Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil--a GABAA-gated chloride channel blocker

OBJECTIVE: Fipronil, a broad spectrum N-phenylpyrazole insecticide that inhibits GABAA-gated chloride channels, has been in use since the mid-1990s. A high affinity for insect compared to mammalian GABA receptors results in lower animal toxicity than other insecticides blocking this channel. To date, only two accidental cases of fipronil poisoning in humans have been published. CASE SERIES: We report seven patients with fipronil self-poisoning seen prospectively in Sri Lanka together with pharmacokinetics for four patients. Non-sustained generalized tonic-clonic seizures were seen in two patients (peak measured plasma fipronil concentrations 1600 and 3744 microg/L); both were managed with diazepam without complications. A patient with a peak measured plasma concentration of 1040 microg/L was asymptomatic throughout his stay. Plasma concentration was still high at discharge 3-4 days post-ingestion when the patients were well. Retrospective review of >1000 pesticide poisoning deaths since 1995 found only one death from fipronil-based products. In contrast to the good outcome of the above cases, this patient required intubation and ventilation and had continuous fits despite therapy with barbiturates and benzodiazepines. CONCLUSIONS: Our experience with prospectively observed patients suggests that fipronil poisoning is characterized by vomiting, agitation, and seizures, and normally has a favorable outcome. Management should concentrate on supportive care and early treatment of seizures. However, further experience is needed to determine whether increased susceptibility to fipronil or larger doses can produce status epilepticus.     

Giant Asian honeybee or Bambara stings causing myocardial infarction,bowel gangrene and fatal anaphylaxis in Sri Lanka: a case series

The sting of Giant Asian honeybee (Apis dorsata) or Bambara in Sinhala and Karunge Kulavi in Tamil is a common environmental hazard in Sri Lanka known to cause immediate allergic reactions, which could be fatal in sensitized individuals. We reported myocardial infarction, bowel gangrene and fatal anaphylaxis in a prospectively proven case series and the association of these uncommon complications with delayed removal of stingers from the patients' skin.     

TRAPPC9-CDG: A novel congenital disorder of glycosylation with dysmorphic features and intellectual disability

PurposeTRAPPC9 deficiency is an autosomal recessive disorder mainly associated with intellectual disability (ID), microcephaly, and obesity. Previously, TRAPPC9 deficiency has not been associated with biochemical abnormalities.MethodsExome sequencing was performed in 3 individuals with ID and dysmorphic features. N-Glycosylation analyses were performed in the patients’ blood samples to test for possible congenital disorder of glycosylation (CDG). TRAPPC9 gene, TRAPPC9 protein expression, and N-glycosylation markers were assessed in patient fibroblasts. Complementation with wild-type TRAPPC9 and immunofluorescence studies to assess TRAPPC9 expression and localization were performed. The metabolic consequences of TRAPPC9 deficiency were evaluated using tracer metabolomics.ResultsAll 3 patients carried biallelic missense variants in TRAPPC9 and presented with an N-glycosylation defect in blood, consistent with CDG type I. Extensive investigations in patient fibroblasts corroborated TRAPPC9 deficiency and an N-glycosylation defect. Tracer metabolomics revealed global metabolic changes with several affected glycosylation-related metabolites.ConclusionWe identified 3 TRAPPC9 deficient patients presenting with ID, dysmorphic features, and abnormal glycosylation. On the basis of our findings, we propose that TRAPPC9 deficiency could lead to a CDG (TRAPPC9-CDG). The finding of abnormal glycosylation in these patients is highly relevant for diagnosis, further elucidation of the pathophysiology, and management of the disease.     

Evaluation of the use of digital images for a national prostate core external quality assurance scheme

Harnden P, Coleman D, Moss S, Kodikara S, Griffin N R & Melia J

(2011) Histopathology 59 , 703–709 Evaluation of the use of digital images for a national prostate core external quality assurance scheme Aims: To evaluate the use of virtual images as an alternative to glass slides to expand the number of participants in the External Quality Assurance Scheme for prostatic biopsies. Methods and results: Benign and neoplastic cases, previously circulated as glass slides, were selected to include cases that had demonstrated a high level of agreement (n = 10) and a lesser degree of agreement (n = 10). Whole slide virtual images were circulated to 68 pathologists; 51 responses were returned. The levels of agreement for the primary diagnosis and for Gleason grading of cancers were analysed using kappa statistics. Responses for glass slides versus images were compared for the 24 pathologists for whom data were available. Levels of agreement for diagnostic categories using virtual slides were moderate to substantial, comparable to those found using glass slides. The level of agreement for Gleason grades 8–10 was substantial, but for lower grades was fair or moderate, poorer than for the glass slide circulation. Conclusions: Circulation of virtual images of biopsy material is a suitable alternative to glass slide‐based schemes for the evaluation of diagnostic consistency. The majority of participants agreed that the ability to evaluate limited diagnostic material outweighed the disadvantages of a virtual system.     

