Long-term clinical outcomes following surgery for spontaneous pneumothorax caused by pulmonary blebs and bullae in dogs - a multicentre (AVSTS Research Cooperative) retrospective study.

OBJECTIVES: To report the clinical characteristics and recurrence rate of spontaneous pneumothorax secondary to pulmonary blebs and bullae following surgical management in a large cohort of dogs. To explore potential risk factors for recurrence and describe outcome. MATERIALS AND METHODS: Medical records were retrospectively reviewed for cases with spontaneous pneumothorax managed surgically between 2000 and 2017. Signalment, clinical presentation, diagnostic imaging, surgery, histopathology findings and patient outcomes were recorded. Follow-up was performed via patient records and telephone contact. RESULTS: Records of 120 dogs with surgically treated pneumothorax were identified and reviewed, with 99 cases appropriate for exploratory statistical analysis. Median follow-up was 850 days (range: 9-5105 days). Two- and 5-year survival rates were 88.4% and 83.5%, respectively. There was recurrence in 14 of 99 dogs (14.1%) with adequate follow-up, with a median time to recurrence of 25 days (1-1719 days). Univariable Cox regression analysis suggested increased risk for recurrence in giant breeds (hazard ratio = 11.05, 95% confidence interval: 2.82-43.35) and with increasing bodyweight (HR = 1.04, 95% confidence interval: 1.00-1.09). Of 14 dogs with recurrence, six were euthanased, two died of causes related to pneumothorax and six underwent further treatment, of which five were resolved. CLINICAL SIGNIFICANCE: Long-term survival for dogs with surgically managed spontaneous pneumothorax was good and associated with a low risk of recurrence. Giant breed dogs and increased bodyweight were the only variables identified as possible risk factors for recurrence. The outcome for dogs with recurrence undergoing a second intervention was also favourable.

Patient characteristics associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (COPD) following primary care COPD diagnosis: a cohort study using linked electronic patient records.

OBJECTIVES: To investigate patient characteristics of an unselected primary care population associated with risk of first hospital admission and readmission for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). DESIGN: Retrospective open cohort using pseudonymised electronic primary care data linked to secondary care data. SETTING: Primary care; Lothian (population approximately 800,000), Scotland. PARTICIPANTS: Data from 7002 patients from 72 general practices with a COPD diagnosis date between 2000 and 2008 recorded in their primary care record. Patients were followed up until 2010, death or they left a participating practice. MAIN OUTCOME MEASURES: First and subsequent admissions for AECOPD (International Classification of Diseases (ICD) 10 codes J44.0, J44.1 in any diagnostic position) after COPD diagnosis in primary care. RESULTS: 1756 (25%) patients had at least 1 AECOPD admission; 794 (11%) had at least 1 readmission and the risk of readmission increased with each admission. Older age at diagnosis, more severe COPD, low body mass index (BMI), current smoking, increasing deprivation, COPD admissions and interventions for COPD prior to diagnosis in primary care, and comorbidities were associated with higher risk of first AECOPD admission in an adjusted Cox proportional hazards regression model. More severe COPD and COPD admission prior to primary care diagnosis were associated with increased risk of AECOPD readmission in an adjusted Prentice-Williams-Peterson model. High BMI was associated with a lower risk of first AECOPD admission and readmission. CONCLUSIONS: Several patient characteristics were associated with first AECOPD admission in a primary care cohort of people with COPD but fewer were associated with readmission. Prompt diagnosis in primary care may reduce the risk of AECOPD admission and readmission. The study highlights the important role of primary care in preventing or delaying a first AECOPD admission.

Seroprevalence of human toxocariasis, Jamaica.

Seroprevalence of human toxocariasis was studied, based on 1544 samples selected from a total of 3524 submitted to the University of the West Indies in Kingston, Jamaica for diagnosis of dengue during an epidemic in 2010. The prevalence of anti-Toxocara IgG using the CELISA® (Cellabs) ELISA was 21.2% and males (24.4%) were significantly more likely to be exposed than females (17.5%) [χ2 =10.4; p=0.001]. No association was foundbetween exposure to Toxocara and area of residence (rural vs. urban) [χ2 =0.835; p = 0.409]. Prevalence of infection peaked in adolescents (10-19 years-old) and declined thereafter although a rise in prevalence was seen in older age classes. There was a high prevalence of toxocariasis in Jamaica with significant exposure among school age children with no predilection to either sex. The study will inform future work on elucidating the public health and clinical significance of toxocariasis in Jamaica.

