Pre-existing mental health disorders and pregnancy

Mental health conditions are independent risk factors for poor obstetric and neonatal outcomes therefore obstetricians need to be able to manage them well. This review will summarize the management of pre-existing mental health disorders in pregnancy. Explanations will be given as to which women are managed in primary care for their mental health conditions and which women are managed in specialist Perinatal Mental Health Services. When women should be referred to perinatal mental health services is described. The article provides recommendations on the obstetric management of these women as well as information on psychotropic medication in pregnancy and lactation.     

Interaction of Avibactam with Class B Metallo-β-Lactamases

β-Lactamases are the most important mechanisms of resistance to the β-lactam antibacterials. There are two mechanistic classes of β-lactamases: the serine β-lactamases (SBLs) and the zinc-dependent metallo-β-lactamases (MBLs). Avibactam, the first clinically useful non-β-lactam β-lactamase inhibitor, is a broad-spectrum SBL inhibitor, which is used in combination with a cephalosporin antibiotic (ceftazidime). There are multiple reports on the interaction of avibactam with SBLs but few such studies with MBLs. We report biochemical and biophysical studies on the binding and reactivity of avibactam with representatives from all 3 MBL subfamilies (B1, B2, and B3). Avibactam has only limited or no activity versus MBL-mediated resistance in pathogens. Avibactam does not inhibit MBLs and binds only weakly to most of the MBLs tested; in some cases, avibactam undergoes slow hydrolysis of one of its urea N-CO bonds followed by loss of CO₂, in a process different from that observed with the SBLs studied. The results suggest that while the evolution of MBLs that more efficiently catalyze avibactam hydrolysis should be anticipated, pursuing the development of dual-action SBL and MBL inhibitors based on the diazabicyclooctane core of avibactam may be productive.     

Inhibition of dendritic cell maturation by malaria is dose dependent and does not require Plasmodium falciparum erythrocyte membrane protein 1

Red blood cells infected with Plasmodium falciparum (iRBCs) have been shown to modulate maturation of human monocyte-derived dendritic cells (DCs), interfering with their ability to activate T cells. Interaction between Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and CD36 expressed by DCs is the proposed mechanism, but we show here that DC modulation does not require CD36 binding, PfEMP1, or contact between DCs and infected RBCs and depends on the iRBC dose. iRBCs expressing a PfEMP1 variant that binds chondroitin sulfate A (CSA) but not CD36 were phagocytosed, inhibited lipopolysaccharide (LPS)-induced phenotypic maturation and cytokine secretion, and abrogated the ability of DCs to stimulate allogeneic T-cell proliferation. CD36- and CSA-binding iRBCs showed comparable inhibition. P. falciparum lines rendered deficient in PfEMP1 expression by targeted gene knockout or knockdown also inhibited LPS-induced phenotypic maturation, and separation of DCs and iRBCs in transwells showed that inhibition was not contact dependent. Inhibition was observed at an iRBC:DC ratio of 100:1 but not at a ratio of 10:1. High doses of iRBCs were associated with apoptosis of DCs, which was not activation induced. Lower doses of iRBCs stimulated DC maturation sufficient to activate autologous T-cell proliferation. In conclusion, modulation of DC maturation by P. falciparum is dose dependent and does not require interaction between PfEMP1 and CD36. Inhibition and apoptosis of DCs by high-dose iRBCs may or may not be physiological. However, our observation that low-dose iRBCs initiate functional DC maturation warrants reevaluation and further investigation of DC interactions with blood-stage P. falciparum.     

