Clinical management of perinatal depression: focus on paroxetine

The literature on antidepressant use during pregnancy and lactation is replete with review articles and clinical decision algorithms. Remarkably, a limited number of such articles include the methodological advances that have served to define the extent of fetal and neonatal exposure to antidepressants. For this review, MEDLINE search for original research articles focusing on obstetrical, neonatal, and infant outcomes associated with antidepressant use was conducted. These articles were scrutinized to include those with data on the selective serotonin reuptake inhibitors (SSRIs) and limited to breast-feeding studies that included infant serum concentrations.Sixty-seven articles were identified that included a total of 3050 cases of SSRI use during pregnancy and 240 cases of use during lactation. The amount of obstetrical outcome data available for each SSRI was proportional to the duration of time each medication has been available. In contrast, the lactation data were heavily weighted toward sertraline and paroxetine relative to other antidepressants. The myriad of confounds, failure to control for maternal depression, lack of prospective documentation of other medications, and environmental exposures preclude any definitive conclusions. There was no clear association between SSRI exposure and obstetrical complications or poor outcome. In contrast, the amniotic fluid, umbilical cord, and nursing infant sera literature demonstrated significantly different exposures to individual medications.     

Prospective randomized study of a protein-based tissue adhesive used as a hemostatic and structural adjunct in cardiac and vascular anastomotic repair procedures

BACKGROUND: The purpose of this study was to determine whether adjunctive use of the bovine serum albumin and glutaraldehyde tissue adhesive BioGlue (BioGlue Surgical Adhesive; CryoLife, Inc) could reduce the rate of anastomotic bleeding in patients undergoing cardiac and vascular repair procedures when compared with a standard repair control. This was a prospective multicenter, randomized, controlled clinical trial conducted in accordance with the IRB at each participating institution. STUDY DESIGN: A total of 151 patients consented to participation and were randomly assigned to standard repair plus BioGlue (n = 76) or standard repair alone (n = 75). These two groups were statistically homogeneous for age, gender, race, procedure, and number of anastomoses. Patients underwent cardiac procedures (n = 49), aortic procedures (n = 105), or peripheral vascular procedures (n = 48). RESULTS: Anastomotic bleeding was significantly reduced in the BioGlue group (18.8% of anastomoses) compared with the control group (42.9% of anastomoses, p < 0.001). Pledget use was reduced in the BioGlue group (26.2%) compared with the control group (35.9%, p = 0.047). Days in the ICU and total days in the hospital were slightly higher in the control group. Adverse event profiles were equivalent between the two groups except for occurrence of neurological defects, which were threefold less in the BioGlue group (p = 0.009). CONCLUSIONS: This study demonstrates that using BioGlue as an adjunct to standard repair methods is safe and significantly reduces the occurrence of intraoperative anastomotic site bleeding in cardiac and vascular repair patients. Using BioGlue along suture lines reinforces anastomoses, thus minimizing pledget use.     

The use of the endothelin receptor antagonist, tezosentan, before or after renal ischemia protects renal function

BACKGROUND: Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. METHODS: In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). RESULTS: Tezosentan significantly decreased (P<0.05) the rise in Scr from I/R injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) compared with untreated animals (4.2+/-0.4 mg/dl). GFR was significantly increased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 and 0.47+/-0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET-1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. CONCLUSIONS: The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting.     

Dynamic holographic imaging of the beating human heart

Background--Currently, the reporting and archiving of echocardiographic data suffer from the difficulty of representing heart motion on printable 2-dimensional (2D) media. Methods and Results--We studied the capability of holography to integrate motion into 2D echocardiographic prints. Images of normal human hearts and of a variety of mitral valve function abnormalities (mitral valve prolapse, systolic anterior motion of the mitral leaflets, and obstruction of the mitral valve by a myxoma) were acquired digitally on standard echocardiographic machines. Images were processed into a data format suitable for holographic printing. Angularly multiplexed holograms were then printed on a prototype holographic "laser" printer, with integration of time in vertical parallax, so that heart motion became visible when the hologram was tilted up and down. The resulting holograms displayed the anatomy with the same resolution as the original acquisition and allowed detailed study of valve motion with side-by-side comparison of normal and abnormal findings. Comparison of standard echocardiographic measurements in original echo frames and corresponding hologram views showed an excellent correlation of both methods (P<0.0001, r2=0.979, mean bias=2.76 mm). In this feasibility study, both 2D and 3D holographic images were produced. The equipment needed to view these holograms consists of only a simple point-light source. Conclusions--Holographic representation of myocardial and valve motion from echocardiographic data is feasible and allows the printing on a 2D medium of the complete heart cycle. Combined with the recent development of online holographic printing, this novel technique has the potential to improve reporting, visualization, and archiving of echocardiographic imaging.     

