Endophthalmitis After Intravitreal Bevacizumab (Avastin) Injections: An Outbreak Investigated.

Purpose To investigate an endophthalmitis outbreak in different eye hospitals after intravitreal (IVT) bevacizumab (Avastin) injections over two days. Place and duration of the study Mughal Eye Hospital, Nov 2022 to Jan 2023. Materials and methods All cases reported with endophthalmitis in Mughal Eye Hospital after administration of anti-vascular endothelial growth factor IVT injections in different hospitals on November 8-9, 2022, were studied. In all endophthalmitis cases, one to five IVT injections of antibiotics (vancomycin, ceftazidime, and dexamethasone) were given depending on the clinical picture. Results Thirty-six eyes of 34 patients who developed endophthalmitis were included in the study. Age (mean 53 years) ranged from 44 years to 70 years. There were 18 males and 16 females. Two patients had bilateral endophthalmitis. Thirty-three patients were given two to four IVT injections of antibiotics depending on the clinical response. Five cases of vitreous tap done before injecting antibiotics were found to have Pseudomonas. Anterior chamber wash was done in 15 cases to improve visualization for doing pars plana vitrectomy (PPV). In 24 patients PPV with silicon oil was done. Eighteen patients showed improvement as their hypopyon disappeared after IVT antibiotic injections. One patient developed corneal sloughing (she refused IVT antibiotic injections). One patient developed malignant/pupil block glaucoma. In two eyes, early PPV was done. Four eyes developed no perception of light. In our series, endophthalmitis patients started reporting one day after the injection. One patient who developed bilateral endophthalmitis developed bilateral cataracts with subluxations. One patient developed retinal detachment. One eye developed choroidal detachment. Conclusion IVT bevacizumab (Avastin) may be associated with an outbreak of endophthalmitis. Pseudomonas endophthalmitis is a very grave condition associated with severe morbidity.

Subtype frequency, demographic features, treatment and outcome of Juvenile Arthritis in one Centre in Abu Dhabi in the United Arab Emirates.

BACKGROUND: Juvenile Idiopathic Arthritis is a chronic inflammatory disease that affects 1 in 1000 children worldwide. Our population in the United Arab Emirates is diverse. The objective of this study is to describe the subtype frequency, demographic features and treatments received and outcome of our patients. METHODS: Patients with the diagnosis of Juvenile Arthritis identified through the hospital electronic medical records system (EMR), which was implemented for all medical documentation in January 2011. All patients included are patients who presented to our center for treatment and follow up from 2011 to end of 2021. Retrospective case notes review of patients electronic medical records with the diagnosis of JIA was performed. RESULTS: One hundred thirty-eight patients in total. Oligoarticular subtype was the most represented with 75 patients (55%) followed by Rheumatoid factor negative polyarticular JIA with 32 patients (23%) then Enthesitis related arthritis (ERA) with 10 patients (7%) then psoriatic (6%) then systemic JIA (5%). Undifferentiated subtype of 2%. The most diagnostic delay is in enthesitis related arthritis subtype with a mean of 11.4 months (6-25) followed by undifferentiated JIA with a mean of 7.5 months (4-8.5). 131 (96%) out of 138 received steroid treatment. Only 6 patients did not receive steroids. Out of 138 patients, 101 (73%) were on synthetic disease modifying medication methotrexate. Sixty-eight patients out of the total 138 required biologic treatment (49%). In total 93 patients achieved clinical remission (67%). In remission on treatment 78 patients which is (56%) of the total number of patients with follow up ranging from 1 to 5 years and 84% of patients in remission. In remission off treatment 15 patients (11% of all patients and 16% of patients in remission). CONCLUSION: The most common subtype in our cohort of patients is oligoarticular JIA. Longest delay is for ERA subtype. All our patients with oligoarticular JIA received Intra articular steroid injection as first line treatment. 49% of our patients received biologic treatment similar to rate in Northern Europe. Our remission rate is 67% with 11% of patients are in remission off treatment. Access to care remains a priority to treat patients effectively.

Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular malformations.