Aminoglycoside Resistance in Clinical Isolates of Gram Negative Bacilli at the University Hospital of the West Indies, Jamaica: Comparison of Two Time Periods.

OBJECTIVE: Aminoglycosides were introduced into use over 60 years ago. The University Hospital of the West Indies (UHWI), a tertiary care teaching hospital, in Kingston, Jamaica, introduced the use of gentamicin in 1973 and amikacin in 1980. This report examined the susceptibility patterns to these agents in 1547 consecutive isolates of Gram negative bacilli (GNB) encountered between September 1 and November 30, 2011, at UHWI and compares the data with those observed previously in 1981 at the same institution. METHODS: The Vitek 2 (bioMeriéux, Durham, NC) was used for isolate identification, minimum inhibitory concentration determination and aminoglycoside susceptibility testing. Quality control was done using American Type Culture Collection standard strains of E coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). RESULTS: Of the 1547 organisms, 267 had resistance to one or both aminoglycosides. Amikacin resistance increased from 0.6% (1981) to 7.2% [2011] (p < 0.05), while gentamicin resistance increased from 6.7% to 14.8% (p < 0.05) for the corresponding period. The majority of samples with aminoglycoside resistant organisms came from the intensive care unit and surgical inpatients. Urine samples persistently produced the largest amount of gentamicin resistant isolates. CONCLUSIONS: Although there has been a statistically significant rise in aminoglycoside resistance, aminoglycosides continue to remain highly effective against approximately 83% of GNB despite continuous usage at this institution for over three decades. Continued national surveillance, implementation of infection control policies and antibiotic stewardship are all essential in retaining low resistance levels.

Brain biopsy in benign neurological disease.

Brain biopsy is well established in clinical practice when there is suspicion of CNS malignancy. However, there is little consensus regarding the indications for brain biopsy in non-malignant neurological disease. This is due in no small part to limitations in the available literature pertaining to diagnostic brain biopsies. The published evidence largely comprises small, retrospective, single-centre analyses performed over long time periods, including non-homogeneous patient groups with considerable variation in reported outcomes. Here we present pragmatic guidance for those clinicians considering diagnostic brain biopsy in a patient with non-neoplastic neurological disease and highlight practice points with the aim of maximising the probability of gaining clinically useful information from the procedure.

Report from the killer immunoglobulin-like receptor (KIR) anthropology component of the 15th International Histocompatibility Workshop: worldwide variation in the KIR loci and further evidence for the co-evolution of KIR and HLA.

The killer immunoglobulin-like receptor (KIR) anthropology component of the 15th International Histocompatibility Workshop (IHIWS) sought to explore worldwide population variation in the KIR loci, and to examine the relationship between KIR genes and their human leukocyte antigen (HLA) ligands. Fifteen laboratories submitted KIR genotype and HLA ligand data in 27 populations from six broad ethnic groups. Data were analyzed for correlations between the frequencies of KIR and their known HLA ligands. In addition, allelic typing was performed for KIR2DL2 and 3DL1 in a subset of populations. Strong and significant correlations were observed between KIR2DL2, 2DL3 genotype frequencies and the frequency of their ligand, HLA-C1. In contrast, only weak associations were seen for 3DL1, 3DS1 and the HLA-Bw4 ligand. Although some aspects of the correlations observed here differ from those reported in other populations, these data provide additional evidence of linked evolutionary histories for some KIR and HLA loci. Investigation of allele-level variation for the B haplotype locus KIR 2DL2 showed that two alleles, *001 and *003, predominate in all populations in this study. Much more allelic variation was observed for the A haplotype locus 3DL1, with several alleles observed at moderate frequencies and extensive variation observed between populations.

Prevalence of pneumococcal polysaccharide vaccine administration and incidence of invasive pneumococcal disease in children in Jamaica aged over 4 years with sickle cell disease diagnosed by newborn screening.