Unsuspected rickettsioses among patients with acute febrile illness, Sri Lanka, 2007

We studied rickettsioses in southern Sri Lanka. Of 883 febrile patients with paired serum samples, 156 (17.7%) had acute rickettsioses; rickettsioses were unsuspected at presentation. Additionally, 342 (38.7%) had exposure to spotted fever and/or typhus group rickettsioses and 121 (13.7%) scrub typhus. Increased awareness of rickettsioses and better tests are needed.     

Osteoporosis and Cardiovascular Risk Among Premenopausal Women in Sri Lanka

We examined the association between bone mineral density (BMD) and cardiovascular risk in a group of premenopausal women selected from the Southern province of Sri Lanka. One hundred six previously healthy premenopausal volunteers (aged 30–54 yr) were recruited by open invitations. Subjects with previous history of diabetes, hypertension, epilepsy, chronic renal or liver disease, hyperlipidemia, ischemic heart disease, endocrine diseases, or prolonged inflammatory conditions were excluded. Subjects who were taking medications that can affect bone density, blood sugar, serum lipids, or blood pressure (BP) were also excluded. Women with the history of previous fractures were not excluded. BMDs in the spine, hip, and total body (TB) were measured using a Hologic Discovery scanner (Hologic Inc, Bedford, MA). BP, fasting glucose, and fasting lipids were also measured. Independent of body mass index (BMI) and age, TB bone mineral content (BMC) and spine BMD showed inverse and significant correlations with total cholesterol (TC), low density cholesterol, and the ratio between TC and high density lipoprotein cholesterol (r ranged from ?0.24 to ?0.27, p < 0.05 for all). The highest mean lipid levels were seen among the women in the lowest third of spine BMD, whereas women in the upper third of spine BMD had the lowest lipid levels. The number of women with metabolic syndrome in the 3 tirtiles of spine BMD was not significantly different. Fasting glucose or BP had no association with either BMD or BMC. In conclusion, our data demonstrates an association, independent of age and BMI, between BMD and BMC or lipid levels among previously healthy, premenopausal women. This may explain the high cardiovascular risk seen in women with osteoporosis in old age.     

Proximal and distal rectal cancers differ in curative resectability and local recurrence

AIM: To evaluate patients with proximal rectal cancer (PRC) (> 6 cm up to 12 cm) and distal rectal cancer (DRC) (0 to 6 cm from the anal verge). METHODS: Two hundred and eighteen patients (120 male, 98 female, median age 58 years, range 19-88 years) comprised 100 with PRC and 118 with DRC. The proportion of T1, T2 vs T3, T4 stage cancers was similar in both groups (PRC: T1+T2 = 29%; T3+T4 = 71% and DRC: T1+T2 = -31%; T3+T4 = 69%). All patients had cancer confined to the rectum -those with synchronous distant metastasis were excluded. Surgical resection was with curative intent with or without pre-operative chemoradiation (c-RT). Follow-up was for a median of 35 mo (range: 12 to 126 mo). End points were: 30 d mortality, complications of operation, microscopic tumour-free margins, resection with a tumour-free circumferential margin (CRM) of 1 to 2 mm and > 2 mm, local recurrence, survival and the permanent stoma rate. RESULTS: Overall 30-d mortality was 6% (12): PRC 7 % and DRC 4%. Postoperative complications occurred in 14% with PRC compared with 21.5% with DRC, urinary retention was the complication most frequently reported (PRC 2% vs DRC 9%, P = 0.04). Twelve percent with PRC compared with 37% with DRC were subjected to preoperative c-RT (P = 0.03). A tumour-free CRM of 1 to 2 mm and > 2 mm was reported in 93% and 82% with PRC and 88% and 75% with DRC respectively (PRC vs DRC, P > 0.05). However, local recurrence was 5% for PRC vs 11% for DRC (P < 0.001). Three and five years survival was 65.6% and 60.2% for PRC vs 67% and 64.3% for DRC respectively. No patient with PRC and 23 (20%) with DRC received an abdomino-perineal resection. CONCLUSION: PRC and DRC differ in the rate of abdomino-perineal resection, post-operative urinary retention and local recurrence. Survival in both groups was similar.