Neuronal apoptosis in human immunodeficiency virus infection

Neuronal apoptosis has been shown to occur in HIV infection by a number of in vivo and in vitro studies, however, the cause of neuronal damage in AIDS is still unclear and its relationships with the cognitive disorders characteristic of HIV dementia remain a matter of debate. In this review, based on our experience, we analyse the techniques used to identify neuronal apoptosis on post-mortem AIDS brains and describe the relationships of neuronal apoptosis with the stage of disease, a history of HIV-dementia, the degree of productive HIV infection, microglial activation, blood-brain barrier involvement and axonal damage. We conclude that the severity of neuronal apoptosis in the cerebral cortex correlates with the presence of cerebral atrophy, but not with the cognitive disorders. There is no global quantitative correlation between neuronal apoptosis and HIV encephalitis, microglial activation or axonal damage. However we found some topographical correlation between these changes. We conclude that neuronal apoptosis and consequent neuronal loss, in HIV infected patients, are probably not related to a single cause. It seems likely that microglial activation, directly or indirectly related to HIV infection of the CNS, plays a major role in its causation possibly through the mediation of oxidative stress. Axonal damage, either secondary to microglial activation, or to the intervention of systemic factors may also contribute to neuronal apoptosis.     

Radiosurgery for childhood intracranial arteriovenous malformations

OBJECTIVE: The optimal management of intracranial arteriovenous malformations (AVMs) in children remains controversial. Children with intracranial AVMs present a special challenge in therapeutic decision-making because of the early recognition of their future life-long risks of hemorrhage if they are treated conservatively. The goals of radiosurgery are to achieve complete AVM obliteration and to preserve neurological function. We present long-term outcomes for a series of children treated using radiosurgery. METHODS: The findings for 53 consecutive children who underwent at least 36 months of imaging follow-up monitoring after radiosurgery were reviewed. The median age at the time of treatment was 12 years (range, 2-17 yr). Thirty-one children (58%) presented after their first intracranial hemorrhaging episodes, two (4%) after their second hemorrhaging episodes, and one (2%) after five hemorrhaging episodes. Nineteen children (36%) presented with unruptured AVMs, and a total of 25 children (47%) exhibited neurological deficits. AVMs were graded as Spetzler-Martin Grade I (2%), Grade II (23%), Grade III (36%), Grade IV (9%), or Grade VI (30%). The median AVM volume was 1.7 ml (range, 0.11-10.2 ml). The median marginal dose was 20 Gy (range, 15-25 Gy). RESULTS: Results were stratified according to AVM volumes (Group 1, < or =3 ml; Group 2, >3 ml to < or =10 ml; Group 3, >10 ml). Twenty-eight patients (80%) in Group 1 and 11 (64.7%) in Group 2 achieved complete obliteration. The only patient in Group 3 did not achieve obliteration. Complications included brainstem edema (n = 1) and transient pulmonary edema (n = 1). Four patients experienced hemorrhaging episodes, 30, 40, 84, and 96 months after radiosurgery. Multivariate logistic regression analysis demonstrated that only volume was significantly correlated with obliteration rates (P = 0.0109). CONCLUSION: Radiosurgery is safe and efficacious for selected children with AVMs. The obliteration rates and the attendant low morbidity rates suggest a primary role for stereotactic radiosurgery for pediatric AVMs.     

Children with autistic spectrum disorders. II: parents are unable to distinguish secretin from placebo under double-blind conditions.

BACKGROUND: Standardised measures of behaviour have failed to detect short term improvement in children with autism following treatment with secretin. However, it is possible that standardised measures are insensitive to dimensions of child behaviour that are nonetheless detectable by parents. AIM: To determine the ability of parents of children with autism to guess, under double blind conditions, whether their child had received secretin or placebo. METHODS: 2x2 crossover randomised blinded study, comparing the effect of synthetic human secretin 2 U/kg to placebo (saline). Sixty two children with autism (aged 43-103 months) were randomly allocated to two groups: group 1 received placebo, followed six weeks later by secretin, and group 2 received secretin followed by placebo. At the conclusion of the study, parents were asked to guess their child's group assignment. RESULTS: Twenty seven families guessed their child's group assignment correctly and 27 guessed incorrectly. In 48 instances, parents based their guess on perceived improvement; in six cases, parents based their guess on perceived deterioration. Six families saw no difference after either infusion, and offered no guess. One family dropped out after the first infusion, and one family was lost to follow up after the second infusion. CONCLUSION: In a controlled setting, parents of young children with autism are unable to distinguish the short term behavioural effects of secretin from placebo.     

