologic examination of the corneal specimen showed a high-grade intraepithelial squamous neoplasia (in situ carcinoma) overlying an atypical fibroxanthoma. CONCLUSION: We report the clinical and histologic appearance of a corneal/limbal neoplasm consisting of an intraepithelial squamous neoplasia and an atypical fibroxanthoma.

Wound healing following anterior keratectomy and lamellar keratoplasty in the pig.

PURPOSE: To examine corneal wound healing in an animal model of two types of mechanical lamellar keratectomy. METHODS: One eye from each of 28 pigs was studied. Using a motorized keratome, corneas were subjected to an anterior lamellar keratectomy with removal of anterior stroma and epithelium, or to automated lamellar keratoplasty (ALK) with reapposition of a corneal flap. The exposed stromal surfaces were labeled intraoperatively with a fluorescent dye (DTAF) to assess deposition of stromal components during subsequent wound healing. Examination before surgery and enucleation included measurement of corneal curvature and intraocular pressure, and assessment of corneal haze. Eyes were prepared for histological examination, fluorescence microscopy, and for fibronectin immunohistochemistry. RESULTS: Both keratectomy procedures produced flattening of corneas by up to 3.80 diopters, 28 days after surgery. Corneal haze was more pronounced in eyes from which epithelium was removed (anterior lamellar keratectomy group). The increased haze in this group was associated histologically with appearance of many reactive keratocytes and inflammatory cells, deposition of new stromal material, and more widespread appearance of fibronectin immunoreactivity. In the lamellar keratoplasty group, only the edges of the corneal wound showed significant reactivity, and included keratocyte activation and epithelial ingrowth. CONCLUSIONS: The pig provides a useful model for studies of refractive surgical techniques using procedures and instruments designed for use in humans. Mechanized keratectomy procedures that minimize disruption of the epithelium and Bowman's layer produce a less reactive corneal wound than procedures in which an expanse of epithelium and anterior stroma are removed.

Nontuberculous mycobacterial keratitis in south Florida.

OBJECTIVE: This study aimed to review the clinical features, therapeutic response, and histopathology of cases of nontuberculous mycobacterial keratitis at the Bascom Palmer Eye Institute. DESIGN AND PARTICIPANTS: Retrospective review of medical records, clinical photographs, histopathology, and microbiology of 24 cases of nontuberculous acid-fast keratitis over the past 15 years. RESULTS: Causal organisms included Mycobacterium chelonae (16), M. fortuitum (3), M. avium-intracellulare (2), M. nonchromogenicum (1), M. triviale (1), and M. asiaticum (1). Clinically, the keratitis had a superficial location except in those patients with a history of surgery. Amikacin was the most commonly used antibiotic (63%). Three patients were treated with Clarithromycin. In one patient, it was stopped because of toxicity; the other two had resolution of their infiltrates. Fifty-five percent did not respond to topical antimicrobial therapy. The organisms as a group were sensitive to amikacin and Clarithromycin and resistant to the fluoroquinolones. Sixty-four percent of the group that failed to respond to medical treatment were treated with steroids after the diagnosis was known, in comparison to 44% of the group treated successfully with medications. The histopathology of the patients treated with steroids showed minimal inflammation despite a large number of organisms, in contrast to the dense infiltrates seen in the specimens from patients not treated with topical steroids. CONCLUSION: Nontuberculous mycobacterial keratitis is a chronic insidious infection that is often unresponsive to medical therapy. The authors recommend that steroids be withheld. Based on the authors' experience of three patients, topical Clarithromycin may hold promise as a therapeutic agent. Lamellar keratectomy or penetrating keratoplasty should be considered in those patients who do not respond to medical therapy or those who have recurrent exacerbations on attempted weaning of topical antibiotic therapy.

Retrospective analysis of a novel method of transscleral suture fixation for posterior-chamber intraocular lens implantation in the absence of capsular support.

