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Biomedical subjects

M Shah

Publications and source records attributed to M Shah.

At least 19 recordsLinked to original sources
PubMed2026

Reduced Length of ADT and ARTA With XRT in High-Risk Prostate Cancer (RELAX): A Randomised Controlled Trial.

AIM: To assess the efficacy of a short, intensified regimen of androgen deprivation therapy (ADT) and androgen receptor-targeted agent (ARTA) with curative-intent external beam radiotherapy (XRT) for high-risk prostate cancer (HRPCa) staged with prostate specific membrane antigen (PSMA) imaging. MATERIALS AND METHODS: The RELAX (Reduced Length of ADT and ARTA with XRT in high-risk prostate cancer) trial is a multicentre, phase II randomised non-inferiority trial comparing 9 months of ADT and 6 months of ARTA against the standard 24-month ADT, with definitive dose-escalated hypofractionated pelvic radiotherapy for PSMA-staged non-metastatic HRPCa. The primary endpoint is 5-year disease-free survival (DFS), defined from randomisation to first biochemical or clinico-radiological recurrence or any-cause death. Secondary endpoints include biochemical failure-free survival, metastasis-free survival, overall survival, testosterone recovery, treatment-related adverse effects, and patient-reported outcomes. Participants are monitored with serial serum PSA and testosterone levels, CTCAE and PRO-CTCAE assessments, and PSMA-PETCT at recurrence. The non-inferiority margin is set at 10% absolute difference from an expected 5-year DFS of 85% in the standard arm, with intention-to-treat analysis. The trial is ethics board approved and funded by institutional intramural grant, and registered on clinicaltrials.gov (NCT06818682). RESULTS: The planned accrual of 206 participants commenced in February 2025, with nearly a third of enrolment completed till date. CONCLUSION: The RELAX trial incorporates contemporary standards of PSMA-based staging, dose-escalated hypofractionated radiotherapy, and ARTA for HRPCa. The results are expected to inform the efficacy of a shorter, intensified androgen suppression strategy against the prevailing standard of long-term ADT for these patients.

Humans↗
PubMed2006

Interactions between genes involved in the antioxidant defence system and breast cancer risk.

The aim of the study is to examine the association between multilocus genotypes across 10 genes encoding proteins in the antioxidant defence system and breast cancer. The 10 genes are SOD1, SOD2, GPX1, GPX4, GSR, CAT, TXN, TXN2, TXNRD1 and TXNRD2. In all, 2271 cases and 2280 controls were used to examine gene-gene interactions between 52 single nucleotide polymorphisms (SNPs) that are hypothesised to tag all common variants in the 10 genes. The statistical analysis is based on three methods: unconditional logistic regression, multifactor dimensionality reduction and hierarchical cluster analysis. We examined all two- and three-way combinations with unconditional logistic regression and multifactor dimensionality reduction, and used a global approach with all SNPs in the hierarchical cluster analysis. Single-locus studies of an association of genetic variants in the antioxidant defence genes and breast cancer have been contradictory and inconclusive. It is the first time, to our knowledge, the association between multilocus genotypes across genes coding for antioxidant defence enzymes and breast cancer is investigated. We found no evidence of an association with breast cancer with our multilocus approach. The search for two-way interactions gave experiment-wise significance levels of P=0.24 (TXN [t2715c] and TXNRD2 [g23524a]) and P=0.58 (GSR [c39396t] and TXNRD2 [a442g]), for the unconditional logistic regression and multifactor dimensionality reduction, respectively. The experiment-wise significance levels for the three-way interactions were P=0.94 (GPX4 [t2572c], TXN [t2715c] and TXNRD2 [g23524a]) and P=0.29 (GSR [c39396t], TXN [t2715c] and TXNRD2 [a442g]) for the unconditional logistic regression and multifactor dimensionality reduction, respectively. In the hierarchical cluster analysis neither the average across four rounds with replacement of missing values at random (P=0.12) nor a fifth round with more balanced proportion of missing values between cases and controls (P=0.17) was significant.

Adult↗
PubMed2006

An assessment of the quality of life in older patients with skin disease.

