Acute compartment syndrome of the lower limb following childbirth : a case report

Background: Acute compartment syndrome is a limb-threatening and occasionally life-threatening emergency that is rarely reported as a complication following childbirth. Prompt diagnosis is crucial to avoid permanent functional restriction or even the loss of the affected limb. Clinical signs and symptoms might be nonspecific, especially in the early stages; therefore, knowledge of predisposing risk factors and signs and symptoms of acute compartment syndrome is necessary to prevent long-term complications and amputation. Case presentation: This paper presents a case of a 26-year-old primiparous Sri Lankan woman who developed acute compartment syndrome of the lower right limb following childbirth by cesarean section. Conclusion: Acute compartment syndrome is an important differential diagnosis in the setting of sudden onset of lower limb pain following childbirth. Predisposing factors for its manifestation within an obstetric environment are augmented labor, the lithotomy position, postpartum hemorrhage, hypotension following epidural analgesia, and the use of vasoconstrictive agents. If left undiagnosed and untreated, acute compartment syndrome may cause permanent neurovascular deficit, leading to a poor functional result, tissue ischemia, limb amputation, and rhabdomyolysis. If severe, and in large compartments, it can lead to renal failure and death. Alertness and a high index of clinical suspicion for the possibility of acute compartment syndrome are required to avoid a delay in diagnosis, and intracompartmental pressure measurement can be used to confirm the diagnosis

Application of Cryopreserved Human Hepatocytes in Trichloroethylene Risk Assessment: Relative Disposition of Chloral Hydrate to Trichloroacetate and Trichloroethanol

BACKGROUND: Trichloroethylene (TCE) is a suspected human carcinogen and a common ground-water contaminant. Chloral hydrate (CH) is the major metabolite of TCE formed in the liver by cytochrome P450 2E1. CH is metabolized to the hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH) and to the noncarcinogenic metabolite trichloroethanol (TCOH) by alcohol dehydrogenase (ADH). ALDH and ADH are polymorphic in humans, and these polymorphisms are known to affect the elimination of ethanol. It is therefore possible that polymorphisms in CH metabolism will yield subpopulations with greater than expected TCA formation with associated enhanced risk of liver tumors after TCE exposure. METHODS: The present studies were undertaken to determine the feasibility of using commercially available, cryogenically preserved human hepatocytes to determine simultaneously the kinetics of CH metabolism and ALDH/ADH genotype. Thirteen human hepatocyte samples were examined. Linear reciprocal plots were obtained for 11 ADH and 12 ALDH determinations. RESULTS: There was large interindividual variation in the V(max) values for both TCOH and TCA formation. Within this limited sample size, no correlation with ADH/ALDH genotype was apparent. Despite the large variation in V(max) values among individuals, disposition of CH into the two competing pathways was relatively constant. CONCLUSIONS: These data support the use of cryopreserved human hepatocytes as an experimental system to generate metabolic and genomic information for incorporation into TCE cancer risk assessment models. The data are discussed with regard to cellular factors, other than genotype, that may contribute to the observed variability in metabolism of CH in human liver

Comparative metabolism and tolerability of racemic primaquine and its enantiomers in human volunteers during 7-day administration

Primaquine (PQ) is an 8-aminoquinoline antimalarial, active against dormant Plasmodium vivax hypnozoites and P. falciparum mature gametocytes. PQ is currently used for P. vivax radical cure and prevention of malaria transmission. PQ is a racemic drug and since the metabolism and pharmacology of PQ’s enantiomers have been shown to be divergent, the objectives of this study were to evaluate the comparative tolerability and metabolism of PQ with respect to its two enantiomers in human volunteers in a 7 days’ treatment schedule. Fifteen subjects with normal glucose-6-phosphate dehydrogenase (G6PDn) completed four arms, receiving each of the treatments, once daily for 7 days, in a crossover fashion, with a 7–14 days washout period in between: R-(−) enantiomer (RPQ) 22.5 mg; S-(+) enantiomer (SPQ) 22.5 mg; racemic PQ (RSPQ) 45 mg, and placebo. Volunteers were monitored for any adverse events (AEs) during the study period. PQ and metabolites were quantified in plasma and red blood cells (RBCs) by UHPLC-UV-MS/MS. Plasma PQ was significantly higher in SPQ treatment group than for RPQ. Carboxy-primaquine, a major plasma metabolite, was much higher in the RPQ treated group than SPQ; primaquine carbamoyl glucuronide, another major plasma metabolite, was derived only from SPQ. The ortho-quinone metabolites were also detected and showed differences for the two enantiomers in a similar pattern to the parent drugs. Both enantiomers and racemic PQ were well tolerated in G6PDn subjects with the 7 days regimen; three subjects showed mild AEs which did not require any intervention or discontinuation of the drug. The most consistent changes in G6PDn subjects were a gradual increase in methemoglobin and bilirubin, but these were not clinically important. However, the bilirubin increase suggests mild progressive damage to a small fraction of red cells. PQ enantiomers were also individually administered to two G6PD deficient (G6PDd) subjects, one heterozygous female and one hemizygous male. These G6PDd subjects showed similar results with the two enantiomers, but the responses in the hemizygous male were more pronounced. These studies suggest that although the metabolism profiles of individual PQ enantiomers are markedly different, they did not show significant differences in the safety and tolerability in G6PDn subjects