Liver allotransplantation after extracorporeal hepatic support with transgenic (hCD55/hCD59) porcine livers: clinical results and lack of pig-to-human transmission of the porcine endogenous retrovirus

BACKGROUND: Whole organ extracorporeal perfusion of a genetically modified humanized (transgenic) pig liver has been proposed as a technology that may sustain patients with severe liver failure while awaiting human liver transplantation. METHODS: We report on two cases of successful extracorporeal perfusion of a transgenic pig liver in patients awaiting transplantation for fulminant hepatic failure. The pig livers used were transgenic for human CD55 (decay-accelerating factor) and human CD59. These transgenic modifications are designed to reduce or eliminate the hyperacute rejection inherent in pig-to-primate xenotransplants. We also report on the results of serial surveillance testing for presence of the porcine endogenous retrovirus (PoERV) in these two patients. RESULTS: Extracorporeal perfusion in two patients was performed for 6.5 and 10 hr, respectively, followed by the successful transplantation of a human liver and resultant healthy patients (18 and 5 months later as of this writing). The porcine livers showed evidence of synthetic and secretory function (decreasing protime and bilirubin, bile production). Serial polymerase chain reaction analysis of these patients' peripheral blood mononuclear cells has failed to show presence of PoERV DNA sequences. CONCLUSIONS: The CD55/CD59 transgenic porcine liver appears capable of safely "bridging" a patient to liver transplantation. Human PoERV infection from these livers has yet to be demonstrated.     

Management of ischemic nephropathy: dialysis-free survival after surgical repair

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.     

Comparing quality of life following liver transplantation for Laennec's versus non-Laennec's patients

The overall success of orthotopic liver transplantation (OLTX) includes not only survival, but quality of life (QOL) as well. We studied one controversial group of OLTX recipients, patients transplanted for alcoholic liver disease (Laennec's), to determine if their post-OLTX QOL was similar to that of patients transplanted for non-alcoholic liver disease (non-Laennec's). Over a 10-yr period, patients undergoing OLTX at our institution were asked to complete a QOL questionnaire addressing a wide range of topics from demographics and employment to symptom distress/frequency, activities of daily living, and effect of loss of health on daily life. Twenty-four Laennec's and 100 non-Laennec's OLTX recipients completed the questionnaire at both their 2- and 5-yr follow-up visits at our institution. Both groups were well-matched in age, race, and patient location status at the time of OLTX. No significant differences could be detected between Laennec's and non-Laennec's scores regarding overall QOL, including one's ability to function, health perception, and self-perception at 2 and 5 years post-OLTX, and between 2 and 5 years post-OLTX. Although not between groups, a significant difference was noted regarding patients' satisfaction with life, with less satisfaction reported at the 5-yr versus the 2-yr time point post-OLTX. Rates of current/recent employment between both groups were also similar at 2 years post-OLTX, and again at 5 years post-OLTX. We conclude that overall QOL and employment levels appear similar between patients transplanted for alcoholic and non-alcoholic liver disease. This similarity appears to extend to 5 years post-OLTX.     

Spiral twist of the spermatic cord: a reliable sign of testicular torsion

Background. Colour Doppler sonography (CDS) has become the procedure of choice in evaluating testicular perfusion but false negative findings have been reported. Objective. To determine if direct visualisation of the twisted spermatic cord using high resolution US is a reliable sign to assess testicular torsion. Material and methods. Thirty patients (aged 2–26 years) with equivocal diagnosis of testicular torsion prospectively underwent high resolution and CDS. The results were correlated with surgical findings. Serial transverse and longitudinal scans were performed to compare the scrotal contents on each side and study the complete spermatic cord course, from inguinal canal to testis, to detect a spiral twist. Results. In 14 of the 23 cases of torsion, the diagnosis was based on the colour Doppler findings in the scrotum because blood flow was absent in the symptomatic testis and detectable without difficulty on the normal side. In nine cases, CDS was unreliable; in six cases intratesticular perfusion was present in a twisted testis and in three small boys, no colour signal was obtained in either testis. In all cases of torsion, the spiral twist of spermatic cord was detected at the external inguinal ring. The twist induced an abrupt change in spermatic cord course, size and shape below the point of torsion. It appeared in the scrotum as a round or oval, homogeneous or heterogeneous extratesticular mass with or without blood flow, that could be connected cephalad with the normal inguinal cord. In the other seven cases (three late torsions of the appendix testis, one epididymo-orchitis and three torsions with spontaneous reduction), no spiral twist was detectable. Conclusion. The detection of spermatic cord spiral twist appears a reliable US sign of torsion whatever the testicular consequences. Received: 1 December 1997 Accepted: 17 June 1998     

Outpatient open Bankart repair

We evaluated satisfaction in 25 consecutive patients who underwent open Bankart repair as an outpatient procedure. The average age of the patients was 22 years. There were 18 men and 7 women. Patients were evaluated postoperatively via a home assessment questionnaire that included the following: home environment, dominant versus nondominant extremity, effectiveness of oral pain medication, ability to perform activities of daily living, and overall satisfaction. Three of the 25 patients would have preferred an overnight hospital stay. There were no admissions to the hospital or postoperative complications. The total charges for outpatient Bankart repair as compared with an inpatient procedure at the same institution resulted in a total cost savings of 56%. We conclude that outpatient Bankart repair is safe and economical. The overall cost savings were significant and patient satisfaction was 88%.