BACKGROUND: Infants with cardiovascular malformations are usually asymptomatic at birth. Earlier diagnosis is likely to improve outcome. OBJECTIVE: To examine trends in the diagnosis of potentially life-threatening cardiovascular malformations. METHODS: Ascertainment of all cardiovascular malformations diagnosed in infancy in the resident population of one English health region between 1985 and 2004. Infants with life-threatening cardiovascular malformations were all with hypoplastic left heart, pulmonary atresia with intact ventricular septum, transposition of the great arteries or interruption of the aortic arch; and those dying or undergoing operation within 28 days with coarctation of the aorta, aortic stenosis, pulmonary stenosis, tetralogy of Fallot, pulmonary atresia with ventricular septal defect or total anomalous pulmonary venous connection. RESULTS: Cardiovascular malformations were diagnosed in infancy in 4444 of 690,215 live births (6.4 per 1000) and were potentially life threatening in 669 (15%). Overall, 55 (8%) were recognised prenatally, 416 (62%) postnatally before discharge from hospital, 168 (25%) in living infants after discharge and 30 (5%) after death. Antenatal diagnoses increased from 0 to around 20% and no case was first diagnosed after death in the past 6 years. However, the proportion going home without a diagnosis remains around 25%. Malformations most likely to remain undiagnosed at discharge were coarctation of the aorta (54%), interruption of the aortic arch (44%), aortic valve stenosis (40%) and total anomalous pulmonary venous connection (37%). CONCLUSIONS: One in three infants with a potentially life-threatening cardiovascular malformation left hospital undiagnosed. Better early diagnosis is likely to be achieved by further improvements in antenatal diagnosis and more widespread use of routine pulse oximetry.

Interleukin-6 signalling in juvenile idiopathic arthritis is limited by proteolytically cleaved soluble interleukin-6 receptor.

OBJECTIVES: Interleukin-6 (IL-6) exerts multiple effects on chondrocytes and fibroblasts within the joint and is associated with disease activity in juvenile idiopathic arthritis (JIA). Although these cells express the ubiquitous signalling receptor for all IL-6-related cytokines, gp130, they do not express a cognate IL-6 receptor. Consequently, IL-6 responses within these cells occur via IL-6 trans-signalling relying on the presence of a soluble receptor (sIL-6R). Levels of sIL-6R in vivo are governed by either proteolytic cleavage (PC) of cognate receptor or by differential sIL-6R mRNA splicing (DS). The aim of this study was to evaluate the contribution of both isoforms to clinical parameters associated with IL-6 signalling in JIA. METHODS: IL-6, sIL-6R and DS-sIL-6R were measured by ELISA in serum and synovial fluid (SF) samples from 86 JIA patients. These data were related to indicators of inflammation-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and compared between patients stratified by subtype, age and disease duration. RESULTS: SF IL-6 significantly correlated with general indicators of activity (ESR and CRP) and SF PC-sIL-6R to a lesser degree with CRP. When the IL-6:sIL-6R ratio was calculated as an indicator of the potential for IL-6 signalling within the joint, 33% of SF samples showed a ratio >1 indicating saturation of sIL-6R by IL-6. Mean DS-sIL-6R levels were 0.71 ng/ml, whereas PC-sIL-6R levels constituted the majority of sIL-6R at 20.89 ng/ml. CONCLUSIONS: IL-6 trans-signalling within the joints of JIA patients is predominantly governed by the presence of PC-sIL-6R, and the data provided suggest that synovial levels of IL-6 and sIL-6R would be sufficient to drive IL-6 responses in chondrocytes and synovial fibroblasts.

Assessment of the clinical significance of gelatinase activity in patients with juvenile idiopathic arthritis using quantitative protein substrate zymography.

