Results of left atrioventricular valve reconstruction after previous correction of atrioventricular septal defects

OBJECTIVE: The objective of this study was to determine causes of severe left atrioventricular (AV) incompetence and the factors leading to the success of valve repair later after correction of atrioventricular septal defects (AVSD). METHODS: A total of 28 patients aged 5 months to 38 years (mean age 6.7 years) were operated for significant (grade II-III) left AV valve incompetence (LAVVI), two months to twenty-five years (median 1.5 years) after correction of complete (11 patients) or partial atrioventricular septal defects. Fourteen patients had initially undergone surgery during infancy. RESULTS: At reoperation a completely open or partially sutured cleft was found in 16 patients combined with dysplastic valve tissue in four cases, with a fibrotic valve in three cases, with posterior leaflet prolapse in two cases, with a double orifice valve in three cases, and a parachute valve in two cases. Partial or complete reopening of a previously sutured cleft caused by suture dehiscence was found in 12 cases combined with a fibrotic valve in five cases, with a dysplastic valve in one case and with severe deformity of valve in one case. A combination of these anomalies was observed in seven patients in both groups. Left atrioventricular valve repair including cleft closure combined with annuloplasty and other surgical procedures resulted in the disappearance or significant diminishing of LAVI in 18 patients (64%). Severe SAVI persisted in six patients, five of them exhibiting a combination of several additional left AV valve anomalies (fibrotic or dysplastic valve, parachute valve). Five of these six patients underwent successful left AV valve replacement with a mechanical prosthesis 7 days to 2 years after reoperation. The presence of additional left AV valve anomalies was the single statistically significant factor for recurrent major LAVVI after reoperation (P = 0.0106). There were two postoperative deaths in patients with mild LAVVI after surgery, and no late deaths. CONCLUSION: An open cleft is the major factor of late severe SAVVI after correction of AVSD. Although suturing the cleft in conjunction with performing annuloplasty improved valvular function in most of the cases, the presence of severe left AV valve anomalies increased the risk of recurrent LAVVI and the need for valve replacement, thus playing a major role in determining the outcome of valve reconstruction in patients after reoperation.     

Herpes simplex virus

CNS infections caused by human herpesvirus 1 and human herpesvirus 2-herpes simplex virus type 1 and herpes simplex virus type 2--are reviewed. The major diseases associated with these viruses are meningitis and encephalitis. Two forms of encephalitis are known, neonatal encephalitis and encephalitis occurring after the neonatal period. Both diseases are associated with high mortality and morbidity and require prompt diagnosis and aggressive antiviral chemotherapy. Methods for the specific diagnosis of these infections are reviewed and the value of intrathecal antibody assay and nucleic acid amplification techniques are emphasised.     

Perspectives on the use of the baboon in embryology and teratology research

This paper summarizes the developmental stages of the baboon during the period of organ formation and provides comparative information for other primates, including the human. Special attention is directed to the early development of the nervous system, eye, ear and nose/palate. The similarity in development of these structures with humans indicates that the baboon is a suitable model for studies of normal and abnormal neurological development. Spontaneous prenatal loss rates in the baboon (2.4-11.2%) are slightly lower than those reported in rhesus and cynomologus monkeys. The baboon, in addition to the cynomologus monkey and macaque, has been used as a model in teratology research to assess the potential risk of thalidomide, sex steroids, Bendectin and rubella virus, as well as to study the pathogenesis of malformations associated with the corticosteroid triamcinolone acetonide. The rate of spontaneous malformations (<1%) in baboons, similar to that reported for other commonly used primates, supports their continued use as a teratological model. In this regard, a sample protocol is provided for the safety evaluation of biotechnology products using nonhuman primates, which are the most appropriate model for those compounds which are bioactive in species closely related to humans.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

Fluoxetine tenth anniversary update: the progress continues

This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depression, patients with eating disorders, and patients with obsessive-compulsive disorder (OCD); its long-term (maintenance) efficacy; its side effects and toxicity; and pharmacoeconomic considerations are reviewed. Pharmacotherapy is currently the only proven method for treating major depressive disorder that is applicable to all levels of severity of major depressive illness. Since its introduction 10 years ago, fluoxetine has been available to psychiatrists, primary care physicians, and other nonpsychiatric physicians as full-dose effective pharmacotherapy for patients with depression. Fluoxetine has been widely prescribed by physicians knowledgeable in pharmacology and in the treatment of depression because of its proven efficacy (ie, equal to that of tricyclic antidepressants [TCAs]), its ease of administration (with full therapeutic dosing usually starting from day 1), its generally benign side-effect profile, its remarkable safety in over-dose, and its proven effectiveness in the most common depressed patient population--anxious, agitated, depressed patients--as well as in patients with various subtypes and severities of depression. In more recent years it has also proved effective in the treatment of bulimia, an entity for which only limited or inadequate treatment options had been previously available. In OCD, fluoxetine, with its more acceptable side-effect profile and greater ease of dosing, presents a favorable alternative to previous drug therapy and is useful in treating both obsessions and compulsions. Fluoxetine is currently recognized among clinicians as efficacious in treating anxiety disorders and is being used successfully in special depressed populations such as patients with medical comorbidity, elderly patients, adolescents, and children. Rapid discontinuation or missed doses of short-half-life selective serotonin reuptake inhibitors, TCAs, and heterocyclic antidepressants are associated with withdrawal symptoms of a somatic and psychological nature, which cannot only be disruptive, but can also be suggestive of relapse or recurrence of depression. In striking contrast to these short-half-life antidepressants, fluoxetine is rarely associated with such sequelae on sudden discontinuation or missed doses. This preventive effect against withdrawal symptoms on discontinuation of fluoxetine is attributed to the unique extended half-life of this antidepressant. Current studies show that the overall increased effectiveness of fluoxetine in treating depression compensates for its higher cost, compared with older drugs, by reducing the need for physician contact because of increased compliance and less need of titration, and by reducing premature patient discontinuation, thereby yielding fewer relapses, less recurrence, and less reutilization of mental health services.     

