Suction rectal biopsy (SRB) in Hirschsprung's Disease: Is a single macroscopically adequate sample sufficient?

Hirschsprung's Disease (HD) is a congenital disorder causing severe constipation in infants and children. Suction rectal biopsy (SRB) is the preferred technique for obtaining tissue samples for histopathological evaluation. In low-resource settings like Malaysia, cost-effective diagnostic approaches are necessary, making single sample SRB valuable. This study evaluates the diagnostic accuracy and sufficiency of a single macroscopically adequate sample in suction rectal biopsies for the histopathological confirmation of HD. We conducted a retrospective study of children who underwent suction rectal biopsies for the diagnosis of HD at Hospital Raja Perempuan Zainab II (HRPZII), Kota Bharu, Kelantan. A total of 68 patients were included in the study. The inadequacy rate for bedside SRB was 14%, comparable to current literature. Our study found no statistically significant association between sample inadequacy and gestational age, gender, birth weight, or weight at biopsy. Complication rates were 0%, consistent with literature reports. Calretinin staining, an additional technique, was performed in 23 biopsy episodes, with a 4.3% inadequacy rate, compared to 20% in specimens not subjected to calretinin staining. The cost of SRB almost doubled with each additional sample taken, significant in low-resource environments. In conclusion, single sample SRBs can be adequately diagnostic and cost-effective in low-resource settings, providing valuable insights for healthcare facilities in Malaysia and other developing countries. The use of adjunctive techniques such as calretinin staining may improve diagnostic accuracy while maintaining cost-effectiveness. Further prospective studies with larger sample sizes are needed to validate these findings.

Paediatric surgical response to an 'adult' COVID-19 pandemic.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) has dramatically affected global healthcare systems. We aimed to determine the response of our paediatric surgical fraternity to a disease that overwhelmingly affects adults. MATERIALS AND METHODS: We conducted a cross-sectional questionnaire-based study over 6 weeks during a federally mandated lockdown. Using snowball sampling, we recruited paediatric surgeons, trainees and medical officers from paediatric surgical units in Malaysia. The anonymous online questionnaire covered sociodemographic information, changes in patient care, redeployment, concerns regarding family members, and impact on training. Mental well-being was assessed using the Depression, Anxiety and Stress Scale (DASS-21). Kruskal-Wallis, ANOVA and multiple regression analysis was used, with significance level 0.05. RESULTS: Of the 129 eligible participants, 100(77%) responded. Junior doctors had clinically higher levels of depression, anxiety, and stress. Age <30 years was significantly associated with anxiety. Junior doctors believed that redeployment led to loss of surgical skills (p<0.001) and trainees felt that clinical application of knowledge had reduced (p<0.020). CONCLUSION: Specific to our paediatric surgical community, this study highlights areas of concern, particularly among junior doctors. It is likely that recurrent cycles of the pandemic will occur soon. These issues must be addressed to preserve the mental and emotional well-being of all health care workers.

Transient Sub-bandgap States in Halide Perovskite Thin Films.

Metal halide perovskites are promising solar energy materials, but their mechanism of action remains poorly understood. It has been conjectured that energetically stabilized states such as those corresponding to polarons, quasiparticles in which the carriers are dressed with phonons, are responsible for their remarkable photophysical properties. Yet, no direct evidence of polarons or other low-energy states have been reported despite extensive efforts. Such states should manifest as below bandgap features in transient absorption and photoluminescence measurements. Here, we use single-particle transient absorption microscopy on MAPbI3 (MA = methylammonium) to unambiguously identify spectrally narrow sub-bandgap states directly; we demonstrate that such signals are completely averaged away in ensemble measurements. Carrier temperature-dependent studies suggest that hot carriers are directed toward transient low-energy states which are immune from permanent defects and traps, thereby giving rise to low carrier recombination rates and ultimately high power conversion efficiency in devices. The utilization of short-lived sub-bandgap states may be a key design principle that propels widespread use of highly heterogeneous materials in optoelectronic applications.

Double-blind randomized clinical trial of percutaneous endoscopic gastrostomy versus radiologically inserted gastrostomy in children.

BACKGROUND: The aim of this RCT was to determine whether radiologically inserted gastrostomy (RIG) in children is associated with more complications than percutaneous endoscopic gastrostomy (PEG). METHODS: Children at a single tertiary children's hospital requiring a primary gastrostomy were randomized to PEG or RIG. Patients were followed by assessors blinded to the insertion method. Complications were recorded, assigned a severity score, and analysed by zero-inflated Poisson regression analysis on an intention-to-treat basis, adjusting for length of follow-up. RESULTS: Over a 3-year period, 214 children were randomized (PEG, 107; RIG, 107), of whom 100 received PEG and 96 RIG. There was no significant difference in the number of complications between PEG and RIG groups (P = 0·875), or in the complication score: patients undergoing RIG had a 1·04 (95 per cent c.i. 0·89 to 1·21) times higher complication score than those who underwent PEG (P = 0·597). Only age had an independent significant effect on complication score, with older patients having a 0·97 (0·95 to 1·00) times lower complication score per year. CONCLUSION: PEG and RIG are both safe methods of gastrostomy insertion with a low rate of major complications. Registration number: NCT01920438 ( http://www.clinicaltrials.gov).

