Prevalence of undiagnosed metabolic syndrome using three different definitions and identifying associated risk factors among apparently healthy adults in Karachi, Pakistan: a cross-sectional survey in the year 2022.

OBJECTIVE: To determine the prevalence and associated risk factors of undiagnosed metabolic syndrome (MetS) using three different definitions among apparently healthy adults of Karachi, Pakistan. METHODS: This community-based cross-sectional survey was conducted in Karachi, Pakistan, from January 2022 to August 2022. A total of 1065 healthy individuals aged 25-80 years of any gender were consecutively included. MetS was assessed using the National Cholesterol Education Program for Adult Treatment Panel (NCEP-ATP) III guidelines, International Diabetes Federation (IDF), and modified NCEP-ATP III. RESULTS: The prevalence of MetS was highest with the modified NCEP-ATP III definition at 33.9% (95% CI: 31-36), followed by the IDF definition at 32.2% (95% CI: 29-35). In contrast, the prevalence was lower at 22.4% (95% CI: 19-25) when using the NCEP ATP III definition. The risk of MetS significantly increases with higher BMI, as defined by the IDF criteria (adjusted OR [ORadj] 1.13, 95% CI 1.09-2.43), NCEP-ATP III criteria (ORadj 1.15, 95% CI 1.11-1.19), and modified NCEP-ATP III criteria (ORadj 1.16, 95% CI 1.12-1.20). Current smokers had significantly higher odds of MetS according to the IDF (ORadj 2.72, 95% CI 1.84-4.03), NCEP-ATP III (ORadj 3.93, 95% CI 2.55-6.06), and modified NCEP-ATP III (ORadj 0.62, 95% CI 0.43-0.88). Areca nut use was associated with higher odds of MetS according to both IDF (ORadj 1.71, 95% CI 1.19-2.47) and modified NCEP-ATP III criteria (ORadj 1.58, 95% CI 1.10-2.72). Furthermore, low physical activity had significantly higher odds of MetS according to the NCEP-ATP III (ORadj 1.36, 95% CI 1.01-1.84) and modified NCEP-ATP III criteria (ORadj 1.56, 95% CI 1.08-2.26). CONCLUSION: One-third of the healthy individuals were diagnosed with MetS based on IDF, NCEP-ATP III, and modified NCEP-ATP III criteria. A higher BMI, current smoking, areca nut use, and low physical activity were significant factors.

Enhancing the production of recombinant adeno-associated virus in synthetic cell lines through systematic characterization.

Recombinant adeno-associated virus (rAAV) is among the most commonly used in vivo gene delivery vehicles and has seen a number of successes in clinical application. Current manufacturing processes of rAAV employ multiple plasmid transfection or rely on virus infection and face challenges in scale-up. A synthetic biology approach was taken to generate stable cell lines with integrated genetic modules, which produced rAAV upon induction albeit at a low productivity. To identify potential factors that restrained the productivity, we systematically characterized virus production kinetics through targeted quantitative proteomics and various physical assays of viral components. We demonstrated that reducing the excessive expression of gene of interest by its conditional expression greatly increased the productivity of these synthetic cell lines. Further enhancement was gained by optimizing induction profiles and alleviating proteasomal degradation of viral capsid protein by the addition of proteasome inhibitors. Altogether, these enhancements brought the productivity close to traditional multiple plasmid transfection. The rAAV produced had comparable full particle contents as those produced by conventional transient plasmid transfection. The present work exemplified the versatility of our synthetic biology-based viral vector production platform and its potential for plasmid- and virus-free rAAV manufacturing.

Simulation Training in a Lower Middle-Income Country: Supporting a New Center and Developing Low-Cost Models for Critical Skill Acquisition.

