Papers by shaheen sher khan
Cancers, 2022
Antibiotic administration is associated with worse clinical outcomes and changes to the gut micro... more Antibiotic administration is associated with worse clinical outcomes and changes to the gut microbiome in cancer patients receiving immune checkpoint inhibitors (ICI). However, the effects of antibiotics on systemic immune function are unknown. We, therefore, evaluated antibiotic exposure, therapeutic responses, and multiplex panels of 40 serum cytokines and 124 antibodies at baseline and six weeks after ICI initiation, with p < 0.05 and false discovery rate (FDR) < 0.2 considered significant. A total of 251 patients were included, of whom the 135 (54%) who received antibiotics had lower response rates and shorter survival. Patients who received antibiotics prior to ICI initiation had modestly but significantly lower baseline levels of nucleolin, MDA5, c-reactive protein, and liver cytosol antigen type 1 (LC1) antibodies, as well as higher levels of heparin sulfate and Matrigel antibodies. After ICI initiation, antibiotic-treated patients had significantly lower levels of MDA5...
British Journal of Cancer, 2018
BACKGROUND: Up to 40% of cancer patients on immune checkpoint inhibitors develop clinically signi... more BACKGROUND: Up to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown. METHODS: Sera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2-3 weeks and after 6 weeks and analysed for correlation with the development of irAEs. RESULTS: Of the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs. CONCLUSIONS: Patients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.
Palliative medicine, 2017
Over half of all deaths in Europe occur in hospital, a location associated with many complaints. ... more Over half of all deaths in Europe occur in hospital, a location associated with many complaints. Initiatives to improve inpatient end-of-life care are therefore a priority. In England, over 78,000 volunteers provide a potentially cost-effective resource to hospitals. Many work with people who are dying and their families, yet little is known about their training in end-of-life care. To explore hospital volunteers' end-of-life care training needs and learning preferences, and the acceptability of training evaluation methods. Qualitative focus groups. Volunteers from a large teaching hospital were purposively sampled. Five focus groups were conducted with 25 hospital volunteers (aged 19-80 years). Four themes emerged as follows: preparation for the volunteering role, training needs, training preferences and evaluation preferences. Many described encounters with patients with life-threatening illness and their families. Perceived training needs in end-of-life care included communic...
BMJ supportive & palliative care, Jan 22, 2015
UK policymakers, clinicians and public wish to see improvements in end-of-life care (EoLC). Howev... more UK policymakers, clinicians and public wish to see improvements in end-of-life care (EoLC). However, healthcare professionals' skills and knowledge to deliver high-quality care are often lacking. Since May 2012, palliative care staff in an inner-city tertiary hospital have run a 2-day Transforming End of Life Care (TEoLC) course to improve EoLC confidence, and competence among hospital and community staff. To evaluate course participants' self-rated confidence, competence and knowledge of EoLC topics. A before-and-after design using self-completion questionnaires, precourse and postcourse. 14 self-assessment questions examined confidence, understanding and knowledge of EoLC topics. Mean change scores and paired t tests were calculated and free-text responses analysed thematically. 236 staff members completed the course between May 2012 and April 2014. 42% worked in hospitals and 55% in the community; the most frequent staff roles were qualified nurses (49%), senior nurses (1...
Phlebology, 2003
Objective: To review current approaches to investigation and management of Paget-Schroetter syndr... more Objective: To review current approaches to investigation and management of Paget-Schroetter syndrome (PSS). Methods: Relevant clinical studies and reports were searched for using MEDLINE and Embase databases and cross-referenced articles. Articles were extracted using keywords by the two authors independently. Principal findings: There is growing evidence of functional or positional anatomical defects, which lead to subtle intimal injury and a tendency for recurrence or poor outcome. Management of PSS remains controversial. Anticoagulation as a stand-alone treatment has lost favour. Active treatment with thrombolysis followed by consideration of thoracic decompression is recommended by most in the recent literature. Thrombolytic therapy appears to be a safe and efficacious method of establishing immediate patency of the axillary/subclavian vein. The timing and indications of decompression surgery are yet to be defined clearly. There are no randomized trials of treatment or managemen...
