Journal of Advances in Medical and Pharmaceutical Sciences

Early Haematological Response and Short-Term Safety of Frontline Imatinib in Adults with Chronic Myeloid Leukaemia: A Retrospective Study in a Resource-Limited Setting

2026-07-16T11:20:38+00:00

Background: Imatinib mesylate is a tyrosine kinase inhibitor that has transformed the treatment of chronic myeloid leukaemia. However, information on its real-world use among sub-Saharan African populations remains limited.

Aims: This study evaluated early haematological response and recorded adverse drug reactions among Sudanese adults receiving first-line imatinib for Philadelphia chromosome-positive chronic myeloid leukaemia.

Methods: A single-centre retrospective cohort study was conducted using the medical records of 89 adults with Philadelphia chromosome-positive chronic myeloid leukaemia who were registered and treated at Khartoum Oncology Hospital in 2019. The hospital was the only authorised dispensing site for the Glivec® International Patient Assistance Program in Sudan during the study period. Patients in the chronic phase received imatinib at an initial dose of 400 mg/day, whereas those in the accelerated phase received 600 mg/day. Haematological parameters and recorded adverse drug reactions were assessed at baseline and after one and three months of treatment. Data were analysed using SPSS.

Results: Of the 89 patients, 52.0% were male, and 37.1% were aged 31–40 years. At diagnosis, 95.5% had chronic-phase disease and 95.5% had splenomegaly. Complete haematological response was achieved by 79.8% of patients at one month and 94.4% at three months. Haematological adverse reactions were the most frequently recorded toxicities, including neutropenia in 20.2% and thrombocytopenia in 10.1%. Seven patients, representing 7.9% of the total cohort and 18.4% of those with recorded adverse drug reactions, permanently discontinued imatinib and transitioned to a second-generation tyrosine kinase inhibitor. Accelerated-phase disease was associated with a lower complete haematological response rate and a greater likelihood of an elevated white blood cell count at three months, although this finding was based on only four accelerated-phase patients. Age and sex were not significantly associated with response.

Conclusion: A high proportion of patients achieved an early complete haematological response following cytoreductive bridging and initiation of imatinib. Interpretation is limited by preceding hydroxyurea exposure, retrospective ascertainment of adverse reactions, short follow-up, and the absence of routine molecular and cytogenetic monitoring. Improved access to standardised molecular testing would strengthen treatment-response assessment and long-term CML care in resource-limited settings.

Evaluation of Fructose, Zinc, Citric Acid, and Sperm Quality in Infertile Male Subjects Attending Fertility Clinic in Lagos Metropolis

2026-07-20T05:52:43+00:00

Background: Male infertility remains a significant reproductive health challenge. Seminal plasma biochemical markers, including fructose, zinc, and citric acid, play essential roles in sperm metabolism, motility, and overall reproductive function. Their evaluation alongside sperm quality parameters may provide valuable clinical insight into male infertility.

Aim: This study aimed to evaluate seminal fructose, zinc, and citric acid concentrations and their relationships with sperm quality parameters among infertile male subjects attending fertility clinics in Lagos Metropolis.

Methods: A total of 150 male volunteers aged 25–45 years, comprising 100 infertile men as test subjects and 50 fertile men as controls, provided consent to participate in the study. Semen samples were collected by masturbation into sterile plastic containers after a minimum of three days of sexual abstinence. All samples were analysed using a computer-assisted semen analyser (CASA). Seminal fructose was measured using the resorcinol method, zinc was quantified using a colourimetric method, and citric acid was assessed using an enzymatic titration method. Data were analysed using the Statistical Package for the Social Sciences (SPSS), version 26.0.

