Gonadotropin independent sexual precocity in a Pakistani male infant from an activating mutation in LHCGR gene.

A male child, aged seven months, visited the out patients clinic of the National Institute of Child Health, Karachi, in May 2020 with the features of iso-sexual puberty. After ruling out the more common causes of early puberty, like congenital adrenal hyperplasia and tumours secreting chorionic gonadotropin hormone, hormonal assessment indicated raised testosterone independent of gonadotropin. The volume of the testicles was symmetric and testicular ultrasonography revealed no mass. Genetic analysis for the LHCGR gene was performed for confirmation which revealed activating heterozygous missense pathogenic mutation in c.1732G>T (p.Asp578Tyr). This is the first reported case of testotoxicosis (FMPP) from Pakistan which was genetically confirmed.

Psychometric evaluation of Urdu-translated Amsterdam preoperative anxiety and information scale and assessment of preoperative anxiety in adult surgical patients of Karachi, Pakistan: A cross-sectional study.

Objective: The primary aim of this study was to develop an Urdu-translated version of the Amsterdam preoperative anxiety and information scale and perform a psychometric evaluation of it. A secondary aim was to estimate the prevalence of preoperative anxiety using Urdu-translated Amsterdam preoperative anxiety and information scale in patients undergoing surgery in Karachi, Pakistan, and the factors contributing to anxiety among them. Method: This cross-sectional survey included 267 patients enrolled for elective surgery under general anesthesia from March 5 to November 20, 2022. In psychometric analysis, face validity, criterion validity, construct validity, and reliability of Urdu-translated Amsterdam preoperative anxiety and information scale were determined. Face validity was evaluated by performing blind-back translation and a pilot study. Criterion validity was evaluated by correlating the Amsterdam preoperative anxiety and information scale with the visual analog scale for anxiety. Exploratory factor analysis and Cronbach's α test were used to analyze construct validity and reliability, respectively. The associate variables were identified by performing a one-sample t-test and one-way analysis of variance on SPSS 26. Results: Cronbach's α test is 0.85 for the Amsterdam preoperative anxiety and information scale anxiety scale and 0.70 for the need for information. 65.3% of the total variance is explained by the Urdu version of Amsterdam preoperative anxiety and information scale items in factor analysis and the intercorrelation of all items was >0.20 (mean: 0.575). Urdu-translated Amsterdam preoperative anxiety and information scale and visual analog scale for anxiety showed a good correlation (r = 0.664, p < 0.001). The overall prevalence of preoperative anxiety among patients is 52.4% suggested by the Amsterdam preoperative anxiety and information scale cutoff score of more than 11. Females, students, and patients elected for major surgery shared significantly higher anxiety levels (p < 0.05). The commonest factors contributing to anxiety are postoperative pain in 140 (52.4%) patients, fear of death in 115 (43.1%), and financial loss in 91 (34.1%). Conclusions: The Urdu-translated Amsterdam preoperative anxiety and information scale is a reliable, valid, and acceptable screening tool for preoperative anxiety. The prevalence of preoperative anxiety was high. The preoperative anxiety level is significantly associated with gender, employment status, and type of surgery.

Isolated Primary Hydatid Disease Of The Breast.

Our study is relevant because our report adds further light on diagnosing and treating the isolated primary hydatid cyst disease of the breast. The purpose of this case report is to educate physicians and health care workers to keep this condition in the differential diagnosis of the breast lump even though the breast is a rare site of primary hydatid disease even in the endemic areas. Awareness of this entity can help in arriving at a pre-operative diagnosis, even without cytological examination, which is important in the management of the cyst. This is the first of its kind case being reported from Pakistan.

Gastric volvulus and wandering spleen; a life-threatening surgical emergency.

Wandering spleen and gastric volvulus are two of the rarely encountered conditions occurring together with or without other congenital and acquired defects. These potentially fatal conditions originate from a shared cause, i.e. the defect of intraperitoneal ligaments resulting in a failure to withhold these organs at their anatomical position and alignment. This can come to attention in both childhood and/or adulthood, and the diagnosis calls for a high degree of suspicion and a failure to diagnose can culminate in death of both the organs, i.e. the spleen and stomach. We are presenting the case of a 20-year-old girl who underwent an emergency laparotomy for gastric volvulus and wandering spleen.

