Postprandial hyperinsulinaemic hypoglycaemia and type 1 diabetes mellitus

A patient with severe postprandial hyperinsulinaemic hypoglycaemia (PPHH) for 4 years developed type 1 diabetes mellitus. She had no insulin or insulin receptor antibodies but was positive for islet cell and glutamic acid decarboxylase (GAD) antibodies. PPHH prior to the onset of type 1 diabetes mellitus has not been previously described and may be a prodrome of type 1 diabetes mellitus.     

Improved outcome of referrals for intestinal transplantation in the UK

Aim

To describe the outcome of children with intestinal failure referred to Birmingham Children''s Hospital (BCH) for consideration of intestinal transplantation (ITx), to determine factors for an adverse outcome and to analyse the impact of post‐1998 strategies on survival.

Subjects and methods

A retrospective analysis was performed of children referred for ITx assessment from January 1989 to December 2003. Children were assessed by a multidisciplinary team and categorised into: (a) stable on parenteral nutrition; (b) unsuitable for transplantation (Tx); and (c) recommended for Tx. To analyse the impact of the post‐1998 strategies on survival, a comparison was made between the two eras (pre‐1998 and post‐1998).

Results

152 children with chronic intestinal failure were identified (63M:89F, median age 10 months (range 1–170)). After assessment, 69 children were considered stable on parenteral nutrition (5‐year survival 95%); 28 children were unsuitable for Tx (5‐year survival 4%); and 55 children were recommended for Tx (5‐year survival 35%, which includes 14 children who died waiting for size‐matched organs). Twenty three ITx and nine isolated liver transplants (iLTx) were performed. In a multivariate analysis, the following factors in combination had an adverse effect on survival: the presence of a primary mucosal disorder (p = 0.007, OR ratio 3.16, 95% CI 1.37 to 7.31); absence of involvement of a nutritional care team at the referring hospital (p = 0.001, OR ratio 2.55, 95% CI 1.44 to 4.52); and a serum bilirubin>100 µmol/l (p = 0.001, OR ratio 3.70, 95% CI 1.84 to 7.47). Earlier referral (median serum bilirubin 78 µmol/l in the post‐1998 era compared with 237 µmol/l in the pre‐1998 era, p = 0.001) may be a contributory factor to improved survival. The strategies of combined en bloc reduced liver/small bowel transplantation and iLTx resulted in fewer deaths on the waiting list in the post‐1998 era (2 deaths in post‐1998 era v 12 deaths in pre‐1998 era). The overall 3‐year survival in the post‐1998 era (69%) has improved compared with the pre‐1998 era (31%; p<0.001)

Conclusion

The changing characteristics at the time of referral, including earlier referral and innovative surgical strategies have resulted in improved long‐term survival of children referred for ITx.Intestinal failure is defined as a condition in which intestinal nutrient absorption is inadequate to sustain life and to support growth without intravenous nutritional supplementation.¹ The prevalence has increased from 2–3 per million to 5–6 per million of the population, as a result of improved survival in the newborn period.² There are three main causes of long‐term intestinal failure: (1) short bowel syndrome (SBS), usually occurring after extensive neonatal surgical resection for necrotising enterocolitis, small bowel atresia and gastroschisis; (2) motility disorders, for example Hirschprung''s disease, pseudo‐obstruction; and (3) primary mucosal disorders, for example microvillous inclusion disease, tufting enteropathy.From the 1970s successful developments in parenteral nutrition and in central venous catheter placement made it possible to maintain children with intestinal failure in a satisfactory nutritional state for many years.^3,4 However, the long‐term use of parenteral nutrition is associated with life‐threatening complications: liver disease, recurrent septicaemia, and thromboses resulting in difficult venous access.⁴ Intestinal transplantation has evolved from an innovative procedure in the late 1980s to a technically feasible option in the late 1990s⁵ and around 1300 intestinal transplants have now been performed worldwide.⁶ Moreover, non‐transplant surgery (for example, bowel lengthening or plication procedures) may be a treatment option in selected patients.⁷ In patients with SBS who develop severe liver disease, isolated liver transplantation may be an option if there is a realistic likelihood of eventual successful intestinal adaptation and recovery from intestinal failure.⁸ Thus, there are various possible treatment options for children with intestinal failure and choosing the best strategy for individual cases poses a major clinical challenge.Children who have developed complications associated with intestinal failure in the UK have been referred to the intestinal transplant program at Birmingham Children''s Hospital (BCH) since 1989, and the first intestinal transplant was performed in 1993. This centre was officially designated as the sole UK centre for paediatric small bowel transplantation in 1997. An earlier analysis of our experience between 1989 and 1997 indicated a poor survival rate (31%). At that time many referred patients were already seriously ill and many died awaiting transplantation (69%). For this reason, several new treatment strategies were implemented in 1998: combined reduced en bloc liver and small bowel transplantation; isolated liver transplantation for selected patients for short bowel syndrome; and non‐transplant surgery for selected patients of short bowel syndrome with dilated dysmotile loops of bowel. The aim of this study was to describe the outcome of children with intestinal failure referred to our centre, to determine risk factors for adverse outcome and analyse the impact of the new strategies implemented since 1998 onwards.     