BACKGROUND: Patients with sickle cell disease (SCD) are susceptible to bacterial infections, especially those caused by encapsulated organisms such as Streptococcus pneumoniae which is an important cause of morbidity and mortality in early childhood. Preventive measures such as penicillin prophylaxis and immunisation are therefore required. Although penicillin is the mainstay of prophylaxis, pneumococcal vaccination is also important for defence against invasive pneumococcal disease (IPD). AIM: To determine the prevalence of pneumococcal polysaccharide vaccination among patients with SCD diagnosed by newborn screening, and the incidence of IPD in this group of patients. METHODS: In this retrospective study, data were obtained from the pneumococcal polysaccharide vaccine (PPV) log books and the electronic clinic database. Patients' dockets were searched to confirm their vaccine status if they were over 4 years of age and PPV data had not been found by the above methods. Episodes of invasive pneumococcal disease (sepsis or meningitis) were obtained from the clinic database. Data were analysed using STATA version 9. RESULTS: Ninety-one per cent of participating patients in the study population who were eligible for PPV had been appropriately immunised. Also, 94.8% of patients with a severe form of SCD had appropriately received PPV. The incidence rate of IPD was 480/100,000 person years in the study population and 160/100,000 person years in patients over 4 years of age. CONCLUSION: The high prevalence of PPV administration in children with SCD diagnosed by newborn screening had a significant impact on the incidence of IPD with improved patient outcomes.

Randomized trial comparing cryoablation and external beam radiotherapy for T2C-T3B prostate cancer.

The objective was to evaluate the relative efficacy of cryoablation (CRYO) versus external beam radiation (EBRT) for clinically locally advanced prostate cancer in a randomized clinical trial. Patients with histologically proven, clinically staged as T2C, T3A or T3B disease were randomized with 6 months of perioperative hormone therapy to one of the two procedures. Owing largely to a shift in practice to longer term adjuvant hormonal therapy and higher doses of radiation for T3 disease, only 64 out of the planned 150 patients were accrued. Twenty-one of 33 (64%) in the CRYO group and 14 of 31 (45%) in the EBRT-treated group who had met the ASTRO definition of failure were also classified as treatment failure. The mean biochemical disease-free survival (bDFS) was 41 months for the EBRT group compared to 28 months for the CRYO group. The 4-year bDFS for EBRT and CRYO groups were 47 and 13%, respectively. Disease-specific survival (DSS) and overall survival (OS) for both groups were very similar. Serious complications were uncommon in either group. EBRT patients exhibited gastrointestinal (GI) adverse effects more frequently. Taking into account the relative deficiency in numbers and the original trial design, this prospective randomized trial indicated that the results of CRYO were less favorable compared to those of EBRT, and was suboptimal primary therapy in locally advanced prostate cancer.

Hospital transmission of hepatitis B virus in the absence of exposure prone procedures.

In February and in June 1998, two people developed acute hepatitis B following in-patient care in a district general hospital. Initial enquiries indicated their infections were not attributable to staff undertaking exposure-prone procedures (EPPs). We report the findings and implications of the subsequent investigation: a multi-disciplinary, multi-agency investigation, including molecular epidemiological analysis. Occupational Health records showed that staff involved in EPPs with the patients were HBsAg negative. No contact between the patients was identified nor were there failures in sterilization. The patients' HBV strains were identical, indicating a common source. A total of 231 out of 232 staff who might have treated either patient were tested for HBsAg; the remaining doctor, working abroad, was HBsAg- and HBeAg-positive and had the same HBV strain as the patients. On two occasions the doctor's hand had been cut while breaking glass vials, but there was no documentation linking these events to the two patients. The doctor had been vaccinated in 1993 and tested for anti-HBs prior to commencing work in 1997. The doctor was recalled to Occupational Health but did not attend and was not followed up. In total, 4948 patients potentially treated by the doctor received an explanatory letter and 3150 were tested for HBsAg. Only one was positive, and HBV sequencing showed no link to the doctor. Occasionally transmission of HBV from heath-care workers can occur in a non-EPP setting and the implications of this require examination by those setting national policy. Occupational Health Services should investigate clinical heath-care workers who do not respond to vaccination. They should ensure HBV carriers are identified and offer them appropriate advice to prevent transmission to patients.

Cyclosporine treatment of anal furunculosis in 26 dogs.

OBJECTIVES: To evaluate the effect of cyclosporine on anal furunculosis lesions in 26 dogs. METHODS: Lesions were graded as mild in 11 dogs, moderate in eight and severe in seven. Each dog was treated with approximately 4 mg/kg cyclosporine orally every 12 hours until the lesions resolved or showed no further improvement. Residual lesions were resected surgically. RESULTS: Eighteen dogs (69 per cent) experienced complete resolution, seven (27 per cent) improved but had residual lesions and one (4 per cent) showed no improvement. The mean duration of treatment until resolution or no further improvement was 8.8 weeks (range four to 24 weeks). Nine dogs (35 per cent) experienced recurrence. Six were from the group that had shown complete resolution and three were from the group that had surgery. Fifteen dogs (58 per cent) developed side effects to cyclosporine, although none required treatment to be discontinued. Mean duration of follow-up was 6.8 months (range one to 20 months). CLINICAL SIGNIFICANCE: Cyclosporine was effective at resolving or reducing anal furunculosis lesions in 25 of 26 dogs (96 per cent). However, residual or recurrent lesions remain a potential problem, and surgical resection or long-term cyclosporine treatment may be necessary in some dogs.

