Enteritis necroticans (pigbel) in a diabetic child

BACKGROUND AND METHODS: Enteritis necroticans (pigbel), an often fatal illness characterized by hemorrhagic, inflammatory, or ischemic necrosis of the jejunum, occurs in developing countries but is rare in developed countries, where its occurrence is confined to adults with chronic illnesses. The causative organism of enteritis necroticans is Clostridium perfringens type C, an anaerobic gram-positive bacillus. In December 1998, enteritis necroticans developed in a 12-year-old boy with poorly controlled diabetes mellitus after he consumed pig intestines (chitterlings). He presented with hematemesis, abdominal distention, and severe diabetic ketoacidosis with hypotension. At laparotomy, extensive jejunal necrosis required bowel resection, jejunostomy, and ileostomy. Samples were obtained for histopathological examination. Polymerase-chain-reaction (PCR) assay was performed on paraffin-embedded bowel tissue with primers specific for the cpa and cpb genes, which code for the alpha and beta toxins produced by C. perfringens. RESULTS: Histologic examination of resected bowel tissue showed extensive mucosal necrosis, the formation of pseudomembrane, pneumatosis, and areas of epithelial regeneration that alternated with necrotic segments--findings consistent with a diagnosis of enteritis necroticans. Gram's staining showed large gram-positive bacilli whose features were consistent with those of clostridium species. Through PCR amplification, we detected products of the cpa and cpb genes, which indicated the presence of C. perfringens type C. Assay of ileal tissue obtained during surgery to restore the continuity of the patient's bowel was negative for C. perfringens. CONCLUSIONS: The preparation or consumption of chitterlings by diabetic patients and other chronically ill persons can result in potentially life-threatening infectious complications.     

Fatal enteritis necroticans (pigbel) in a diabetic adult.

Enteritis necroticans is a segmental necrotizing infection of the jejunum and ileum caused by Clostridium perfringens, Type C. The disease occurs sporadically in parts of Asia, Africa, and the South Pacific, where it primarily affects children with severe protein malnutrition. The disease is extremely rare in developed countries, where it has been seen primarily in diabetics. Two cases have previously been reported in the United States, one in a child with poorly controlled Type 1 diabetes. A 66-year-old woman with a 12-year history of Type 2 diabetes mellitus developed severe abdominal pain and bloody diarrhea after eating a meal of turkey sausage. She died unattended at home. An autopsy showed peritonitis and segmental necrosis of the jejunum and ileum. Microscopic examination showed Gram-positive club-shaped bacilli consistent with Clostridia coating a necrotic mucosa. Products of cpa and cpb genes of C. perfringens, Type C were identified in the necrotic jejunum by polymerase chain reaction amplification.     

Clostridium difficile cytotoxin B in adults with diarrhea: a comparison of patients treated or not treated with antibiotics prior to infection

Objective   To study the detection rate of Clostridium difficile cytotoxin B in stool specimens from adults with diarrhea as related to previous antimicrobial treatment.
Methods   Stool specimens from 802 adult patients with diarrhea and 203 healthy controls were tested for C. difficile cytotoxin B using a cell cytotoxicity assay. Antibiotic susceptibility testing of C. difficile was performed with the E test.
Results   Of 173 patients treated with antimicrobial medication within 5 weeks of onset of diarrhea, 60 (35%) were positive for C. difficile cytotoxin B (group A) compared to only 41 (7%) of 629 untreated patients (group B) and two of the 203 (1%) healthy controls. Compared to patients in group A, patients in group B possessed characteristics not usually connected with C. difficile disease. They were generally younger (median age 40 years vs. 73 years), had been hospitalized less frequently (10% vs. 67%), had more often travelled abroad within the previous 2 weeks (46% vs. 1%), and more often had multiple enteropathogens (41% vs. 3%). Minimal inhibitory concentrations for vancomycin, metronidazole and fucidic acid to C. difficile isolates ranged from 0.5 to 4 mg/L, from 0.125 to 256 mg/L and 0.25 to 4 mg/L, respectively.
Conclusions   The detection rate of C. difficile cytotoxin B in patients with diarrhea, not associated with antibiotic treatment, is comparable to that in healthy control subjects. It probably merely reflects a carrier state without clinical significance.     

