The Vascular Basis of the Pronator Quadratus Muscle Flap and Its Use in Clinical Cases.

Background Pronator quadratus (PQ) is a deeply situated muscle in the forearm which may occasionally be utilized for soft-tissue reconstruction. The purpose of this anatomical and clinical study was to confirm vascular supply of PQ muscle (PQM) in order to optimize its transfer and confirm its utility in clinical situations. Methods In Part A of the anatomical study, fresh human cadavers ( n = 7) were prepared with an intra-arterial injection of lead oxide and gelatin solution, and PQM and neurovascular pedicle were dissected ( n = 14). In the anatomical study Part B, isolated limbs of embalmed human cadavers ( n = 12) were injected with India ink-gelatin mixture and PQ were dissected. Results PQ is a type II muscle flap, with one major pedicle, the anterior interosseous (AI) vessels and two minor pedicles from the radial and ulnar vessels. The mean dimensions of the muscle were 5.5 × 5.0 × 1.0 cm 3 , mean pedicle length was 9.6 cm, and the mean diameter of the artery and the vein was 2.3 mm and 2.8 mm, respectively. The dorsal cutaneous perforating branch (DPB) of the artery supplied the skin over the dorsal forearm and wrist. This branch also anastomosed with the 1, 2 intercompartmental supraretinacular artery (ICSRA). Conclusion This study confirms the potential utility and vascular basis of the PQM flap and its associated cutaneous paddle. In the clinical part, two patients with nonhealing wounds exposing the median nerve and flexor tendons in the distal forearm were treated using the PQM flap with good results.

Pharmacokinetic and pharmacogenomic modelling of the CYP3A activity marker 4ß-hydroxycholesterol during efavirenz treatment and efavirenz/rifampicin co-treatment.

OBJECTIVES: To assess the effect of the major efavirenz metabolizing enzyme (CYP2B6) genotype and the effects of rifampicin co-treatment on induction of CYP3A by efavirenz. PATIENTS AND METHODS: Two study arms (arm 1, n = 41 and arm 2, n = 21) were recruited into this study. In arm 1, cholesterol and 4ß-hydroxycholesterol were measured in HIV treatment-naive patients at baseline and then at 4 and 16 weeks after initiation of efavirenz-based antiretroviral therapy. In arm 2, cholesterol and 4ß-hydroxycholesterol were measured among patients taking efavirenz during rifampicin-based tuberculosis (TB) treatment (efavirenz/rifampicin) just before completion of TB treatment and then serially following completion of TB treatment (efavirenz alone). Non-linear mixed-effect modelling was performed. RESULTS: A one-compartment, enzyme turnover model described 4ß-hydroxycholesterol kinetics adequately. Efavirenz treatment in arm 1 resulted in 1.74 (relative standard error = 15%), 3.3 (relative standard error = 33.1%) and 4.0 (relative standard error = 37.1%) average fold induction of CYP3A for extensive (CYP2B6*1/*1), intermediate (CYP2B6*1/*6) and slow (CYP2B6*6/*6) efavirenz metabolizers, respectively. The rate constant of 4ß-hydroxycholesterol formation [mean (95% CI)] just before completion of TB treatment [efavirenz/rifampicin co-treatment, 7.40 × 10(-7) h(-1) (5.5 × 10(-7)-1.0 × 10(-6))] was significantly higher than that calculated 8 weeks after completion [efavirenz alone, 4.50 × 10(-7) h(-1) (4.40 × 10(-7)-4.52 × 10(-7))]. The CYP3A induction dropped to 62% of its maximum by week 8 of completion. CONCLUSIONS: Our results indicate that efavirenz induction of CYP3A is influenced by CYP2B6 genetic polymorphisms and that efavirenz/rifampicin co-treatment results in higher induction than efavirenz alone.

Outcomes Following Excision of Toe Glomus Tumors.

BACKGROUND: Glomus tumors are uncommon tumors and their occurrence in the foot is even less common. Glomus tumors of the toes are often missed, causing delays in diagnosis and treatment. We report an ambispective observational study of glomus tumors of the toes that were treated at our institution. METHODS: We reviewed the records of all the patients who underwent excision of toe glomus tumors in our department from January 2010 to September 2022. The follow-up data were collected from the outpatient records and by telephonic interview. Single Assessment Numeric Evaluation (SANE) score, Foot and Ankle Outcome Score (FAOS), and the Foot Function Index (FFI) were collected. RESULTS: Out of all the patients treated for glomus tumors, we found that 7 patients had glomus tumors of the toes. Of the 7 patients, 6 were women and 1 was a male. The mean follow-up of our patients was 66.4 months (range, 7-109 months). Of the 7 patients, 1 presented with recurrent glomus tumor 30 months following the primary operation, for which she underwent excision again, after which she was symptom free. Another patient who developed recurrent symptoms on telephonic interview refused any further treatment. Among the 6 patients who were symptom-free at follow-up (including the patient who underwent excision for the recurrent tumor), the median SANE score, and FFI were 99.5 (IQR, 96-100) and 0.5 (IQR, 0-2) respectively. The mean FAOS was 96 (SD, 3.3). CONCLUSION: Surgical excision of the subungual toe glomus tumors can be curative. Recurrence of toe glomus tumors was noted in 2 patients (29%), one of whom refused further surgery. Re-excision in the other patient resulted in complete resolution of symptoms. LEVEL OF EVIDENCE: Level III, ambispective observational study.

