The TWEAK: application in a prenatal setting.

OBJECTIVE: The TWEAK is a screening instrument used to identify women who are risk drinkers. Potential limitations of previous studies of the TWEAK in the prenatal setting include indirect administration of the instrument to minority, indigent pregnant women. The purpose of this study is to assess the efficacy of the TWEAK when it is given directly to a sample of pregnant women of different socioeconomic backgrounds. METHOD: The original TWEAK, with two different tolerance questions, was administered to a sample of 135 pregnant women enrolled in a study of alcohol use during pregnancy at the obstetrics practices of the Brigham and Women's Hospital in Boston, Massachusetts. RESULTS: The TWEAK, using the first tolerance question (number of drinks before feeling the first effects of alcohol) with the cut point set at more than two drinks, had the best predictive ability for lifetime alcohol diagnoses and risk drinking. The sensitivity of the TWEAK can be increased if the cut point for the first tolerance question is set at two drinks, with some loss of specificity and predictive ability. Medical record assessment was the least sensitive but most specific method of identifying alcohol use by pregnant women. CONCLUSIONS: The TWEAK has promise as a screening instrument for identifying risk drinking during pregnancy. Future work should include testing in other clinical populations.     

Potential role of LIF as a modifier gene in the pathogenesis of amyotrophic lateral sclerosis

Leukemia inhibitory factor (lif) is a potent survival factor for motoneurons in cell culture and in vivo. The authors screened 104 patients with ALS and 338 control subjects for mutations in the LIF gene. In four ALS patients, but in no control subject, a G-to-A point mutation at position 3400 was identified, which leads to an amino acid exchange of valine to methionine at position 64 of the mature lif protein. This region of the lif protein (AB loop) interacts with the lif receptor. The authors suggest that LIF could act as a modifier gene which, in combination with other genetic predispositions, might lead to motoneuron disease.     

Subsidence resulting from simulated postoperative neck movements: an in vitro investigation with a new cervical fusion cage

STUDY DESIGN: A biomechanical in vitro subsidence test of different cervical interbody fusion devices was performed using a new testing protocol that simulates physiologic conditions. OBJECTIVES: To investigate the effect of simulated postoperative neck movements on the subsidence of the new WING cervical interbody fusion cage in comparison with two other cages and bone cement. SUMMARY OF BACKGROUND DATA: Cervical interbody fusion cages sometimes cause complications because of subsidence into the adjacent vertebrae with collapse of the intervertebral space. Complications such as cage dislocation or nonunion with instability also have been reported. To prevent such complications, the new WING cervical interbody fusion cage (Medinorm AG, Quierschied, Germany) has been developed. Its area of contact with the adjacent vertebrae is supposed to be large enough to resist excessive subsidence and small enough to prevent stress protection of the tissue growing in the cage. METHODS: In this study, 24 human cervical spine specimens were tested after stabilization with either a WING, BAK/C, AcroMed I/F cage or bone cement. Then, in a new testing protocol, 700 pure-moment loading cycles (+/-2 Nm) were applied in randomized directions (lateral bending, flexion-extension, and axial rotation alone or in combination with each other) to simulate the patient's neck movements during the first few postoperative days. Measurements of the subsidence depth (total height loss) in combination with flexibility tests (+/-2.5 Nm) were performed before cyclic loading and after 50, 100, 200, 300, 500, and 700 loading cycles. RESULTS: Cyclic loading caused subsidence in all four device groups, most distinct with BAK/C-cages (1.63 mm after 700 loading cycles) followed by the new WING (0.90 mm) and the AcroMed (0.82 mm) cages. No statistically significant difference could be found among the three cage designs. However, all three cage types showed a significantly higher subsidence depth than bone cement (0.48 mm;P = 0.023 between each of the three cage-types and bone cement). A moderate correlation between bone mineral density and subsidence depth could be found only in the BAK/C group (r2 = 0.495). A large subsidence depth after 700 loading cycles was associated with a large flexibility increase in the WING (r2 = 0.786) and AcroMed groups (r2 = 0.21), but with a small flexibility increase in the BAK/C group (r2 = 0.58). CONCLUSIONS: Postoperative neck movements caused subsidence in all cervical interbody implant types. The new WING cage and the AcroMed cage seemed to have a better resistance against subsidence than the BAK/C cage. However, all three cage types had a significantly higher subsidence tendency than bone cement.     

Ataque de Nervios and History of Childhood Trauma

Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.     

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Indocyanine green and laser light for the treatment of AIDS-associated cutaneous Kaposi's sarcoma.

Indocyanine green (ICG) is clinically approved for the determination of liver function, cardiac output and plasma volume. In this pilot study, ICG was used as photosensitizer in combination with a diode laser to treat AIDS-associated Kaposi''s sarcoma (KS) in three patients. Directly and up to 50 min after intravenous administration of ICG (2-4 mg kg(-1) body weight), KS (n=57), mainly plaque-type, were irradiated using a diode laser (lambda em=805 nm, 100 J cm[-2], 0.5-5 W cm[-2]) matching the absorption maximum. Complete remission of KS (n=16) was achieved when irradiated 1-30 min after injection of the second dose of ICG (2 x 2 mg kg(-1) b.w., 30 min apart) with 3-5 W cm(-2) and 100 J cm(-2). Biopsies (n=3) revealed necrosis of the tumour 24 h and complete remission 4 weeks after therapy. In general, systemic side-effects were not observed and cosmetic results were very good. However, hyperpigmentation occurred temporarily in lesions located on the lower extremities. These findings show that AIDS-associated KS can be effectively treated after photosensitization with ICG and subsequent irradiation with an appropriate diode laser. However, additional investigations need to elucidate the exact mechanism of action of ICG-mediated phototherapy and have to show the efficacy for the treatment of other highly vascularized solid tumours.     

Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt.     

Health-related quality of life and post-traumatic stress disorder in patients after cardiac surgery and intensive care treatment

OBJECTIVES: Health-related quality of life and patient satisfaction have become important end points in cardiac surgery. Post-traumatic stress disorder has been described in patients with life-threatening heart disease. In this study, we investigated the occurrence of post-traumatic stress disorder in a sample of patients after cardiac surgery and compared health-related quality of life and patient satisfaction between patients with and without evidence of post-traumatic stress disorder. METHODS: We studied 80 patients serially admitted to the intensive care unit after cardiac surgery (bypass grafting, n = 51; aortic valve replacement, n = 29). Health-related quality of life was assessed with the use of the SF-36 Health Status Questionnaire. Post-traumatic stress disorder was measured with a previously validated instrument (the Post-Traumatic Stress Syndrome 10-Questions Inventory), and 20 different aspects of life satisfaction were quantified on a scale ranging from 0 to 10. For measurements of health-related quality of life and post-traumatic stress disorder, age- and gender-comparable healthy individuals, as well as patients with cardiovascular diseases, served as control groups. RESULTS: Patients who had cardiac surgery described high life satisfaction summary scores (156 of a maximum of 200 points) and only small impairments in physical and mental SF-36 summary scores when compared with healthy control groups (median reduction 7.15, P <.05). Patients with evidence of post-traumatic stress disorder (n = 15) reported the lowest SF-36 mental health summary scores when compared with patients without stress disorder (38.3 vs 48.4, P =.004) and rated their life satisfaction lower (121.5 vs 162.0, P =.002). CONCLUSIONS: Patients who have had cardiac surgery demonstrate a high life satisfaction with an acceptable degree of physical and mental health-related quality of life. Impairments in psychosocial function and life satisfaction were found in a subgroup of patients with evidence of post-traumatic stress disorder.