BACKGROUND: There are few data regarding quality of life in older people with skin disease, particularly concerning those with skin cancer. Access to U.K. secondary care dermatological services is increasingly focusing on skin cancer, which may have a negative effect on waiting times for patients with rashes. OBJECTIVES: To assess the quality of life in patients aged 65 years and over and to determine how this relates to type and extent of skin disease. METHODS: One hundred consecutive new dermatology patient referrals aged 65 years and above had quality of life assessed by the Dermatology Life Quality Index (DLQI), the Hospital Anxiety and Depression Scale (HADS) and the Illness Perception Questionnaire. Patients were examined for type and extent of skin disease. RESULTS: There were 49 men (mean age 75.1 years) and 51 women (mean age 75.0 years). Fifty-five per cent of patients had been referred with one or more lesions (76% premalignant or malignant) and 45% had rashes. There was no significant difference between the quality of life scores of men vs. women regarding all three of the questionnaires. However, patients with rashes scored significantly higher (i.e. poorer quality of life) on all but one of the questionnaire parts compared with patients with lesions. Patients with more extensive disease had significantly higher DLQI scores. CONCLUSIONS: Older people suffering from rashes had significantly poorer quality of life than patients with lesions, even those with skin cancer. The quality of life is negatively associated with extent of skin disease. Access to specialist dermatological care should take into account the suffering caused by extensive skin diseases. DLQI and a general quality of life questionnaire such as the HADS are quick to deliver and to score, particularly in the setting of a busy outpatient department. They provide an excellent screening tool for psychological problems in older people with skin disease.

Aged↗
PubMed2006

Successful umbilical cord blood stem cell transplantation in a patient with Rothmund-Thomson syndrome and combined immunodeficiency.

The ATP-dependent DNA helicase Q4 (RECQL4) belongs to a family of conserved RECQ helicases that are felt to be important in maintaining chromosomal integrity (Kitao et al., 1998, Genomics: 54 (3): 443-452). Deletions in the RECQL4 gene located on chromosome 8 region q24.3 have been associated with Rothmund-Thomson syndrome (RTS, OMIM 268400), a condition characterized by poikiloderma, sparse hair, small stature, skeletal abnormalities, cataracts and an increased risk of malignancy. We present a patient with a molecularly confirmed diagnosis of RTS with two unique genetic alterations in RECQL4 (IVS16-2A>T and IVS2+27_51del25), who at the age of 7 months nearly succumbed to Pneumocystis carinii pneumonia. Evaluation of his immune system demonstrated a T- B+ NK- phenotype with agammaglobulinemia consistent with combined immunodeficiency (CID). Studies to evaluate for known genetic causes of CID were not revealing. The patient received an umbilical cord blood (UCB) transplant with complete immune reconstitution. This report represents the first description of a CID phenotype and UCB transplantation in a patient with RTS.

Agammaglobulinemia↗
PubMed2006

A case of miliary tuberculosis presenting with bowel perforation.

Tuberculosis is a disease that should never be underestimated. It can affect anybody at any age. Doctors in the West do not have much experience of peritonitis secondary to tuberculosis. It is a condition that requires urgent and aggressive management as it can be fatal, even in the young and fit, as this case report illustrates.

Abdomen, Acute↗
PubMed2005

Benefits and limitations of image guidance in the surgical treatment of intracranial dural arteriovenous fistulas.

BACKGROUND: Despite major advances in endovascular embolization techniques, microsurgical resection remains a reliable and effective treatment modality for dural arteriovenous fistulas (DAVF). However, intraoperative detection of these lesions and identification of feeding arteries and draining veins can be challenging. In a series of 6 patients who were not candidates for definitive treatment by endovascular embolization we evaluated the benefits and limitations of computer-assisted image guidance for surgical ablation of DAVF. METHODS: Of the 6 patients, 5 presented with haemorrhage and one with seizures. Diagnosis of DAVF was made by conventional angiography and dynamic contrast enhanced MR angiography (CE-MRA). All patients were surgically treated with the assistance of a 3D high resolution T1-weighted MR data set and time-of-flight MR angiography (MRA) obtained for neuronavigation. Registration was based on cranial fiducials and image-guided surgery was performed with the navigation system. FINDINGS: Four of the 6 patients suffered from DAVF draining into the superior sagittal sinus, one fistula drained into paracavernous veins adjacent to the superior petrosal sinus and one patient had a pial fistula draining in the straight sinus. DAVF diagnosed with conventional angiography could be located on CE-MRA and MRA prior to surgery. MRI and MRA images were combined on the neuronavigation workstation and DAVF were located intraoperatively by using a tracking device. In 4 out of 6 cases neuronavigation was used for direct intraoperative identification of DAVF. Brain shift prevented direct tracking of pathological vessels in the other 2 cases, where navigation could only be used to assist craniotomy. Microsurgical dissection and coagulation of the fistulas led to complete cure in all patients as confirmed by angiography. CONCLUSIONS: Neuronavigation may be used as an additional tool for microsurgical treatment of DAVF. However, in this small series of 6 cases, surgical procedures have not been substantially altered by the use of the neuronavigation system. Image guidance has been beneficial for the location of small, superficially located DAVF, whereas a navigated approach to deep-seated lesions was less accurate due to the familiar problem of brain shift and brain retraction during surgery.