JPMA. The Journal of the Pakistan Medical Association, 1995
A set of procedures, based on DNA analysis, has been developed to detect deletions and point muta... more A set of procedures, based on DNA analysis, has been developed to detect deletions and point mutations causing Beta thalassemia in the Pakistani population. These procedures can be used to analyze the presence of relevant changes in DNA, thus providing a reliable means for screening the high risk families, to provide them genetic counselling and prenatal diagnosis during early pregnancy. We have identified two mutations IVS-1 nt.5 (G--C) and codon 8-9 (+G) in 4 of the 6 families analyzed for these mutations.
India is highest producer of raw milk and dairy products in all over the world. It is also one of... more India is highest producer of raw milk and dairy products in all over the world. It is also one of the largest exporter of dairy products. The quality of these dairy products including raw milk should be examined regularly for maintaining the good hygienic qualities of these products. However, In India, the limited study is available on microbiological quality of raw milk. Therefore the microbiological quality and safety of raw milk from different dairy farms and dairy shops in Bareilly city (Northern India) was examined. Bovine raw milk samples (n = 150) were aseptically collected and analyzed for several microbial quality attributes including total aerobic plate count (TAPC), total coliform count (TCC), and L. monocytogenes count (LC). The mean log counts for TAPC, TCC were observed in between 3.3–5.9 cfu/mL and 1.6–3.8 cfu/mL respectively. The LC of two samples, found positive for the presence of L. monocytogenes, was 3.8 cfu/mL and log 4.0 cfu/mL. Results indicated that the secur...
This study was designed to determine the presence of Salmonella in various meat samples. A total ... more This study was designed to determine the presence of Salmonella in various meat samples. A total of 400 meat samples from chicken, fish and cattle were collected locally in Bareilly city, Izatnagar, India. The highest prevalence (11.0%) was observed in fish followed by chicken (8.0%) and beef (4.0%) using cultural and PCR methods. Among spiking samples 100% detection of S. enteritidis was found using both cultural and PCR method. The results of the study indicate that considerable prevalence of Salmonella spp. were observed from various meat samples which is representing use of poor hygienic conditions during slaughtering. Thus the consumer is under potential health threat of Salmonellosis and it is suggested that good hygiene practices should be ensured to maintain good quality of the food in favour of public health. All copyrights reserved to Nexus® Academic Publishers
Molecular vision, Jan 24, 2010
To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous ... more To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistani family. All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples were collected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellite markers. Logarithm of odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2), residing in the critical interval, was sequenced bidirectionally. The clinical and ophthalmological examinations suggested that all affected individuals have nuclear cataracts. Genome-wide linkage analyses localized the critical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p, with a maximum two-point LOD score of 5.21 at theta=0. Sequencing of EPHA2 residing in the critical interval identified a missense mutation: c.2353G>A, which results in an alanine to threonine substitution (p.A785T). Here, we report for the first time a missense mutation in EPHA2 a...
Nature Reviews Clinical Oncology, 2013
Patients with cancer frequently suffer from debilitating physical symptoms and psychological dist... more Patients with cancer frequently suffer from debilitating physical symptoms and psychological distress, particularly at the end of life. Interventions to help alleviate these problems are often complex and multifactorial. Palliative care services and therapeutic interventions have developed in a variable manner, often with limited evaluation of clinical effectiveness and affordability, resulting in a relatively weak evidence base. The health care provided to patients with advanced-stage cancer does not always correlate with what is known about their preferences for care. In this Review, we discuss the preferences of patients with cancer regarding their end of life care, including the importance of early provision of palliative care, and the central role of advance care planning in meeting patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; preferences. It has been shown that many patients with cancer wish to die at home. We discuss the factors that contribute to the place of death, including environmental factors, disease-specific issues, and the availability of resources. There has been a recent upward trend in the number of patients with cancer who die in their preferred place of care, and important contributors--such as community palliative care, advance care planning, and improvements in palliative care services as a result of robust research studies--are considered.