Results: Comparative analysis between infertile men and fertile controls revealed differences in seminal biochemical markers and sperm quality parameters. The mean seminal fructose concentration was lower in infertile men than in fertile controls (7.14 ± 3.46 vs 8.79 ± 0.48 µmol/mL). Similarly, the mean seminal zinc concentration was lower in infertile subjects (0.44 ± 0.13 vs 2.99 ± 0.46 µmol/mL), as was the mean citric acid concentration (12.71 ± 4.19 vs 58.26 ± 5.27 mmol/L). Infertile men also had lower sperm counts (64.84 ± 37.94 vs 101.80 ± 21.89 × 10⁶/mL) and reduced sperm motility (29.20 ± 13.76 vs 40.50 ± 3.23%) compared with fertile controls. The reductions in seminal fructose, zinc, and citric acid concentrations were statistically significant (P < .05). Correlation analysis showed weak positive correlations between seminal fructose and all measured sperm quality parameters. Seminal zinc showed weak negative correlations with sperm count and motility. Citric acid was positively correlated with zinc and weakly negatively correlated with sperm count and motility.

Conclusion: Seminal plasma fructose, zinc, and citric acid concentrations were significantly lower in infertile men than in fertile controls. The findings indicate the potential diagnostic relevance of these biochemical markers. Their assessment alongside conventional semen analysis may provide a more complete evaluation of male infertility.

Neuroprotective Role of S-Allyl-L-Cysteine in Pentylenetetrazol-induced Epileptic Seizure in a Rat Model

2026-07-21T10:25:26+00:00

Epilepsy is a chronic non-communicable brain disease affecting approximately 50 million people of all ages worldwide. Antiepileptic drugs (AEDs) are used to manage epileptic seizures. However, AEDs may fail to control seizure activity in some patients and may cause unwanted effects of varying severity, including impairment of central nervous system (CNS) functions. Oxidative stress and imbalances between the excitatory and inhibitory neurotransmitters glutamate and GABA have been implicated in epileptic seizures, highlighting the need for acceptable treatments with fewer adverse effects. S-allyl-L-cysteine (SAC), a natural antioxidant compound, may help prevent epileptic seizures at lower cost and with fewer adverse effects. This study investigated the neuroprotective role of SAC in pentylenetetrazol (PTZ)-induced epileptic seizures in rats. Sixty male Wistar rats were divided into six groups of 10 animals each. Four groups were pretreated with SAC at 100, 200, or 400 mg/kg or with valproic acid (VPA) at 150 mg/kg before PTZ administration. Hippocampal tissues were harvested, homogenised, and centrifuged, and the supernatants were assayed for MDA, SOD, CAT, GSH, glutamate, and GABA. SAC reduced MDA and increased SOD, CAT, and GSH, indicating attenuation of oxidative stress and enhancement of antioxidant defence. Reduced glutamate and increased GABA concentrations suggest improved neurochemical balance and reduced neuronal hyperexcitability. These combined effects support the neuroprotective action of SAC in PTZ-induced seizures and its potential to limit seizure-associated oxidative and excitotoxic brain damage.

Clinical Response and Safety of Letrozole-based Therapy in Postmenopausal Sudanese Women with Estrogen Receptor-positive/HER2-Negative Breast Cancer: A Retrospective Cohort Study

2026-08-04T06:26:58+00:00

Introduction: Estrogen receptor-positive/HER2-negative breast cancer is the most common molecular subtype of breast cancer. Aromatase inhibitors such as letrozole are part of the standard endocrine treatment regimen for postmenopausal patients; however, real-world evidence on patient outcomes from resource-limited African countries remains sparse. This study assessed the efficacy and safety of letrozole-based treatment regimens in postmenopausal Sudanese patients with ER-positive/HER2-negative breast cancer.

Methods: A retrospective cohort study was conducted among postmenopausal women at Khartoum Oncology Teaching Hospital, Sudan, between March 2018 and March 2020. Eligible participants were postmenopausal women with ER-positive/HER2-negative breast cancer who had received letrozole-based treatment regimens. Four groups were defined: docetaxel + letrozole, docetaxel + letrozole + radiotherapy, letrozole + radiotherapy, and mastectomy + letrozole. Data were collected from medical records, and the outcomes assessed included changes in tumour size, metastasis status, relapse, radiographic findings, and adverse effects. Descriptive and inferential non-parametric statistical analyses were performed using SPSS. Statistical significance was set at p < 0.05.