Adult↗
PubMed2005

Identification of an anonymous RFLP DNA probe through multiple arbitrary amplicon profiling and its use for strain differentiation in a field isolate of cellulose-degrading Aspergillus niger.

The genome of Aspergillus niger (MPS-002) was subjected to RAPD fingerprinting using none different random oligonucleotide primers. A 0.7 Kb PCR amplicon, generated by primer-3 could be used as a RFLP probe to differentiate A. niger (ATCC 16880) from A. niger (MPS-002). The probe revealed DNA polymorphism internal to two different EcoRI recognition sequences spaced apart at a distance of 0.4 Kb within a 4.0 Kb EcoRI fragment of the genome of both the strains. Localized genome mapping analysis further revealed that the 0.7 Kb RFLP probe was positioned at a distance of 2.7 Kb and 0.6 Kb from the two ends of a 4.0 Kb EcoRI fragment, respectively within the genome of the two strains of A. niger.

Aspergillus niger↗
PubMed2005

A phase I clinical and pharmacokinetic study of fenretinide combined with paclitaxel and cisplatin for refractory solid tumors.

BACKGROUND: Fenretinide is a semi-synthetic retinoid that has pro-apoptotic effects as a single agent and synergistically with chemotherapy in vitro. We performed this study to determine the toxicity of cisplatin, paclitaxel and fenretinide in patients with advanced cancer, the recommended phase II dose of these agents together, and the pharmacokinetics (PK) of fenretinide when administered with chemotherapy. PATIENTS AND METHODS: Fourteen patients (mean age 57.3) were assessable for pharmacokinetics, toxicity and response. Fenretinide was given orally in 2 divided daily doses for 7 days, starting 24 hours prior to cisplatin and paclitaxel. Cisplatin and paclitaxel were given in standard fashion. Cycles were repeated every 3 weeks. Cycle one fenretinide PK was obtained on days 2 and 8. RESULTS: Dose limiting toxicity (Gr 3 diarrhea and Gr 4 neutropenia) was encountered in two patients during cycle one at 80/175/1,800 mg/m(2) of cisplatin/paclitaxel/fenretinide (dose level 2), respectively. Seven patients received 2-8 cycles at the recommended level of 60/135/1,800 (dose level 1). Severe cumulative toxicities included fatigue, nausea/vomiting, neuropathy, and dehydration. Two patients had a partial response and 4 patients had stable disease for up to 8 cycles. PK analysis demonstrated a reduction in fenretinide Cmax on day 8 compared to day 2, accompanying a decrease in AUC. CONCLUSIONS: Cisplatin/paclitaxel/fenretinide can be administered safely at 60/135/1,800 mg/m(2) respectively on an every three-week schedule. This combination may have activity in a variety of tumors, however, the number of pills required complicates oral dosing of fenretinide, and limits the applicability of this regimen.

Administration, Oral↗
PubMed2005

The role of diet, exercise and smoking in dyslipidaemia in HIV-infected patients with lipodystrophy.