INTRODUCTION:  There is a demand for surgical simulation training to be made accessible in low-resource countries. We conducted a pilot workshop at a new state-of-the-art simulation center and evaluated two novel low-cost surgical simulation models in a lower middle-income country (LMIC). METHODS: A hands-on workshop to train local educators about simulation training was held at a new simulation center. Participant surveys were analyzed following the "training-the-trainer" workshop. Low-cost, hybrid-fidelity pericardiocentesis and thoracic cavity simulation training models were created using locally available materials. These models recreated the pertinent anatomy at a cost under 20 US dollars each. The models were used to train 109 postgraduate anesthesiology trainees during two hands-on medical education workshops. Participant surveys were collected and analyzed. RESULTS: Of the local educators who participated in the "training-the-trainer" workshop, 65% "agreed" and 35% "strongly agreed" with the claim that the simulations better prepared the trainees to teach the clinical scenarios. Additionally, 65% of local educators "agreed" and 35% "strongly agreed" that the simulations prepared them to navigate interprofessional care in those scenarios. The low-cost pericardiocentesis simulation was ranked as "good" or "outstanding" by 100% of survey respondents. The low-cost thoracostomy simulation was ranked as "good" or "outstanding" by 64% of survey respondents. Both the pericardiocentesis and thoracostomy simulators were valued for their low-cost design, the recreation of essential anatomy, and immersive design elements. CONCLUSION: Our team successfully implemented novel simulators for skill training in an LMIC by working in close collaboration with local experts, with the advancement of local simulation instruction practices. Collaboration is key to increasing access to surgical simulations, particularly in low- to middle-income countries.

Assessment of risk factors associated with potential drug-drug interactions among patients suffering from chronic disorders.

Patients suffering from chronic diseases are more likely to experience pDDIs due to older age, prolonged treatment, severe illness and greater number of prescribed drugs. The objective of the current study was to assess the prevalence of pDDIs and risk factors associated with occurrence of pDDIs in chronic disease patients attending outpatient clinics for regular check-ups. Patients suffering from diabetes, chronic obstructive pulmonary disease (COPD), stroke and osteoporosis were included in the study. This study was a cross sectional, observational, prospective study that included 337 patients from outpatient clinics of respiratory ward, cardiac ward and orthopedic ward of Nishter Hospital Multan, Pakistan. The mean number of interactions per patient was 1.68. A greater risk for occurrence of pDDI was associated with older age ≥ 60 years (OR = 1.95, 95% CI = 1.44-2.37, p<0.001); polypharmacy (≥ 5 drugs) (OR = 3.74, 95% CI 2.32-4.54, p<0.001); overburden (OR = 2.23, 95% CI = 1.64-3.16, p<0.01); CCI score (OR = 1.28, 95% CI = 1.04-1.84, p<0.001); multiple prescribers to one patient (OR = 1.18, 95% CI = 1.06-1.41, p<0.01); and trainee practitioner (OR = 1.09, 95% CI = 1.01-1.28, p<0.01). Old age, polypharmacy, overburden healthcare system, higher comorbidity index, multiple prescribers to one patient and trainee practitioner were associated with increased risk of occurrence of pDDIs in chronic disease patients.

Development of an Inducible, Replication-Competent Assay Cell Line for Titration of Infectious Recombinant Adeno-Associated Virus Vectors.

An important quality attribute of a recombinant adeno-associated virus (rAAV) as a therapeutic vector is its infectivity. Current assays to quantify infectious rAAV rely on coinfection with a helper virus such as adenovirus (Ad), which requires helper virus preparation and introduces additional variability. A simple method that has high sensitivity and removes the need for helper virus would improve assay consistency and facilitate high-throughput applications such as rAAV producer cell line development. In this study, we describe a stable assay cell line that was generated by integrating the coding sequences for AAV Rep68 and Ad E4orf6 and DNA binding protein under the control of inducible promoters. The Rep68 protein expression was further modulated by a ligand-responsive destabilization domain. In several benchmarks, the cell line gave comparable titers with those obtained using a classical Ad coinfection method. The cell line was also used to titer vectors of multiple rAAV serotypes. This cell line has the potential to serve as an effective and robust tool for quantifying infectious rAAV titers to advance gene therapy vector biomanufacturing.

