Culture-proven endogenous endophthalmitis: clinical features and visual acuity outcomes

PURPOSE: To investigate clinical features and visual acuity outcomes associated with endogenous endophthalmitis. DESIGN: Retrospective, observational case series. METHODS: Twenty-one eyes of 21 patients treated at Bascom Palmer Eye Institute for culture-proven endogenous endophthalmitis between 1996 and 2002 were reviewed. RESULTS: Patients were followed a mean of 3 months (range, 1 to 12 months). Fungal isolates occurred in 13 eyes (62%), gram-positive isolates in 7 (33%), and gram-negative isolates in 1 (5%). Twelve patients (57%) were hospitalized at the time of diagnosis and 6 patients (29%) died within 2 months of diagnosis. Initial treatment included tap and injection of intravitreal medication in 10 eyes (48%) and pars plana vitrectomy with injection of intravitreal medication in 11 eyes (52%). Final visual outcomes were obtainable for 18 eyes (two patients died within 10 days of diagnosis, and one patient was lost to follow-up). Eight (44%) of these 18 eyes achieved a visual acuity of 20/400 or better and 10 (56%) of 18 eyes achieved a visual acuity worse than 20/400, including 3 that were either enucleated or eviscerated. Three eyes with Aspergillus endophthalmitis had worse visual outcomes than eyes with either Candida (P =.036) or bacterial endophthalmitis (P =.024). CONCLUSIONS: Compared with published series of postoperative or post-traumatic endophthalmitis, patients with endogenous endophthalmitis are more likely to have fungal isolates with a predominance of Candida albicans. Endogenous endophthalmitis is generally associated with high mortality and poor visual acuity outcomes, particularly when caused by more virulent species such as Aspergillus.     

Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation

Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia/reperfusion (I/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male Lewis rats served as donors and recipients of heterotopic syngeneic pancreaticoduodenal transplantation. Recipient animals were divided into two experimental groups: group Tx (n=7) received grafts without IPC, group Tx&IPC received grafts with IPC. Animals that had not undergone transplantation but whose pancreata had been exteriorized served as controls (n=5). All pancreatic grafts were preserved in University of Wisconsin solution for 6 h at 4°C. IPC was induced by interruption of the arterial blood flow for 10 min followed by 10 min of reperfusion. One and two hours after reperfusion, graft microcirculation was assessed by means of intravital microscopy (IVM). Rats were immediately killed after the second measurement and DNA breaks of acinar cells were detected by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end-labelling (TUNEL) assay and gel electrophoresis (laddering). The apoptotic index (AI) was defined as the number of apoptotic cells per high-power field. Analysis of both groups of transplanted grafts showed a significant decrease in functional capillary density (FCD) and a significant increase in leukocyte sticking to postcapillary venules (LAV) at 1 h and 2 h of reperfusion, compared with animals that had not undergone transplantation (P<0.01). In parallel, AI was significantly increased in transplanted grafts compared to the controls (P<0.01). Grafts subjected to IPC showed no significant differences, neither for FCD nor LAV, at both time points if compared with grafts of group Tx. However, IPC resulted in a significant increase in AI (P<0.05). We can conclude that IPC has no effect on pancreatic microcirculation but enhances acinar cell apoptosis in experimental pancreas transplantation. These results indicate that IPC might increase I/R injury after pancreatic cold ischemia.     

Current techniques of decompression of the lumbar spine

Lumbar spinal decompression is a commonly performed procedure. Although the conventional open techniques of decompression remain the gold standard of treatment, problems with paraspinal musculature denervation and resultant lumbar instability have focused attention on less invasive techniques. A multitude of spinal instrumentation systems have been developed to stabilize the spine and improve arthrodesis rates. A stronger emphasis on restoration of anterior column height and stability has increased the use of anterior interbody fusion devices. Developing technology is allowing for better visualization and possibly improved outcomes with minimally-invasive techniques. The results of all lumbar decompressive and stabilization procedures however, remain closely related to careful patient selection.     

