Progression of diabetic retinopathy after bariatric surgery.

AIM: To assess the impact of bariatric surgery on the progression of diabetic retinopathy in patients with Type 2 diabetes. METHOD: We conducted a retrospective, observational study of patients with Type 2 diabetes who underwent bariatric surgery between 1 January 2001 and 31 December 2012 and had hospital-based retinal screening records. Data were collected from four surgical centres. Those who had pre-operative retinal screening and at least one post-operative retinal screen were eligible for analysis. A generalized linear mixed model was used to explore significant clinical predictors on the post-operative grade severity over time, controlling for important baseline characteristics. RESULTS: Three hundred and eighteen patients were eligible for analysis. Of these, 68.6% had no diabetic retinopathy pre-operatively compared with 18.9%, 8.5% and 4% with a diabetic retinopathy grade of minimal, mild or moderate and higher, respectively. First post-operative retinal screening results showed that after surgery 73% had no change in their diabetic retinopathy grade, 11% regressed and 16% progressed. The probability of having a diabetic retinopathy grade of moderate or higher over time post surgery was significantly associated with the magnitude of HbA1c reduction from pre-surgery HbA1c levels, a shorter post-operative retinal screening duration, more severe pre-operative retinal screening grade, male gender and non-Maori/Pacific ethnicity. CONCLUSIONS: A higher pre-operative diabetic retinopathy grade, and a large decrease in HbA1c post surgery warrant closer monitoring of diabetic retinopathy after bariatric surgery. Further prospective, randomized studies are required to investigate the gender and ethnic differences found.

Simultaneous infection of pigs and people with triple-reassortant swine influenza virus H1N1 at a U.S. county fair.

Influenza-like illness was noted in people and pigs in attendance at an Ohio county fair in August 2007. The morbidity rate in swine approached 100% within 1-2 days of initial clinical signs being recognized, and approximately two dozen people developed influenza-like illness. Triple-reassortant swine H1N1 influenza viruses were identified in both pigs and people at the fair. The identified viruses (A/Sw/OH/511445/2007, A/Ohio/01/2007, and A/Ohio/02/2007) were similar to H1N1 swine influenza viruses currently found in the U.S. swine population. This case illustrates the possibility of transmission of swine influenza in settings where there is close human/swine interaction.

Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus.

The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine δ-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, 6-week-old, cross-bred pigs were randomly allocated into 3 groups of 28 pigs to represent vaccinated/challenged (V/C), non-vaccinated/challenged (NV/C), and non-vaccinated/non-challenged (NV/NC) control groups. Pigs were intratracheally inoculated with pH1N1 and euthanized at 1, 2, 5, and 21 days post inoculation (dpi). Macroscopically, V/C pigs demonstrated greater percentages of pneumonia compared to NV/C pigs. Histologically, V/C pigs demonstrated severe bronchointerstitial pneumonia with necrotizing bronchiolitis accompanied by interlobular and alveolar edema and hemorrhage at 1 and 2 dpi. The magnitude of peribronchiolar lymphocytic cuffing was greater in V/C pigs by 5 dpi. Microscopic lung lesion scores were significantly higher in the V/C pigs at 2 and 5 dpi compared to NV/C and NV/NC pigs. Elevated TNF-α, IL-1ß, IL-6, and IL-8 were detected in bronchoalveolar lavage fluid at all time points in V/C pigs compared to NV/C pigs. These data suggest H1 inactivated vaccines followed by heterologous challenge resulted in potentiated clinical signs and enhanced pulmonary lesions and correlated with an elevated proinflammatory cytokine response in the lung. The lung alterations and host immune response are consistent with the vaccine-associated enhanced respiratory disease (VAERD) clinical outcome observed reproducibly in this swine model.