PURPOSE: To determine the safety and efficacy of an alternative method for transscleral fixation of a secondary posterior-chamber intraocular lens (pcIOL) during penetrating keratoplasty. METHODS: Eighty-nine eyes that underwent secondary pcIOL implantation by using a modified transscleral suture-fixation technique during penetrating keratoplasty were retrospectively evaluated. The surgical technique used suture fixation to the surface of the sclera 5 mm posterior to the limbus, with the knot buried beneath Tenon's capsule and conjunctiva. Patient records were reviewed for postoperative complications, including suture erosion, pcIOL subluxation, vitreous hemorrhage, and retinal detachment. Mean follow-up was 24.4 months, with a range of 4-68 months. RESULTS: All eyes had successful fixation of their pcIOL immediately after surgery. Three (3.3%) eyes had graft failure. Six (6.7%) of 89 eyes showed evidence of suture erosion or partial exposure. Postoperative suture breakage occurred in two (2.2%) eyes. Posterior-segment complications included retinal detachment in one (1.1%) eye, vitreous hemorrhage in one (1.1%) eye, and limited choroidal hemorrhage in two (2.2%) eyes. Median visual acuity at 1-year follow-up was 20/70 (range, 20/25 to light perception). CONCLUSION: This transscleral fixation technique provides a straightforward alternative to previously described techniques. Suture erosion, IOL dislocation, and posterior-segment complications occurred at relatively low rates compared with other pcIOL implantation techniques.

Topical 5-fluorouracil in treating epithelial neoplasia of the conjunctiva and cornea.

PURPOSES: To evaluate the efficacy of topical 5-fluorouracil (5-FU) in treating conjunctival and corneal epithelial neoplasia. METHODS: Three patients underwent surgical excision of bulky disease followed by topical 1% 5-FU in artificial tear base for 2 to 3 weeks or until epithelial separation occurred. An additional three patients underwent treatment with topical 1% 5-FU alone. RESULTS: Minimum follow-up was 6 months. In one patient with conjunctival in situ carcinoma and no detectable normal conjunctiva, who had normal findings on conjunctival histologic examination after application of topical 5-FU, a focus of invasive disease requiring orbital exenteration. One patient had a favorable response to 5-FU therapy but required a repeat excision for control of bulky disease. Four patients have remained disease-free for 10, 13, 18, and 30 months after topical 5-FU therapy. CONCLUSION: With its potential selective toxicity on dysplastic epithelium, topical 5-FU shows promise as an adjunctive treatment for managing conjunctival and corneal epithelial neoplasia.

Solid-phase hybridization capture of low-abundance target DNA sequences: application to the polymerase chain reaction detection of Mycobacterium paratuberculosis and Mycobacterium avium subsp. silvaticum.

Polymerase chain reaction (PCR) has been widely applied to the detection of microorganisms. Overall sensitivity of PCR tests may be substantially reduced due to a large excess of nontarget DNA and inhibitory substances in the sample. We used a 5'-biotinylated 513-bp probe from the 3' region of the IS 900 element specific for Mycobacterium paratuberculosis (Mptb) to capture target Mptb DNA from crude sample DNA extracts. Captured target DNA was separated using streptavidin-coated magnetic particles (Dynal). Since the IS 900 element shares homology over this region with IS 902 in Mycobacterium avium subsp. silvaticum (Mavs), target DNA from this other pathogen was also retained. Highly specific PCR for the detection of either organism directed to the 5' regions of IS 900 or IS 902 was then performed directly on the solid phase. Hybridization capture of target DNA using sequence adjacent to the desired specific PCR site applied to Mptb increased overall sensitivity of detection in tissue and fecal extracts 10- to 100-fold. False positives due to contamination artifact were substantially excluded since the capture probe did not retain amplicons from the detection PCR. Development of the method to involve covalent 5' immobilization of capture probes on heat-resistant polymers should, in the future, provide a simple system with broad potential applications.

Air pollution health risks: do class and race matter?

Air pollution is not spread evenly across demographic groups. Exposures and associated health risks appear to fall disproportionately on populations that are poor and nonwhite. Although scientific evidence documenting disparities in air pollution exposures, doses, and health effects is scant, the available data strongly support the contention that disadvantaged groups, many of whom are ethnic and racial minorities, routinely encounter levels of air pollution that are higher than average. The extent to which exposure differentials contribute to observed differences in health status by class and race is unknown, but worthy of further investigation. We recommend several steps, all of them feasible and most of them relatively inexpensive, to improve our understanding and ability to address environmental health disparities.