Identifying fibromyalgia subgroups using cluster analysis: Relationships with clinical variables.

BACKGROUND: Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns. METHODS: A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K-means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventor and Social Support Scale. RESULTS: Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome. CONCLUSIONS: We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms. SIGNIFICANCE: FM patients can be clustered into four distinct subgroups based on clinically measurable variables - pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.

Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case-control study.

BACKGROUND: Although polymorphisms of the catechol-O-methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single-nucleotide polymorphisms (SNP) and FM risk and symptom severity. METHODS: In total, 409 FM patients and 423 controls were enrolled. Alleles and genotypes at five positions [rs6269 (A>G), rs4633 (C>T), rs4818 (C>G), rs4680 (C>G) and rs165599 (A>G)] in the COMT gene were genotyped from peripheral blood DNA. RESULTS: Alleles and genotypes of the rs4818 COMT gene polymorphism were significantly associated with increased susceptibility to FM. The rs4818 GG genotype was more strongly associated with FM compared to the CC genotype (OR = 1.680, 95% CI: 1.057, 2.672, p = 0.027). Although allele and genotype frequencies did not differ among groups, the rs4633 CT genotype was not associated with the presence of FM following adjustment for age and sex (OR = 0.745; 95% CI: 0.558, 0.995; p = 0.046). However, no association was observed between clinical measures and individual COMT SNPs. In haplotype analysis, there was a significant association between ACG haplotype and FM susceptibility sex (OR = 2.960, 95% CI: 1.447, 6.056, p = 0.003) and the number of tender points (p = 0.046). CONCLUSIONS: This large-scale study suggests that polymorphisms of the COMT gene may be associated with FM risk and pain sensitivity in Korean FM patients. However, our results differed to those of previous studies, suggesting ethnic variation in COMT gene polymorphisms in FM. WHAT DOES THIS STUDY ADD: By contrast to Caucasian and Latin-American populations, the COMT gene polymorphisms are associated with FM risk and pain sensitivity in Korean FM patients, suggesting ethnic variation in COMT gene polymorphisms.

The effects of fasting in Muslim patients taking warfarin.

BACKGROUND: Anticoagulation with warfarin is influenced by dietary changes but the effect of fasting on warfarin therapy is unknown. OBJECTIVES: To study changes in international normalized ratio (INR) and the percentage of time within therapeutic range (%TTR) before, during and after the Muslim fasting month (Ramadan) in stable warfarinised Muslim patients. METHODS/PATIENTS: In this prospective study, weekly INR readings were taken at home visits from participating patients during three study periods: before, during and after Ramadan. Readings were blinded to patients and their primary physicians except for when pre-set study endpoints were reached. RESULTS: Among 32 participating patients, mean INR increased by 0.23 (P = 0.006) during Ramadan from the pre-Ramadan month and decreased by 0.28 (P < 0.001) after Ramadan. There was no significant difference (P = 1.000) in mean INR between the non-Ramadan months. %TTR declined from 80.99% before Ramadan to 69.56% during Ramadan (P = 0.453). The first out-of-range INR was seen around 12.1 days (95% CI, 9.0-15.1) after the start of fasting and returned to range at about 10.8 days (95% CI, 7.9-13.7) after Ramadan. Time above range increased from 10.80% pre-Ramadan to 29.87% during Ramadan (P = 0.027), while time below range increased from 0.57% during Ramadan to 15.49% post-Ramadan (P = 0.006). No bleeding or thrombotic events were recorded. CONCLUSIONS: Fasting significantly increases the mean INR of medically stable patients taking warfarin and the likelihood of having an INR above therapeutic targets. For patients maintained at the higher end of INR target ranges or at increased risk of bleeding, closer monitoring or dosage adjustment may be necessary during fasting.

Molecular mechanisms of large-conductance ca (2+) -activated potassium channel activation by ginseng gintonin.

