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.     

Tissue distribution of bovid herpesvirus-4 in inoculated rabbits and its detection by DNA hybridization and polymerase chain reaction

Summary A DNA hybridization technique, using the polyrepetitiveEcoRI L-fragment of bovid herpesvirus (BHV-4) as a probe, was developed to determine virus distribution in the tissues of BHV-4-infected pregnant rabbits. The cloned fragment did not react with the DNA of rabbits or of other herpesviruses, e.g., infectious bovine rhinotracheitis, bovine herpes virus mammillitis, and pseudorabies viruses. The detection limit was 10^–13g of DNA or approximately 600 genome equivalents of viral DNA, which indicates a level of sensitivity of one viral genome per 500 cells in our assay. Using conventional cell culture techniques, the virus was isolated from only one of fifteen infected rabbits and a few aborted fetuses. However, when organ culture or dot blot hybridization was used, BHV-4 was detected in all rabbits and their fetuses. Viral DNA was detected by DNA hybridization in spleen, ovary, uterus, lung, liver, salivary gland, lymph node, and placentome of adult rabbits and in a composite of fetal tissues. When polymerase chain reaction (PCR) was used, the virus was detected in several organs (including the nervous tissues) that were found negative by other techniques. These results indicate that blot hybridization and PCR are more sensitive than conventional techniques for studying the pathogenesis of BHV-4 in animals. The data obtained by these methods suggest that BHV-4 may be maintained in infected rabbits in a latent state in a variety of tissues including the nervous system.     

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.     

The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome

Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.     

Reconstitution of T-cell repertoire after autologous stem cell transplantation: influence of CD34 selection and cytomegalovirus infection.

The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor beta-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation (P =.08) that became significant by 3 months (P=.007), and that was associated with decreased T-cell receptor beta-chain variable region spectratype diversity (P =.01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution.     

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.     

Concurrent cisplatin and radiotherapy in advanced head and neck cancer

Management of Head and Neck Cancers poses a challenge inspite of several advances because of poor success in terms of response rate, survival and reduced morbidity of the patients. In the present study 30 untreated histologically proven cases of head and neck cancers were subjected to weekly radiotherapy with adjuvant chemotherapy (cisplatin 30 mg/m² intravenously). This study group was compared with a group of 30 patients who were given only radiotherapy. Results have shown that combination of chemotherapy with radiotherapy gives a significantly better results in tumour as well as nodal response with minimal toxicities.