Collagenous gastritis in a young Japanese woman

Collagenous gastritis, a counterpart of collagenous colitis, is a rare disorder with less than 20 cases reported in the literature. A case of collagenous gastritis in a Japanese woman in her early 20s who had been receiving treatment for atopic dermatitis and bronchial asthma is reported. The patient complained of repeated epigastric pain, and endoscopy revealed multifocal atrophic areas and scars in the gastric body. Biopsy specimens showed a thickened eosinophilic band-like structure with entrapped capillaries approximately 30–70 µm thick beneath the surface epithelium. It was regarded as a collagen band because it was positive on Azan staining but negative on amyloid staining. This finding was accompanied by marked infiltration of mononuclear cells and eosinophils in the lamina propria; however, no evidence of lymphocytic gastritis was found. Helicobacter pylori infection was not detected and inflammatory cell infiltration was minimal in the mucosa without the collagen band. Immunohistochemical analysis revealed that the band was positive for type III and type VI collagen. The size of the collagen band did not change for 2 years. These findings suggest that subepithelial collagen deposition was due to an abnormal local immune response based on generalized allergic disorder.     

Dyshormonogenetic goiter‐like changes in a child with congenital hypothyroidism and a euthyroid adult

Dyshormonogenetic goiter is a rare entity that presents in patients who typically have a history of congenital hypothyroidism, and generally arises from a genetic mutation compromising the production of functional thyroxine or thyroglobulin. Clinically, physical manifestations of goiter can result if left untreated. Histologically, the thyroid lesions usually show prominent bridging fibrosis, multiple thyroid nodules with different architectures, microfollicular arrangement, scant colloid, and enlarged vesicular or hyperchromatic nuclei. Cytologically, the features of the lesion are not distinguishable from follicular lesion and follicular neoplasm. We describe two patients exhibiting similar histological and cytological features resembling dyshormonogenetic goiter with cytologic misinterpretation as follicular neoplasm. One was a child with an established history of congenital hypothyroidism. The other was an adult euthyroid patient who presented with an associated parathyroid adenoma. These findings further affirm that cytologically and histologically, morphologic features associated with dyshormonogenetic goiter can also be found in patients without a history of congenital hypothyroidism. Diagn. Cytopathol. 2013;41:720–724. © 2013 Wiley Periodicals, Inc.     

Differentiation of ectopic retinal structures in the hypothalamo-hypophysial area in the adult crested newt bearing a permanent hypothalamic lesion

Summary Ectopic differentiation of retinal structures in contact with the pituitary, after insertion of a methylene blue stained celloidin lamina at the level of the median eminence was observed in the adult crested newt (Triturus cristatus carnifex Laur.). Retinal components ranging from pigmented cells to early retinal vesicles and fully developed neural retina and visual cells are described. Indications pointing to the ependymal cells which line the infundibular sac sequestered between the intermediate lobe and the pars distalis, as the source of the neural retina and visual cells are presented.The present study was supported by a grant from the Consiglio Nazionale delle Ricerche-Impresa di Endocrinologia-Gruppo di Endocrinologia comparata. I wish to thank Prof. V. Mazzi and Prof. A. Guardabassi for helpful discussion. I am grateful to Prof. V. Mazzi, Prof. A. Peyrot and Dr. C. Vellano for entrusting me with the material prepared by them, and to Mr. G. Gendusa and Mr. A. Merlo for technical assistance.     

