Cleft closure for the treatment of unhealed perineal sinus

OBJECTIVE: Despite improvements in surgical practice, persistent perineal wound sinus is still a common complication after proctectomy. This study presents the success of a modified cleft closure technique in dealing with this problem. METHODS: From May 1997 patients with a persistent perineal sinus after surgery underwent a cleft closure - similar to that performed for patients with pilonidal sinus disease. RESULTS: Eight patients (6 male, 2 female) with an average age of 52 years underwent a cleft closure for a persistent perineal sinus after surgery. Four patients had undergone a proctocolectomy (ulcerative colitis), 2 an abdominoperineal excision of the rectum (adenocarcinoma) and 2 a proctectomy (1 Crohn's disease, 1 complication of diverticular disease). Symptoms had been present for an average of 41 months (range 5-152 months) and 3 patients had undergone other procedures attempted previously to deal with the problem. The first three patients had the procedure as an inpatient with an average stay of 4.7 days. The next 5 patients had the procedure as a day case (2 local anaesthetic, 3 general anaesthetic). Two patients developed a postoperative wound infection and all but one wound had healed completely by 8 weeks. In this patient the procedure was repeated to achieve healing. There was no other associated morbidity and no postoperative deaths. There have been no recurrences to date. CONCLUSION: Modified cleft closure for persistent perineal sinus is a simple procedure with low morbidity that can be performed under local anaesthetic in the day surgery unit.     

TANDEM URETEROCYSTOPLASTY

Background : Bladder augmentation may be undertaken by using various gastrointestinal segments but their use is associated with a multitude of well-recognized complications. The mega-ureter has proven to be a satisfactory alternative; in patients with bilateral mega-ureters, both ureters may be used for this purpose. Methods : Seventeen patients had augmentation ureterocystoplasty, including three in whom both distal ureters were used in tandem. The latter included two patients with neurogenic bladder and one with bladder exstrophy. Results : Satisfactory augmentation was achieved in all patients undergoing tandem ureterocystoplasty. The neurogenic bladder patients are managed by urethral clean intermittent catheterization (CIC) and the exstrophy patient is managed by CIC of an appendico-vesicostomy (Mitrofanoff). All are continent. Conclusions : The mega-ureter provides an excellent source of augmentation material in patients with small non-compliant bladders. In those with bilateral mega-ureters, consideration should be given to using both ureters in tandem to achieve the maximum possible bladder capacity.     

Depletion of neuropeptides during wound healing in rat skin

The peptides substance P, calcitonin gene-related peptide and somatostatin are present in nerve fibres in mammalian, including human, skin. There is evidence that in addition to having a putative neurotransmitter role, they may be trophic agents: a study was therefore undertaken of peptide changes during wound healing in rat skin. A significant depletion of the neuropeptides was found in the region of the wound within two days, and this persisted for two weeks. A smaller and delayed depletion also occurred in intact skin of the same dermatome, but not in an adjacent dermatome.     

Zinc depletion and complications of surgery

Zinc is essential for protein synthesis and reduced levels may impair recovery from surgery. To study this prospectively, clinical, anthropometric, haematological and biochemical indices of malnutrition were measured in 46 patients undergoing elective surgery and were related to the frequency and type of post-operative complications. In addition, leucocyte zinc levels, which are an estimate of tissue zinc levels, were measured. The diagnoses of the patients did not correlate with any of these parameters. Many patients were malnourished. 39% of the patients had a post-operative complication, of whom 8 had a wound complication. The frequency of complications as a whole was inversely related to serum albumin and transferrin levels, while wound complications were in addition associated with low leucocyte zinc levels. Malnutrition may therefore increase post-operative complications in general, but tissue zinc deficiency may contribute to wound problems.     

Tobacco carcinogen induces both lung cancer and non‐alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non‐alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4‐(N‐methyl‐N‐nitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8–10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF‐κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK‐induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF‐κB and CYP2E1 in the liver and attenuated the NNK‐induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen‐associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen‐induced pulmonary and hepatic injury.     

Prevalence of signs and symptoms of ocular surface disease in individuals treated and not treated with glaucoma medication

Background: To determine the prevalence of signs and symptoms of ocular surface disease in two hospital‐based cohorts; glaucoma patients and non‐glaucoma patients. Design: A cross‐sectional, comparative case series. Participants: Glaucoma patients (n = 300) prescribed topical glaucoma medications for ≥6 months were compared with control patients (n = 100) who were not applying prescribed topical medications. Methods: A validated self‐report questionnaire was used to elicit the extent of ocular symptoms. Signs of ocular surface and eyelid disease were assessed along with medication history. Main Outcome Measures: Signs and symptoms of ocular surface pathology were determined including the tear film break‐up time, fluorescein staining of the cornea and conjunctiva, meibomian gland dysfunction and Schirmer's test. Results: A significant increase in the prevalence of ocular surface disease signs was observed in the glaucoma population, 70.3%, compared with controls, 33% (P < 0.001). The overall prevalence of clinically significant ocular surface disease symptoms was not significantly different between cohorts, 30.7% versus 24.0%, respectively (P = 0.252). Logistic regression analysis showed that the number of anti‐glaucoma medications and duration of therapy were key predictors of significant ocular surface disease signs in the glaucoma group. There was no significant correlation between signs and symptoms of ocular surface disease in either group after adjusting for age and gender. Conclusions: Signs and symptoms of ocular surface disease are relatively common in older patients, but signs of ocular surface disease are significantly higher in individuals who instil topical glaucoma therapy.     

Associations of ERAP1 coding variants and domain specific interaction with HLA-C106 in the early onset psoriasis patients of India

Interferon-γ-induced aminopeptidase ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto MHC class I and presented to the CD8⁺ T-cells. ERAP1 association and its interaction with HLA-C106 is controversial across different populations. We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: Lys528Arg and rs27044: Gln730Glu) and their interactions with HLA-C106 in psoriasis. Significant associations of HLA-C106 (OR = 5.47, P < 2.2 × 10^?16), rs30187 (OR 1.35, P = 7.4 × 10^?4) and rs27044 (OR = 1.24, P = 5.8 × 10^?3) were observed. All three ERAP1 SNPs showed significant association only for HLA-C106 positive patients, while rs30187 and rs27044 showed significant association only for early onset patients (rs30187: OR = 1.47, P = 9.6 × 10^?5; rs27044: OR = 1.36, P = 3.3 × 10^?4). No differential expression of ERAP1 was observed either between paired uninvolved and involved skin tissues of psoriasis patients or between non-risk and risk variants in the involved skin. Significant epistatic interaction was observed between HLA-C106 and the SNP (rs27044) located at the peptide-binding cavity of ERAP1. Evolutionary conservation analysis among mammals showed confinement of Lys528 and Gln730 within highly conserved regions of ERAP1 and suggested the possible detrimental effect of this allele in ERAP1 regulation.