Cryogenic burns from aerosol sprays: a report of two cases and review of the literature.

Cryogenic burns are uncommon. We present two patients who presented to a Regional Burns Unit on consecutive days with almost identical burn injuries caused by exposure to a unique source of sub-zero temperature, the spray from an aerosol deodorant. The clinical features and management of the cases are outlined, and we discuss the mechanism of a cryogenic burn.     

CpG island methylation in aberrant crypt foci of the colorectum

Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesion in colorectal carcinogenesis, and CpG island methylation has been described as an important molecular pathway. We therefore studied methylation in ACF from patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer. We assessed methylation status of the p16 tumor suppressor gene, MINT1 (methylated in tumor 1), MINT2, MINT31, O(6)-methylguanine-DNA methyltransferase gene, and hMLH1 mismatch repair gene. We compared methylation to ACF histopathology, K-ras proto-oncogene mutation, loss of heterozygosity at chromosome 1p, and microsatellite instability. Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation was the only molecular abnormality identified in 16% (10 of 61) of ACF. Our findings suggest that methylation in ACF is an early event in the pathogenesis of a subset of colorectal carcinomas, and that ACF from FAP patients and patients with sporadic colorectal cancer have distinct epigenetic changes that reflect differences in molecular pathogenesis.     

Novel mechanism of tumorigenesis: increased transforming growth factor-beta 1 suppresses the expression of connexin 43 in BALB/cJ mice after implantation of poly-L-lactic acid

Poly-L-lactic acid (PLLA) is a widely used promising material for surgical implants such as tissue-engineered scaffolds. In this study, we aimed to determine the in vivo effect of PLLA plates on the cellular function of subcutaneous tissue in the two mouse strains, BALB/cJ and SJL/J, higher and lower tumorigenic strains, respectively. Gap-junctional intercellular communication (GJIC) and the expression of connexin 43 (Cx43) protein were significantly suppressed, whereas the secretion of transforming growth factor-beta 1 (TGF-beta 1) level was significantly increased in PLLA-implanted BALB/cJ mice compared with BALB/cJ controls. However, no significant difference in TGF-beta 1 secretion was observed between the SJL/J-implanted and SJL/J control mice. We found for the first time that a significant difference was observed between the two strains; thus, the PLLA increased the secretion of TGF-beta 1 and suppressed the mRNA expression of Cx43 at the earlier stage after implantation into the higher-tumorigenic strain, BALB/cJ mice. This novel mechanism might have a vital role in the inhibition of GJIC and promote the tumorigenesis in BALB/cJ mice.     

Colonoscope flexural rigidity measurement

A testing device is developed that determines the stiffness, or flexural rigidity, of an endoscope at specific locations down its length by subjecting it to a compressive axial force, a situation similar to the actual forces applied to the endoscope during a clinical procedure. The endoscope is made to deform in a similar fashion to a slender buckled column and the force causing this deformation is related to the flexural rigidity using column buckling theory. A direct relationship between the critical load needed to cause buckling and the square of column length L is demonstrated experimentally and is expected theoretically, giving confidence in the application of column buckling theory to endoscope testing. Additional confidence in the validity of the columnbuckling test results is obtained by their similarity to data obtained by subjecting the endoscope to a transverse load, determining deflection, and modelling the endoscope as a bent elastic beam. Several makes and models of endoscopes were tested, with flexural rigidity values typically ranging between 160 to 240 Ncm². The effect of a metal stiffener inserted in an endoscope's accessory channel is quantified, as is the change in flexural rigidity down the insertion shaft of a graded-stiffness endoscope. Significant differences in flexural rigidity were obtained between identical endoscopes, each sharing similar usage histories, indicating the need for flexural rigidity measurements for each individual endoscope of a particular model line, though a more extensive study is required to reliably determine scope-to-scope stiffness variations for a particular model line.     

Novel sequence variants in the TMC1 gene in Pakistani families with autosomal recessive hearing impairment