Nonvascularized Double Metatarsal Transfer After Excision of Epithelioid Hemangioma of Hand: A Case Report.

CASE: Epithelioid hemangioma (EH) is an uncommon, benign, locally aggressive neoplasm, and it may present as multifocal lytic lesions with soft tissue involvement in the hand. We report the midterm follow-up of a patient with recurrent EH of the hand that was reconstructed successfully, with a nonvascularized double metatarsal transfer, after tumor excision. To the best of the authors' knowledge, this is the first case report where a nonvascularized double metatarsal transfer has been used successfully after tumor resection. CONCLUSION: Osteoarticular replacement with matched metatarsal transfer after en bloc resection may be used successfully for reconstruction, after the resection of EH involving the metacarpal.

Characterisation of metabolic acidosis in Kenyan children admitted to hospital for acute non-surgical conditions.

Metabolic acidosis is associated with most severe malaria deaths in African children, and most deaths occur before maximum antimalarial action is achieved. Thus, specific acidosis treatment may reduce mortality. However, the underlying mechanisms remain poorly understood and no specific interventions have been developed. A detailed characterisation of this acidosis is critical in treatment development. We used the traditional and Stewart's approach to characterise acidosis in consecutive paediatric admissions for malaria and other acute non-surgical conditions to Kilifi District Hospital in Kenya. The overall acidosis prevalence was 21%. Gastroenteritis had the highest prevalence (61%). Both the mean albumin-corrected anion gap and the strong ion gap were high (>13 mmol/l and >0 mmol/l, respectively) in malaria, gastroenteritis, lower respiratory tract infection and malnutrition. Presence of salicylate in plasma was not associated with acidosis but was associated with signs of severe illness (odds ratio 2.11, 95% CI 1.1-4.2). In malaria, mean (95% CI) strong ion gap was 15 (14-7) mmol/l, and lactate, creatinine and inorganic phosphorous explained only approximately 40% of the variability in base excess (adjusted R2 = 0.397). Acidosis may be more common than previously recognised amongst paediatric admissions in Africa and is characterised by the presence of currently unidentified strong anions. In malaria, lactate and ketones, but not salicylate, are associated with acidosis. However, unidentified anions may be more important.

Acute Traumatic Musculotendinous Avulsion of the Flexor Pollicis Longus Tendon Treated with Primary Flexor Digitorum Superficialis Transfer: A Novel Technique of Management.

Traumatic musculotendinous junction avulsions are rare injuries except in avulsion amputations. They pose a significant challenge to the treating surgeon. We present a 24-year-old male who sustained an open musculotendinous avulsion of the flexor pollicis longus tendon. He was treated with primary tendon transfer using the flexor digitorum superficialis of ring finger, in flexor zone 3. The functional result at 10 months following surgery was excellent.

Salicylate poisoning in children: report of three cases.

To raise clinicians' awareness of chronic (therapeutic) salicylate poisoning as a common cause of admission in paediatric patients presenting to hospital with respiratory distress (a clinical manifestation of metabolic acidosis) and a history of 'over the counter' treatment with salicylate (Aspirin). We present two complex cases and provide a review of the literature on pathogenesis, clinical presentation and management of salicylate poisoning. A complete history of the illness, including questions on drug use, is vital in assessing the cause of metabolic acidosis in children. Due to the limited options available in managing such patients in many developing countries, emphasis should be placed on prevention of poisoning by educating the community and health care providers.

Colorimetric determination of piperazine.

A sensitive method for the quantitative determination of piperazine is described. The method is precise and responds linearly from 25 g to 500 mug and above of the material. The procedure is based on the formation of a complex of piperazine with reineckate in neutral or acid medium. The complex can be separated by centrifugation. It is then dissolved in acetone and estimated at 530 nm in a colorimeter. Piperazine present in trichloroacetic acid extractrs of biological samples can also be estimated by this method.

Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model.