Losartan reduces the onset of type 2 diabetes in hypertensive Japanese patients with chronic hepatitis C

The aim of this retrospective cohort study is to assess the cumulative development incidence and predictive factors for type 2 diabetes (T2DM) in HCV positive and hypertensive patients treated with losartan. Eighty Japanese patients were given 50 mg of losartan per day after diagnosis of hypertension (losartan group). Another 160 treated with spironolactone were selected as control (spironolactone group). Patients in spironolactone group were matched 1:2 with losartan group for age and sex. The mean observation period was 5.2 years in losartan group and 5.4 years in spironolactone group. An overnight (12 hr) fasting blood sample or a casual blood sample was taken for routine analyses during follow‐up. The primary goal is the onset of T2DM. Evaluation was performed by using the Kaplan–Meier method and the cox proportional hazards analysis. Three patients in losartan group and 20 in spironolactone group developed T2DM. The 5th year cumulative appearance rates of T2DM were 5.4% in losartan group and 14.4% in spironolactone group. Multivariate cox proportional hazards analysis showed that T2DM development after the initiation of anti‐hypertensive drugs occurred when anti‐hypertensive drug was spironolactone (hazard ratio: 6.10; 95% confidence interval = 1.78–20.84; P = 0.004), histological staging was advanced (hazard ratio: 4.31; 95% confidence interval = 1.94–9.60; P < 0.001), fatty liver was present (hazard ratio: 3.28; 95% confidence interval = 1.47–7.27; P = 0.004), and patient had pre‐diabetes (hazard ratio: 2.47; 95% confidence interval = 1.08–5.63; P = 0.032). Our results indicate losartan causes about 60% reduction of the onset of T2DM compared to patients treated with spironolactone. J. Med. Virol. 81:1584–1590, 2009. © 2009 Wiley‐Liss, Inc.     

Pathogenesis of extra efferent vessel development in diabetic glomeruli

The development of extra efferent vessels (EEV) is a little-known feature of diabetic glomerulopathy. The only previous large study [Min W, Yamanaka N. Three-dimensional analysis of increased vasculature around the glomerular vascular pole in diabetic nephropathy. Virchows Archiv A Pathol Anat 1993; 423:201-7] known to us found that up to 5 EEV per glomerulus (glom) each drained a separate lobule. Most EEV connected to the second- and third-order branches of the afferent arteriole (AA), and drained into peritubular capillaries. Although not so stated, the illustrations suggested that some EEV could be shunts, and thus detrimental to glom function, and possibly glom health. There was no correlation between the unquantitated presence of increased EEV at the vascular pole (VP) and the severity of the major diabetic glomerular (glom) lesions. The authors opined that efferent arteriole (EA) stenosis by insudative lesions (IL) stimulated the formation of EEV. To confirm and extend these findings, we have repeated the study in 18 diabetic cases with mild to severe, but not end-stage, diffuse and nodular lesions (DL and NL), 8 controls, and the 2 normal traumatic nephrectomy cases. Up to 18 EEV per glom were found in diabetic cases along with occasional EEV in controls. EEV contained muscle and were almost identical to the EA in structure. Nearly all EEV connected with efferent glom capillaries at the VP, where they exited the glom through apparently preexisting gaps in the Bowman's capsule and/or glomerular capillary basement membranes (BCBM/GCBM). The EA exited through a similar gap, so the exit of EEV was accomplished without altering the anatomical relationships between the exiting vessels and the components of the VP thought to be important in the control of glom outflow. The largest number of EEV occurred in long-standing T2DM cases with mild to moderate DL and NL. Complete photographic glom reconstructions revealed numerous anastomoses among efferent glom capillaries in normal and diabetic gloms with mild to moderate DL and NL. No disproportionately dilated EEV were seen. The findings just cited confirm that EEV are common and surprisingly numerous in diabetic gloms. They suggest that EEV formation served to preserve glom function, and that EEV could neither shunt nor restrict glom outflow locally. In our opinion, the formation of EEV represents a significant, possibly hemodynamically induced, remodeling of the glom that should be added to the list of changes that occur in diabetes. It is hypothesized that EEV develop because of increased glom inflow, and that the latter may be attributable to AA muscle damage that impairs its contractile ability.     

