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.

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.

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.

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.

Necrotising ventriculitis due to combined infection with Rhizopus microsporus var. chinensis and Candida krusei in an eclectus parrot (Eclectus roratus).

Acute necrosis of the ventriculus is a very uncommon lesion in birds. We describe a fatal case of acute necrotising ventriculitis caused by Rhizopus microsporus var. chinensis in a mature female eclectus parrot (Eclectus roratus). The bird presented acutely dull and lethargic, was vomiting and had bright green droppings, suggestive of acute heavy metal poisoning. It was treated with fluids and chelation therapy, but died within 12 h. Necropsy, cytology, histopathology and culture results demonstrated fungal invasion of the ventriculus associated with transmural necrosis, haemorrhage, acute inflammation and abundant R. microsporus var. chinensis and lesser numbers of Candida krusei.

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.

The need for early angiography in patients with penetrating renal injuries.

BACKGROUND: Renal injuries occur in as many as 10% of penetrating abdominal wounds. Today, these wounds are often managed selectively, but there is little contemporary information on the natural history of kidney injuries after penetrating trauma. The purpose of this study was to examine the clinical outcomes of penetrating injuries to the kidney, and to determine if these patients may benefit from routine early angiography. METHODS: All trauma patients admitted to three Level I Trauma Centers with penetrating renal injuries over a 10 year study period were retrospectively reviewed. RESULTS: We identified 237 patients with a penetrating renal injury, of whom 39 died within the first 24 h and were excluded from analysis. Among the remaining 198 individuals, 130 (66%) underwent immediate exploratory laparotomy. Of the 68 subjects not undergoing immediate surgery, seven had early angiography. The remaining 61 patients (31%) were observed, with 12 (20%) ultimately requiring an intervention to treat the renal injury. Those subjects who failed nonoperative management had significantly fewer hospital-free days compared to those who did not need a procedure (19.2 ± 8.1 vs. 25.7 ± 4.5, p = 0.002). CONCLUSIONS: Nearly one in three patients with penetrating renal injuries are currently managed with serial observation, although one in five of these subjects ultimately require either angiographic or surgical treatment. We feel that routine use of early angiography may reduce the failure rate and improve outcomes for patients whose penetrating renal injuries are managed nonoperatively.

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.

Calcium phosphate fibres synthesized from a simulated body fluid.

The biomimetic coating method was used for fabricating calcium phosphate fibres for biomedical applications such as bone defect fillers. Natural cotton substrate was pre-treated with phosphorylation and a Ca(OH)2 saturated solution. The pre-treated samples were then soaked in simulated body fluid (SBF) of two different concentrations, 1.5 times and 5.0 times the ion concentration of blood plasma. The cotton was then burnt out via sintering of the ceramic coating at 950 degrees C, 1050 degrees C, 1150 degrees C, and 1250 degrees C. The results demonstrated that osteoblastic cells were able to cover the entire surface cotton fibres, and the cell coverage appeared to be independent of surface roughness and Ca/P ratio of fibres.

Dental follicle infection following a dog bite.

Animal bite wounds and their subsequent infection are relatively common. Incidence rates for dog bites are significantly higher among children aged 0-9 years, especially among boys. Although bite wounds may initially look innocuous, they frequently lead to serious infection with a potential for life-threatening complications. The microbiology of dog bite wounds is usually polymicrobial, typically including anaerobes, Staphylococcus aureus and Pasteurella species. A case is described of a 22-month-old boy who, subsequent to a dog bite over the left maxilla, suffered infection of the dental follicle of the primary maxillary canine with Pasteurella multocida. The infection proved difficult to treat, requiring several attempts at incision and drainage of the abscess together with systemic antibiotics, and resulted in the eventual loss of the tooth.

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.

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds.

A randomized controlled trial to prevent patient lift and transfer injuries of health care workers.

STUDY DESIGN: Randomized controlled trial (RCT). OBJECTIVES: To compare the effectiveness of training and equipment to reduce musculoskeletal injuries, increase comfort, and reduce physical demands on staff performing patient lifts and transfers at a large acute care hospital. SUMMARY OF BACKGROUND DATA: Back injury to nursing staff during patient handling tasks is a major issue in health care. The value of mechanical assistive devices in reducing injuries to these workers is unclear. METHODS: This three-armed RCT consisted of a "control arm," a "safe lifting" arm, and a "no strenuous lifting" arm. A medical, surgical, and rehabilitation ward were each randomly assigned to each arm. Both intervention arms received intensive training in back care, patient assessment, and handling techniques. Hence, the "safe lifting" arm used improved patient handling techniques using manual equipment, whereas the "no strenuous lifting" arm aimed to eliminate manual patient handling through use of additional mechanical and other assistive equipment. RESULTS: Frequency of manual patient handling tasks was significantly decreased on the "no strenuous lifting" arm. Self-perceived work fatigue, back and shoulder pain, safety, and frequency and intensity of physical discomfort associated with patient handling tasks were improved on both intervention arms, but staff on the mechanical equipment arm showed greater improvements. Musculoskeletal injury rates were not significantly altered. CONCLUSIONS: The "no strenuous lifting" program, which combined training with assured availability of mechanical and other assistive patient handling equipment, most effectively improved comfort with patient handling, decreased staff fatigue, and decreased physical demands. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators.