Construction of an rAAV Producer Cell Line through Synthetic Biology.

Recombinant adeno-associated viruses (rAAV) are important gene delivery vehicles for gene therapy applications. Their production relies on plasmid transfection or virus infection of producer cells, which pose a challenge in process scale-up. Here, we describe a template for a transfection-free, helper virus-free rAAV producer cell line using a synthetic biology approach. Three modules were integrated into HEK293 cells including an rAAV genome and multiple inducible promoters controlling the expression of AAV Rep, Cap, and helper coding sequences. The synthetic cell line generated infectious rAAV vectors upon induction. Independent control over replication and packaging activities allowed for manipulation of the fraction of capsid particles containing viral genomes, affirming the feasibility of tuning gene expression profiles in a synthetic cell line for enhancing the quality of the viral vector produced. The synthetic biology approach for rAAV production presented in this study can be exploited for scalable biomanufacturing.

Persistent inter-observer variability of breast density assessment using BI-RADS® 5th edition guidelines.

OBJECTIVES: Due to most states' legislation, mammographic density categorization has potentially far-reaching implications, but remains subjective based on BIRADS® guidelines. We aimed to determine 1) effect of BI-RADS® 5th edition (5th-ed) vs 4th-edition (4th-ed) guidelines on reader agreement regarding density assessment; 2) 5th-ed vs 4th-ed density distribution, and visual vs quantitative assessment agreement; 3) agreement between experienced vs less experienced readers. METHODS: In a retrospective review, six breast imaging radiologists (BIR) (23-30 years' experience) visually assessed density of 200 screening mammograms performed September 2012-January 2013 using 5th-ed guidelines. Results were compared to 2016 data of the same readers evaluating the same mammograms using 4th-ed guidelines after a training module. 5th-ed density categorization by seven junior BIR (1-5 years' experience) was compared to eight experienced BIR. Nelson et al.'s kappas (κm, κw), Fleiss' κF, and Cohen's κ were calculated. Quantitative density using Volpara was compared with reader assessments. RESULTS: Inter-reader weighted agreement using 5th-ed is moderately strong, 0.73 (κw, s.e. = 0.01), similar to 4th-ed, 0.71 (κw, s.e. = 0.03). Intra-reader Cohen's κ is 0.23-0.34, similar to 4th-ed. Binary not-dense vs dense categorization, using 5th-ed results in higher dense categorization vs 4th-ed (p < 0.001). 5th-ed density distribution results in higher numbers in categories B/C vs 4th-ed (p < 0.001). Distribution for 5th-ed does not differ based on reader experience (p = 0.09). Reader vs quantitative weighted agreement is similar (5th-ed, Cohen's κ = 0.76-0.85; 4th-ed, Cohen's κ = 0.68-0.83). CONCLUSION: There is persistent subjectivity of visually assessed mammographic density using 5th-ed guidelines; experience does not correlate with better inter-reader agreement.

The Association between Chronic Heroin Smoking and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Little is known about the correlation between chronic obstructive pulmonary disease (COPD) and heroin smoking. Heroin smoking is a recent underinvestigated problem. The goal of this study is to study the impact of heroin smoking among COPD patients. METHODS: This is a descriptive clinical study. A combination of self-reporting questionnaires and data extraction tools were used to collect information during baseline tests, interviews, and follow-ups. Patients' medical, clinical, and socioeconomic history were recorded. Participants were recruited using random sampling from multiple centers. RESULTS: Out of 1034 COPD patients, heroin smokers represented the vast majority of addiction cases (n = 133). Heroin smokers were leaner than non-addicts (19.78 ± 4.07 and 24.01 ± 5.6, respectively). The most common type of comorbidities among heroin smokers was emphysema (27%). Both the forced expiratory volume (FEV1)/forced vital capacity ratio and FEV1% predicted were lower among heroin smokers than non-addicts (52.79 ± 12.71 and 48.54 ± 14.38, respectively). The majority of heroin smokers (55%) had advanced COPD, and at least 15% of heroin smokers suffered from frequent respiratory failure. The mean ± SD for COPD onset age among heroin smokers was 44.23 ± 5.72, and it showed a statistically significant correlation (P < 0.001). CONCLUSION: Heroin smoking might be linked to the onset of COPD. Heroin smokers showed a significantrespiratory impairment compared to tobacco smokers of the same age group.