Clinical heterogeneity in a sibship with Niemann-Pick disease type C

The clinical presentation of Niemann-Pick type C is variable. However, in families hitherto described, the affected individuals in a given sibship show a similar clinical course. A family with histological and biochemical findings of Niemann-Pick type C is described. Four of the affected siblings presented with an early onset and a fulminant course resembling Niemann-Pick type A, whereas in the fifth sibling a later onset and a much slower neurological deterioration was observed. Genetic counseling in families with Niemann-Pick type C should take into consideration the possibility of clinical heterogeneity within the same sibship.     

Effect of chlorpromazine on changes in cortical electrical activity caused byClostridium perfringens type a toxin

Experiments on cats showed that injection of chlorpromazine (3 mg/kg, intramuscularly) 1 h before injection ofClostridium perfringens type A toxin prevents the desynchronization of cortical electrical activity which usually arises in the first phase of poisoning, delays the phase of depression of electrical activity in the second phase, and increases by 50–100% the duration of survival of the animals. The effect of chlorpromazine is evidently connected with blocking of adrenergic structures of the reticular formation of the brain stem.Department of Microbiology and Department of Pathological Physiology, N. I. Pirogov Odessa Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 10, pp. 412–416, October, 1977.     

C283Y gamma-sarcoglycan gene mutation in the Bulgarian Roma (Gypsy) population: prevalence study and carrier screening in a high-risk community

Limb-girdle muscular dystrophy type 2C (LGMD2C) is caused by mutations in the gamma-sarcoglycan gene where a founder Gypsy mutation C283Y was detected. The Bulgarian Gypsy LGMD2C patients, as the Gypsy patients from other countries, were found to be homozygous for this mutation. Considering the large number of Gypsies in Bulgaria and the high percent of consanguinity and endogamy a raised carrier frequency of the C283Y mutation was expected especially in North-Eastern Bulgaria where most of the patients originate from. Here, we present the precise geographic distribution of the C283Y mutation in the general Roma population from the whole Bulgarian territory by determining the carrier frequency of the mutation in dry blood newborn samples. Our results show that the geographic distribution of this founder mutation and the disease are not geographically restricted only among Gypsies from North-Eastern Bulgaria. We stress upon the regions with detected high carrier and/or disease frequency and upon the results from the performed carrier screening on volunteers in one of these regions. The ongoing carrier-screening programs in isolated Gypsy groups would be of a great benefit for the genetic prophylaxis of the disease. Such regions should be with priority in the Bulgarian healthcare system for performing a carrier-screening program.     

Natural history of Niemann-Pick disease type C in a multicentre observational retrospective cohort study

Niemann-Pick disease type C (NP-C) is a devastating genetic disorder characterised by progressive neurological deterioration. However, data on the progression of neurological manifestations, particularly across different patient age-of-disease onsets, are limited. This is an observational retrospective cohort study designed to assess the progression of neurological disease in patients with NP-C. Physicians were asked to retrospectively complete a web-based questionnaire for each patient, at diagnosis and at up to three follow-up visits. An NP-C-specific disability scale was used to measure disease progression. The scale comprised four key parameters of neurological disease progression; ambulation, manipulation, language and swallowing. Disease progression was evaluated based on the annual rate of change in each parameter and the composite score using a linear mixed model analysis, and by classifying patients according to the number of worsened parameters during the observation period. Data were collected from 57 patients. The rate of deterioration was similar across the four individual parameters of the disability scale. The mean (95% CI) annual disease progression was +0.12 (0.09, 0.15) units. Among patients with a time interval of at least 1 year between diagnosis and last visit (n = 49), 42 (86%) patients had progressed disease and 7 (14%) patients had stable disease. Disease progression was consistently more rapid in patients diagnosed in early childhood, compared with those diagnosed in late childhood, or with juvenile or adult presentation. In conclusion, our findings showed a progression in all four parameters of the disability scale, representing a continuous, unbroken progression of neurological manifestations.     