OBJECTIVE: To measure gelatinase activities in paired synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to assess how these activities relate to clinical and laboratory measures of disease activity. METHODS: A quantitative protein substrate zymography method was adapted and validated for use with serum and SF. Bands of activity were measured by densitometry and correlated with standard laboratory indicators of inflammation: erythrocyte sedimentation rate and platelet count. RESULTS: Gelatinase activity was found consistently in patients with JIA, with reproducible, quantified bands of activity corresponding to pro-matrix metalloproteinase-9 (pro-MMP-9), including the neutrophil associated lipocalin complex, and pro- and active forms of MMP-2. Both active MMP-2 and pro-MMP-9 were higher in JIA serum than in controls, though no differences were seen between patients grouped according to age, disease duration, or JIA subtype. However, SF MMP-9 correlated significantly with the laboratory indicators of inflammation, as did the relative level of active MMP-2. CONCLUSIONS: Both MMP-2 and MMP-9 gelatinolytic activities are raised during active JIA and associated with inflammatory activity regardless of age and disease duration, supporting a role for MMPs in the breakdown of joint components from early in disease. These MMPs may be specific markers of active joint destruction linked to inflammatory JIA, MMP-9 as a product of infiltrating cells, and the activation of MMP-2 produced within the joint.

Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study.

OBJECTIVES: To measure levels of the collagenases matrix metalloproteinase (MMP)-1 and -13 in the synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to correlate these measurements with inflammatory activity, levels of the collagenase activator MMP-3 and the tissue inhibitor of metalloproteinases-1 (TIMP-1). METHODS: Levels of MMP-1, -3, -13 and TIMP-1 were measured in paired SF and serum from 82 JIA patients using enzyme-linked immunsorbent assay and compared between subtypes and patients of different ages and disease durations. These levels were also correlated to the active joint count (AJC) and standard measures of inflammatory activity and therapeutic response, including erythrocyte sedimentation rate (ESR) and platelet count (PLT). RESULTS: MMP-1 was detected in JIA SF and correlated with PLT. MMP-3 levels were high in SF and detectable in serum where they correlated with PLT, ESR and AJC. MMP-13, however, was not detected in SF or serum. No differences were observed between patients grouped by subtype, age or disease duration. MMP-3 contributed the majority of total MMP in SF samples resulting in excess MMP levels over TIMP-1. CONCLUSIONS: MMP-1 is up-regulated in SF concordant with inflammatory activity in JIA. This was true for patients in all JIA subtypes and age groups, suggesting that the capability for degradation of type II collagen is present in early disease, and throughout the disease course. MMP-3 may be important in the activation of collagenases and the saturation of exogenous inhibitors. Serum MMP-3 may therefore be a useful, measurable and specific marker of active disease in JIA.

Primary hyperaldosteronism with normokalaemia secondary to an adrenal adenoma (Conn's syndrome) in a 12 year-old boy.

A 12-1/2 year-old boy presented to the Accident Department following an episode of dizziness and was found to be hypertensive. Investigations revealed primary hyperaldosteronism secondary to an adrenal adenoma (Conn's syndrome). He had normal electrolytes during the period of investigation and potassium concentrations were > or = 4.2 mmol/l on all but one occasion. The hypertension resolved following excision of the adrenal tumour. Normokalaemia with potassium >4.0 mmol/l is very unusual in patients with Conn's syndrome and has not been described in childhood before. Primary hyperaldosteronism needs to be considered in hypertensive children even when potassium concentrations are well within the laboratory reference range.

Hypercalcaemia in infancy; a presenting feature of spinal muscular atrophy.

A 10 month old girl presented with a history of constipation from early life. She was found to be hypercalcaemic with hypercalciuria and nephrocalcinosis. Her mild motor delay and hypotonia were thought to be linked to chronic hypercalcaemia, but when these features failed to improve despite normocalcaemia on a low calcium diet the possibility of neuromuscular disease was explored in more detail. She was subsequently found to have spinal muscular atrophy type 2. We suspect that the hypercalcaemia with hypercalciuria observed in this case reflects altered bone turnover secondary to reduced muscular activity.

Bone marrow transplantation for CD40 ligand deficiency: a single centre experience.