BACKGROUND: Lipodystrophy in HIV-infected (LDHIV) patients receiving protease inhibitors (PIs) is associated with dyslipidaemia. Whether lifestyle factors play a role in dyslipidaemia in LDHIV subjects on PIs is not well characterized. METHODS: A total of 45 LDHIV male and six LDHIV female patients on PIs were recruited, and data were collected on smoking, exercise, diet (by 3-day food record), and fasting levels of serum lipids and lipoproteins. The relationships between lifestyle factors and metabolic variables were analysed in male patients by Spearman's correlation test and the significant relationships were further analysed by adjusting for age, PI duration, and waist circumference by Spearman's partial correlation test. RESULTS: In men, mean (+/-standard deviation) serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C were 212+/-70, 35+/-7.3, 325+/-230 and 169+/-44 mg/dL, respectively. Sixty-seven percent of the men exercised regularly and 31.1% smoked. The reported diet was high in cholesterol (390+/-212 mg) and percentage energy from saturated (12.2+/-3.3%) and trans (2.4+/-1.2%) fats, and low in soluble fibre (6.9+/-2.3 g) compared with recent dietary guidelines. Following adjustments for the confounding variables, percentage energy intake from total protein and animal protein was positively related to TC (r=0.44, P<0.01 and r=0.37, P<0.05, respectively), TG (r=0.40, P<0.01 and r=0.46, P<0.01, respectively) and non-HDL-C (r=0.56, P<0.001 and r=0.49, P<0.01, respectively), that from trans fat was positively related to TG (r=0.34, P<0.05), and soluble fibre was negatively related to non-HDL-C (r=-0.41, P<0.01). Moderate to heavy aerobic exercise tended to be associated with higher HDL-C (r=0.30, P=0.07) whereas smoking was not associated with any of the metabolic variables. CONCLUSIONS: Increased intake of total protein, animal protein and trans fat, and reduced soluble fibre consumption contribute to dyslipidaemia in LDHIV subjects on PIs.

Adult↗
PubMed2005

Scald injury from the Guthrie test: should the heel be warmed?

A 6 day old boy sustained scalds to his right foot from application of a "warm nappy" to increase blood flow to facilitate heel pricking for a routine Guthrie test. It is proposed that active warming of the heel in isolation is not necessary in heel blood sampling.

Ankle Injuries↗
PubMed2003

Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome.

OBJECTIVE: To determine whether early seizures that occur frequently after intracerebral hemorrhage (ICH) lead to increased brain edema as manifested by increased midline shift. METHODS: A total of 109 patients with ischemic stroke (n = 46) and intraparenchymal hemorrhage (n = 63) prospectively underwent continuous EEG monitoring after admission. The incidence, timing, and factors associated with seizures were defined. Serial CT brain imaging was conducted at admission, 24 hours, and 48 to 72 hours after hemorrhage and assessed for hemorrhage volume and midline shift. Outcome at time of discharge was assessed using the Glasgow Outcome Scale score. RESULTS: Electrographic seizures occurred in 18 of 63 (28%) patients with ICH, compared with 3 of 46 (6%) patients with ischemic stroke (OR = 5.7, 95% CI 1.4 to 26.5, p < 0.004) during the initial 72 hours after admission. Seizures were most often focal with secondary generalization. Seizures were more common in lobar hemorrhages but occurred in 21% of subcortical hemorrhages. Posthemorrhagic seizures were associated with neurologic worsening on the NIH Stroke Scale (14.8 vs 18.6, p < 0.05) and with an increase in midline shift (+ 2.7 mm vs -2.4 mm, p < 0.03). There was a trend toward increased poor outcome (p < 0.06) in patients with posthemorrhagic seizures. On multivariate analysis, age and initial NIH Stroke Scale score were independent predictors of outcome. CONCLUSION: Seizures occur commonly after ICH and may be nonconvulsive. Seizures are independently associated with increased midline shift after intraparenchymal hemorrhage.

Adult↗
PubMed2003

C-1 esterase inhibitor dysfunction localised to the periodontal tissues: clues to the role of stress in the pathogenesis of chronic periodontitis?

BACKGROUND: C1-esterase inhibitor (C1eIn) is an important modulator of complement activation via the classical pathway. Deficiencies or dysfunction involving this inhibitor underlie the condition of angioneurotic oedema. AIM: The purpose of this report is to describe a female patient who presented at the age of 24 years with an apparently aggressive form of periodontitis and severe oedema, localised to the free gingival tissues. After 21 years of repeated surgical reduction of the gingiva, a diagnosis of C1eIn dysfunction was made. METHODS: Exhaustive serological investigations were performed along with histopathology. RESULTS: All investigations were unremarkable, until the function of the C1eIn molecule was investigated. These demonstrated a functional activity of only 29% and a raised C1q at 157 mg/l. Subsequent repeated investigation with careful specimen handling demonstrated undetectable levels of C1eIn and normal C1q. A diagnosis of C1eIn dysfunction was made, although at present it is unclear whether this represents an unusual variant of hereditary dysfunctional C1eIn deficiency. The patient was managed by various means, including steriodal and non-steroidal drugs, the latter forming part of her maintenance regime. CONCLUSIONS: To our knowledge, this is the first case of angio-oedema localised to the free gingiva. The role of stress in the acute exacerbations of oedema and bone loss is discussed along with the diagnostic pitfalls associated with this case.

Adult↗