Goal attainment scaling in evaluating a multidisciplinary pain management programme.

OBJECTIVE: To examine the value of Goal Attainment Scaling (GAS) as a therapeutic tool and an outcome measure in a rehabilitation programme in the management of chronic pain. DESIGN: A prospective observational study. SETTING: A 15-day pain management programme, day case or residential, in an NHS Regional rehabilitation centre. SUBJECTS: One hundred and forty-nine consecutive patients enrolled during a 15-month period. INTERVENTIONS: Multidisciplinary structured educational programme of physiotherapy, occupational therapy and clinical psychology. MAIN OUTCOME MEASURES: GAS; timed tests of physical mobility measures; McGill Pain Questionnaire (MPQ); Pain Intensity Numerical Rating Scale (NRS); Oswestry low back pain Disability Questionnaire (ODQ); General Health Questionnaire (GHQ); Pain and Impairment Relationship Scale (PAIRS). GAS and physiotherapy measures were compared with baseline data at enrollment and at discharge 15 days later. At six-month follow-up all measures were repeated. RESULTS: Significant improvements at discharge were found for GAS, and physiotherapy measures. One hundred and twelve patients returned for review at six months, when improvements were maintained for GAS, sit/stand, Pain, ODQ and GHQ. GAS was shown to be a valid measure of ability, correlating significantly with walking improvement and somewhat less with a therapist-defined measure, suggesting some ability to discriminate. CONCLUSIONS: The improvement measured by GAS showed that patients were enabled by the programme to achieve personally valued goals over a six-month period and to improve on these more than on other more conventional outcome measures.

Molecular basis of amplification in Drosophila phototransduction: roles for G protein, phospholipase C, and diacylglycerol kinase.

In Drosophila photoreceptors, the amplification responsible for generating quantum bumps in response to photoisomerization of single rhodopsin molecules has been thought to be mediated downstream of phospholipase C (PLC), since bump amplitudes were reportedly unaffected in mutants with greatly reduced levels of either G protein or PLC. We now find that quantum bumps in such mutants are reduced approximately 3- to 5-fold but are restored to near wild-type values by mutations in the rdgA gene encoding diacylglycerol kinase (DGK) and also by depleting intracellular ATP. The results demonstrate that amplification requires activation of multiple G protein and PLC molecules, identify DGK as a key enzyme regulating amplification, and implicate diacylglycerol as a messenger of excitation in Drosophila phototransduction.

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

Phototransduction in Drosophila melanogaster.

As in most invertebrate microvillar photoreceptors, phototransduction in Drosophila melanogaster uses a G-protein-coupled phosphoinositide pathway, whereby hydrolysis of phosphatidyl inositol 4,5-bisphosphate (PIP(2)) by phospholipase C generates inositol 1,4,5-trisphosphate (InsP(3)) and diacyl glycerol (DAG), leading to activation of two classes of Ca(2+)-permeable light-sensitive channel, encoded by the trp and trpl genes. In some invertebrate photoreceptors, excitation is mediated by release of Ca(2+) from intracellular stores by InsP(3); however, in Drosophila melanogaster, recent evidence suggests instead that a lipid messenger, such as DAG, its metabolites and/or the reduction in PIP(2) levels, may mediate excitation. Like vertebrate rods, Drosophila melanogaster photoreceptors generate quantum bumps in response to single photons, but their kinetics is approximately 10-100 times faster, and this reflects a fundamentally different strategy incorporating a threshold, positive and negative feedback by Ca(2+) acting downstream of phospholipase C and a refractory period.

Visual transduction in Drosophila.

The brain's capacity to analyse and interpret information is limited ultimately by the input it receives. This sets a premium on information capacity of sensory receptors, which can be maximized by optimizing sensitivity, speed and reliability of response. Nowhere is selection pressure for information capacity stronger than in the visual system, where speed and sensitivity can mean the difference between life and death. Phototransduction in flies represents the fastest G-protein-signalling cascade known. Analysis in Drosophila has revealed many of the underlying molecular strategies, leading to the discovery and characterization of signalling molecules of widespread importance.

Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors.