Microbes and Microbial Technology, 2011
... Chapter 8 Molecular Strategies: Detection of Foodborne Bacterial Pathogens Javed Ahamad Khan,... more ... Chapter 8 Molecular Strategies: Detection of Foodborne Bacterial Pathogens Javed Ahamad Khan, RS Rathore, Iqbal Ahmad, and Shaheen Khan Page 2. 190 ... The fragments are scored as dominant Mendelian elements, and the protocols are relatively simple. Hamza et al. ...
Investigative Opthalmology & Visual Science, 2012
PURPOSE. Congenital stationary night blindness is a nonprogressive retinal disorder manifesting a... more PURPOSE. Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family. METHODS. A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals. RESULTS. The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at ϭ 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inher-From the
European Journal of Vascular and Endovascular Surgery, 2007
Background. Peripheral arterial disease (PAD) is often associated with risk factors including cig... more Background. Peripheral arterial disease (PAD) is often associated with risk factors including cigarette smoking, hypertension and hypercholesterolaemia, and patients have a high risk of future vascular events. Good medical management results in improved outcomes and quality of life, but previous studies have documented sub-optimal treatment of risk factors. We assessed the management of cardiovascular risk factors in patients with PAD referred to specialist vascular clinics. Methods. This was a prospective, protocol driven registry carried out in UK vascular clinics. Patients who were first-time referrals for evaluation of PAD were eligible if they had claudication plus ankle-brachial pressure index (ABPI) 0.9. Statistical associations between key demographic and treatment variables were explored using a chi-squared test. Results. We enrolled 473 patients from 23 sites. Mean age was 68 years (SD 10) and 66% were male. Mean estimated claudication distance was 100 m, and ABPI was 0.74. Mean systolic blood pressure (SBP) was 155 mmHg, and 42% had a SBP >160 mmHg. Forty percent were current smokers and half had tried to give up in the prior 6 months, but there was no evidence of a systematic method of smoking cessation. Mean total cholesterol was 5.4 (SD1.2) mmol/l and 30% had levels >6 mmol/l. Antiplatelet therapy had been given to 70% and statins to 44%. Prior CHD was present in 29% and these patients had significantly higher use of antiplatelet therapy, statins and ACE-inhibitors. Conclusions. In spite of attempts to raise awareness about PAD as an important marker of cardiovascular risk, patients are still poorly treated prior to referral to a vascular clinic. In particular, the use of evidence-based treatments is suboptimal, while hypertension and cigarette smoking are poorly managed. More work needs to be done to educate health professionals about the detection and optimal medical management of PAD.
European Journal of Vascular and Endovascular Surgery, 2005
Objective. To review the published evidence supporting the use of lifestyle modification in perip... more Objective. To review the published evidence supporting the use of lifestyle modification in peripheral arterial disease (PAD). Design. A systematic search of the medical literature was performed for relevant studies. Materials. The publications obtained were then searched for randomised clinical trials which reported end-points of mortality or major cardiovascular event rates with various lifestyle modifications. Results. Only one randomised controlled trial was found reporting relevant end-points. Other trials were of other endpoints such as walking distance or biochemical markers. Conclusions. There is a lack of randomised controlled data proving the benefit of lifestyle modification in improving mortality and reducing cardiovascular events in patients with PAD. Despite this there is sufficient evidence to recommend some lifestyle modification as part of the overall approach to risk reduction in these patients. There is compelling evidence to support smoking cessation, increased exercise and improved diet.
European Journal of Vascular and Endovascular Surgery, 2005
European Journal of Medicinal Chemistry, 2010
A series of tetrahydro-b-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluate... more A series of tetrahydro-b-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of racemic compounds 69, 71 and 75, which are selectively cytotoxic towards KB (oral cancer) cell line with IC 50 values of 105.8, 664.7 and 122.2 nM, respectively; while their enantiopure forms are less active and not selective. Enantiopure compound 42 showed 2.5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC 50 value of 740 nM, also arrests cell cycle in G 1 phase and induces apoptosis in MCF7 and MDA MB231cell lines.