Leukogram abnormalities in gnotobiotic pigs infected with porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) is a single-stranded circular DNA virus that is the causative agent of porcine circovirus associated disease (PCVAD), a disease complex affecting swine around the world. Although this virus is believed to negatively affect the host's immune system, the mechanism by which PCV2 induces disease is not completely understood. This report describes a series of PCV2 experiments using the gnotobiotic pig model in which a relationship was demonstrated between abnormal leukograms and development of clinical disease in PCV2-infected pigs. When compared to control pigs the leukogram was characterized by a decrease in lymphocytes within 14 days post inoculation (dpi) followed by an increase in neutrophils 7-14 days later. No significant changes in the circulating monocyte, basophil, and eosinophil cell populations were detected. The combination of an absolute neutrophilia and lymphopenia produced a neutrophil/lymphocyte ratio that was predictive of clinical disease and was inversely correlated with the presence of neutralizing antibodies. Based on previous reports, the lymphopenia may be attributed to a direct cytolytic effect of the virus and could negatively affect the pig's immune response. The role of the neutrophilia in the pathogenesis of PCVAD in gnotobiotic pigs is unknown.

Postweaning multisystemic wasting syndrome produced in gnotobiotic pigs following exposure to various amounts of porcine circovirus type 2a or type 2b.

In late 2005, a postweaning, high mortality syndrome spread rapidly through finishing barns in swine dense areas of the United States. Diagnostic investigations consistently detected porcine circovirus type 2 (PCV2) from diseased tissues. Subsequent genetic analysis revealed that the infectious agent was a PCV2 type termed "PCV2b". Prior to late 2004, only the PCV2a type, but not PCV2b, had been reported in North America. In this communication, we produce severe postweaning multisystemic wasting syndrome (PMWS) in gnotobiotic pigs using infectious PCV2a and PCV2b generated from DNA clones constructed from field isolates identified in the 2005 outbreak. Clinical signs exhibited by diseased pigs included anorexia, dyspnea and listlessness. Mortality was typically observed within 12h of onset of dyspnea. The most striking microscopic lesions in affected animals were severe hepatic necrosis and depletion of germinal centers in lymph nodes with associated abundant PCV2 viral antigen. Clinical signs and lesions observed in these studies were comparable to those reported in experiments with gnotobiotic pigs inoculated with a PCV2a isolate while concurrently receiving immune-stimulation or co-infection with porcine parvovirus or torque teno virus. The animals in these studies were confirmed to be free of detectable porcine parvovirus, porcine reproductive and respiratory syndrome virus, bovine viral diarrhea virus, swine hepatitis E virus, and aerobic and anaerobic bacteria. Seven out of 24 PCV2 inoculated pigs had a detectable congenital torque teno virus infection with no correlation to clinical disease. Thus, in these studies, both PCV2a and PCV2b isolates were singularly capable of inducing high mortality in the absence of any detectable infectious co-factor.

The role of swine in the generation of novel influenza viruses.

The ecology of influenza A viruses is very complicated involving multiple host species and viral genes. Avian species have variable susceptibility to influenza A viruses with wild aquatic birds being the reservoir for this group of pathogens. Occasionally, influenza A viruses are transmitted to mammals from avian species, which can lead to the development of human pandemic strains by direct or indirect transmission to man. Because swine are also susceptible to infection with avian and human influenza viruses, genetic reassortment between these viruses and/or swine influenza viruses can occur. The potential to generate novel influenza viruses has resulted in swine being labelled 'mixing vessels'. The mixing vessel theory is one mechanism by which unique viruses can be transmitted from an avian reservoir to man. Although swine can generate novel influenza viruses capable of infecting man, at present, it is difficult to predict which viruses, if any, will cause a human pandemic. Clearly, the ecology of influenza A viruses is dynamic and can impact human health, companion animals, as well as the health of livestock and poultry for production of valuable protein commodities. For these reasons, influenza is, and will continue to be, a serious threat to the wellbeing of mankind.

Detection of two porcine circovirus type 2 genotypic groups in United States swine herds.