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Anaerobiosis revisited: growth of Saccharomyces cerevisiae under extremely low oxygen availability

The budding yeast Saccharomyces cerevisiae plays an important role in biotechnological applications, ranging from fuel ethanol to recombinant protein production. It is also a model organism for studies on cell physiology and genetic regulation. Its ability to grow under anaerobic conditions is of interest in many industrial applications. Unlike industrial bioreactors with their low surface area relative to volume, ensuring a complete anaerobic atmosphere during microbial cultivations in the laboratory is rather difficult. Tiny amounts of O2 that enter the system can vastly influence product yields and microbial physiology. A common procedure in the laboratory is to sparge the culture vessel with ultrapure N2 gas; together with the use of butyl rubber stoppers and norprene tubing, O2 diffusion into the system can be strongly minimized. With insights from some studies conducted in our laboratory, we explore the question ‘how anaerobic is anaerobiosis?’. We briefly discuss the role of O2 in non-respiratory pathways in S. cerevisiae and provide a systematic survey of the attempts made thus far to cultivate yeast under anaerobic conditions. We conclude that very few data exist on the physiology of S. cerevisiae under anaerobiosis in the absence of the anaerobic growth factors ergosterol and unsaturated fatty acids. Anaerobicity should be treated as a relative condition since complete anaerobiosis is hardly achievable in the laboratory. Ideally, researchers should provide all the details of their anaerobic set-up, to ensure reproducibility of results among different laboratories. A correction to this article is available online at http://eprints.whiterose.ac.uk/131930/ https://doi.org/10.1007/s00253-018-9036-

Oleic Acid Synthesis in the Mammal

The presented work describes a search for an oleic acid synthesizing system in liver and fat tissue of the rat, guinea pig, rabbit, ox, sheep and pig; a more detailed examination of the system found in rat liver and some attempts to characterize it. The major assay system used employs radioactive stearic acid ; some time was given to an investigation of the efficiency of methods of separation of stearic and oleic acids. Prior to a discussion of the experimental approach used, it is necessary to review the available literature on which it is based and to consider the importance of the substance and its synthesis from a chemical viewpoint. This introduction also includes a discussion of the principle of separation of stearic and oleic acids. The formulation of the experimental approach used in attempts to isolate the system from rat liver is described in section 2 (page 77 ). Oleic acid occurs in the phospholipids and triglycerides of all organisms with the exception of some bacteria. The significance of the unsaturation to its structural role in phospholipid membranous material is completely unknown; indeed it is only in the last few years that its metabolic relationships are emerging. That it is significant can be inferred from its ubiquitous distribution, and from the fact that it is an essential nutrient for anaerobic yeast

Diminished serum Gc (vitamin D‐binding protein) levels and increased Gc:G‐actin complexes in a hamster model of fulminant hepatic necrosis

Evidence for increased plasma levels of complexes containing Gc (vitamin D‐binding protein) and cellular actin has been previously reported during fulminant hepatic necrosis in man. In order to study this process in more detail, we produced liver injury in hamsters using increasing doses of acetaminophen, with serial collection of sera for up to 168 hr after acetaminophen injection. Hamster Gc was purified using a three‐step procedure and was shown to resemble closely human Gc. Polyclonal antihamster Gc was prepared and used in rocket immunoelectrophoresis and radial immunodif‐fusion studies for quantitation of total serum Gc and the percentage of Gc complexed with actin. Serum Gc levels were depressed in animals having liver damage, and the extent of depression 42 hr after acetaminophen correlated with the extent of elevation of AST. The proportion of the total Gc that was present in the complexed form increased in relation to the severity of the liver disease. In serial studies, diminution in Gc level preceded the rise in AST and increase in the percent complexed. These changes closely resemble observations in man and suggest that the hamster‐acetaminophen hep‐atotoxicity model may be of value in further study of interactions of Gc with intracellular actin components and its role in actin homeostasis in conditions of massive tissue necrosis