Comparison of cystatin C and creatinine-based estimated glomerular filtration rate equations among elderly chronic kidney disease patients attending a tertiary care hospital: A prospective cross-sectional study
.

BACKGROUND: Serum creatinine has been solely used in clinical practice to identify chronic kidney disease (CKD) staging in the elderly population. Serum cystatin C is believed to more accurately define the CKD staging and is also ratified as an endogenous biomarker by Kidney Disease Improving Global Outcomes (KDIGO) guidelines. MATERIAL AND METHODS: A total of 300 elderly Malay participants (age ≥ 65 years) with CKD, attending the Hospital University Sains Malaysia were included in the study. Demographic data and history were also recorded. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe method). While serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader. RESULTS: Out of 300 study participants, 169 (56.3%) were females. Mean age of patients was 67.6 ± 6.7 years. 64 male (64.6%) and 35 female (35.4%) patients were between 70 and 79 years. When estimated by MDRD equation, the prevalence of CKD stage 3 (defined as eGFR = 30 - 59 mL/min/1.73m2) was 27.7%, while based on CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, it was 28%, 36.3%, and 36.3%, respectively. The prevalence of CKD stage 4 (defined as eGFR = 15 - 29 mL/min/1.73m2) when estimated by MDRD was 37.6%, whereas based on CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, it was 36.3%, 46.4%, and 46.4%, respectively. CKD stage 5 (defined as eGFR < 15 mL/min/1.73m2) when estimated by the MDRD equation was 34.7%. While based on CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys equations, the prevalence of CKD stage 5 was 35.7%, 17.3%, and 17.3%, respectively. CONCLUSION: The staging of CKD is different between the creatinine- and cystatin C-based equations. Creatinine-based equations classify patients as having CKD stage 5 twice as often as cystatin C-based equations.

Plasma Cell Leukaemia: A Rare Yet Aggressive Plasma Cell Dyscrasia With A Very Poor Response To Conventional Therapy.

Plasma cell leukaemia (PCL) is a very rare plasma cell dyscrasia with a significant number of monoclonal plasma cells in the peripheral blood. It is diagnosed by the presence of ≥ 2x109 /L plasma cells in the blood or by plasma cells making up ≥20% of the leukocyte count. It can arise from a leukemic transformation of multiple myeloma, or more commonly it can be primary. Regardless of its origin, it carries a very dire prognosis. It responds very poorly to the traditional chemotherapy regimens used for multiple myeloma. We present the case of a 50 years old female who presented to our hospital with a complicated UTI and severe generalized body aches. She was diagnosed as a case of plasma cell leukaemia and was treated with cyclophosphamide and dexamethasone, however she failed to go into remission. Her condition deteriorated and she ultimately passed away 1.5 months after diagnosis. The recommended treatment for PCL is aggressive combination chemotherapy followed by stem cell transplantation. However, there is no consensus regarding the treatment of plasma cell leukaemia, and treatment should be individualized based on the patient profile. Once diagnosed, the prognosis is poor.

Comparison of Breast Density Between Synthesized Versus Standard Digital Mammography.