Regrowth of retinal ganglion cell axons into a peripheral nerve graft in the adult hamster is enhanced by a concurrent optic nerve crush

Summary Transplantation of a segment of peripheral nerve to the retina of the adult hamster resulted in regrowth of damaged ganglion cell axons into the graft, with the fastest regenerating axons extending at 2 mm/day after an initial delay of 4.5 days (Cho and So 1987b). In this study, the effect of making 2 lesions on the same axon (the conditioning lesion effect) on the regrowth of ganglion cell axons into the peripheral nerve graft was examined. When a conditioning lesion (first lesion) was made by crushing the optic nerve 7 or 14 days before the peripheral nerve grafting (the second lesion) to the retina, the distance of regrowth achieved by the fastest regenerating axons in the graft, measured at the 7th post-grafting day, was lower than in animals with a peripheral nerve grafted to a normal eye. This indicated that in contrast to the situation in peripheral nerve axons (Forman et al. 1980) and goldfish optic axons (Edwards et al. 1981), the conditioning lesion was unable to enhance the regrowth of mammalian retinal ganglion cell axons. However, when crushing of the optic nerve was followed immediately by peripheral nerve grafting, an enhancement in axonal regrowth could be observed. The initial delay time before the axons extended into the peripheral nerve graft was reduced by 1 day while the rate of elongation of the fastest regrowing axons in the graft apparently remained unchanged. Moreover, the shortening of the initial delay could still be observed even when the sequence of performing the 2 lesions was reversed. From these data, it was concluded that the classical conditioning lesion effect was not responsible for the enhancement observed. Rather it was suggested that changes in the intra-retinal environment brought about by crushing of the optic nerve might account for it.     

Identification of a significant association of a single nucleotide polymorphism in TNXB with systemic lupus erythematosus in a Japanese population

Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with complex genetic components. Here, we report on a case–control association study of 178 SLE patients and 899 control subjects, using genome-wide gene-based single nucleotide polymorphism (SNP) markers. An SNP, rs3130342, in a 5’ flanking region of the TNXB gene revealed a significant association with SLE [P = 0.000000930, odds ratio (OR) 3.11, with 95% confidence interval (95%CI) of 1.89–5.28] in a Japanese population. This association was replicated independently with 203 cases and 294 controls (P = 0.0440, OR 1.52, with 95%CI of 1.01–2.78). Although a copy number variation (CNV) of the C4 gene adjacent to the TNXB gene was reported to be associated with SLE, our analysis on this CNV revealed that the association of CNV of the C4 gene was weaker than the SNP in the TNXB gene and likely to reflect the linkage disequilibrium between C4 CNV and this particular SNP. Stratified analysis also revealed that the association of SNP rs3130342 with SLE was independent of the HLA-DRB1*1501 allele that has been shown to be associated with SLE. Our findings strongly imply that the TNXB gene is a candidate gene susceptible to SLE in the Japanese population. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Autoantibodies in recent onset type-1 diabetic patients to a Mr 60K microsomal hepatic protein: new evidence for autoantibodies to the type-2 glucose transporter

Here we describe the presence of IgG antibodies, in the sera of patients presenting with insulin-dependent diabetes mellitus (IDDM), that react in Western blots with a 60-kD protein (Mr 60K) from rat hepatic microsomal extracts. Sera from 60 IDDM patients were screened and 31.6% were positive for the Mr 60K band. This antibody reactivity was indistinguishable in terms of both molecular weight and isoelectric point (pI 5.4) from that described in some patients presenting with autoimmune hepatitis who may also develop IDDM. We hypothesized that the type-2 glucose transporter (Glut-2) that is expressed on both hepatocytes and pancreatic beta cells could be a putative target for the detected antibodies. A polyclonal antisera to rat Glut-2 used in the liver microsome Western blot identified a 60-kD band superimposable upon that evidenced by IDDM sera. Antisera to Glut-2 successfully inhibited the binding of the patient's IgGs to liver microsomes, further suggesting that the two proteins may be identical. Using protein extracts from a rat insulinoma cell line (RIN) transfected with the human Glut-2 cDNA, further evidence was obtained suggesting that these IDDM IgGs are specific for the human Glut-2 transporter.