In late 2005, sporadic cases of an acute onset disease of high mortality were observed in 10- to 16-week-old growing pigs among several swine herds of the United States. Tissues from the affected pigs in Kansas, Iowa, and North Carolina were examined, and porcine circovirus type 2 (PCV2) was detected consistently among these tissues. Phylogenetically, PCV2 can be divided into two major genotypic groups, PCV2-group 1 and PCV2-group 2. Whereas PCV2-group 1 isolates were detected in all the diseased animals, only two of the diseased animals harbored PCV2-group 2 isolates. This observation is important because PCV2-group 1 isolates had never been reported in the United States before (GenBank as of May 16, 2006), and they are closely related to the PCV2-group 1 isolates that have been described in Europe and Asia, previously. Our analysis revealed that each genotypic group contains a distinct stretch of nucleotide or amino acid sequence that may serve as a signature motif for PCV2-group 1 or PCV2-group 2 isolates.

An investigation of susceptibility to porcine reproductive and respiratory syndrome virus between two genetically diverse commercial lines of pigs.

The objective of this study was to determine whether host genetics play a role in susceptibility to the respiratory disease in growing pigs caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Based on a previous study, 2 genetically diverse commercial lines of pigs that also were divergent in the susceptibility of monocyte-derived macrophages to PRRSV infection in vitro were selected for an in vivo challenge study. Based on the average percentage of infected macrophages for each line, a line derived from the Large White breed was characterized as fluorescence-activated cell sorting(hi) (FACS(hi)), and a line derived from Duroc and Pietrain breeds was characterized as FACS(lo). Pigs from each line were challenged at 6 wk of age with PRRSV VR-2385 and necropsied at 10 or 21 d after infection. Data collected included clinical evaluation of disease, virus titration in serum and lung lavage fluid, macroscopic lung lesion scores, and microscopic lung lesion scores. The FACS(lo) line had consistently more severe clinical disease compared with the FACS(hi) line in the early stages of infection. Differences between line means were significant (P < 0.05) at 10 d after infection for all variables just described, and the FACS(lo) line showed more severe signs of disease. By 21 d after infection, clinical signs and lesions were resolving, and the differences between lines were significant (P < 0.04) only for microscopic lung lesion scores but approached significance (P < 0.08) for virus titer in serum. At 21 d after infection, the relationship between the lines reversed; the FACS(hi) line had higher serum virus titers than the FACS(lo) line. This report provides evidence that strongly suggests the existence of a host genetic component in disease susceptibility to PRRSV and indicates that further study is warranted to define the cellular mechanisms that affect disease susceptibility.

Blepharophimosis and bilateral Duane syndrome associated with a FOXL2 mutation.

This case describes the novel coexistence of sporadic blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and bilateral type I Duane syndrome in a female infant, with a FOXL2 mutation. Mutational analysis of FOXL2 demonstrated a 30-nucleotide duplication (c.672(-)701dup30) within the polyalanine tract of FOXL2. The association of BPES and Duane syndrome represents a novel phenotype which may suggest a greater pleiotropic effect of FOXL2 in development. During the period of the 4-8th week of embryonic development, the cranial nerves, their nuclei and the corresponding innervation to the extraocular muscles develop, the extraocular muscles undergo development and differentiation. This coincides with the period of time that FOXL2 is expressed strongly in the developing eyelids and the surrounding tissues. Forkhead genes are transcription factors and likely to be involved in signal transduction pathways. This case expands the spectrum of FOXL2 mutations associated with BPES.