The trp (transient receptor potential) gene encodes a Ca2+ channel responsible for the major component of the phospholipase C (PLC) mediated light response in Drosophila. In trp mutants, maintained light leads to response decay and temporary total loss of sensitivity (inactivation). Using genetically targeted PIP2-sensitive inward rectifier channels (Kir2.1) as biosensors, we provide evidence that trp decay reflects depletion of PIP2. Two independent mutations in the PIP2 recycling pathway (rdgB and cds) prevented recovery from inactivation. Abolishing Ca2+ influx in wild-type photoreceptors mimicked inactivation, while raising Ca2+ by blocking Na+/Ca2+ exchange prevented inactivation in trp. The results suggest that Ca2+ influx prevents PIP2 depletion by inhibiting PLC activity and facilitating PIP2 recycling. Without this feedback one photon appears sufficient to deplete the phosphoinositide pool of approximately 4 microvilli.

Acanthocytosis and neurological disorders.

Acanthocytosis occurs because of ultrastructural abnormalities of the erythrocyte membranous skeleton resulting in reduced membrane fluidity. At least three hereditary neurological conditions are associated with it, although as yet the pathogenesis of the neurological features is unknown. In abetalipoproteinaemia, an autosomal recessive condition, vitamin E deficiency results in a progressive spinocerebellar syndrome associated with peripheral neuropathy and retinitis pigmentosa. Neuroacanthocytosis is also probably an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysarthria, areflexia, seizures and dementia. McLeod syndrome is an X-linked recessive disorder usually presenting in males as a benign myopathy with areflexia, in association with a particular abnormality of expression of Kell blood group antigens. However, occasionally the neurological features are more severe and indistinguishable from those of neuroacanthocytosis. Recent advances in molecular genetics may assist better understanding of the disease mechanisms and the search for more effective treatments.

Light adaptation in Drosophila photoreceptors: I. Response dynamics and signaling efficiency at 25 degrees C.

Besides the physical limits imposed on photon absorption, the coprocessing of visual information by the phototransduction cascade and photoreceptor membrane determines the fidelity of photoreceptor signaling. We investigated the response dynamics and signaling efficiency of Drosophila photoreceptors to natural-like fluctuating light contrast stimulation and intracellular current injection when the cells were adapted over a 4-log unit light intensity range at 25 degrees C. This dual stimulation allowed us to characterize how an increase in the mean light intensity causes the phototransduction cascade and photoreceptor membrane to produce larger, faster and increasingly accurate voltage responses to a given contrast. Using signal and noise analysis, this appears to be associated with an increased summation of smaller and faster elementary responses (i.e., bumps), whose latency distribution stays relatively unchanged at different mean light intensity levels. As the phototransduction cascade increases, the size and speed of the signals (light current) at higher adapting backgrounds and, in conjunction with the photoreceptor membrane, reduces the light-induced voltage noise, and the photoreceptor signal-to-noise ratio improves and extends to a higher bandwidth. Because the voltage responses to light contrasts are much slower than those evoked by current injection, the photoreceptor membrane does not limit the speed of the phototransduction cascade, but it does filter the associated high frequency noise. The photoreceptor information capacity increases with light adaptation and starts to saturate at approximately 200 bits/s as the speed of the chemical reactions inside a fixed number of transduction units, possibly microvilli, is approaching its maximum.

Light adaptation in Drosophila photoreceptors: II. Rising temperature increases the bandwidth of reliable signaling.

It is known that an increase in both the mean light intensity and temperature can speed up photoreceptor signals, but it is not known whether a simultaneous increase of these physical factors enhances information capacity or leads to coding errors. We studied the voltage responses of light-adapted Drosophila photoreceptors in vivo from 15 to 30 degrees C, and found that an increase in temperature accelerated both the phototransduction cascade and photoreceptor membrane dynamics, broadening the bandwidth of reliable signaling with an effective Q(10) for information capacity of 6.5. The increased fidelity and reliability of the voltage responses was a result of four factors: (1) an increased rate of elementary response, i.e., quantum bump production; (2) a temperature-dependent acceleration of the early phototransduction reactions causing a quicker and narrower dispersion of bump latencies; (3) a relatively temperature-insensitive light-adapted bump waveform; and (4) a decrease in the time constant of the light-adapted photoreceptor membrane, whose filtering matched the dynamic properties of the phototransduction noise. Because faster neural processing allows faster behavioral responses, this improved performance of Drosophila photoreceptors suggests that a suitably high body temperature offers significant advantages in visual performance.