Treatment of tuberculous infection and disease in children: the North American perspective

The standard preventive therapy for paediatric patients with tuberculous infection centres on isoniazid therapy. The chosen regimen of isoniazid therapy is based on individual patient factors. In the case of known or suspected resistance, combination therapy [e.g. isoniazid and rifampicin (rifampin)] or alternative therapies (e.g. pyrazinamide, a fluoroquinolone and/or ethambutol) should be employed. The goal of treatment of tuberculous disease is to achieve sterilisation in the shortest possible time. More intensive multiple drug combination regimens (e.g. isoniazid, rifampicin and pyrazinamide) have resulted in successful 6- and 9-month treatment regimens in children. If drug resistance is suspected then a fourth drug is added to the initial treatment regimen and the length of therapy may be extended to 18 months. The paediatric information available on the commonly used antituberculous agents (e.g. isoniazid, rifampicin, pyrazinamide and ethambutol) is reviewed in this article. Agents are described with an emphasis on their formulation availability, mechanism of action, pharmacokinetic properties (e.g. absorption, distribution, metabolism and elimination), adverse effects, and interactions (e.g. drug-drug, drug-food and drug-disease).     

Phosphodiesterase type 5 inhibition enhances vasorelaxation caused by nitroprusside in guinea pig intact heart and isolated aorta

Increased vascular smooth muscle cyclic guanine monophosphate (cGMP) results in vascular relaxation. The vascular effects of stimulating cGMP production with 10(-8)-10(-4) M nitroprusside (NP) and inhibiting cGMP hydrolysis with 10(-8)-10(-4) M zaprinast (ZAP), a selective type V inhibitor of cGMP phosphodiesterase (PDE), were assessed in isolated guinea pig hearts and aortic rings. Coronary flow (CF) IC50 values for NP and ZAP, respectively, were 0.8+/-0.1 x 10(-6) M and 3.6+/-0.1 x 10(-6) M; for coronary sinus pO2 IC50 values were 0.7+/-0.1 x 10(-6) M and 3.7+/-0.1 x 10(-6) M. CF increased by 13+/-2% with 10(-6) NP, and by 12+/-2% with 10(-5) M ZAP; percentage O2 extraction (%O2E) decreased by 17+/-3% with NP and 28+/-4% with ZAP. Together, 10(-6) M NP + 10(-5) M ZAP augmented the increased in CF to 23+/-3% of control, and the decrease in percentage O2 extraction (%O2E) to 40+/-4% of control. Other cardiac effects of NP and ZAP were minimal. In norepinephrine preconstricted aortic rings, the IC50 for relaxation was elicited at 0.4+/-0.1 x 10(-6) M NP and 6.1+/-0.1 x 10(-6) M ZAP. NP given with ZAP gave a logarithmic relation so that IC50 [NP] = -(57 log10 [ZAP]) + 416; R2 = 0.95. NP, 3 x 10(-7) M; ZAP, 3 x 10(-6) M; and NP + ZAP combined increased aortic tissue cGMP by eight-, nine-, and 15-fold, respectively. Inhibiting cGMP hydrolysis may be an effective approach to augment vasorelaxation elicited by cGMP synthesis in the heart.     

Attention‐deficit hyperactivity disorder reduces automatic attention in young adults

Previous ERP studies have provided mixed information about ADHD, especially in adults and when conscious attention to stimuli is not required. We used the auditory N1 to assess automatic attention in adults with and without ADHD. While participants watched a silent video, trains of 5 tones (400‐ms onset‐to‐onset time) were presented with intertrain intervals (ITIs) of 1 or 5 s. The P1, N1, P2, and N2 were analyzed. Compared to controls, participants with ADHD had relatively little N1 attenuation after the 5‐s ITI, which was driven by uniformly small N1s to all tones. However, after the 1‐s ITI, the ADHD group had relatively large N2s to all 5 tones in the train. The reduced N1 in adults with ADHD indicated reduced automatic attention to salient sound stimuli, which may be due to reduced function of brain‐stem arousal mechanisms. However, the increased N2 in these participants suggests they had developed certain compensatory mechanisms.     

Elevated CNS inflammation in patients with preclinical Alzheimer's disease

Alzheimer''s disease (AD) is a progressive, neurodegenerative disease that may involve inflammatory responses in the central nervous system (CNS). Our objective was to determine whether patients with amnestic mild cognitive impairment (aMCI), a preclinical stage of AD, have inflammatory characteristics similar to patients with multiple sclerosis (MS), a known CNS inflammatory disease. The frequency of lymphocytes and levels of pro-inflammatory cytokines in the cerebrospinal fluid of aMCI patients was comparable to MS patients or patients at high risk to develop MS. Thus, brain inflammation occurs early at the preclinical stage of AD and may have an important role in pathology.