In vitro susceptibility of macrophages to porcine reproductive and respiratory syndrome virus varies between genetically diverse lines of pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be responsible for financial losses in the swine industry worldwide. It remains undetermined whether genetic variability of the host in susceptibility to PRRSV exists and if this variability can be exploited to help control this important disease. The objective of this study was to determine if an in vitro flow cytometry (FACS) assay that detects the percentage of monocyte-derived macrophages (MDM) infected with PRRSV could be utilized to demonstrate genetic variability in the susceptibility between distinct lines of pigs. Over 400 growing pigs from six genetic lines maintained in a single commercial breeding herd were screened using an in vitro FACS assay. From this initial screening, two genetically diverse lines of pigs that were also divergent in their FACS results were selected for further study. An additional 264 pigs from these two lines were subsequently tested for in vitro susceptibility to PRRSV. As in the preliminary screening, the Large White line had significantly higher average percent positive MDM over the Duroc-Pietrain synthetic line. This report suggests a genetic component for susceptibility to PRRSV exists and that the in vitro assay may be useful in predicting the relative susceptibility to PRRSV in large groups of animals.

A molecular perspective on corneal dystrophies.

Corneal dystrophies refer to a group of corneal diseases and that are genetically determined. These have been traditionally classified with respect to the layer of cornea involved. We now know that this does not reflect the underlying pathobiology. Most of the corneal dystrophies are of Mendelian inheritance with some phenotype diversity and a variable degree of penetrance. The dystrophies involving enzymatic processes tend to be of autosomal recessive inheritance. In some cases, such as keratoconus, the inheritance pattern is not always clear and is considered complex. The age of onset of the disease, as in most inherited eye disorders, is variable and does not reflect the underlying pathogenic defect. Few cases are congenital. Our understanding of corneal dystrophies is undergoing somewhat of a revolution as over 12 chromosomes have been associated with corneal dystrophies with mutations identified in at least 14 genes if one includes anterior segment dysgenesis in this group of conditions. Several dystrophies remain without a gene or a genetic location (locus) and more familial studies are required. The new molecular information is challenging the traditional thinking about these conditions that was usually guided by the histopathological findings. As this new knowledge becomes more refined, the classification of this group of disorders will eventually be revisited to have a molecular basis. The elucidation of the underlying biochemical pathways may allow us to envisage the possibility of modulating these phenotypes in the future.

Generating mouse models of retinal disease using ENU mutagenesis.

We used the chemical mutagen, N-ethyl-N-nitrosourea, to induce random point mutations in the germline of the mouse strain C57BL/6 in order to generate models of retinal diseases. 1163 mutagenised first generation mice produced using this approach were examined for eye abnormalities. Approximately one-third (412) presented with some form of ocular abnormality. Most changes were unilateral and confined to the anterior segment of the eye. Less than 10% (44) of identified changes affected the posterior segment of the eye. 21 mice with varying ocular abnormalities, including 17 with retinal changes, were bred to produce second generation mice to confirm genetic inheritance. Genetic inheritance was confirmed in several of these lines including three with retinal changes.

Filariasis and erisipela in Santo Domingo.

This study examined acute-convalescent changes in diagnostic anti-streptococcal antibodies by the anti-streptolysin O (ASO) and anti-DNAase B (ADAB) tests among patients (n 28) with lymphedema and recurrent erisipela of the lower limb, comparing them with endemic normal control residents (n=25). The study was based in Villa Francisca, an urban focus of Bancroftian filariasis in eastern Santo Domingo, capital of the Dominican Republic. The acute signs and symptoms of erisipela were consistent with a diagnosis of bacterial cellulitis. The ASO test was especially successful at demonstrating a rise in mean titer during convalescence, whereas the ADAB produced about the same frequency of significant increases (0.2 log titer) as did the ASO. When subjects were scored as responders if mounting a minimal titer increase by either test, patients were found more frequently positive than were controls (chi2=5.3, P=0.02). About half (54%) of all patients mounted at least a minimal antibody increase. Filaria-specific IgG4 antibodies were absent from all sera of 20 residents of a nonendemic Dominican mountain town but appeared in about two-thirds of the sampled residents of the endemic barrio. Notably however, levels did not change between the acute phase and convalescence. These findings are consistent with the hypothesis that recurrent streptococcal invasion of the lymphatics may be a significant factor triggering or amplifying lymphedema and elephantiasis in patients with chronic filariasis.