Tuberculosis (TB) is highly endemic in India. The first-line anti-TB therapy (ATT) involving isoniazid (INH), rifampicin and pyrazinamide causes hepatotoxicity in approximately 11.5% of Indian patients. Studies have shown that ATT-induced hepatotoxicity is primarily due to oxidative stress caused by the drugs and metabolites. Herbal drugs with antioxidative properties have been tested in animal studies and clinical trials for the management of hepatotoxicity. The objective of this study was to investigate the role of curcumin (CUR), silymarin (SILY) and N-acetylcysteine (N-ACET) on hepatotoxicity by ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). HepG2 cells were treated with ATT drugs alone or along with CUR, SILY or N-ACET for a 48-h duration. The cells were monitored for viability, morphology, respiring mitochondria and cell cycle. Our results suggest that the presence of hepatoprotective drugs during treatment of HepG2 cells with ATT drugs lowers the hepatotoxic effect of the latter. This is observed in terms of (a) increased cell viability, (b) healthy-looking cell morphology as revealed by phase contrast microscopy, (c) active respiring cells as observed with confocal microscopy upon staining with a mitochondrial membrane-specific dye, MitoTracker(®) Red, and reduction in the sub-G(1) peak in cell cycle analysis by flow cytometry. Our results suggest that these hepatoprotective drugs need to be further explored as potential adjuvant therapy along with ATT drugs.

Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis.

We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction.

Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients.

We investigated the influence of gender and pharmacogenetic variations on long-term efavirenz autoinduction and disposition among patients with HIV in Tanzania (N = 129). Plasma concentrations (at 16 h) of efavirenz and 8-hydroxyefavirenz were quantified at weeks 4 and 16 of therapy. Genotyping was performed to identify cytochrome P450 (CYP) 2B6*6, CYP3A5*3, *6, and *7, and ABCB1-3435 C/T genotypes. There were reductions in the median efavirenz concentration (Wilcoxon matched-pair test P < 0.001) and efavirenz/8-hydroxyefavirenz ratio (P < 0.001) by 19 and 32%, respectively, at week 16 as compared with week 4. The proportion of patients with efavirenz concentration <1 µg/ml at week 16 was higher by 67, 25, and 5% in CYP2B6*1/*1, *1/*6, and *6/*6 genotypes, respectively. The defined therapeutic range based on observed plasma concentrations is affected by the time point of sampling and the CYP2B6 genotype. The effect of efavirenz autoinduction on reducing plasma exposure continues up to week 16 and predominantly affects CYP2B6 extensive metabolizers. Among CYP2B6 slow metabolizers, the presence of a CYP3A5 genotype allele is associated with greater effects of efavirenz autoinduction on plasma concentrations of the drug. The cumulative induction may influence the long-term antiretroviral therapy outcome, particularly in CYP2B6*1 carriers.

Effect of piperazine on the level of phospholipids and on the activities of certain enzymes of phospholipid metabolism in human Ascaris lumbricoides.

The phospholipid level in the human parasitic nematode Ascaris lumbricoides is decreased by piperazine, by partially stimulating catabolic enzymes such as phospholipase C and partially inhibiting anabolic enzymes such as choline kinase.

Evidence for the metabolism of phospholipids and triacylglycerols in human Ascaris lumbricoides.

Human Ascaris lumbricoides has the necessary mechanism for the biosynthesis and degradation of phospholipids and triacylglycerols, as in most other species. Piperazine decreases the level of triacylglycerols of this parasite by stimulating the activity of lipase and partially inhibiting the activity of phosphatidate phosphatase.

Lipolytic activity from Rhizopus arrhizus using solid state fermentation in biphasic system

The hydrolytic activity of extracellular lipases (Triacylglycerol hydrolase EC 3.1.1.3) from Rhizopus arrhizus; in a water-organic solvent biphasic system was investigated. The purpose of the work was to examine the conditions for best lipolysis reactions by microbial lipase in microaqueous biphasic system with special emphasis on the involvement of surfactants; metal ions and a chelating agent in the system for biocatalysis and enzyme stability. The lipases were produced from a Rhizopus arrhizus strain; using rice bran as solid substrate; by solid state fermentation. The activity of lipases was found to be optimum at 30 oC and pH 6.5. The effect of different solvents on hydrolytic activity was carried out and isooctane was selected as the solvent of choice. The hydrolytic power exhibited by lipases in a biphasic system was compared with that displayed in aqueous system (phosphate buffer pH 6.5). The effects of various metal ions and a chelating agent on hydrolytic activity in biphasic system were also studied. Among the metal ions tested; Ca2+ had an activating effect; Zn2+; Cu2+; Co2+ and the chelating agent (EDTA) had little inhibitory effect; and Fe3+ showed the highest inhibitory effect. The activating effect of Ca2+ on hydrolytic activity was highest at pH 6.5. Mg2+; Na+ and K+ had no significant effect on lipolysis. The Km value for the enzyme in the solvent isooctane (Km = 91.6 mg/ml) was less as compared to the Km value in the buffer (Km =110 mg/ml). Among the surfactants tested; non-ionic surfactants had the highest effect with Triton X-100