Results: Forty-six participants with a median age of 58.5 years (45–73) were included. Localised disease was present in 73.9% of participants, and T3 tumours accounted for 71.7%. Docetaxel + letrozole achieved complete tumour clearance in all 11 patients and produced a statistically significant reduction in tumour size (p = 0.001). Letrozole + radiotherapy reduced tumour size by 97.1% (p < 0.001), while mastectomy + letrozole resulted in complete absence of detectable tumour after surgery (p = 0.031). The metastatic multimodal group did not demonstrate statistically significant tumour control (p = 0.063). Overall, 37.0% of participants experienced relapse, predominantly among those with metastatic or T4 disease. Arthralgia was the most common adverse effect (26.1%), followed by hot flushes (23.9%).

Conclusion: Letrozole-based therapy showed favourable tumour responses in postmenopausal Sudanese women with localised hormone receptor-positive/HER2-negative breast cancer, particularly when combined with docetaxel, radiotherapy, or surgery. In contrast, metastatic disease was associated with a poor response and relapse despite combination therapy. Further studies are required to confirm these findings and evaluate survival outcomes.

Effectiveness of Diuretics Compared with Other Antihypertensive Agents in the Control of Hypertension in Black Adults: A Systematic Review

2026-07-16T10:41:27+00:00

Background: Hypertension is highly prevalent among Black adults and contributes substantially to stroke, heart failure, kidney disease, and premature cardiovascular morbidity. Thiazide and thiazide-like diuretics are widely recommended as foundational antihypertensive agents, but their comparative effectiveness against calcium-channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and alpha-blockers remains clinically important.

Objective: To systematically review evidence published from 1 January 2000 to 30 March 2026 on the effectiveness of diuretic-based antihypertensive therapy compared with other antihypertensive agents for blood-pressure control and clinical outcomes in Black adults with hypertension.

Methods: A PRISMA 2020-, PRISMA-S-, and SWiM-aligned systematic review without meta-analysis was conducted as a completed open-source verification search. The search used PubMed/MEDLINE, PubMed Central, Europe PMC, publisher pages, ClinicalTrials.gov-linked records, guideline pages, DOI checks, and citation chasing. Subscription-database export counts were unavailable. Eligible reports were randomized trials, trial subgroup analyses, secondary trial analyses, indirect comparative analyses, and comparative observational studies involving Black adults with hypertension and a diuretic comparator.

Results: The open-source verification search logged 37 records. Seven methodologic or guideline records were separated from clinical screening, leaving 30 clinical candidate records. After screening and eligibility assessment, 10 reports from four evidence families were included: ALLHAT, PEAR/PEAR-2, CREOLE, and a large HCA Healthcare retrospective cohort. ALLHAT provided the strongest evidence that chlorthalidone was at least comparable to amlodipine and more favorable than lisinopril or doxazosin for several cardiovascular outcomes in Black participants. CREOLE showed that amlodipine-containing dual regimens, including amlodipine plus hydrochlorothiazide, lowered blood pressure more effectively than perindopril plus hydrochlorothiazide in Black African adults. PEAR/PEAR-2 suggested favorable hydrochlorothiazide response compared with atenolol for night blood pressure and greater blood-pressure lowering with chlorthalidone than hydrochlorothiazide, although the latter comparison was indirect. Observational evidence suggested lower cardiovascular event likelihood with calcium-channel blockers than with diuretics but was at serious risk of confounding.

Conclusions: Diuretics, particularly chlorthalidone and hydrochlorothiazide-containing regimens, are effective antihypertensive options in Black adults. Evidence most strongly supports thiazide/thiazide-like diuretics over ACE inhibitors, beta-blockers, and alpha-blockers as default initial therapy for uncomplicated hypertension, while calcium-channel blockers are also highly effective and may be particularly useful in combination therapy. Certainty is moderate for major randomized-trial evidence and lower for indirect, post hoc, and observational findings. No pooled estimate was calculated because of clinical, methodological, comparator, and outcome heterogeneity.