Oral health of patients with hepatitis C virus infection: a pilot study.

OBJECTIVES: This study examined the oral health of a cohort of hepatitis C virus (HCV) patients. In particular, the prevalence of lichen planus and xerostomia were determined. Experiences of discrimination against HCV-infected patients by their dentists were also recorded. METHODS: Forty patients infected with HCV, who were not undergoing anti-viral treatment, were examined. Patient information collected included demographic details together with patients' perception of their oral health and access to dental care since being diagnosed with hepatitis C. Both extra-oral and intra-oral examinations were conducted. Teeth present and visible caries were recorded, periodontal condition was measured using a Community Periodontal Index of Treatment Need (CPITN) probe and denture fit and hygiene were assessed where appropriate. The soft tissues were examined and lichen planus diagnosed clinically. Salivary flow rates were estimated by the Salivette system. RESULTS: The oral health of this cohort was poor. Eight patients had clinical evidence of oral lichen planus (OLP), although this was not confirmed histologically. The salivary flow rates were significantly lower (P < 0.001) than in previously reported healthy controls. Of the 15 (37.5%) regular dental attenders, two had encountered problems accessing dental care. CONCLUSIONS: Chronic hepatitis C patients have significant oral health needs. More effective oral health education is required for both HCV-infected patients and their carers, including dental practitioners.

Dissociation of osmoregulation from plasma arginine vasopressin levels following thermal injury in childhood.

Although the syndrome of inappropriate anti-diuretic hormone secretion has been recognised as a complication associated with burn and other trauma in adults, relatively little is known about its incidence in children. The objective of this study was to investigate whether it is a complication associated with burn injury in children. Plasma and urine levels of arginine vasopressin (anti-diuretic hormone), sodium and osmolality were measured in samples collected from 16 burn-injured children admitted to the burns unit of the regional children's hospital. No significant correlations were found between plasma vasopressin and plasma sodium or osmolality levels, but there were significant correlations between plasma vasopressin and urine osmolality, 36 (r=0.74, p=0. 009), 60 (r=0.92, p=0.000) and 84 h (r=0.84, p=0.001) after admission, respectively. There were also significant correlations between plasma sodium and plasma osmolality, 24 (r=0.7, p=0.005), 36 (r=0.57, p=0.04) and 84 h (r=0.84, p=0.004) after admission. The data suggest dissociation between the osmolar control of vasopressin secretion and vasopressin levels after burn injury in children, but do not support the incidence of inappropriate secretion of antidiuretic hormone.

Non-bullous congenital ichthyosiform erythroderma, with ocular albinism and Noonan syndrome.

A 21-year-old woman presented with non-bullous congenital ichthyosiform erythroderma; she was born a collodion baby. Associated features were ocular albinism, anterior segment dysgenesis of both eyes and Noonan syndrome. X-linked ichthyosis (steroid sulphatase deficiency) and X-linked ocular albinism have been mapped to the Xp22.3 region and cases have been reported with both conditions due to a partial short-arm deletion of the X chromosome. The ichthyosis and ocular albinism in the present case, however, are likely to be of the autosomal recessive type - a very rare association - and the combination with Noonan syndrome has not been reported previously.

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Keratocyte density and size in conscious humans by digital image analysis of confocal images.

PURPOSE: Confocal microscopy can give images of high magnification and resolution in undisturbed living tissue. It provides new information about the cellular structure of the cornea. Our aim was to measure the density, size and distribution of keratocytes. METHODS: Healthy cornea in four subjects was examined using tandem scanning confocal microscopy. Methods for digital analysis of images were developed. RESULTS: Keratocyte density in confocal cross-sections was greatest immediately under Bowman's membrane (maximum 800 cells/mm2) and decreased sharply towards posterior cornea (minimum 65 cells/mm2). Cross-sectional cell size ranged from 78 to 211 microns2, but did not correlate with depth in the tissue. CONCLUSIONS: Results are consistent with those of earlier work using histological and biochemical techniques in isolated tissue. The methods we have developed enable studies of ongoing processes in conscious humans and can be used to examine diseased tissue as well as the response to injury.