PURPOSE: To evaluate perceptual difference in breast density classification using synthesized mammography (SM) compared with standard or full-field digital mammography (FFDM) for screening. MATERIALS AND METHODS: This institutional review board-approved, retrospective, multireader study evaluated breast density on 200 patients who underwent baseline screening mammogram during which both SM and FFDM were obtained contemporaneously from June 1, 2016, through November 30, 2016. Qualitative breast density was independently assigned by seven readers initially evaluating FFDM alone. Then, in a separate session, these same readers assigned breast density using synthetic views alone on the same 200 patients. The readers were again blinded to each other's assignment. Qualitative density assessment was based on BI-RADS fifth edition. Interreader agreement was evaluated with κ statistic using 95% confidence intervals. Testing for homogeneity in paired proportions was performed using McNemar's test with a level of significance of .05. RESULTS: For patients across the SM and standard 2-D data set, diagnostic testing with McNemar's test with P = 0.32 demonstrates that the minimal density transitions across FFDM and SM are not statistically significant density shifts. Taking clinical significance into account, only 8 of 200 (4%) patients had clinically significant transition (dense versus not dense). There was substantial interreader agreement with overall κ in FFDM of 0.71 (minimum 0.53, maximum 0.81) and overall SM κ average of 0.63 (minimum 0.56, maximum 0.87). CONCLUSION: Overall subjective breast density assignment by radiologists on SM is similar to density assignment on standard 2-D mammogram.

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study.

PURPOSE: Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country. METHODS: The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥ 65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader. RESULTS: The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value < 0.05 in serum creatinine level for the three age groups [F (2, 297) = 1.98, p value 0.045]. Patients were divided into four groups on the basis of BMI. The results of one-way ANOVA revealed a statistically significant difference at the p value < 0.05 in the mean serum creatinine level for the four groups [F (3, 396) = 2.99, p value 0.032]. However, no statistically significant differences between mean serum cystatin C levels were observed on the basis of patient's age and BMI. CONCLUSION: Cystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.

Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation

Abstract Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1-q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.

An approach to estimate spatial distribution of analyte within cells using spectrally-resolved fluorescence microscopy.

While fluorescence microscopy has become an essential tool amongst chemists and biologists for the detection of various analyte within cellular environments, non-uniform spatial distribution of sensors within cells often restricts extraction of reliable information on relative abundance of analytes in different subcellular regions. As an alternative to existing sensing methodologies such as ratiometric or FRET imaging, where relative proportion of analyte with respect to the sensor can be obtained within cells, we propose a methodology using spectrally-resolved fluorescence microscopy, via which both the relative abundance of sensor as well as their relative proportion with respect to the analyte can be simultaneously extracted for local subcellular regions. This method is exemplified using a BODIPY sensor, capable of detecting mercury ions within cellular environments, characterized by spectral blue-shift and concurrent enhancement of emission intensity. Spectral emission envelopes collected from sub-microscopic regions allowed us to compare the shift in transition energies as well as integrated emission intensities within various intracellular regions. Construction of a 2D scatter plot using spectral shifts and emission intensities, which depend on the relative amount of analyte with respect to sensor and the approximate local amounts of the probe, respectively, enabled qualitative extraction of relative abundance of analyte in various local regions within a single cell as well as amongst different cells. Although the comparisons remain semi-quantitative, this approach involving analysis of multiple spectral parameters opens up an alternative way to extract spatial distribution of analyte in heterogeneous systems. The proposed method would be especially relevant for fluorescent probes that undergo relatively nominal shift in transition energies compared to their emission bandwidths, which often restricts their usage for quantitative ratiometric imaging in cellular media due to strong cross-talk between energetically separated detection channels.

Development and bioevaluation of 99mTc(CO)3-labeled (1-azido-1-deoxy-ß-D-glucopyranoside) complex as a potential tumor-seeking agent.