Adherent biofilms in adenotonsillar diseases in children

OBJECTIVE: To study biofilm formation on the epithelial surfaces of tonsils and adenoids in children undergoing adenotonsillectomy (T&A). DESIGN: Prospective study. SETTING: Tertiary academic hospital. PATIENTS: Between September 2005 and August 2006, 76 patients (mean [SD] age, 5.7 [3.3] years; age range, 1-18 years; male-female ratio, 1.8:1) undergoing T&A to treat infection, obstruction, or both were included. Of these, 44 had obstruction (58%), 26 had infection (34%), and 6 had both (8%). INTERVENTIONS: Scanning electron microscopy was used to assess for the presence of biofilms. MAIN OUTCOME MEASURE: Presence of adherent biofilms on the surface epithelium of tonsils and adenoids. RESULTS: Adherent biofilm formation was demonstrated in 46 patients (61%). Among 26 patients with infections, adherent biofilm formation was detected in 22 (85%), whereas in the group of 44 patients with obstruction only 18 were found to have biofilms (41%). Comparative analysis of the data revealed that the difference was statistically significant (P = .01). CONCLUSIONS: Biofilms were identified on the surfaces of infected or enlarged tonsils and adenoids in most patients undergoing T&A. The presence of biofilms in a significantly higher proportion of patients with chronically inflamed tonsils and adenoids vs patients with obstruction indicates an association between the presence of biofilms and chronic inflammation.     

Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention

Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion.     

Subthreshold micropulse diode laser photocoagulation for clinically significant diabetic macular oedema: a three-year follow up

PURPOSE: To report the long-term visual outcome of subthreshold micropulse diode laser photocoagulation for clinically significant diffuse diabetic macular oedema (CSME). DESIGN: Non-comparative case-series. METHODS: The main outcome measures of this 3-year follow-up study of infrared (810 nm) subthreshold diode micropulse laser photocoagulation for CSME were visual outcome and the angiographic CSME status of 19 patients (25 eyes). RESULTS: Visual acuity stabilized or improved in 84% of treated eyes by the end of the first year. The result was maintained in the second year and by the third year, 92% maintained vision. However, more patients needed supplementary grid laser in the third year than in the second year. CSME decreased in 92% of the eyes and resolved in 88% in the first year. By the second year, 92% showed complete resolution. However, in the third year, recurrent CSME was noted in 28% of patients. CONCLUSION: This study has the longest follow up reported so far and demonstrating that subthreshold micropulse diode laser photocoagulation has a beneficial long-term effect on visual acuity and resolution of CSME with minimal chorio-retinal damage.     