Arterial-wave reflections are increased in heart failure patients with a left-ventricular assist device

BACKGROUND: Chronic heart failure (HF) is associated with increased central arterial pulse-wave reflections, which may contribute to increased myocardial oxygen demand. Although the treatment of HF via left-ventricular assist device (LVAD) placement has recently become widespread, the effects of LVAD therapy on central arterial pulse-wave reflections are unknown. METHODS: Central aortic pulse-wave analysis was performed on patients with end-stage HF awaiting cardiac transplantation and on healthy age-matched controls using the SphygmoCor (Akor Medical, Sydney, Australia) system. Arterial pulse-wave data were compared between patients receiving LVAD support versus those receiving intravenous inotropic drugs and healthy control patients. RESULTS: Five patients on LVAD support were compared with 10 patients on inotropic drugs and 10 healthy control patients. Aortic augmented pressure and the aortic augmentation index (AI(a)) were higher in LVAD patients compared with inotrope and control patients, despite similar brachial and aortic blood pressures between groups. The AI(a) was significantly higher in LVAD patients than in patients on inotropic drugs (28.2% +/- 10% v 7.9% +/- 9%, P < or = .01). Additionally, there was a significantly higher aortic systolic tension time index, an index of left-ventricular myocardial oxygen demand, in the LVAD group compared with the inotrope group (2655 +/- 298 mm Hg/sec/min v 1748 +/- 303 mm Hg/sec/min, P < .01). CONCLUSIONS: Central arterial pressure-wave reflection is increased in end-stage HF patients on LVAD support compared with those on inotropic drugs, leading to an increase in aortic augmented pressure, AI(a), and systolic tension time index. The AI(a) is also higher in LVAD patients than in healthy controls. This increased central arterial-wave reflection places an additional hemodynamic load on the LVAD device and may have relevance to the medical management of patients after LVAD placement and to the longevity of the LVAD device itself.     

Diabetes care in general practice: an approach to audit of process and outcome.

As a chronic condition in which the major adverse outcomes only occur after many years, diabetes poses special problems for continuing medical audit. The feasibility of continuous audit of process and outcome in diabetes care has been tested in four general practices with organized diabetes care in Newcastle upon Tyne. For all patients with previously diagnosed non-insulin dependent diabetes, the data already collected according to published protocols were assembled into a single database. The time and resource costs of this exercise, together with measures of process, complications, risk factors, and metabolic outcomes were analysed. Data were successfully collected at minimal cost where structured records were completed. Recommended processes had been completed in a high percentage of patients, adverse patient outcomes were limited, and metabolic output measures not unsatisfactory. Nevertheless, attention has been directed to areas where care could be improved. Continuing diabetes audit in primary health care is feasible and helpful, and can use the same measures as in the hospital setting.     

Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis

BACKGROUND AND AIMS: Colonoscopic surveillance for cancer in longstanding extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies. Chromoendoscopy can aid detection of subtle mucosal abnormalities. We hypothesised that routine pancolonic indigo carmine dye spraying would improve the macroscopic detection of dysplasia and reduce the dependence on non-targeted biopsies. PATIENTS AND METHODS: One hundred patients with longstanding extensive ulcerative colitis attending for colonoscopic surveillance underwent "back to back" colonoscopies. During the first examination, visible abnormalities were biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic indigo carmine (0.1%) was used during the second colonoscopic examination, and any additional visible abnormalities were biopsied. RESULTS: Median extubation times for the first and second colonoscopies were 11 and 10 minutes, respectively. The non-targeted biopsy protocol detected no dysplasia in 2904 biopsies. Forty three mucosal abnormalities (20 patients) were detected during the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both were considered to be dysplasia associated lesions/masses. A total of 114 additional abnormalities (55 patients) were detected following dye spraying, of which seven (five patients) were dysplastic: all were considered to be adenomas. There was a strong trend towards statistically increased dysplasia detection following dye spraying (p = 0.06, paired exact test). The targeted biopsy protocol detected dysplasia in significantly more patients than the non-targeted protocol (p = 0.02, paired exact test). CONCLUSIONS: No dysplasia was detected in 2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine dysplastic lesions, seven of which were only visible after indigo carmine application. Careful mucosal examination aided by pancolonic chromoendoscopy and targeted biopsies of suspicious lesions may be a more effective surveillance methodology than taking multiple non-targeted biopsies.