Though many hearing impairment genes have been identified, only a few of these genes have been screened in population studies. For this study, 168 Pakistani families with autosomal recessive hearing impairment not due to mutations in the GJB2 (Cx26) gene underwent a genome scan. Two-point and multipoint parametric linkage analyses were carried out. Twelve families had two-point or multipoint LOD scores of 1.4 or greater within the transmembrane cochlear expressed gene 1 (TMC1) region and were subjected to further screening with direct DNA sequencing. Five novel putatively functional non-synonymous sequence variants, c.830A>G (p.Y277C), c.1114G>A (p.V372M), c.1334G>A (p.R445H), c.2004T>G (p.S668R), and c.2035G>A (p.E679K), were found to segregate within seven families, but were not observed in 234 Pakistani control chromosomes. The variants c.830A>G (p.Y277C), c.1114G>A (p.V372M), and c.1334G>A (p.R445H) occurred at highly conserved regions and were predicted to lie within hydrophobic transmembrane domains, while non-synonymous variants c.2004T>G (p.S668R) and c.2035G>A (p.E679K) occurred in extracellular regions that were not highly conserved. There is evidence that the c.2004T>G (p.S668R) variant may have occurred at a phosphorylation site. One family has the known splice site mutation c.536 -8T>A. The prevalence of non-syndromic hearing impairment due to TMC1 in this Pakistani population is 4.4% (95%CI: 1.9, 8.6%). The TMC1 protein might have an important function in K(+) channels of inner hair cells, which would be consistent with the hypothetical structure of protein domains in which sequence variants were identified.     

Morbidity and Mortality Associated with Typhoid Fever Among Hospitalized Patients in Hyderabad District,Pakistan, 2017-2018: Retrospective Record Review

BackgroundHyderabad, Pakistan, was the first city to witness an outbreak of extensively drug resistant (XDR) typhoid fever. The outbreak strain is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, thus greatly limiting treatment options. However, despite over 5000 documented cases, information on mortality and morbidity has been limited.ObjectiveTo address the existing knowledge gap, this study aimed to assess the morbidity and mortality associated with XDR and non-XDR Salmonella serovar Typhi infections in Pakistan.MethodsWe reviewed the medical records of culture-confirmed typhoid cases in 5 hospitals in Hyderabad from October 1, 2016, to September 30, 2018. We recorded data on age, gender, onset of fever, physical examination, serological and microbiological test results, treatment before and during hospitalization, duration of hospitalization, complications, and deaths.ResultsA total of 1452 culture-confirmed typhoid cases, including 947 (66%) XDR typhoid cases and 505 (34%) non-XDR typhoid cases, were identified. Overall, ≥1 complications were reported in 360 (38%) patients with XDR typhoid and 89 (18%) patients with non-XDR typhoid (P<.001). Ileal perforation was the most commonly reported complication in both patients with XDR typhoid (n=210, 23%) and patients with non-XDR typhoid (n=71, 14%) (P<.001). Overall, mortality was documented among 17 (1.8%) patients with XDR S Typhi infections and 3 (0.6%) patients with non-XDR S Typhi infections (P=.06).ConclusionsAs this first XDR typhoid outbreak continues to spread, the increased duration of illness before hospitalization and increased rate of complications have important implications for clinical care and medical costs and heighten the importance of prevention and control measures.     

The Radiologic Features of Non-Neoplastic Tumors of Soft Tissue

Neoplasms of the soft tissues cause localized swelling and a variable degree of tissue response on the part of the host; these features they share with many non-neoplastic disorders. A spectrum of lesions that may simulate soft tissue neoplasms are described, with their radiologic appearances. The cellular nature of the matrix of a lesion cannot be identified absolutely as neoplastic by current imaging methods. Although sonography and magnetic resonance imaging can each produce valuable diagnostic information hitherto not provided by imaging the soft tissues, they do not per se show evidence of neoplasia. The differentiation of the two types of tumor, neoplastic and non-neoplastic, can only be achieved by a combination of clinical, radiologic and histologic information. Ultimately, biopsy with histologic examination may be required for the definitive diagnosis.     

An audit of MRI for bone and soft-tissue tumours performed at referral centres

AIM: Magnetic resonance imaging (MRI) is essential in the pre-operative staging of suspected primary bone and soft-tissue sarcomas. Such lesions are ideally managed in specialist centres but it is becoming increasingly common for patients to undergo MRI before referral. The aim of this study was to assess the adequacy of such studies. MATERIALS AND METHODS: Fifty patients (30 men, 20 women; mean age 39 years, range 9-89 years) were included over a 1-year period. Tumours included 31 suspected primary bone tumours and 19 soft-tissue tumours. RESULTS: The total number of sequences used was 225 (mean 4, range 2-8). Enhancement was used in 19 cases. The commonest mistake was the failure to image the whole bone for 'skip' metastases in 50% of appropriate cases (high-grade malignant lesions of bone). Reports were available in 40 cases. Specific information regarding precise intraosseous and extraosseous extent of tumour and relationship to the neurovascular bundle and adjacent joint was commonly not included. CONCLUSIONS: This audit indicates that a greater awareness is needed amongst general radiologists of the MR imaging and reporting requirements for musculoskeletal tumours. In particular, all important axial imaging is sometimes omitted.Saifuddin, A. (2000). Clinical Radiology 55, 537-541.