Conjunctival posttransplantation lymphoproliferative disorder

PURPOSE: To describe a patient with conjunctival posttransplantation lymphoproliferative disorder (PTLD). DESIGN: Interventional case report. METHODS: A 8-year-old boy, three months status post bone marrow transplantation with bilateral enlarged gelatinous bulbar conjunctiva was examined. Biopsy of the bulbar conjunctiva was performed. RESULTS: Conjunctival biopsy revealed a polymorphous infiltrate of lymphoid cells with large atypical immunoblastic lymphoma cells, plasmacytoid lymphocytes, and plasma cells. B-cell markers CD20 and CD79a were positive. Plasma cells exhibited restriction for kappa immunoglobulin light chain and were positive for CD79a. Most cells were positive for Epstein-Barr virus (EBV) encoded ribonucleic acid. EBV-related polymorphic PTLD was diagnosed and treated with discontinuation of cyclosporine, reduction in prednisone dosage and administration of EBV-specific cytotoxic T lymphocytes. The conjunctival lesions resolved during the next five weeks. CONCLUSIONS: Posttransplantation lymphoproliferative disorder rarely involves the ocular structures with most cases presenting as a masquerade syndrome. This case illustrates that PTLD can involve the conjunctiva and further expands the clinical spectrum of ocular PTLD.     

Metastatic disease to the liver: Locoregional therapy strategies and outcomes

Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.     

Hepatic granuloma: decreasing trend in a high‐incidence area

Background: Hepatic granuloma (HG) has a high reported incidence in Saudi Arabia (14.6%). We aimed to identify the incidence of HG in our centres and review its presenting features and underlying aetiology. Methods: A total of 5531 liver biopsies were screened through a computer database over 13 years. Sixty‐six (1.2%) patients fulfilled our inclusion criteria. The patients were then divided into three groups according to the aetiology. Group 1, tuberculosis (n=26); Group 2, viral hepatitis B and C (n=11); and Group 3, idiopathic (n=9). The demographical data and the clinical and biochemical features of all the groups were analysed. Results: Infections comprised of 72.2% of HG. The incidence of tuberculosis was 42.6%, viral hepatitis 16.3% and idiopathic 14.8%. Fever (47.5%), weight loss (42.6%) and fatigue (45.9%) were commonly found symptoms. Fever and weight loss were significantly more frequently presenting symptoms in Group 1 than in Groups 2 and 3 (P=0.0002, 0.04, 0.001 and 0.02 respectively). The mean bilirubin levels in Group 1 were significantly lower than in Groups 2 and 3 (P=0.04 and 0.03 respectively). The mean albumin levels were significantly lower in Group 3 compared with Group 2 (P=0.002), and Group 1 had lower levels compared with Group 2 (P=0.018). Conclusion: The incidence of HG is much lower than reported previously from this region. Tuberculosis and viral hepatitis are the most common causes and, contrary to previous reports, schistosomiasis is rare. Fever and weight loss distinguished tuberculous HG.     

Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.     

Relation of plasma total homocysteine, folate and vitamin B12 levels to bone mineral density in Moroccan healthy postmenopausal women

To test whether in Moroccan healthy postmenopausal women, levels of plasma total homocysteine (tHcy), folate, and vitamin B12 are related to BMD. A total of 188 volunteer postmenopausal women were recruited from our blood taking center between April 2008 and December 2008. Each subject completed a standardized questionnaire designed to document putative risk factors of osteoporosis. Bone mineral density was determined by a Lunar Prodigy Vision DXA system, and blood samples for plasma tHcy, folate, vitamin B12, and serum parathyroid hormone (PTH) were taken. Comparison between women with osteoporosis, osteopenia and normal BMD showed that the osteoporotic women were significantly older, had lower weight and height than the women of the other groups. Plasma tHcy was significantly higher in the osteoporotic group. Levels of tHcy were inversely related to BMD at the lumbar spine, at the total hip and plasma vitamin B12 and positively related to age and creatinine. Multiple regression analysis showed that age and BMI were the main predictors of BMD at the lumbar spine, whereas the main predictors of BMD at the total hip were age, BMI, plasma tHcy, and plasma vitamin B₁₂. tHcy and vitamin B12 are independent risk factors for osteoporosis in Moroccan healthy postmenopausal women.