Peroperative extent of peritoneal metastases affects the surgical outcome and survival in advanced ovarian cancer.

OBJECTIVE: Determining whether cytoreductive surgery (CRS) is feasible in patients with advanced ovarian cancer and whether extensive surgery is justified is challenging. Accurate patient selection for CRS based on pre- and peroperative parameters will be valuable. The aim of this study is to assess the association between the extent of peritoneal metastases as determined during surgery and completeness of interval CRS and survival. METHODS: This single-center observational cohort study included consecutive patients with newly diagnosed stage III-IV epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent interval CRS. The 7 Region Count (7RC) was recorded during surgical exploration to systematically quantify the extent of peritoneal metastases. Logistic regression analysis was performed to predict surgical outcomes, and Cox regression analysis was done for survival outcomes. RESULTS: A total of 316 patients were included for analyses. The median 7RC was 4 (interquartile range: 2-6). Complete CRS was performed in 58%, optimal CRS in 30%, and incomplete CRS in 12% of patients. A higher 7RC was independently associated with lower odds of complete or optimal CRS in multivariable analysis (odds ratio [OR] = 0.45, 95% confidence interval [CI]: 0.33-0.63, p < 0.001). Similarly, a higher 7RC was independently associated with worse progression-free survival (hazard ratio [HR] = 1.17, 95% CI 1.08-1.26, p < 0.001) and overall survival (HR = 1.14, 95% CI 1.04-1.25, p = 0.007). CONCLUSION: The extent of peritoneal metastases, as expressed by the 7RC during surgery, is an independent predictor for completeness of CRS and has independent prognostic value for progression-free survival and overall survival in addition to completeness of CRS.

Ocular deposition of copper associated with multiple myeloma.

PURPOSE: To report a case of hypercupremia with deposits in both eyes on the Descemet's membrane, surface of the iris, and lens capsule associated with multiple myeloma. METHOD: Case report. RESULTS: A 64-year-old white woman had metallic deposits in both eyes on the central Descemet's membrane, surface of the iris, and the anterior and posterior lens capsule. A systemic examination revealed an elevated serum copper, normal serum ceruloplasmin, and an increased level of total protein and IgG kappa gammaglobulin. Based on these results, she was diagnosed with multiple myeloma. CONCLUSIONS: Copper deposits on the Descemet's membrane, surface of the iris, and lens capsule may be the first sign of multiple myeloma.

Latino physician supply in California: sources, locations, and projections.

PURPOSE: To determine the number of Latino physicians in California, identify the schools and countries where they were educated, determine the percentage located in Latino areas, and project the supply of Latino physicians to 2020. METHOD: From a 1999 list of 74,345 licensed physicians, the authors identified Latino U.S. medical graduates (USMGs) by "heavily Hispanic" surnames and Latino international medical graduates (IMGs) by country and school of graduation. The 1999 license addresses of all physicians in Los Angeles County were analyzed against 1998 Latino-population data by zip code. A baseline projection of the supply of Latino physicians was based on the ten-year (1986 to 1995) average annual production of Latino physicians educated in California, out of state, and in Latin America. A worst-case projection assumed the continuation of recent trends: a 32% decrease in California-educated Latino USMGs, a 19% decrease in out-of-state Latino USMGs, and a reduction of Latino IMGs to five per year. RESULTS: In 1999, 3,578 Latino physicians comprised 4.8% of all Californian physicians. In contrast, Latinos made up 30.4% of the state's population. Latino physicians were more likely than non-Latinos to have addresses in a heavily Latino zip code. In the baseline projection, while the overall supply of Latino physicians will increase by nearly 30% by 2020, that growth will be dwarfed by the 74% growth in the Latino population over the same time. In the worst-case projection, the actual number of Latino physicians will decrease from the 1999 figure of 3,578 to 3,448 by 2020, while the Latino population continues to grow. CONCLUSIONS: (1) The Latino USMG supply must be markedly increased in the number of first-year matriculants in both California and out-of-state schools. (2) The issue of Latino IMGs requires special attention, and may provide a temporary solution to the Latino physician shortfall. (3) Non-Latino physicians need to be prepared to be culturally effective with a large and growing Latino patient population.

Corneal cooling and rehydration during photorefractive keratectomy to reduce postoperative corneal haze.

PURPOSE: An increase in corneal temperature has been implicated in subepithelial haze after surface photorefractive keratectomy. We aimed to determine if cooling the cornea by means of hydration between ablations and immediately after final surface ablation in PRK reduces haze. METHODS: One hundred five eyes of 61 patients with myopia ranging from -6.00 to -9.75 D were included. One of the surgeons irrigated with cool balanced salt solution between ablation passes and immediately at the end of the surface ablation while two others did not. Results of haze grading were analyzed at the end of 3 and 6 months and 1 year after PRK by an independent examiner. RESULTS: Haze was significantly reduced in those eyes in which irrigation (cooling) with balanced salt solution was performed intraoperatively and immediately after ablation. CONCLUSION: Cooling and rehydration of the cornea with chilled balanced salt solution between passes during PRK significantly reduces haze in patients with baseline myopia between -6.00 and -9.75 D.