Limb-girdle Muscular Dystrophy Type 2I/R9: Future Gene Therapy Options of an Extremely Rare Fukutin Protein-related Dystroglycanopathy

2026-07-16T11:15:03+00:00

Limb-girdle muscular dystrophy type 2I, now designated R9 (LGMD2I/R9), is an autosomal recessive dystroglycanopathy caused by biallelic pathogenic variants in the fukutin-related protein (FKRP) gene. Loss of FKRP glycosyltransferase activity disrupts the ribitol-phosphate-mediated glycosylation of alpha-dystroglycan, reducing matriglycan formation and weakening the link between the sarcolemma and the extracellular matrix. The resulting phenotype ranges from mild, adult-onset limb-girdle weakness to a severe congenital muscular dystrophy, and frequently includes dilated cardiomyopathy and restrictive respiratory failure. No disease-modifying treatment is currently licensed, and management remains supportive. Over the past decade, three broad experimental strategies have moved toward clinical evaluation: adeno-associated virus (AAV)-mediated gene replacement, small-molecule substrate supplementation with ribitol, and combinatorial approaches that pair gene replacement with muscle-anabolic transgenes such as follistatin. Registered early-phase AAV-FKRP programmes and the placebo-controlled FORTIFY trial of oral ribitol provide important translational context, but peer-reviewed clinical efficacy and long-term safety data remain limited; interim registry, conference and sponsor-reported findings should therefore be interpreted cautiously. This narrative review synthesises the molecular pathophysiology of FKRP-related dystroglycanopathy, appraises the natural history and outcome measures relevant to trial design, and critically evaluates the preclinical and early clinical evidence for gene-based and substrate-based therapies. It concludes with a discussion of unresolved translational barriers and a forward-looking assessment of the therapeutic pipeline for this ultra-rare neuromuscular disorder.

From Harmonisation to Practice: A Critical Appraisal of the Global Implementation of ICH M10 for Bioanalytical Method Validation and Study Sample Analysis

2026-08-01T09:45:33+00:00

Concentration measurements of drugs and their metabolites in biological matrices underpin regulatory decisions on safety, efficacy and labelling, and the technical requirements governing those measurements were, for three decades, set regionally. Guideline M10 of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, adopted at Step 4 in May 2022, replaced the principal regional texts with a single harmonised standard covering chromatographic and ligand binding assays for chemical and biological drugs. Four years of implementation experience now exist, yet the literature describing that experience has not been critically synthesised. This review appraises what harmonisation of the written standard has and has not achieved in practice. Adoption across regulatory authorities was staggered rather than simultaneous, and a substantial regulatory population remains outside the harmonised text. Convergence is asserted mainly through workshop reports, closed industry forums and annual white papers, with almost no primary quantitative evidence comparing regulatory outcomes before and after adoption. Four fault lines recur: cross-validation is mandated without an acceptance criterion; incurred sample reanalysis retains a fixed sampling burden whose diagnostic yield appears low; provisions for endogenous analytes and surrogate matrices have required substantial post hoc elaboration by professional bodies; and partial validation and method transfer remain under-specified for multi-site programmes. The exclusion of biomarkers and immunogenicity assays has produced a harmonisation paradox in which a guideline that disclaims these applications is nonetheless directed as their validation template in at least one region. The uniform criterion architecture, largely inherited rather than re-derived, is increasingly challenged by proposals for context-of-use-driven validation. The evidence base is concentrated in a small number of overlapping author networks and geographical regions, is predominantly consensus-based, and provides weak support for strong claims in either direction. Priorities for research include regulator-side outcome data, statistically justified acceptance criteria, and prospective evaluation of context-of-use frameworks.