Ecological Economics, 2009
This paper contributes to the debate on the links between poverty and forestry degradation; the v... more This paper contributes to the debate on the links between poverty and forestry degradation; the view that due to poverty and the meeting of subsistence needs the poor use natural resources more intensively and hence cause them to degrade. Using the case of forest rich Swat district, Pakistan, the paper addresses the issue empirically, historically, and institutionally. We do not find empirical support for the "poverty-environment nexus," in that the poor and other income groups are equally resource dependent and also show that resource degradation is not associated with poverty. Our historical and institutional analyses provide alternative explanations for resource degradation. Selective and rotating ownership patterns, starting with the 17 th century, provided limited incentive for resource conservation. It also created tension between de jure and de facto owners, that has persisted, and is one source of forest degradation. Ill-defined resource rights have also exacerbated the impacts of several other factors contributing to forest degradation which is compounded by poor management, corruption, and perverse incentives.
Cell, 2013
The molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways... more The molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways remain incompletely understood. Here, we identified a previously uncharacterized mammalian-specific protein, Beclin 2, which, like Beclin 1, functions in autophagy and interacts with class III PI3K complex components and Bcl-2. However, Beclin 2, but not Beclin 1, functions in an additional lysosomal degradation pathway. Beclin 2 is required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) through its interaction with GASP1. Beclin 2 homozygous knockout mice have decreased embryonic viability, and heterozygous knockout mice have defective autophagy, increased levels of brain cannabinoid 1 receptor, elevated food intake, and obesity and insulin resistance. Our findings identify Beclin 2 as a converging regulator of autophagy and GPCR turnover and highlight the functional and mechanistic diversity of Beclin family members in autophagy, endolysosomal trafficking, and metabolism.
British Journal of Ophthalmology, 2011
Objective-To identify disease-causing mutations in two consanguineous Pakistani families with fun... more Objective-To identify disease-causing mutations in two consanguineous Pakistani families with fundus albipunctatus. Methods-Affected individuals in both families underwent a thorough clinical examination including funduscopy and electroretinography. Blood samples were collected from all participating members and genomic DNA was extracted. Exclusion analysis was completed with microsatellite short tandem repeat markers that span all reported loci for fundus albipunctatus. Two-point logarithm of odds (LOD) scores were calculated, and coding exons and exon-intron boundaries of RLBP1 were sequenced bi-directionally. Results-The ophthalmic examination of affected patients in both families was consistent with fundus albipunctatus. The alleles of markers on chromosome 15q flanking RLBP1 segregated with the disease phenotype in both families and linkage was further confirmed by two-point LOD scores. Bi-directional sequencing of RLBP1 identified a nonsense mutation (R156X) and a missense mutation (G116R) that segregated with the disease phenotype in their respective families. Conclusions-These results strongly suggest that mutations in RLBP1 are responsible for fundus albipunctatus in the affected individuals of these consanguineous Pakistani families.
British Journal of Ophthalmology, 2010
Background-Retinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one... more Background-Retinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one in approximately 5000 people worldwide. A nuclear family was recruited from the Punjab province of Pakistan to study the genetic basis of autosomal recessive RP. Methods-All affected individuals underwent a thorough ophthalmic examination and the disease was characterised based upon results for fundus photographs and electroretinogram recordings. Genomic DNA was extracted from peripheral leucocytes. Exclusion studies were performed with short tandem repeat (STR) markers flanking reported autosomal recessive RP loci. Haplotypes were constructed and results were statistically evaluated. Results-The results of exclusion analyses suggested that family PKRP173 was linked to chromosome 2q harbouring mer tyrosine kinase protooncogene (MERTK), a gene previously associated with autosomal recessive RP. Additional STR markers refined the critical interval and placed it in a 13.4 cM (17 Mb) region flanked by D2S293 proximally and D2S347 distally. Significant logarithm of odds (LOD) scores of 3.2, 3.25 and 3.18 at θ=0 were obtained with markers D2S1896, D2S2269 and D2S160. Sequencing of the coding exons of MERTK identified a mutation, c.718G→T in exon 4, which results in a premature termination of p.E240X that segregates with the disease phenotype in the family. Conclusion-Our results strongly suggest that the nonsense mutation in MERTK, leading to premature termination of the protein, is responsible for RP phenotype in the affected individuals of the Pakistani family.
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Papers by shaheen sher khan