Limiting the location of putative human prostate cancer tumor suppressor genes on chromosome 18q.

We studied loss of heterozygosity (LOH) on the long arm of human chromosome 18 in prostate cancer to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the pathological grade and stage of the cancer. Of 48 specimens analysed 17 (35.4%) lost at least one allele on chromosome 18q. All the specimens with allelic losses lost at least one allele within chromosomal region 18q21. Allelic losses picked at D18S51 (19%) and D18S858 (17%). A 0.58 cM DNA segment that includes the D18S858 locus and is flanked by the microsatellite loci D18S41 and D18S381, was lost in eight (47%) of 17 specimens with allelic losses. This segment was designated as a LOH cluster region 1 (LCR 1). Although Smad2 resides within LCR 1, it was not mutated in any of the six prostate cell lines (five prostate cancer cell lines and one immortalized prostate epithelial cell line) analysed, suggesting that it is not a candidate TSG in prostate cancer. A second LCR at 18q21, LCR 2, includes the D18S51 locus and is flanked by the D18S1109 and D18S68 loci, which are separated by 7.64 cM. LCR 2 was lost in six (35%) of the 17 specimens with chromosome 18q losses. These results suggest that chromosome 18q21 may harbor two candidate prostate cancer TSGs. The candidate TSGs DCC and Smad4 are located centromeric to the LCRs. No alleles were lost within or in close proximity to these genes, suggesting that they are not targets for inactivation by allelic losses in prostate cancer. Although there was no obvious correlation between chromosome 18q LOH and the pathological grade or stage, three (37.5%) of eight low-grade cancers and nine (32.1%) of 28 organ-confined cancers lost alleles at 18q21, suggesting that allelic losses are relatively early events in the development of invasive prostate cancer.

Cluster of allele losses within a 2.5 cM region of chromosome 10 in high-grade invasive bladder cancer.

A limited number of previous studies have indicated a low frequency of chromosome 10 allele losses and deletions in bladder cancers. We investigated the involvement of chromosome 10 in advanced bladder cancers. Loss of heterozygosity (LOH) was analysed in 19 microsatellite loci in 20 grade III invasive transitional cell carcinomas. Nine (45%) of the 20 tumors had at least one allele loss on the long arm of chromosome 10. The short arm of chromosome 10 was not affected. The most frequent LOH occurred at D10S215, where four (29%) of 14 of the informative cases had an allele loss. The minimal region with allele losses was located between the centromeric marker D10S1644 and the telomeric marker D10S541, which are separated by 2.52 cM. The results strongly suggest the existence within that region of a tumor suppressor gene or genes for advanced bladder cancer.

Quality of life with macular degeneration: perceptions of patients, clinicians, and community members.

BACKGROUND/AIMS: Age related macular degeneration (ARMD) is a common ophthalmological disorder that can significantly impair a patient's ability to function independently and potentially have a dramatic impact on health related quality of life. The aim of this study is to evaluate the quality of life of patients with ARMD, through the use of utility evaluation, and assess whether clinicians and healthy volunteers appreciate the impact of ARMD on health related quality of life. METHODS: A standardised questionnaire using the time-tradeoff method of utility analysis was created to assess health related quality of life. This questionnaire was distributed to 115 patients with ARMD. A similar questionnaire was distributed to 142 healthy volunteers and 62 clinicians who were asked to assume that they had ARMD. Comparisons were made among the responses from the members of the three groups. RESULTS: There was a significant difference in the utility scores among respondents with mild, moderate, and severe ARMD when compared to members of the general public and clinicians who were asked to assume they had each severity of ARMD. For mild ARMD the mean utility scores were 0.932, 0.960, and 0.832, for the general public, clinicians, and patients respectively (F = 21.7; p <0.001). No significant difference was found between the community members and clinicians (p <0.166); however, the patient group differed significantly from the general public (p<0.001) and clinician (p <0.001) groups. The utility scores for moderate ARMD for the general public, clinicians, and patients were 0.918, 0.877, and 0.732, respectively. (F = 34.6, p <0.001). There was no significant difference between the general public and clinicians (p <0.143); however, the patient group differed significantly compared with the general public (p <0.001) and clinician (p <0.001) groups. The utility scores for people with severe ARMD in the general public, clinician, and patient groups were 0.857, 0.821, and 0.566, respectively (F = 45.5; p <0.001). No significant difference was shown between the community members and clinicians (p <0.386); however, a significant difference was seen when comparing the patient group with the community member and clinician (p<0.001) groups. CONCLUSION: Clinicians and community members may greatly underestimate the impact of mild, moderate, and severe ARMD on health related quality of life.

The quality of life of patients with hypertension.

The authors evaluated the self-reported quality of life in patients with systemic arterial hypertension and assessed whether clinicians and normotensive respondents from the general public appreciate the impact that hypertension has on health-related quality of life. A quality-of-life questionnaire was completed by 385 individuals: persons with hypertension (n=188), normotensive persons (n=148), and clinicians (n=49). A utility score, which represents one's self-perceived health-related quality of life, was generated for each group by using standardized time tradeoff questionnaires. Quality of life with hypertension was judged to be significantly higher according to affected individuals (mean utility score, 0.980), compared with normotensive persons (mean utility score, 0.948) and clinicians (mean utility score, 0.942), who were asked to assume that they had hypertension (p<0.0005). Clinicians and normotensive individuals tend to overemphasize the impact that hypertension has on quality of life, as compared to affected patients. The relatively low impact that hypertensive individuals indicate high blood pressure has on their quality of life may contribute to their lack of compliance with treatment regimens.

Air bags and ocular injuries.

PURPOSE: This investigation retrospectively examined ocular injuries associated with air bag deployment to gain a better appreciation of potential risk factors in motor vehicle accidents. National statistics regarding the efficacy of air bags were reviewed. METHODS: Review of the literature from 1991 to 1998 identified 44 articles describing 97 patients with air-bag-induced ocular injuries. Variables extracted from each case were age, sex, height, position in the car, eye wear, vehicle impact speed, visual acuity, and specific ocular injuries. RESULTS: Corneal abrasions occurred in 49% of occupants, hyphemas in 43%, vitreous or retinal hemorrhages in 25%, and retinal tears or detachments in 15%. The globe was ruptured in 10 patients. Patients involved in higher-speed accidents (over 30 mph) sustained a greater percentage of vitreous or retinal hemorrhages and traumatic cataracts, while those at slower speeds were more prone to retinal tears or detachments. In a subset of 14 patients with serious ocular injuries, the impact speed of 11 patients was recorded at 30 mph or less. Slower speed may be a risk factor for some ocular injuries. Occupant height was not a significant factor. National statistics confirm that air bags reduce fatalities in motor vehicle accidents. However, children sitting in the front seat without a seat belt and infants in passenger-side rear-facing car seats are at risk for fatal injury. CONCLUSION: Air bags combined with seat belts are an effective means of reducing injury and death in adults during motor vehicle accidents. However, this study has documented a wide variety of ocular injuries associated with air bag deployment. It is hoped that researchers can develop modifications that continue to save lives while minimizing additional harm.

Acetophenone as an anti-attractant for the western pine beetle, Dendroctonus Brevicomis LeConte (Coleoptera: Scolytidae).

Host location and colonization by bark beetles is dependent upon the relative and absolute amounts of attractant and antiattractant compounds available. Many investigations have lead to use of antiattractants for the management of these pests and have been especially focused on verbenone. However, recent studies have identified new antiattractants for several species of bark beetles. We report results of recent investigations of the response of western pine beetle, Dendroctonus brevicomis LeConte, to two recently identified antiattractants, acetophenone, and fenchyl alcohol, with verbenone as a standard of comparison, in northern California. Release of both acetophenone and verbenone resulted in significantly lower trap catches of D. brevicomis in aggregation pheromone-baited traps, while fenchyl alcohol was inactive. Acetophenone was the only antiattractant that did not reduce numbers of the most abundant predator of D. brevicomis, Temnochila chlorodia (Mannerheim), responding to the attractant pheromone of its prey. Aggregation pheromone-baited traps with acetophenone also had the highest predator/prey ratio. Our results suggest that acetophenone may be part of the intra- and interspecific interactions among sympatric species of bark beetles and may have application in their control.

Response to host volatiles by native and introduced populations of Dendroctonus valens (Coleoptera: Curculionidae, Scolytinae) in North America and China.

Bark beetles (Coleoptera: Curculionidae, Scolytinae) have specialized feeding habits, and commonly colonize only one or a few closely related host genera in their geographical ranges. The red turpentine beetle, Dendroctonus valens LeConte, has a broad geographic distribution in North America and exploits volatile cues from a wide variety of pines in selecting hosts. Semiochemicals have been investigated for D. valens in North America and in its introduced range in China, yielding apparent regional differences in response to various host volatiles. Testing volatiles as attractants for D. valens in its native and introduced ranges provides an opportunity to determine whether geographic separation promotes local adaptation to host compounds and to explore potential behavioral divergence in native and introduced regions. Furthermore, understanding the chemical ecology of host selection facilitates development of semiochemicals for monitoring and controlling bark beetles, especially during the process of expansion into new geographic ranges. We investigated the responses of D. valens to various monoterpenes across a wide range of sites across North America and one site in China, and used the resulting information to develop an optimal lure for monitoring populations of D. valens throughout its Holarctic range. Semiochemicals were selected based on previous work with D. valens: (R)-(+)-alpha-pinene, (S)-(-)-alpha-pinene, (S)-(-)-beta-pinene, (S)-(+)-3-carene, a commercially available lure [1:1:1 ratio of (R)-(+)-alpha-pinene:(S)-(-)-beta-pinene:(S)-(+)-3-carene], and a blank control. At the release rates used, (+)-3-carene was the most attractive monoterpene tested throughout the native range in North America and introduced range in China, confirming results from Chinese studies. In addition to reporting a more effective lure for D. valens, we present a straightforward statistical procedure for analysis of insect trap count data yielding cells with zero counts, an outcome that is common but makes the estimation of the variance with a Generalized Linear Model unreliable because of the variability/mean count dependency.

Chromosome painting supports lack of homology among sex chromosomes in Oncorhynchus, Salmo, and Salvelinus (Salmonidae).

The sex chromosome pair has been identified previously as the largest submetacentric pair in the genome in several species of the genus Salvelinus (eastern trouts and chars) including S. namaycush (lake trout) and as a large subtelocentric/acrocentric pair in several species of the genus Oncorhynchus (Pacific trouts and salmon). Sex chromosomes have not been identified in Salmo (Atlantic salmon and brown trout). Two paint probes, one specific for the short arm (Yp) and the other for the long arm (Yq) of the sex chromosome pair in Salvelinus namaycush were hybridized to chromosomes of Oncorhynchus mykiss (rainbow trout) and O. tshawytscha (chinook salmon) and Salmo salar (Atlantic salmon) and S. trutta (brown trout). The two probes hybridized to two different autosomal pairs in each of the Oncorhynchus species, supporting lack of homology between the sex chromosomes in the two genera. The Yp probe hybridized to interstitial regions on two different chromosome pairs in S. salar and one pair in S. trutta. The Yq probe hybridized to a different pair in both species.

Treatment strategies for postoperative Propionibacterium acnes endophthalmitis.

PURPOSE: Propionibacterium acnes endophthalmitis after cataract extraction and posterior chamber intraocular lens (IOL) implantation is characterized by a chronic indolent course, frequently associated with recurrence after standard endophthalmitis treatment. This study was designed to evaluate the efficacy of various therapeutic methods in the treatment of primary and recurrent episodes of postoperative P. acnes endophthalmitis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-five patients treated at Wills Eye Hospital for P. acnes endophthalmitis. METHODS: The authors retrospectively reviewed the clinical charts and microbiology files of all patients treated at Wills Eye Hospital between January 1991 and April 1998 with culture-proven P. acnes endophthalmitis after cataract extraction and posterior chamber IOL implantation. MAIN OUTCOME MEASURES: Results of cultures and microbiologic examinations, efficacy of various treatment methods in the prevention of recurrent inflammatory episodes, and final visual outcome. RESULTS: Twenty-five patients who met inclusion criteria were identified; initial therapy consisted of 1 of the following: intraocular antibiotic (IOAB) injections alone (2 patients); IOAB combined with pars plana vitrectomy (PPV) (10 patients); IOAB and PPV combined with partial capsulectomy (9 patients); and IOAB, PPV, total capsulectomy, and IOL exchange (4 patients). Nearly half of the patients (10 of 21, or 48%) initially treated with IOAB alone (1 of 2), IOAB and PPV (5 of 10), and IOAB combined with PPV and partial capsulectomy (4 of 9) required further therapeutic interventions for recurrent disease. Retreatment with IOAB alone or combined with PPV and partial capsulectomy in these patients failed to eradicate the infection in three (75%) of four patients. None of the patients (0 of 4) treated initially with total capsulectomy and IOL exchange required additional surgical intervention. Furthermore, none of the patients (0 of 13) who underwent total capsulectomy with IOL removal or exchange or IOL exchange alone as an initial, secondary, or tertiary treatment required further intervention. CONCLUSION: In the authors' series, approximately half of the patients with P. acnes endophthalmitis were treated successfully initially with nonsurgical or limited surgical intervention. All patients treated with total capsulectomy and IOL exchange or removal, either as an initial treatment or for recurrent disease, were cured. Removal of the entire capsular bag and the IOL may be performed as a definitive initial therapy and should be performed for recurrent inflammation.

Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis.

OBJECTIVE: To compare visual outcomes between cases of acute postoperative endophthalmitis that did or did not receive intravitreal steroids. DESIGN: Retrospective nonrandomized comparative trial. PARTICIPANTS: Fifty-seven patients with postoperative endophthalmitis. INTERVENTION: Thirty-one patients with postoperative endophthalmitis resulting from cataract extraction received both intravitreal antibiotics and steroids, whereas the remaining 26 received only intravitreal antibiotics. MAIN OUTCOME MEASURES: Improvement in visual acuity. RESULTS: Multivariate logistic regression was used to analyze the variables that potentially influence a three-line visual acuity improvement. The mean baseline visual acuities of both groups were comparable. The use of intravitreal steroids reduced the probability of developing a three-line improvement in visual acuity (odds ratio [OR] = 0.287; 95% confidence interval [CI] [0.072-0.852]). On the basis of logistic regression analysis using our multivariate model, gender, baseline visual acuity, and pars plana vitrectomy were not significantly associated with visual outcome differences between the two groups. CONCLUSIONS: Patients who received intravitreal steroids had a significantly reduced likelihood of obtaining a three-line improvement in visual acuity. At a minimum our study provides no support for their use and, therefore, steroids may not be efficacious for acute endophthalmitis related to cataract extraction.

Cases of cat-associated human plague in the Western US, 1977-1998.

Exposure to cats infected with Yersinia pestis is a recently recognized risk for human plague in the US. Twenty-three cases of cat-associated human plague (5 of which were fatal) occurred in 8 western states from 1977 through 1998, which represent 7.7% of the total 297 cases reported in that period. Bites, scratches, or other contact with infectious materials while handling infected cats resulted in 17 cases of bubonic plague, 1 case of primary septicemic plague, and 5 cases of primary pneumonic plague. The 5 fatal cases were associated with misdiagnosis or delays in seeking treatment, which resulted in overwhelming infection and various manifestations of the systemic inflammatory response syndrome. Unlike infections acquired by flea bites, the occurrence of cat-associated human plague did not increase significantly during summer months. Plague epizootics in rodents also were observed less frequently at exposure sites for cases of cat-associated human plague than at exposure sites for other cases. The risk of cat-associated human plague is likely to increase as residential development continues in areas where plague foci exist in the western US. Enhanced awareness is needed for prompt diagnosis and treatment.