Gintonin is a unique lysophosphatidic acid (LPA) receptor ligand found in Panax ginseng. Gintonin induces transient [Ca(2+)]i through G protein-coupled LPA receptors. Large-conductance Ca(2+)-activated K(+) (BKCa) channels are expressed in blood vessels and neurons and play important roles in blood vessel relaxation and attenuation of neuronal excitability. BKCa channels are activated by transient [Ca(2+)]i and are regulated by various Ca(2+)-dependent kinases. We investigated the molecular mechanisms of BKCa channel activation by gintonin. BKCa channels are heterologously expressed in Xenopus oocytes. Gintonin treatment induced BKCa channel activation in oocytes expressing the BKCa channel α subunit in a concentration-dependent manner (EC50 = 0.71 ± 0.08 µg/mL). Gintonin-mediated BKCa channel activation was blocked by a PKC inhibitor, calphostin, and by the calmodulin inhibitor, calmidazolium. Site-directed mutations in BKCa channels targeting CaM kinase II or PKC phosphorylation sites but not PKA phosphorylation sites attenuated gintonin action. Mutations in the Ca(2+) bowl and the regulator of K(+) conductance (RCK) site also blocked gintonin action. These results indicate that gintonin-mediated BKCa channel activations are achieved through LPA1 receptor-phospholipase C-IP3-Ca(2+)-PKC-calmodulin-CaM kinase II pathways and calcium binding to the Ca(2+) bowl and RCK domain. Gintonin could be a novel contributor against blood vessel constriction and over-excitation of neurons.

Surgical repair of incarcerated inguinal hernia in children: laparoscopic or open?

PURPOSE: The management of Incarcerated Inguinal Hernia (IIH) in children is challenging and may be associated with complications. We aimed to compare the outcomes of laparoscopic vs. open repair of IIH. METHODS: With institutional ethical approval (09SG13), we reviewed the notes of 63 consecutive children who were admitted to a single hospital with the diagnosis of IIH between 2000 and 2008. Data are reported as median (range). Groups were compared by chi-squared or t-tests as appropriate. RESULTS: · Open repair (n=35): There were 21 children with right and 14 with left IIH. 2 patients also had contralateral reducible inguinal hernia. Small bowel resection was required in 2 children. · Laparoscopic repair (n=28): All children had unilateral IIH (19 right sided, 9 left sided). 15 children (54%) with no clinical evidence of contralateral hernia, had contralateral patent processus vaginalis at laparoscopy, which was also repaired. The groups were similar with regard to gender, age at surgery, history of prematurity, interval between admission and surgery, and proportion of patients with successful preoperative manual reduction. However, the duration of operation was longer in the laparoscopy group (p=0.01). Time to full feeds and length of hospital stay were similar in both groups. Postoperative follow-up was 3.5 months (1-36), which was similar in both groups. 5 patients in the group undergoing open repair had serious complications: 1 vas transaction, 1 acquired undescended testis, 2 testicular atrophy and 1 recurrence. The laparoscopic group had a single recurrence. CONCLUSION: Open repair of incarcerated inguinal hernia is associated with serious complications. The laparoscopic technique appears safe, avoids the difficult dissection of an oedematous sac in the groin, allows inspection of the reduced hernia content and permits the repair of a contralateral patent processus vaginalis if present.

Serum cholesterol in idiopathic and lupus-related protein-losing enteropathy.

Abstract The characteristics of protein-losing enteropathy were evaluated in patients with systemic lupus erythematosus. Among the patients with systemic lupus erythematosus (n=380) in a tertiary hospital, we reviewed the records of seven patients with generalized edema, hypoalbuminemia without proteinuria and positive results on 99mTc-labelled human serum albumin scintigrams. Patient characteristics and laboratory findings were compared between these seven patients and patients with lupus enteritis (n=15) or idiopathic protein-losing enteropathy (n=11). Compared with the lupus enteritis patients, the erythrocyte sedimentation rate and serum total cholesterol levels were significantly increased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Compared with idiopathic protein-losing enteropathy patients, the level of serum total cholesterol was significantly increased, but the level of serum albumin was decreased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Among patients with systemic lupus erythematosus-related protein-losing enteropathy, four patients had high serum total cholesterol levels (>or=248 mg/dL) and achieved complete remission after receiving high doses of steroid treatment. However, three patients who had low serum total cholesterol levels (

Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes.