Evidence for non-synchronous rotation of Europa. Galileo Imaging Team

Non-synchronous rotation of Europa was predicted on theoretical grounds, by considering the orbitally averaged torque exerted by Jupiter on the satellite's tidal bulges. If Europa's orbit were circular, or the satellite were comprised of a frictionless fluid without tidal dissipation, this torque would average to zero. However, Europa has a small forced eccentricity e approximately 0.01 , generated by its dynamical interaction with Io and Ganymede, which should cause the equilibrium spin rate of the satellite to be slightly faster than synchronous. Recent gravity data suggest that there may be a permanent asymmetry in Europa's interior mass distribution which is large enough to offset the tidal torque; hence, if non-synchronous rotation is observed, the surface is probably decoupled from the interior by a subsurface layer of liquid or ductile ice. Non-synchronous rotation was invoked to explain Europa's global system of lineaments and an equatorial region of rifting seen in Voyager images. Here we report an analysis of the orientation and distribution of these surface features, based on initial observations made by the Galileo spacecraft. We find evidence that Europa spins faster than the synchronous rate (or did so in the past), consistent with the possibility of a global subsurface ocean.     

Changes in folate status as determined by reduction in total plasma homocysteine levels during leucovorin modulation of 5-fluorouracil therapy in cancer patients

We measured plasma total homocysteine (tHcy) in 14 patients (13 patients with colorectal cancer and 1 patient with breast cancer) during their first treatment with 5-fluorouracil (5-FU) plus leucovorin [LV (5-FULV)]. Eight of these patients were investigated a second time after 3-10 cycles (median, 4 cycles) with 5-FULV. Each cycle consisted of two administrations of 5-FU (500 mg/m2) and LV (60 mg/m2) given 24 h apart. The first administration of 5-FULV on day 1 of the first cycle induced a rapid reduction of the tHcy level from 12.5 micromol/liter (10.4-15.1 micromol/liter; geometric mean with 95% confidence interval of the mean) to 9.1 micromol/liter (7.5-11.1 micromol/liter) in 24 h. tHcy remained stable at this level after the second administration of 5-FULV. In addition, the 5-FULV regimen caused a concurrent 4-fold increase in both serum and erythrocyte folate. The fifth cycle with 5-FULV had only marginal effects on the tHcy level. 5-FU without LV modulation had no effect on the plasma tHcy or folate status in eight breast cancer patients. Our data establish the reduction of tHcy as a responsive indicator of LV pharmacodynamics.     

Ultrasonographic assessment of bladder neck mobility in continent bitches and bitches with urinary incontinence attributable to urethral sphincter mechanism incompetence

OBJECTIVE: To determine bladder neck positional changes between standing and recumbent positions in bitches and whether change is related to continence status or general anesthesia, or both, and to evaluate reproducibility of measurements. ANIMALS: 45 continent animals and 46 incontinent bitches with urethral sphincter mechanism incompetence (SMI). PROCEDURE: Distance between the bladder neck and perineal skin was measured ultrasonographically via the perineum while each dog was conscious in standing and right lateral recumbency and in right lateral recumbency under general anesthesia. Measurements of the bladder neck position obtained in right lateral recumbency under anesthesia were compared with radiographic measurements of the same parameter. Reproducibility of the ultrasonographic measurements of the distance between bladder neck and perineum was assessed on 3 occasions for each position in 50 dogs. RESULTS: In all dogs, differences in bladder neck position between standing and recumbent conscious-associated positions were not significant. However, caudal bladder neck movement between standing conscious- and recumbent anesthesia-associated positions and between recumbent conscious- and anesthesia-associated positions was significant for all dogs. Incontinent bitches had greater degree of caudal bladder movement during anesthesia. Mean difference in bladder neck positions between recumbent conscious- and recumbent anesthesia-associated positions was 0.24 cm in continent, compared with 0.73 cm in incontinent, bitches. Radiographic measurements were significantly greater than ultrasonographic measurements. Differences between repeated measurements for standing position were not significant, but those for recumbent conscious- and recumbent anesthesia-associated positions were significant. CONCLUSIONS: Additional vesicourethral support mechanisms in continent dogs, are deficient in bitches with SMI, allowing the bladder neck to move further caudad.