Impairment of semantic and figural memory by acute ethanol: age-dependent effects.

Alcohol drinking is prevalent among young adults in the U.S. Moreover, heavy drinking is acknowledged by a substantial percentage of young adults in both college and military subpopulations, despite the known cognitive demands associated with these endeavors and the cognitive impairments associated with alcohol usage. We assessed the acute effects of ethanol (0.6 g/kg) on the acquisition of both semantic and figural memory in a sample of young adults from 21 to 29 years of age using a repeated-measures, placebo-controlled experimental design. Ethanol significantly impaired memory acquisition in both domains. In addition, the effect of ethanol on three of the four memory measures assessed was dependent on the age of the subjects. Subjects in a young subgroup (21 to 24 years of age) were significantly more impaired in memory measures than those in the subgroup that was 25 to 29 years of age. These results indicate a divergence of the potency of ethanol against memory acquisition across a narrow age range in early adulthood. Whereas these data are preliminary, and should be generalized cautiously, they are also consistent with a growing literature using animal models that indicates that acute ethanol is a more potent antagonist of memory and memory-related hippocampal activity in adolescent animals compared with adults.

The development of substance-abuse curricular content by five North Carolina schools.

In 1992, the four medical schools in North Carolina and that state's dental school initiated a four-year project to more thoroughly integrate content about substance abuse into their curricula. The project was based on the premise that medical schools are failing to provide their students with adequate training about substance abuse issues, yet substance abuse is a large and growing source of health problems nationwide. While the authors indicate in broad ways the kinds of curricular content that the project sought, in this article they concentrate on the processes by which key faculty, administrators, and staff members from all the schools worked together in the curriculum development process, with each school tailoring the project's findings to the needs of its own students. Phase I of the project focused on the selection and orientation of the key faculty and members of the working committee at each institution, and garnering institutional support. Phase II focused on the development by key faculty of the project's philosophy, goals, and objectives; conducting needs assessment and curriculum analysis at each school; and identifying the content needed. During Phase III, project participants refined the needed content and integrated it, in individual ways, into each school's curriculum. Some (but not enough) evaluation of these curricular implementations was done. The authors highlight the lessons learned, both positive and negative, in hopes that these will be useful to other educators who wish to design, implement, and institutionalize substance-abuse curricular content.

Alcohol removal of the epithelium for excimer laser ablation: outcomes analysis.

PURPOSE: To determine whether removing the corneal epithelium by dilute alcohol is equal to other epithelial removal techniques. SETTING: The Bochner Eye Institute, Toronto, Ontario, Canada. METHODS: Epithelium was removed using 25% alcohol placed on a circular pledget; the alcohol remained on the cornea for 3 minutes. Irrigation was performed with cold balanced salt solution. The epithelium was then lifted with forceps and removed. Ninety-one eyes having photorefractive keratectomy for low myopia (less than 8.00 diopters) were treated; 41 eyes were followed between 4 and 10 months (mean 6 months). Complications such as haze and loss of best corrected visual acuity (BCVA) were recorded. RESULTS: All alcohol-treated eyes achieved a BCVA of 20/40 or better, 65.9% had 20/20 and 92.7%, 20/25 or better. There were no complications or adverse effects. CONCLUSIONS: Epithelial removal using 25% alcohol did not adversely affect the algorithms used with the VISX 20/20 excimer laser, indicating the technique is safe, predictable, and effective. There was no significant loss of BCVA, toxic effects, or stromal hydration.

Topical mitomycin-C for pterygia: is single application appropriate?

BACKGROUND AND OBJECTIVE: Mitomycin-C has been shown to dramatically reduce pterygium recurrence rates; however, its use has been associated with serious complications, especially in higher cumulative doses. The authors investigated the safety and efficacy of progressively reducing dosages of mitomycin-C as an adjunct to pterygium surgery. PATIENTS AND METHODS: Four hundred eighty-one consecutive primary and recurrent pterygia were surgically excised in a prospective nonrandomized trial using five different mitomycin-C dosages. Recurrence was defined as fibrovascular tissue over the corneoscleral limbus onto clear cornea in the area of previous pterygium excision. RESULTS: Seventy-seven patients in a control group without mitomycin-C had a recurrence rate of 65% with a mean follow-up of 33 months. A group of 77 patients treated with 0.4 mg/ml of mitomycin-C, four times per day for 2 weeks, had a recurrence rate of 2.5% with 6 (10%) serious complications (mean follow-up 34 months). A group of 22 patients treated with 0.2 mg/ml of mitomycin-C, four times per day for 10 days, had a recurrence rate of 55% with 3 (7.3%) non-vision-threatening complications (mean follow-up 32 months). A group of 16 patients treated with 0.2 mg/ml of mitomycin-C intraoperatively for 3 minutes without conjunctival closure had a recurrence rate of 44% with no complications (mean follow-up 35 months). Finally, a group of 289 patients treated with 0.2 mg/ml of mitomycin-C intraoperatively for 3 minutes with conjunctival closure had a recurrence rate of 2.7% and no complications (mean follow-up 26 months). CONCLUSION: Although the authors' results with single application are encouraging, the use of mitomycin for pterygia remains controversial. The biologic potency of this agent, the duration of its action, and the dearth of large-scale controlled, randomized trials demand cautious individual judgment by the surgeon when considering the use of this potent drug.