OBJECTIVE: Advanced glycation end products (AGE) accumulate in articular cartilage with age. We investigated the effects of AGE in primary-cultured human OA chondrocytes. METHODS: Chondrocytes were cultured with/or without AGE-bovine serum albumin (AGE-BSA) and the expression levels of inducible nitric oxide (iNOS), cyclooxygenase (COX)-2 microsomal prostaglandin E synthase-1 (mPGES-1) were evaluated using RT-PCR and western blot analysis. Prostaglandin E(2) (PGE(2)) was analysed by ELISA and nitric oxide (NO) was analysed by Griess reaction assay. Pharmacological studies to elucidate the involved pathway were executed using specific inhibitors of MAPK and receptor for AGE (RAGE). RESULTS: We found that treatment of OA chondrocytes with AGE-BSA increased COX-2, mPGES-1 and iNOS mRNA and protein, as well as elevating production of PGE(2) and NO. Pre-treatment with the MAPK inhibitors SP600125 (JNK inhibitor), SB202190 (p38 inhibitor) or PD98059 (ERK inhibitor) significantly inhibited AGE-BSA induction of COX-2 expression and production of PGE(2). In contrast, SN50, a nuclear factor-kappaB (NF-kappaB) inhibitor, had no effect on levels of COX-2 and PGE(2). SB202190 and SN50, but not SP600125 and PD98059, decreased AGE-BSA-induced production of NO. Pre-treatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated COX-2, iNOS and PGE(2), implicating the involvement of RAGE. CONCLUSIONS: These results show that AGE may augment inflammatory responses in OA chondrocytes by increasing PGE(2) and NO levels, possibly via the MAPK pathway for PGE(2) and the NF-kappaB pathway for NO.

Association of TIMP-4 gene polymorphism with the risk of osteoarthritis in the Korean population.

Due to an imbalance in the MMP:TIMP ratio determined a tissue damage in arthritis, it is hypothesized that polymorphic variations of the TIMP genes are associated with regulation of the MMP:TIMP balance. To test this hypothesis, the presence of single nucleotide polymorphisms (SNPs) located in the human TIMP-2 and TIMP-4 genes was confirmed in the Korean RA and OA patients. We performed a case-control study comprising 109 unrelated Korean OA patients, 177 unrelated Korean RA patients and 175 healthy subjects. There were statistically significant differences in the genotype distribution and allele frequencies of the C/T polymorphism of TIMP-4 gene between OA and control groups (P = 0.0002 and P = 0.001, respectively). However, no significant association between TIMP-2 polymorphisms and OA was observed. Also, no difference was observed when allele or genotype frequencies of both TIMP-2 and TIMP-4 gene polymorphisms were compared between RA and controls. We demonstrated that the C/T polymorphism which is located on the 3'-untranslational regions of the TIMP-4 gene might be associated with susceptibility to OA patients.

The difference between lupus nephritis class IV-G and IV-S in Koreans: focus on the response to cyclophosphamide induction treatment.

OBJECTIVES: To evaluate the response to induction therapy with intravenous (i.v.) cyclophosphamide (CYC) in Korean patients with class IV-G (diffuse global proliferative glomerulonephritis) and class IV-S (diffuse segmental proliferative glomerulonephritis) lupus nephritis (LN) according to the classification system of the International Society of Nephrology/Renal Pathology Society (ISN/RPS). METHODS: Of the 52 patients with biopsy-proven diffuse proliferative LN, who had been treated with i.v. CYC over a 10-yr period, 42 had been treated with i.v. CYC (equal to or more than 500 mg) for 6 consecutive months and had biopsy specimens containing more than nine glomeruli. The renal pathology of these 42 patients was reclassified according to the International Society of Nephrology and the Renal Pathology Society 2003 classification, and their renal response rates and laboratory indices after induction therapy were analysed. RESULTS: Of the 42 patients assessed, 30 (71%) had IV-G and 12 (29%) had IV-S. Pre-treatment 24 h urinary protein was significantly higher and pre-treatment concentration of anti-dsDNA antibody was significantly lower in IV-G than in IV-S patients. Following induction therapy, complete remission rates were significantly higher in patients with IV-S (67%, 8/12) than in patients with IV-G (33%, 10/30) LN. CONCLUSIONS: Class IV-G LN responded more poorly to induction therapy with i.v. CYC pulse than class IV-S LN.

Characterization of a new HLA-DRB1*1405 variant, HLA-DRB1*140503, identified by sequence-based typing.

A new human leukocyte antigen-DRB1*140503 differs from DRB1*140501 with T to C transition at codon 78 (TAT-->TAC) of exon 2 without coding change.

Identification of a novel HLA-A*26 allele, HLA-A*2632, by sequence-based typing in the Korean population.

HLA-A*2632 shows three nucleotides difference with HLA-A*260101 and HLA-A*2624 in exon 3 at codon 95 (ATC--> ATG) and codon 97 (AGG --> GTG), resulting in two amino acids change from Ile to Met (I95M) and Arg to Val (R97V).

HLA-A*2634, a new allele identified by sequence-based typing in the Korean population.

A new HLA-A*2634 allele differs from A*260101 by a change from C to T at the nucleotide 559 of exon 3, with a coding change R163W.

Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice.

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-D-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D(1) and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.