Impairment of microcirculation in the early reperfusion period predicts the degree of graft pancreatitis in clinical pancreas transplantation

BACKGROUND: Graft pancreatitis is thought to be induced by ischemia/reperfusion. Animal experiments have suggested that an impaired microcirculation is crucial in this process. We have therefore studied the relevance of microcirculation in clinical pancreas transplantation. METHODS: In 17 patients undergoing pancreas transplantation, tissue pO2 was monitored continuously by an electrode implanted into the pancreatic tail. A catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were taken from this catheter and blood flow was measured by the venous outflow method. The degree of graft pancreatitis was assessed by peak-C-reactive protein (CRP) defined as highest CRP within 3 days after transplantation. RESULTS: Tissue pO2 increased within 5 min after reperfusion. Thereafter, in most patients a transient decrease was noted, indicating impairment of nutritive perfusion. During this period there was an increasing negative correlation between peak-CRP and tissue pO2 which was highly significant at 60 min after reperfusion (r=-0.70, P<0.002). Also donor age correlated significantly with peak-CRP (r=0.64, P<0.005) and to a somewhat lesser extend with tissue pO2 60 min after reperfusion (r= -0.55, P<0.03). CONCLUSION: These data show that the degree of organ damage in clinical pancreas transplantation is directly related to an impairment of microcirculation in the early reperfusion period. These data also support the idea that grafts from older donors have a higher probability to develop graft pancreatitis and that this might be due to an increased incidence of microcirculatory disturbances in these organs.     

Distinct time courses of increase in cytochromes P450 1A2, 2A5 and glutathione S-transferases during the progressive hepatitis associated with Helicobacter hepaticus

Mice naturally infected by Helicobacter hepaticus develop a chronic active hepatitis leading to hepatocellular carcinoma. This mouse model of liver cancer was used to examine the impact of bacterial infection on the hepatic expression and activity of enzymes involved in carcinogen bioactivation (phase I enzymes) and detoxification (phase II enzymes). No major differences in total cytochrome P450 (CYP) content were found between control and infected mice during the course of the study. The most striking modulations of individual isoenzymes were the increases in immunohistochemical staining observed for CYP1A and CYP2A5 in relation to increasing age and liver lesions. The increase in CYP2A5 in mice aged over 12 months was confirmed by the observed increases in coumarin 7-hydroxylation (CYP2A5 substrate) in vitro and CYP2A5 mRNA levels by Northern blot analysis. Immunoblotting confirmed the specific induction of CYP1A2 in infected mice 12 and 18 months of age. Perfusion of liver with nitroblue tetrazolium, an indicator for superoxide formation, demonstrated that in livers of infected mice, hepatocytes often co-expressed CYP2A5 and formazan deposition. Concerning phase II enzymes, an enhancement of glutathione S-transferase (GST) activities, related to the disease process, was observed in infected mice. An age- specific increase of GSTpi and A4.4 (early stage of disease) and GST YaYa (>9 months) expression was also demonstrated by immunohistochemical staining. In contrast, catalase and glutathione- peroxidase activities, as well as reduced glutathione content were decreased in the early stages of disease (3-9 months) in infected mice compared to age-matched control mice. Overall, these results suggest that alterations in CYP and GST expression may contribute to the aetiology of tumour incidence due to H. hepaticus infection via production of reactive oxygen species.      

Relationship between acetylator status, smoking, and diet and colorectal cancer risk in the north-east of England

Some previous studies have suggested that the fast phenotype of the N- acetyltransferase NAT2 may confer susceptibility to colorectal cancer because of greater activation of dietary heterocyclic amines, particularly in individuals who also consume well-done red meat, but other studies have not supported this. We describe a large case-control study examining the interaction between dietary, smoking and drinking habits, and acetylation genotype in relation to susceptibility to colorectal cancer. One-hundred-and-seventy-four incident cases and 174 matched controls were recruited. Genotyping for polymorphisms in NAT2 was performed using a method that detects >95% of slow alleles and data on personal habits were collected using a standardized questionnaire. We found no difference in the frequency of the fast acetylator genotype between cases and controls [odds ratio = 0.95 (95% CI 0.61-1.49)], and analysis by sex, age and site also revealed no difference in acetylator genotype. There was, however, considerable heterogeneity in dietary risk factors between fast and slow acetylators. Analysis by acetylator type shows that recent smoking was more frequent in slow acetylator cases than matched controls [OR = 2.31 (1.16-4.6)] and that heavy alcohol consumption was also more frequent in the slow acetylator cases than controls [OR = 2.5 (1.02-7.29)]. In contrast, frequent fried meat intake was seen more frequently in fast acetylator cases than matched controls [OR = 6.0 (1.34-55)]. The odds ratio for the combination of fast acetylator status and frequent fried meat consumption in cases was 6.04 (1.6-26). Our study suggests that there may be different risk factors for colorectal cancer in slow and fast acetylators, and reveals a new observation that slow acetylators may be at risk of colon cancer from smoking. In our community, the overall effect of acetylator status on colorectal cancer risk is neutral.      

Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history

The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.