Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

Non-robotic minimally invasive gastrectomy as an independent risk factor for postoperative intra-abdominal infectious complications: A single-center,retrospective and propensity score-matched analysis

BACKGROUND Minimally invasive surgery for gastric cancer(GC) has gained widespread use as a safe curative procedure especially for early GC.AIM To determine risk factors for postoperative complications after minimally invasive gastrectomy for GC.METHODS Between January 2009 and June 2019, 1716 consecutive patients were referred to our division for primary GC. Among them, 1401 patients who were diagnosed with both clinical and pathological Stage Ⅲ or lower GC and underwent robotic gastrectomy(RG) or laparoscopic gastrectomy(LG) were enrolled. Retrospective chart review and multivariate analysis were performed for identifying risk factors for postoperative morbidity.RESULTS Morbidity following minimally invasive gastrectomy was observed in 7.5% of the patients. Multivariate analyses demonstrated that non-robotic minimally invasive surgery, male gender, and an operative time of ≥ 360 min were significant independent risk factors for morbidity. Therefore, morbidity was compared between RG and LG. Accordingly, propensity-matched cohort analysis revealed that the RG group had significantly fewer intra-abdominal infectious complications than the LG group(2.5% vs 5.9%, respectively; P = 0.038), while no significant differences were noted for other local or systemic complications.Multivariate analyses of the propensity-matched cohort revealed that non-robotic minimally invasive surgery [odds ratio = 2.463(1.070–5.682); P = 0.034] was a significant independent risk factor for intra-abdominal infectious complications.CONCLUSION The findings showed that robotic surgery might improve short-term outcomes following minimally invasive radical gastrectomy by reducing intra-abdominal infectious complications.     

Attachment to Caregivers and Type 1 Diabetes in Children

Attachment is a behavioral and physiological system, which enables individual’s dynamic adaptation to its environment. Attachment develops in close interaction between an infant and his/her mother, plays an important role in the development of the infant’s brain, and influences the quality of interpersonal relationships throughout life.Security of attachment is believed to influence individual response to stress, exposing insecurely organized individuals to deregulated autonomic nervous system and exaggerated hypothalamic-pituitary-adrenal activity, which, in turn, produces increased and prolonged exposure to stress-hormones. Such stress responses may have considerable implications for the development of diverse health-risk conditions, such as insulin resistance and hyperlipidemia, shown by numerous studies.Although the mechanisms are not yet fully understood, there is compelling evidence highlighting the role of psychological stress in the development of type 1 diabetes (T1D). One of the possible contributing factors for the development of T1D may be the influence of attachment security on individual stress reactivity. Thus, the suggestion is that insecurely attached individuals are more prone to experience increased and prolonged influence of stress hormones and other mechanisms causing pancreatic beta-cell destruction.The present paper opens with a short overview of the field of attachment in children, the principal attachment classifications and their historic development, describes the influence of attachment security on individual stress-reactivity and the role of the latter in the development of T1D. Following is a review of recent literature on the attachment in patients with T1D with a conclusion of a proposed role of attachment organization in the etiology of T1D.     

Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.     

A case of diaphragmatic hernia incarceration after a heart transplant operation

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.     

Prevalence and Predictors of Quality of Recovery at Home After Day Surgery

Traditionally, major complications and unanticipated admission/readmission rates were used to assess outcome after day surgery. However, in view of the relative absence of major complications the quality of recovery (QOR) should be considered one of the principal endpoints after day surgery. In our study, the level of QOR is defined by a combination of the Global Surgical Recovery (GSR) Index and the Quality of Life (QOL).The aim of this study was to analyze prevalence and predictors of QOR after day surgery on the fourth postoperative day.Elective patients scheduled for day surgery from November 2008 to April 2010 were enrolled in a prospective cohort study. Outcome parameters were measured by using questionnaire packages at 2 time points: 1 week preoperatively and 4 days postoperatively. Primary outcome parameter is the QOR and is defined as good if the GSR index >80% as well as the postoperative QOL is unchanged or improved as compared with baseline. QOR is defined as poor if both the GSR index ≤80% and if the postoperative QOL is decreased as compared with baseline. QOR is defined as intermediate in all other cases. Three logistic regression analyses were performed to determine predictors for poor QOR after day surgery.A total of 1118 patients were included. A good QOR was noted in 17.3% of patients, an intermediate QOR in 34.8%, and a poor QOR in 47.8% 4 days after day surgery. The best predictor for poor QOR after day surgery was type of surgery. Other predictors were younger age, work status, and longer duration of surgery. A history of previous surgery, expected pain (by the patient) and high long-term surgical fear were significant predictors of poor QOR in only 1 of 3 prediction models.The QOR at home 4 days after day surgery was poor in the majority of patients and showed a significant procedure-specific variation. Patients at risk for poor QOR can be identified during the preoperative period based on type of surgery, age, work status, and the duration of the surgery.