BACKGROUND: CD40 ligand (CD40L) deficiency is a rare X linked immunodeficiency disorder leading to recurrent bacterial infection, with cryptosporidial enteritis and subsequent hepatic cirrhosis. Bone marrow transplantation offers the only cure. OBJECTIVE: To analyse retrospectively the outcome of bone marrow transplantation for this condition in one centre. DESIGN: A retrospective case note analysis was performed, identifying all patients with CD40L deficiency who had undergone bone marrow transplantation between May 1988 and December 2000. Details of pre-existing infection, pretransplantation immunological and infective data, transplant procedure (particularly donor type and HLA match), conditioning regimen, and marrow manipulation were analysed. Post-transplantation data including infective episodes, engraftment details, immune function, complications, and outcome were recorded. RESULTS: Eight boys (age 1-14 years, median 5.75) had transplants. Six received T cell depleted unrelated donor marrow. Four survive and have normal immune function. Six had previous Pneumocystis carinii pneumonia and three had histological liver damage. Survival was associated with younger age at transplantation and normal liver histology. CONCLUSIONS: Bone marrow transplantation can be curative in CD40L deficiency. Better outcome is associated with younger age at transplantation and normal liver histology.

Clinico-pathological features of postural hypotension in diabetic autonomic neuropathy.

We report the clinico-pathological features and management of a 49-year-old male with a 30-year history of Type 1 diabetes mellitus who had nephropathy (proteinuria 1.81 g/24 h, creatinine 136 micromol/l), proliferative retinopathy and severe somatic and autonomic neuropathy. A sural nerve biopsy demonstrated marked myelinated fibre loss with unmyelinated fibre degeneration and regeneration combined with extensive endoneurial microangiopathy. The management of the patient's blood pressure problems (supine hypertension) and symptomatic postural hypotension is discussed.

Infant and child mortality in Palestinian camps in Lebanon.

"This study aims at producing acceptable estimates of a number of indicators of infant and child mortality in Palestinian camps in Lebanon by using the Brass technique. The study utilized data provided by two comprehensive surveys...carried out in 1979 and 1989." Results are provided on the decline in infant mortality between 1977 and 1989; the reduction in the probability of dying between ages one and five; life expectancy at birth; sex differences in infant mortality; and changes in death rates and life expectancy by mother's educational level.

A multiscale stochastic image model for automated inspection.

We develop a novel multiscale stochastic image model to describe the appearance of a complex three-dimensional object in a two-dimensional monochrome image. This formal image model is used in conjunction with Bayesian estimation techniques to perform automated inspection. The model is based on a stochastic tree structure in which each node is an important subassembly of the three-dimensional object. The data associated with each node or subassembly is modeled in a wavelet domain. We use a fast multiscale search technique to compute the sequential MAP (SMAP) estimate of the unknown position, scale factor, and 2-D rotation for each subassembly. The search is carried out in a manner similar to a sequential likelihood ratio test, where the process advances in scale rather than time. The results of this search determine whether or not the object passes inspection. A similar search is used in conjunction with the EM algorithm to estimate the model parameters for a given object from a set of training images. The performance of the algorithm is demonstrated on two different real assemblies.

Pharmacokinetics of aditoprim and trimethoprim in buffalo calves.

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.

A clinicopathological analysis of ovarian tumours.

We performed a retrospective analysis of patients with ovarian tumors who were admitted to the Aga Khan University Hospital from January 1985 to December 1989. Sixty one cases were reviewed. Mean age of the whole group was 44 years. Majority of the patients presented with abdominal pain and distention. Most frequent physical finding was a palpable mass on pelvic or abdominal examination. Overall these patients had a higher incidence of breast cancer than expected in the general population. Two-thirds of the tumors were malignant. Comparison of the patients with malignancy against those with benign tumors failed to show any correlation with parity. Majority of the patients with malignant disease were above forty and had ultrasound showing a cystic mass over 10 cms in size. Cancer was mostly epithelial in origin, with widespread disease (stage III or IV) at the time of presentation. Benign tumors, mostly of germ cell type, were predominantly seen in patients under the age of forty with ultrasound showing cystic mass of any size from under 5 cms to over 10 cms.