DFNB39, a recessive form of sensorineural hearing impairment, maps to chromosome 7q11.22-q21.12

This article describes the identification of a novel locus (DFNB39) responsible for an autosomal recessive form of hearing loss segregating in a Pakistani consanguineous family. The hearing impaired members of this family present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 7q with a maximum multipoint lod score of 3.8. The region of homozygosity spans a 19 cM region that is bounded by markers D7S3046 and D7S644.     

Management of Isolated Blunt Duodenal Injury

Five cases of duodenal injuries were treated in our hospital between January 1, 1975 and June 18, 1979. They belonged to the Class II and early Class III of duodenal injuries. They were treated with simple closure of the perforation in a single or double layer with external drainage. Only in one case were gastrojejunostomy and bilateral vagotomy added because the patient had a history of ulcer disease. The delay in operative treatment ranged between five and 48 hours. All responded well to the surgical treatment. In the instance of the longest operative delay, a purulent drainage occurred and it responded promptly to a selective antibiotic therapy. The average hospitalization stay was nine days for the patients operated upon early, whereas it was 15 days for the two delayed cases. No mortality was recorded.     

Intracranial peripheral primitive neuroectodermal tumors of the cavernous sinus: a diagnostic peculiarity

Peripheral primitive neuroectodermal tumors (pPNETs) are aggressive, poorly differentiated neoplasms that occur in children and young adults. These tumors are associated with a peak incidence in the second decade and a slight male preponderance. Recently, Ewing sarcoma and pPNET tumors have been proven to carry identical translocations, the most common being t(11;22)(q24;q12). Intracranial Ewing sarcoma/pPNETs have rarely been described in the literature. We studied a case of intracranial pPNET arising in the right cavernous sinus of a 46-year-old man. On imaging, the tumor had both sellar and suprasellar components and was centered within the right parasellar region. Histologically, the tumor was composed of intermediate to large cells with round to oval hyperchromatic nuclei with distinct nucleoli. The cells contained a moderate amount of slightly basophilic cytoplasm. The tumor was markedly fibrotic and had collagen bands surrounding both individual and groups of cells. A large immunohistochemical panel was positive only for CD99 and vimentin. Fluorescence in situ hybridization did not show translocations associated with Ewing sarcoma/pPNET. However, a small percentage of these tumors can be negative for this translocation. In these cases, histology and immunohistochemical techniques in the absence of an alternative diagnosis are the only tools available to establish the diagnosis.     

P300, N400, aerobic fitness, and maximal aerobic exercise

Electrophysiological effects of aerobic fitness and maximal aerobic exercise were investigated by comparing P300 and N400 before and after a maximal cycling test. Event-related potentials (ERPs) were obtained from 20 students divided into two matched groups defined by their aerobic fitness level (cyclists vs. sedentary subjects). The session of postexercise ERPs was performed immediately after body temperature and heart rate returned to preexercise values. At rest, no significant differences were observed in ERP parameters between cyclists and sedentary subjects. This finding argued against the hypothesis that ERP modifications may be directly assumed by aerobic fitness level. The postexercise session of ERPs showed a significant P300 amplitude increase and a significant P300 latency decrease in all subjects. Similarly, N400 effect increased significantly after the maximal exercise in all subjects. ERP changes were of the same magnitude in the two groups. The present study argues for a general arousing effect of maximal aerobic exercise, independently of the aerobic fitness level.     

Lyme disease spirochete,Borrelia burgdorferi endemic at epicenter in Rondeau Provincial Park,Ontario

The Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt, and Brenner was discovered in blacklegged ticks, Ixodes scapularis Say at Rondeau Provincial Park, Ontario, Canada During this 2-yr study, spirochetes were found in B. burgdorferi-positive I. scapularis larvae attached to B. burgdorferi-infected white-footed mice, Peromyscus leucopus Rafinesque. Isolates of B. burgdorferi were cultured from blacklegged tick adults, and confirmed positive with polymerase chain reaction by targeting OspA and rrf (5S)-rrl (23S) genes. These findings show an endemic area for B. burgdorferi within an established population of L. scapularis at Rondeau Provincial Park.     

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.     

An Overview of the Treatment Options Used for the Management of COVID-19 in Pakistan: Retrospective Observational Study

BackgroundSince the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll.ObjectiveThe aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan.MethodsA retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020).ResultsAntibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%).ConclusionsGuidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19.