Evaluation of the preclinical analgesic efficacy of naturally derived, orally administered oil forms of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their 1:1 combination.

Chronic neuropathic pain (NP) is a growing clinical problem for which effective treatments, aside from non-steroidal anti-inflammatory drugs and opioids, are lacking. Cannabinoids are emerging as potentially promising agents to manage neuroimmune effects associated with nociception. In particular, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination are being considered as therapeutic alternatives for treatment of NP. This study aimed to examine whether sex affects long-term outcomes on persistent mechanical hypersensitivity 7 weeks after ceasing cannabinoid administration. Clinically relevant low doses of THC, CBD, and a 1:1 combination of THC:CBD extracts, in medium chain triglyceride (MCT) oil, were orally gavaged for 14 consecutive days to age-matched groups of male and female sexually mature Sprague Dawley rats. Treatments commenced one day after surgically inducing a pro-nociceptive state using a peripheral sciatic nerve cuff. The analgesic efficacy of each phytocannabinoid was assessed relative to MCT oil using hind paw mechanical behavioural testing once a week for 9 weeks. In vivo intracellular electrophysiology was recorded at endpoint to characterize soma threshold changes in primary afferent sensory neurons within dorsal root ganglia (DRG) innervated by the affected sciatic nerve. The thymus, spleen, and DRG were collected post-sacrifice and analyzed for long-term effects on markers associated with T lymphocytes at the RNA level using qPCR. Administration of cannabinoids, particularly the 1:1 combination of THC, elicited a sustained mechanical anti-hypersensitive effect in males with persistent peripheral NP, which corresponded to beneficial changes in myelinated Aß mechanoreceptive fibers. Specific immune cell markers associated with T cell differentiation and pro-inflammatory cytokines, previously implicated in repair processes, were differentially up-regulated by cannabinoids in males treated with cannabinoids, but not in females, warranting further investigation into sexual dimorphisms that may underlie treatment outcomes.

An evaluation of the anti-hyperalgesic effects of cannabidiolic acid-methyl ester in a preclinical model of peripheral neuropathic pain.

BACKGROUND AND PURPOSE: Chronic neuropathic pain (NEP) is associated with growing therapeutic cannabis use. To promote quality of life without psychotropic effects, cannabinoids other than Δ9-tetrahydrocannabidiol, including cannabidiol and its precursor cannabidiolic acid (CBDA), are being evaluated. Due to its instability, CBDA has been understudied, particularly as an anti-nociceptive agent. Adding a methyl ester group (CBDA-ME) significantly enhances its stability, facilitating analyses of its analgesic effects in vivo. This study examines early treatment efficacy of CBDA-ME in a rat model of peripherally induced NEP and evaluates sex as a biological variable. EXPERIMENTAL APPROACH: After 14 consecutive days of intraperitoneal CBDA-ME administration at 0.01, 0.1 and 1 µg·kg-1 , commencing 1 day after surgically implanting a sciatic nerve-constricting cuff to induce NEP, the anti-nociceptive efficacy of this cannabinoid was assessed in male and female Sprague-Dawley rats relative to vehicle-treated counterparts. In females, 2 and 4 µg·kg-1 daily doses of CBDA-ME were also evaluated. Behavioural tests were performed for hind paw mechanical and thermal withdrawal thresholds once a week for 8 weeks. At endpoint, in vivo electrophysiological recordings were obtained to characterize soma threshold changes in primary sensory neurons. KEY RESULTS: In males, CBDA-ME elicited a significant concentration-dependent chronic anti-hyperalgesic effect, also influencing both nociceptive and non-nociceptive mechanoreceptors, which were not observed in females at any of the concentrations tested. CONCLUSION AND IMPLICATIONS: Initiating treatment of a peripheral nerve injury with CBDA-ME at an early stage post-surgery provides anti-nociception in males, warranting further investigation into potential sexual dimorphisms underlying this response.