The 1,2,3-triazole-containing (1-azido-1-deoxy-ß-D-glucopyranoside) complex was synthesized using click chemistry approach and evaluated its potential as a tumor-seeking agent. In the present study, (99m)Tc-tricarbonyl labeled (1-azido-1-deoxy-ß-D-glucopyranoside) radiotracer [(99m)Tc(CO)(3)-BM], (where BM stands for biomolecule, e.g., (1-azido-1-deoxy-ß-D- glucopyranoside)) was synthesized via click chemistry approach and then labeled with technetium-99m through isolink kit. Radio labeled drug was tested for radiochemical purity and in vitro stability by chromatographic techniques. Normal distribution and tumoral uptake were studied in Swiss Webster mice. Radiochemical purity results show 97.9 ±1.5% labeling and its in vitro stability were studied at room temperature up to 5h. The radio labeled drug exhibited 73.6±1.1% binding with blood proteins. Normal distribution of drug shows prominent uptake in brain while in case of tumor-bearing mice, the uptake was maximum in tumor tissue and negligible amount was shown in brain. The biodistribution was further compared with 2-fluoro-2-deoxy glucose ((18)F-FDG), which was used as a positive control. The data indicate that (99m)Tc-tricarbonyl labeled (1-azido-1-deoxy-ß-D- glucopyranoside) radiotracer might be a feasible candidate with reasonable potential for tumor diagnosis.

The role of repetition and reinforcement in school-based oral health education-a cluster randomized controlled trial.

BACKGROUND: Repetition and reinforcement have been shown to play a crucial role in the sustainability of the effect of Oral Health Education (OHE) programs. However, its relevance to school-based OHE imparted by different personnel is not depicted by the existing dental literature. The present study was undertaken to determine the effectiveness of the repeated and reinforced OHE (RR-OHE) compared to one-time OHE intervention and to assess its role in school-based OHE imparted by dentist, teachers and peers. METHODS: The study was a cluster randomized controlled trial that involved 935 adolescents aged 10-11 years. Twenty four boys' and girls' schools selected at random in two towns of Karachi, Pakistan were randomly assigned to three groups to receive OHE by dentist (DL), teachers (TL) and peer-leaders (PL). The groups received a single OHE session and were evaluated post-intervention and 6 months after. The three groups were then exposed to OHE for 6 months followed by 1 year of no OHE activity. Two further evaluations at 6-month and 12-month intervals were conducted. The data were collected by a self-administered questionnaire preceded by a structured interview and followed by oral examination of participants. RESULTS: The adolescents' oral health knowledge (OHK) in the DL and PL groups increased significantly by a single OHE session compared to their baseline knowledge (p < 0.05) and the increase was sustained over 6 months. Although one-time OHE resulted in a significant improvement in adolescents' oral health behavior (OHB) related to the prevention of gingivitis in the two groups (p < 0.05), no significant change was observed in their behavior towards prevention of oral cancer. One-time teacher-led OHE was ineffective in improving adolescents' OHK and OHB. The oral hygiene status (OHS) of the participants in all three groups did not change statistically after one-time OHE. The OHK, OHB and OHS indices increased significantly 6 months after RR-OHE than the initial scores (p < 0.001) irrespective of OHE strategy. Although the OHK scores of the DL and PL groups decreased significantly at 12-month evaluation of RR-OHE (p < 0.05), the said score of the TL group; and OHB and OHS scores of all three groups remained statistically unchanged during this period. CONCLUSIONS: The repetition and reinforcement play a key role in school-based OHE irrespective of educators. The trained teachers and peers can play a complementary role in RR-OHE.

Pediatric Upper Cervical Spine Giant Cell Tumor: Case Report.

