RESUMO
Pyrazinamide (PZA) is a key first-line antibiotic used for the short-course treatment of drug-sensitive and multidrug-resistant (MDR) isolates of tuberculosis. PZA exhibits potent action against semi-dormant bacilli in acidic environments. However, mutations that occur in target genes may cause technical difficulties in the diagnosis of PZA resistance during drug susceptibility testing. The objective of the current study is to identify mutations in pncAWT rpsA and rpsAWT panD genes among PZA-resistant isolates of Mycobacterium tuberculosis (MTB) circulating in the Pashtun dominant region, Khyber Pakhtunkhwa, Pakistan. We selected 18 PZA-resistant pncAWT strains from the Provincial Tuberculosis Reference Laboratory (PTRL) Khyber Pakhtunkhwa to investigate mutations in the coding region of rpsA and panD genes. The experiments were repeated for drug susceptibility testing using MGIT 960 automated system. In addition, eighteen PZA-resistant rpsA genes along with 5 susceptible strains and one H37Rv strain were sequenced. All 18 isolates were PZA-resistant. The majority of these isolates exhibited multidrug resistance (MDR) (13/18). We identified 14 non-synonymous and one synonymous mutation in the coding region of rpsA in 11 strains. All mutations were scattered throughout the gene and not reported previously. Further, we did not identify any mutation in 7 rpsAWT panD genes. Mutations in rpsA but not in panD occur in PZA-resistant pncAWT MTB isolates circulating in Khyber Pakhtunkhwa, Pakistan.
Assuntos
Amidoidrolases/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Humanos , PaquistãoRESUMO
UNLABELLED: The importance of an adequate caliber neo-meatus for success of any hypospadias repair cannot be overstated. TIP repair incorporates a midline relaxing incision thus enabling tubularization but ultimately may not result in adequate neourethral caliber to avoid fistulas or meatal stenosis when the plate was narrow or flat, respectively. Objectives of this study is to evaluate results of a modification of TIP - "wide skeletonization" tubularized incised plate (TIP) - for repair of distal penile hypospadias with narrow urethral plate (UP), with regard to meatal stenosis and urethrocutaneous fistula. MATERIALS & METHODS: Total of 108 hypospadias patients were operated upon. 26 were found to have distal penile ypospadias with narrow UP (Narrow UP defined as any plate less than 6 mm width). 22 were selected for the study; All underwent "wide skeletonization" of the UP distally ("Wide Skeletonization" implies meatal based ventral "V" shaped incisions on outer margins of UP so as to incorporate generous portions of adjoining skin thereby allowing recruitment of penile and glandular skin lateral to the urethral plate to facilitate tubularization). Urethroplasty was fashioned over 10mm circumference of native UP with adjoining skin over a urethral stent. Repair was started with meatus first (calibrated over size 10-12F bougie). Meatal stitch was followed proximally with subepithelial tubularization of the neourethra; second layer comprising of spongiosal tissue. Barrier flaps were interposed between the neourethra and overlying glans and shaft skin closure, using inner prepucial mucosal flap. RESULTS: Two patients had urethrocutaneous fistulae; one child had superficial dehiscence of glans. All three children were managed conservatively with no child requiring further surgery. All children had a good sized meatus and good stream of urine without any splaying. CONCLUSIONS: "Wide Skeletonization" of the urethral plate distally (in a "V" fashion rather than "U") gives an adequate caliber aesthetic neo-meatus especially in hypospadias children with narrow UP. It further helps in decreasing incidence of neourethral and/or meatal stenosis without increasing urethroplasty complication leading to an excellent functional outcome. Whether this leads to better long term functionality of neourethra remains to be seen.
Assuntos
Hipospadia , Uretra , Humanos , Lactente , Masculino , Pênis , Procedimentos de Cirurgia Plástica , Retalhos CirúrgicosRESUMO
The asymmetric unit of the title compound, C(17)H(13)N, contains two independent butterfly-shaped mol-ecules. The seven-membered azepine rings both adopt a boat conformation. The dihedral angles between the benzene rings in the two mol-ecules are 46.95â (11) and 52.21â (11)°.
RESUMO
INTRODUCTION: Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases. FINDINGS: This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington's disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface. CONCLUSIONS: Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer's and Parkinson's as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.
Assuntos
Doença de Huntington , Doenças Neurodegenerativas , Animais , Ritmo Circadiano , Modelos Animais de Doenças , Doença de Huntington/complicações , Doença de Huntington/genética , SonoRESUMO
Primary osteogenic sarcoma of the skull is an exceedingly rare condition. An adult male patient is described, who had a painless swelling in the right forehead that had rapidly enlarged in the previous 6 months. Radiological investigations showed a large destructive mass lesion involving the right side of the frontal bone with extension into the frontal sinus, causing marked extradural compression of brain parenchyma. Histopathological examination confirmed the lesion to be primary osteogenic sarcoma.
Assuntos
Osteossarcoma/diagnóstico por imagem , Neoplasias Cranianas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Meios de Contraste , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The students and faculty of the Aga Khan University School of Nursing, working in collaboration with other groups and organizations, have made a considerable contribution to Pakistan's polio immunization programme in the area of District Council West and Malir, Karachi. Recommendations for improving the programme are presented on the basis of the experience gained.
PIP: 5486 cases of poliomyelitis were reported in Pakistan between 1988 and 1993. In 1994, the country joined the international polio eradication program and has since conducted eight national polio campaigns during which oral polio vaccine was given to children at special community centers throughout Pakistan under the auspices of the Expanded Program on Immunization. The students and faculty of the Aga Khan University School of Nursing, working together with other groups and organizations, participated in all but one of the campaigns to provide technical and professional support, motivate parents and families to have their children immunized, promote a positive attitude in communities toward the national polio program, and identify high-risk groups. The school's involvement was planned and coordinated by its Community Health Nursing Interest Group. Recommendations for improving the program are presented on the basis of the experience gained.