Computerized videokeratography of keratoconus kindreds.

OBJECTIVE: To assess the role of heredity in the development of keratoconus. DESIGN: Prospective study. SETTING: Eye clinic providing secondary and tertiary ophthalmic care in Toronto. PATIENTS: Thirty-nine patients with keratoconus (57 eyes) and 48 relatives of 11 patients with keratoconus. The corneal topography of the family members was compared with that of a group of 68 volunteer control subjects (136 eyes) without clinical evidence or a family history of keratoconus. OUTCOME MEASURES: Three quantitative measures derived from computerized videokeratography: the relative steepness of the inferior cornea versus the superior cornea, central corneal power and the difference in central corneal power between the two eyes. All the data were statistically analysed with the use of nonparametric discriminant analysis. RESULTS: Fifteen family members who were believed to be clinically normal on the basis of refraction, keratometry and slit-lamp examination has statistically significant topographic abnormalities suggestive of early or mild keratoconus. CONCLUSIONS: The presence of these findings in family members of patients with keratoconus may represent the incomplete expression of a gene contributing to the development of the condition. Pedigree analysis suggested an autosomal dominant inheritance pattern in 9 of the 11 families. Our results underline the value of videokeratography for accurate family pedigree analysis and the diagnosis of keratoconus.

Ocular toxicity of mitomycin C and 5-fluorouracil in the rabbit.

We studied the histotoxic effects of mitomycin C and 5-fluorouracil (5-FU) in the eyes of New Zealand white rabbits using light microscopy. Twenty-four eyes of 24 rabbits received subconjunctival injections of mitomycin C (0.025, 0.05, 0.10, 0.20, 0.40 or 0.80 mg/mL) or 5-FU (10.0 mg/mL), either alone (0.25 mL) or in combination with anterior chamber injections (0.05 mL), once daily for 4 consecutive days. Two eyes of two rabbits received subconjunctival and anterior chamber injections of unpreserved sterile saline. The eyes were examined regularly for external signs of toxicity and were enucleated 4 weeks after the last injection. Mitomycin C produced considerable tissue damage in the anterior segment, the severity being related to both the concentration and the route of administration. Eyes that received both subconjunctival and anterior chamber injections showed more damage than those that received subconjunctival injections alone. At the highest concentration of mitomycin C the cornea was inflamed, with stromal necrosis and marked endothelial loss. Hemorrhagic iris necrosis was also seen. In contrast, the 5-FU-treated eyes showed no microscopic evidence of toxicity. We conclude that there is greater risk of toxic anterior segment effects when mitomycin C is used as adjunctive therapy following filtration or pterygium surgery.

Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone.

OBJECTIVE: To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation. METHODS: This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms. RESULTS: The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite. CONCLUSIONS: Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.

Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking.

A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation. This study replicated this effect, in addition, nicotine skin patches were found to decrease a variety of withdrawal effects, including craving for cigarettes, negative affect, hypoarousal, and increased appetite. This study also assessed the depressive symptoms shown by smokers before and after they quit smoking. Control subjects showed a significant increase in depressive symptoms after smoking cessation, whereas the subjects given the nicotine skin patch were not as affected. If the subjects slipped and smoked a cigarette during the time they were wearing the patch, they were asked to rate the effects of that cigarette. These "slip" cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls. The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking. This latter effect may prove to be effective in preventing slips from turning into relapses.

Remedial medical education.

Continuing medical education plays an essential role in efforts to improve physician performance. This article deals with remedial or personalized physician education. The experience of selected institutions and state organizations that have and/or continue to provide such remedial education is reviewed. The emphasis of remedial or focused physician education is educational enhancement, not suspension or revocation of license.

Predicting response to amitriptyline in posttraumatic stress disorder.

OBJECTIVE: This study evaluated the relation between baseline clinical phenomena and response to amitriptyline in patients with posttraumatic stress disorder (PTSD). METHOD: Data were obtained from an 8-week placebo-controlled, double-blind study of combat veterans. Bivariate and multivariate statistics were used to evaluate the relations between the following variables and outcome: age, depression, anxiety, severity of PTSD symptoms, personality, psychiatric comorbidity, level of exposure to trauma, and individual symptoms of depression, anxiety, and traumatic stress. Outcome measures were scores on the Clinical Global Impression scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Impact of Event Scale. RESULTS: Drug response was related to lower baseline levels of depression, neuroticism, combat intensity, anxious mood, impaired concentration, somatic symptoms, feelings of guilt, and one intrusion and four avoidance symptoms of PTSD. CONCLUSIONS: The results demonstrate that response to amitriptyline is related to measures of depression, anxiety, PTSD, personality, and intensity of combat trauma. Similar relationships were not observed in the placebo group, suggesting a specific relationship to the drug.

Serious complications of topical mitomycin-C after pterygium surgery.

BACKGROUND: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. METHODS: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. RESULTS: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). CONCLUSION: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed.