Prevalence of factors associated with edentulousness (no natural teeth) in adults with intellectual disabilities.

BACKGROUND: Poor oral health is largely preventable. Prevention includes toothbrushing and regular dental checks. Oral health has important consequences for general nutrition, chewing, communication, wider systemic disease, self-confidence and participation in society. This study investigated the prevalence of edentulousness (no natural teeth) in adults with intellectual disabilities (IDs) compared with the general population and associated factors. METHODS: An adult cohort with IDs residing in Greater Glasgow and Clyde, Scotland, underwent detailed health assessments between 2002 and 2004. Between 2004 and 2006, a subsample had an oral check. Data on edentulousness in the cohort were compared with adult participants from Greater Glasgow and Clyde in the 2008 Scottish Health Survey. Within the IDs cohort, binary logistic regression analyses investigated potential relationships between edentulousness and demographic and clinical factors. RESULTS: Five hundred sixty adults with IDs were examined [53.2% (298) male, mean age = 46.3 years, range 18-81 years] and compared with 2547 general population: edentulousness was 9% vs. 1% aged 25-34 years; 22% vs. 2% aged 35-44 years; 39% vs. 7% aged 45-54 years; 41% vs. 18% aged 55-64 years; and 76% vs. 34% aged 65-74 years. In both groups, edentulousness increased with age. After stratification for age, rates of edentulousness were consistently higher in the ID cohort. Odds ratios within age strata were not homogenous (Mantel-Haenszel test, P < 0.0001). Edentulousness was more likely in those with more severe IDs (adjusted odds ratio (AOR) = 2.36; 95% confidence interval (CI) [1.23 to 4.51]); those taking antipsychotics (AOR = 2.09; 95% CI [1.25 to 3.51]) and those living in the most deprived neighbourhoods (AOR = 2.69; 95% CI [1.11 to 6.50]). There was insufficient evidence for associations with sex, type of accommodation/support, antiepileptics, problem behaviours or autism. CONCLUSIONS: Adults with IDs have a high prevalence of edentulousness and need supported daily oral care to reduce the need for extractions. Despite previous reports on poor oral care and the move towards person-centred care, carers and care-giving organisations need greater support to implement daily oral care. Prescribers need awareness of the potentially contributory role of antipsychotics, which may relate to xerostomia.

Non-speech oro-motor exercises in post-stroke dysarthria intervention: a randomized feasibility trial.

BACKGROUND: There has been little robust evaluation of the outcome of speech and language therapy (SLT) intervention for post-stroke dysarthria. Non-speech oro-motor exercises (NSOMExs) are a common component of dysarthria intervention. A feasibility study was designed and executed, with participants randomized into two groups, in one of which NSOMExs were a component of the intervention programme. AIMS: To examine (1) operational feasibility of the programme; (2) participants' views of the programme; and (3) speech intelligibility, communication effectiveness and tongue and lip movement at four points (A1 and A2 before, and A3 and A4 after intervention). METHODS & PROCEDURES: Thirty-nine participants were randomized into Group A (n=20) and Group B (n=19). Groups were equivalent at enrolment in demographic variables and A1 measures. Intervention was behavioural, delivered in eight home-based SLT sessions, and included practise of individually appropriate words, sentences and conversation, and for Group B also NSOMExs. Between-session practice was recorded in a diary. Data on speech intelligibility, effectiveness of communication in conversation, self-rated situational communication effectiveness, and tongue and lip movement were collected at 8-week intervals, twice before and twice after intervention. Anonymous evaluation (AE) questionnaires were completed. OUTCOME & RESULTS: The recruited number was 20% below the target of 50. Thirty-six participants completed the intervention and 32 were followed through to A4. The programme was delivered to protocol and fidelity was verified. Thirty-four AEs were returned. These showed high satisfaction with the programme and its outcome. According to diary records from 32 participants, 59% carried out at least the recommended practice amount. Outcome measure performance across the four assessment points did not indicate any group effect. For the whole sample both externally rated and self-rated communication effectiveness measures showed statistically significant gains across the intervention period (A2/A3), which were maintained for 2 months after intervention (A2/A4). Non-intervention period changes (A1/A2 and A3/A4) were not present. There were no intervention-related gains in tongue and lip movement or speech intelligibility, but the latter is likely to be attributable to a ceiling effect on scores. CONCLUSIONS & IMPLICATIONS: The results indicate positive outcomes associated with a short period of behavioural SLT intervention in the post-stroke dysarthria population. The inclusion of NSOMExs, delivered in accordance with standard clinical practice, did not appear to influence outcomes. The results must be viewed in relation to the nature of feasibility study and provide a foundation for suitably powered trials.

The Living with Dysarthria group for post-stroke dysarthria: the participant voice.

BACKGROUND: The Living with Dysarthria group programme, devised for people with post-stroke dysarthia and family members, was piloted twice. Feedback from those who experience an intervention contributes to the evaluation of speech and language therapy programmes, giving the participant view of the intervention's value and guiding further developments. RESEARCH QUESTION: What feedback do participants in the Living with Dysarthria programme provide, informing on its perceived usefulness and guiding its future development? METHODS & PROCEDURES: Nine people with chronic dysarthria following stroke and four family members who completed the Living with Dysarthria programme all contributed to Focus Group (FG) discussion, transcribed and thematically analysed, and completed an Anonymous Questionnaire Evaluation (AQE), comprising closed statements and open questions. An anonymous descriptive adjective selection task (ADAST) was also used. OUTCOMES & RESULTS: The varied forms of feedback provided complementary information. Thematic analysis of FG data and AQE open question responses were configured around programme benefits, programme structure and content, and programme practicalities. Benefits associated with participation included learning and insight, being supported by peers and professionals, and improved speech and confidence. These are consistent with the main programme elements of education, support and speech practice. All activities were seen as relevant and positively received. Flexibility, recognition of and catering to individual needs were valued characteristics. The community location was approved by all. Most participants thought the format of eight weekly sessions of 2 h was appropriate. Responses to AQE closed statements provided almost unanimous confirmation of the very positive feedback conveyed in FG discussions. The main response to suggested improvements in AQEs was that the number of sessions should be increased. Feedback indicated that for a few individuals there was negative reaction to some facts about stroke, home practice tasks were difficult to complete, the person with dysarthria/family member pair may not be the optimum combination for paired practice activities and pre-programme information should be extended. The ADAST showed that the programme was enjoyable, interesting, stimulating and useful. CONCLUSIONS & IMPLICATIONS: Participant feedback indicates that group therapy, with family member participation, is a valid form of management for chronic post-stroke dysarthria. Education, peer and professional support, and speech practice are confirmed as relevant programme components. Consistent majority opinions were communicated in different situations and via varied mediums. Some individuals expressed views relevant to their own needs, and these responses also inform future implementation of the Living with Dysarthria programme.

Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer.

BACKGROUND: Trastuzumab and pertuzumab target the Human Epidermal growth factor Receptor 2 (HER2). Combination therapy has been shown to provide enhanced antitumour activity; however, the downstream signalling to explain how these drugs mediate their response is not clearly understood. METHODS: Transcriptome profiling was performed after 4 days of trastuzumab, pertuzumab and combination treatment in human ovarian cancer in vivo. Signalling pathways identified were validated and investigated in primary ovarian xenografts at the protein level and across a timeseries. RESULTS: A greater number and variety of genes were differentially expressed by the combination of antibody therapies compared with either treatment alone. Protein levels of cyclin-dependent kinase inhibitors p21 and p27 were increased in response to both agents and further by the combination; pERK signalling was inhibited by all treatments; but only pertuzumab inhibited pAkt signalling. The expression of proliferation, apoptosis, cell division and cell-cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting the heterogeneity of response in ovarian cancer and a need to establish predictive biomarkers. CONCLUSION: This first comprehensive study of the molecular response to trastuzumab, pertuzumab and combined therapy in vivo highlights both common and distinct downstream effects to agents used alone or in combination, suggesting that complementary pathways may be involved.

Functional alpha1- and beta2-adrenergic receptors in human osteoblasts.

Central (hypothalamic) control of bone mass is proposed to be mediated through beta2-adrenergic receptors (beta2-ARs). While investigations in mouse bone cells suggest that epinephrine enhances both RANKL and OPG mRNA via both beta-ARs and alpha-ARs, whether alpha-ARs are expressed in human bone cells is controversial. The current study investigated the expression of alpha1-AR and beta2-AR mRNA and protein and the functional role of adrenergic stimulation in human osteoblasts (HOBs). Expression of alpha1B- and beta2-ARs was examined by RT-PCR, immunofluorescence microscopy and Western blot (for alpha1B-ARs). Proliferation in HOBs was assessed by (3)H-thymidine incorporation and expression of RANKL and OPG was determined by quantitative RT-PCR. RNA message for alpha1B- and beta2-ARs was expressed in HOBs and MG63 human osteosarcoma cells. alpha1B- and beta2-AR immunofluorescent localization in HOBs was shown for the first time by deconvolution microscopy. alpha1B-AR protein was identified in HOBs by Western blot. Both alpha1-agonists and propranolol (beta-blocker) increased HOB replication but fenoterol, a beta2-agonist, inhibited it. Fenoterol nearly doubled RANKL mRNA and this was inhibited by propranolol. The alpha1-agonist cirazoline increased OPG mRNA and this increase was abolished by siRNA knockdown of alpha1B-ARs in HOBs. These data indicate that both alpha1-ARs and beta2-ARs are present and functional in HOBs. In addition to beta2-ARs, alpha1-ARs in human bone cells may play a role in modulation of bone turnover by the sympathetic nervous system.

Solar Wind Control of the Earth's Electric Field.

The sun-weather problem is placed within an electrical framework subject to experimental investigation. An explanation is suggested for how solar variability modulates the earth's electric field. The solar wind velocity is inversely correlated with the electrical potential of the ionosphere, a measure of the overall intensity of the earth's fair-weather atmospheric electric field. In seeking a physical cause of this relationship, galactic cosmic radiation was studied and it was also found to be inversely correlated with solar wind velocity. Thus, the earth's electric field intensity which is maintained by worldwide thunderstorm currents-a meteorological phenomenon-varies in phase with cosmic radiation. Since cosmic radiation is the primary source of atmospheric ionization, these findings support a proposed mechanism in which solar control of ionizing radiation modulates atmospheric electrification and thus possibly cloud physical processes. If the latter occurred, atmospheric energetics would be affected. Sun-weather research need no longer only consist of statistical correlations; an experimental approach is described. Establishment of a proposed geoelectric index would add a new dimension to solar-terrestrial studies.

Dynamic Contrast-Enhanced MRI in Patients with Brain Metastases Undergoing Laser Interstitial Thermal Therapy: A Pilot Study.

BACKGROUND AND PURPOSE: Tumor recurrence is difficult to predict in patients receiving laser ablation for intracranial malignancy. We assessed the efficacy of the initial area under the time-to-signal intensity curve at 60 seconds (iAUC60) from dynamic contrast-enhanced MR imaging in predicting progression-free survival in patients with brain metastases following laser interstitial thermal therapy. MATERIALS AND METHODS: The study population was a consecutive series of patients undergoing laser interstitial thermal therapy for brain metastases. Patient demographics including age, sex, tumor histology, and Karnofsky Performance Scale were collected prospectively. Preoperative, postoperative, and 1-month follow-up dynamic contrast-enhanced MRIs were analyzed. Values of iAUC60 were computed using a trapezoidal rule applied to the time history of contrast uptake over the first 60 seconds postenhancement. The change in iAUC60 (ΔiAUC60) was calculated by taking the difference between the values of iAUC60 from 2 time points. Pearson correlation coefficients were calculated between progression-free survival, defined as the time from laser interstitial thermal therapy to tumor recurrence, and iAUC60 or ΔiAUC60 values. RESULTS: Thirty-three cases of laser interstitial thermal therapy for 32 brain metastases in a cohort of 27 patients were prospectively analyzed. A significant relationship was observed between the values of iAUC60 from postoperative dynamic contrast-enhanced MR imaging and progression-free survival with Pearson correlation (P = .03) and Cox univariate analysis (P = .01). The relationship between preoperative and 1-month follow-up dynamic contrast-enhanced MR imaging was not significantly correlated with progression-free survival. Similarly, no statistically significant relationship was observed with ΔiAUC60 and progression-free survival between any time points. CONCLUSIONS: Progression-free survival is difficult to predict in patients undergoing laser interstitial thermal therapy for brain metastases due to confounding with posttreatment change. iAUC60 extracted from postoperative dynamic contrast-enhanced MR imaging shows promise for accurately prognosticating patients following this operative therapy.

Anti-tumour activity in non-small cell lung cancer models and toxicity profiles for novel ruthenium(II) based organo-metallic compounds.

Novel ruthenium(II) organo-metallic compounds are active in ovarian cancer models [Aird RE, Cummings J, Ritchie AA, Muir M, Morris RE, Chen H, et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(II) organometallic arene complexes in human ovarian cancer. Br J Cancer 2002;86(10):1652-7]. [(eta6-C6H5C6H5)Ru(en)Cl]+ (as a PF6 salt, where en=ethylenediamine (RM175)) has been evaluated in a 13-cell line panel. Particular sensitivity (approximately 10-fold lower than mean IC50) was noted in breast cancer and non-small cell lung cancer cell lines. In addition, IC50 in the A549 was 2 microM and RM175 (25 mg kg-1, days 1 and 5, i.p.) caused a significant (p=0.004) growth delay in a xenograft model. HC11 [(eta6-tetrahydroanthracene)Ru(en)Cl]PF6 was more potent in the A549 cell line (IC50 0.5 microM). HC11 (25 mg kg-1, days 1, 8 and 15, i.p.) was also active in vivo. Following RM175 25 mg kg-1, days 1 and 5, and 15 mg kg-1, days 1-5, HC11 25 and 40 mg kg-1, day 1, elevated alanine transaminase levels were detected, suggesting hepatotoxicity. No changes were observed in kidney or haematological parameters. In liver sections, multi-focal hepatic necrosis was seen, becoming confluent at high doses of HC11. In vitro studies confirmed that HC11 was more toxic than RM175 to fresh human hepatocytes and equitoxic to mithramycin. Liver toxicity may be related to the arene ligand and modification may reduce the potential for hepatic toxicity, while maintaining the anti-tumour activity seen.

Broad spectrum neuropeptide antagonists inhibit the growth of small cell lung cancer in vivo.

The proliferation of small cell lung cancer (SCLC) cells appears sustained by multiple autocrine and paracrine circuits involving Ca2+ mobilizing neuropeptides. Consequently, broad spectrum neuropeptide antagonists which inhibit SCLC growth in vitro have been suggested as potential anticancer agents. Here we evaluated this hypothesis using xenografts of WX322 cells, a SCLC cell line that responds to multiple Ca2+ mobilizing neuropeptides. The broad spectrum neuropeptide antagonists [Arg6,D-Trp7,9,MePhe8]substance P(6-11) and [D-Arg1,D-Phe5,Trp7,9Leu11[substance P were shown to inhibit the growth of WX322 xenografts in nude mice. Similar results were obtained with xenografts of the SCLC cell line H69. The results indicate that broad spectrum neuropeptide antagonists can inhibit the growth of SCLC in vivo and suggest that these antagonists could be useful in the treatment of SCLC.

Time is the enemy: Mortality in trauma patients with hemorrhage from torso injury occurs long before the "golden hour".

INTRODUCTION: The concept of the "Golden Hour" has been a time-honored tenet of prehospital trauma care, despite a paucity of data to substantiate its validity. Non-compressible torso hemorrhage has been demonstrated to be a significant cause of mortality in both military and civilian settings. We sought to characterize the impact of prehospital time and torso injury severity on survival. Furthermore, we hypothesized that time would be a significant determinant of mortality in patients with higher Abbreviated Injury Scale (AIS) grades of torso injury (AIS ≥ 4) and field hypotension (prehospital SBP ≤ 110 mmHg) as these injuries are commonly associated with hemorrhage. METHODS: Data for this analysis was generated from a registry of 2,523,394 injured patients entered into the National Trauma Data Bank Research Data Set from 2012 to 2014. Patients with torso injury were identified utilizing Abbreviated Injury Scale (AIS) for body regions 4 (Thorax) and 5 (Abdomen). Specific inclusion criteria for this study included pre-hospital time, prehospital SBP ≤110 mmHg, torso injury qualified by AIS and mortality. Patients with non-survivable torso injury (AIS = 6), severe head injuries (AIS ≥ 3), no signs of life in the field (SBP = 0), interfacility transfers, or those with any missing data elements were excluded. This classification methodology identified a composite cohort of 42,135 adult patients for analysis. RESULTS: The overall mortality rate of the study population was 7.9% (3326/42,135); Torso AIS and prehospital time were noted to be strong independent predictors of patient mortality in all population strata of the analysis (P < 0.05). The data demonstrated a profound incremental increase in mortality in the early time course after injury associated with torso AIS ≥4. CONCLUSION: In patients with high-grade torso injury, AIS grades ≥4, the degree anatomic disruption is associated with significant hemorrhage. In our study, a precipitous rise in patient mortality was exhibited in this high-grade injury group at prehospital times <30 min. Our data highlight the critical nature of prehospital time in patients with non-compressible torso hemorrhage. However, realizing that evacuation times ≤30 min may not be realistic, particularly in rural or austere environments, future efforts should be directed toward the development of therapies to increase the window of survival in the prehospital environment.

Isolation of mutants of Escherichia coli uncoupled in oxidative phosphorylation using hypersensitivity to streptomycin.

Mutants of Escherichia coli, harbouring the uncA401 or uncB402 alleles, were found to take up streptomycin more rapidly than the coupled parent strains. The increased rate of uptake results in greater sensitivity of the uncoupled strains, compared to the parent strains, to low concentrations of streptomycin. Studies with unc+ revertants showed that hypersensitivity to streptomycin is attributable to the mutation causing uncoupling. The uptake of streptomycin in an unc- strain is abolished by addition of the chemical uncoupler carbonylcyanide m-chlorophenylhydrazone. The phenotype of hypersensitivity to streptomycin can be used as a selection procedure for the isolation of uncoupled strains. In an experiment reported here, nine out of 12 strains isolated as being sensitive to streptomycin (at 2.5 micrograms/ml), were found to be unable to grow on succinate as a sole source of carbon. Five of the nine Suc- strains were found to be uncoupled in oxidative phosphorylation, and two of the five uncoupled strains lacked Mg2+-ATPase activity. The mutations causing uncoupling were cotransducible with the ilv genes.

Substrate specificity of the Escherichia coli maltodextrin transport system and its component proteins.

Maltooligosaccharides up to maltoheptaose are transported by the maltodextrin transport system of Escherichia coli. The overall substrate specificity of the transport system was investigated by using 15 maltodextrin analogues with various modifications at the reducing end of the oligosaccharides as competing substrates. The binding interaction of the analogues with maltoporin in the outer membrane and the periplasmic maltose-binding protein, the two protein components of the transport system with known specificity for maltodextrins, was also investigated. All analogues containing several alpha, 1----4-glucosyl linkages were bound with high affinity by maltoporin and maltose-binding protein, regardless of O-methyl, O-nitrophenyl, beta-glucosyl or beta-fructosyl substitutions at the reducing end of the dextrins. Introduction of a negative charge or lack of a ring structure at the reducing end were also ineffective in abolishing binding by these two proteins. These results suggest that the structure of the reducing glucose is not important in the binding specificity of maltoporin or maltose-binding protein. However, the high affinity of these proteins for analogues was not in itself sufficient for recognition by the transport system overall. Maltohexaitol, 4-nitrophenyl alpha-maltotetraoside and 4-beta-D-maltopentaosyl-D-glucopyranose were bound with the same affinity as comparable maltodextrins by both maltoporin and maltose-binding protein but were poorly recognized by the transport system. These results suggest that another, yet uninvestigated component of the transport system has a more restricted specificity towards changes at the reducing end of the maltodextrin molecule.

Characterization of a respiratory mutant of Escherichia coli with reduced uptake of aminoglycoside antibiotics.

A strain of Escherichia coli (NSW77) which is partially resistant to streptomycin was isolated by selecting for growth on plates supplemented with 12.5 micrograms/ml streptomycin, a concentration which completely inhibits growth of wild-type strains. The low-level resistance of the mutant appears to result from a reduced ability to accumulate streptomycin intracellularly. In addition, the mutant strain is unable to use succinate for growth because of a defective respiratory chain. Thus, membranes of the mutant strain were found to have approximately half the NADH and D-lactate oxidase activity of the parent strain. Moreover, membranes of the mutant were found to contain demethyl-menaquinone and, in place of ubiquinone, a structural analogue, 2-octaprenyl-3-methyl-6-methoxy-1,4 benzoquinone. The mutation responsible for both the Suc-phenotype and partial resistance to streptomycin was found to be located near minute 15 on the bacterial chromosome. Both the biochemical and genetic evidence suggests the the mutation in strain NSW77 resides in the ubi F gene. Another previously characterized ubi F strain was also found to have a reduced capacity to take up an aminoglycoside antibiotic (gentamicin). These results suggest that the respiratory defects in ubi F strains are responsible for the reduced capacity of such strains to accumulate aminoglycosides.

Growth inhibition of oestrogen receptor-positive human ovarian carcinoma by anti-oestrogens in vitro and in a xenograft model.

This paper presents results of the in vitro and in vivo effects of anti-oestrogens on the growth of human ovarian cancer cells. Tamoxifen and the "pure" anti-oestrogens, ICI 164,384 and ICI 182,780, inhibited the oestrogen-stimulated growth of the oestrogen receptor (ER)-positive PE04 and PE01 cell lines grown in culture, the latter two compounds being more potent than tamoxifen. In the absence of 17 beta-oestradiol (E2), tamoxifen, but not the pure anti-oestrogens, produced a small degree of growth stimulation in the PE01 and PE04 lines at concentrations between 10((7) and 10(-9) M. In contrast, growth of the ER-negative PE014 line was unaffected by E2 and all three anti-oestrogens. The effects of tamoxifen and ICI 182,780 on PE04 cells grown as xenografts in nude mice were also studied. Both anti-oestrogens produce significant growth inhibitory effects. These results indicate that ovarian carcinoma cells may be sensitive to anti-oestrogens in vitro and in vivo, and support the view that anti-oestrogens merit further clinical studies in patients with ER-positive tumours.

Antitumour activity and schedule dependency of 8-chloroadenosine-3',5'-monophosphate (8-ClcAMP) against human tumour xenografts.

8-Chloroadenosine-3',5'-monophosphate (8-ClcAMP) is a novel antitumour agent currently undergoing phase I clinical trials in several European centres. In this study, its antitumour activity against human tumour xenografts and its dependence on schedule were investigated. When administered by continuous infusion at doses of 100 or 50 mg/kg/day to nude mice bearing human tumour xenografts, 8-ClcAMP inhibited the growth of the HT 29 colorectal, ZR-75-1 breast, HOX 60 and PE04 ovarian and PANC-1 pancreatic carcinoma xenografts. However, these infusion schedules produced hypercalcaemia and severe weight loss. In an attempt to optimise antitumour activity and minimise toxicity, several other schedules were studied. In comparison with continuous administration of 8-ClcAMP at 50 mg/kg/day for 14 days which, although producing complete growth inhibition in the HOX 60 model, was associated with a marked body weight loss, schedules in which the infusion was interrupted (infusion on either days 0-4; 7-11 or days 0-2; 6-8) produced minimal weight loss but also reduced antitumour activity. However, co-administration of salmon calcitonin with continuous infusion of 8-ClcAMP prevented both hypercalcaemia and body weight loss in 3/6 animals while still producing marked inhibition of tumour growth. These data indicate that 8-ClcAMP has broad-spectrum antitumour activity and the major side-effect of hypercalcaemia may at least in part be ameliorated by the use of salmon calcitonin.

Glaucoma and the iridocorneal endothelial syndrome.

The records of 66 patients with the iridocorneal endothelial (ICE) syndrome were retrospectively reviewed. Glaucoma occurred in 33 (50%) of the patients with ICE syndrome and was most common in the variants in which abnormal cells involve the entire posterior corneal surface (disseminated ICE and total ICE). Of 25 patients with glaucoma, the diagnosis of ICE syndrome was overlooked initially in 17 (68%). Medical glaucoma treatment was generally ineffective. Of 22 patients (88%) who underwent surgery (typically trabeculectomy), 10 (45%) required more than one procedure. The success rates of first operations at 1 and 5 years were 60% and 21%, and those of second and third operations at 1 year were 20% and 17%. During the course of their management, 11 patients (44%) developed visual field loss. The diagnosis of ICE syndrome should be considered in younger patients with unilateral glaucoma and confirmed by specular microscopy. Management of glaucoma due to ICE syndrome is surgical, and means of improving its long-term success need to be addressed.

The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy. A prospective, randomized, double-blind trial.

In this study, we report the results of a prospective, double-blind trial to determine whether high-dose topical corticosteroids have an effect on refractive outcome or anterior stromal haze after photorefractive keratectomy. A total of 113 patients were allocated randomly to either placebo- or steroid-treated groups (0.1% dexamethasone metasulphobenzoate for 3 months) and underwent either -3.00-diopter (D) or -6.00-D procedures. At 6 weeks, the mean change in refraction was significantly greater in the steroid-treated group than in the placebo-treated group (-3.00-D group, P = .0015; -6.00-D group, P = .0011). However, when corticosteroids were discontinued at 3 months, this difference became statistically insignificant. There was no statistically significant effect on anterior stromal haze at any stage. Since long-term use of corticosteroids to maintain the initial beneficial effect on refraction would be unacceptable, we conclude that these agents should not be used after photorefractive keratectomy.

The effects of ablation diameter on the outcome of excimer laser photorefractive keratectomy. A prospective, randomized, double-blind study.

OBJECTIVE: To determine the effects of the ablation diameter on the outcome of excimer laser photorefractive keratectomy. DESIGN: Eighty patients were randomized to either a 5.00-mm or a 6.00-mm treatment group and within these groups underwent either a -3.00-diopter (D) or a -6.00-D correction based on their preoperative refraction. A Summit Omnimed excimer laser was used throughout the study. RESULTS: In eyes treated with a 6.00-mm-diameter ablation, the initial hyperopic shift was reduced, with significant differences at 1 week with -3.00-D corrections and at 1 and 4 weeks with -6.00-D corrections (P < .01). At 6 months, the refractive changes were greater and closer to that intended with 6.00-mm-diameter ablations. The predictability of photorefractive keratectomy was significantly improved with 6.00-mm zones, with a reduction in variance of the refractive changes at all stages postoperatively (P < .05 to P < .001). With -3.00-D corrections, objective measurements showed significantly less anterior stromal haze in eyes treated with 6.00-mm zones at 6 months (P < .05). With -6.00-D corrections, haze was significantly reduced at 1, 3, and 6 months in the eyes treated with 6.00-mm zones (P < .05). Five eyes treated with 5.00-mm zones experienced severe regression of the correction, with marked corneal haze and a reduction of 3 or more lines of best corrected Snellen visual acuity at 6 months. No eyes treated with 6.00-mm zones were similarly affected. Computerized measurements of "night" halo were significantly lower in the 6.00-mm treatment groups at 1 week and at 1 and 6 months in the eyes with -3.00-D corrections and at 1 week and at 1 month in the eyes with -6.00-D corrections (P < .05). At 6 months, seven patients treated with 5.00-mm zones complained of severe disturbances of night vision. No eyes in the 6.00-mm group were similarly affected. CONCLUSIONS: Treatment with 6.00-mm ablation diameters precipitated less initial overcorrection, greatly improved the predictability of photorefractive keratectomy, and was associated with a reduction in complications impairing postoperative visual performance.

Mucosal-associated lymphoid tissue lymphoma of the conjunctiva.

The recognition of mucosal-associated lymphoid tissue as a distinct entity has lead to the separate classification of tumors arising in this tissue, ie, the mucosal-associated lymphoid tissue lymphoma. Five patients with mucosal-associated lymphoid tissue lymphoma of the conjunctiva are described herein; four of the five patients had bilateral tumors. Laboratory analysis was done using microscopy, immunophenotyping, gene rearrangement analysis using both Southern blot and polymerase chain reaction techniques, and oncogene (bcl-1, bcl-2, and c-myc) rearrangement studies. Typical mucosal-associated lymphoid tissue lymphoma features were seen in all patients; three of four patients who underwent testing with immunphenotyping had light-chain restriction, four of five patients had a clone detected using Southern blot analysis, and all five patients showed clones on polymerase chain reaction analysis. No patient demonstrated oncogene rearrangement. In all patients, complete physical examinations and laboratory tests did not detect any evidence of systemic spread. After treatment, no evidence of local recurrence or dissemination was found during follow-up ranging from 2 to 3 years.

Comparison of serum vitamin B12 estimation by saturation analysis with intrinsic factor and with R-protein as binding agents.

It has been reported that serum vitamin B12 levels assayed by saturation analysis methods may give misleadingly high results, so much so that the diagnosis of vitamin B12 deficiency may be obscured. This defect was ascribed largely to assays using a vitamin B12 binder other than pure intrinsic factor. To test out this hypothesis two assays were set up, one using saliva (non-intrinsic factor R-binder) and the other using human gastric (intrinsic factor) as B12-binding agents. Both assays were able to differentiate sera from patients with pernicious anaemia from those from control subjects. Published results accumulated over the past 10 years indicate that properly designed and performed saturation analysis vitamin B12 assays are as reliable as microbiological assay methods for detecting low serum B12 levels. The failure of some methods to do does not appear to be due to the nature of the B12-binding agent.