Study Design Case report. Objective The purpose of this work is to report the case of a giant cell tumor involving the second cervical vertebra in a pediatric patient. Surgical management included a combined posterior and anterior cervical approach. There has been no recurrence in 2 years of follow-up. Case Report A 13-year-old girl presented with scoliosis with incidentally lytic lesion involving the second cervical vertebra. The radiologic investigations and biopsy result indicated a giant cell tumor of the bone. A combined posterior and anterior cervical approach was performed to resect the lesion, reconstruct the spine, and restore stability. Two years of follow-up revealed no recurrence of the lesion with stable reconstruction of the spine. Results The lesion was surgically managed for excision and spinal fusion by combining a posterior occipitocervical arthrodesis with an anterior retropharyngeal cervical approach. The final histopathology result confirmed a giant cell tumor of the bone. Conclusions Giant cell tumor involving the second cervical vertebra is uncommon; this tumor can be managed surgically by using a combined posterior and anterior cervical retropharyngeal approach. The presented case was unique in terms of the tumor location, patient age, and surgical management.

Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours.

OBJECTIVES: To determine the frequency of completeness of resection for intra-axial solid brain tumours with the help of intra-operative ultrasound to detect residual brain tumour. METHODS: The cross-sectional study was conducted at the Department of Neurosurgery, Dow University of Health Sciences and Civil Hospital Karachi, from September 2009 to June 2010 and comprised patients with intra-axial solid brain lesion. During operation following standard craniotomy, multi-plane sonographic examination was performed using intra-operative ultrasound for tumour localisation and calculation of dimension, followed by tumour resection in the standard fashion. At the end of tumour resection ultrasound was again used for the detection of any residual tumour. Results of intra-operative ultrasound were compared with post-operative contrast magnetic resonance imaging. RESULTS: Of the 39 cases in which intra-operative ultrasound was performed, 32(82.1%) were males and 7(17.9%) were females, with an overall mean age of 42.6±19.7 years. Intra-operative ultrasonography was able to localise and delineate the tumour in all 39 (100%) cases. It showed no residual tumour in 36 (92.3%) cases, but in 3(7.7%) cases residual tumour was detected. Post-operative contrast enhancing magnetic resonance imaging showed no residual tumour in 35(89.7%) cases and in 4(10.3%) cases residual tumour was detected. The frequency of completely resected intra-axial solid brain tumour was 35(89.7%), while in 4(10.3%) cases incomplete resection was observed. CONCLUSION: The study concluded that intra-operative ultrasonography has an important role in achieving increased frequency of completely resected intra-axial solid brain tumours.

Trilateral retinoblastoma with unilateral eye involvement.

Trilateral retinoblastoma (TRb) is a rare combination of unilateral or bilateral retinoblastoma with an ectopic midline intracranial neuroblastic neoplasm (primitive neuroectodermal tumour) usually in the area of pineal gland or sellar region. TRb can occur with both familial and sporadic forms of retinoblastoma. An occurrence of this rare tumour in a 12-year-old boy who had unilateral retinoblastoma in association with ectopic suprasellar primitive neuroectodermal tumour (PNET) is reported here. To the best of our knowledge, this is the first case report in Pakistan on TRb with suprasellar mass.

Development of 99mTc-5-fluorouracil as a potential tumor diagnostic agent.

5-Fluorouracil is a well know drug for chemotherapy of various types of cancer. In the present study, we radiolabeled 5-fluorouracil with (99m)Tc for a diagnostic study of cancer. After successful labeling of the drug we performed an animal study to evaluate the potential of this radiopharmaceutical as a tumor diagnostic agent. The results showed 98.1 ± 1.2% labeling efficacy of 5-fluorouracil with (99m)Tc. The in vitro stability of the radiolabeled drug at room temperature at 4 hr of post-labeling was >96.5 ± 0.4%. The binding of the radiolabeled drug with plasma proteins was 66.6 ± 3%. Partition coefficient results showed that this drug is hydrophilic in nature. Biodistribution study in rabbit models displayed faint uptake in liver. Both kidney and bladder were prominent as excretory route of the labeled drug. Bioevaluation was performed in Swiss Webster mice having naturally developed tumor. Mice were dissected, uptake of drug in various organs was studied and results showed prominent uptake in liver and tumor. Tumor was further investigated by histopathological study.