Why put yourself on a pedestal? The pathogenic role of the A/E pedestal.

Certain Escherichia coli (E. coli) strains are attaching and effacing (A/E) lesion pathogens that primarily infect intestinal epithelial cells. They cause actin restructuring and polymerization within the host cell to create an actin-rich protrusion below the site of adherence, termed the pedestal. Although there is clarity on the pathways initiating pedestal formation, the underlying purpose(s) of the pedestal remains ambiguous. The conservation of pedestal-forming activity across multiple pathogens and redundancy in formation pathways indicate a pathogenic advantage. However, few decisive conclusions have been drawn, given that the results vary between model systems. Some research argues that the pedestal increases the colonization capability of the bacterium. These studies utilize A/E pathogens specifically deficient in pedestal formation to evaluate adhesion and intestinal colonization following infection. There have been many proposed mechanisms for the colonization benefit conferred by the pedestal. One suggested benefit is that the pedestal allows for direct cytosolic anchoring through incorporation of the established host cortical actin, causing a stable link between the pathogen and cell structure. The pedestal may confer enhanced motility, as enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are better able to migrate on the surface of host cells and infect neighboring cells in the presence of the pedestal. Additionally, some research suggests that the pedestal improves effector delivery. This review will investigate the purpose of pedestal formation using evidence from recent literature and will critically evaluate the methodology and model systems. Most importantly, we will contextualize the proposed functions to reconcile potential synergistic effects.

Dutasteride in men receiving testosterone therapy: a randomised, double-blind study.

We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty-three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (-0.46 ± 0.81 ng ml(-1) ; P = 0.04) and in PV (-6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (-0.46 versus 0.21 ng ml(-1) ; P = 0.11), PV (-6.65% versus 3.4%; P = 0.08) and MSHQ scores (-10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy.

Assessment of EndoPAT scores in men with vasculogenic and non-vasculogenic erectile dysfunction.

PURPOSE: The role of endothelial function testing using peripheral artery tonometry (PAT) in the evaluation of ED is not well established. Endothelial dysfunction is expected to be more common in men presenting with general or vasculogenic ED, compared with men who develop ED after prostatectomy. This study evaluated whether PAT could help identify men in whom endothelial cell dysfunction was the underlying cause of ED. MATERIALS AND METHODS: A chart review of 194 men with general ED and 98 men with postprostatectomy ED was performed to abstract data on demographics, medical comorbidities, SHIM-5 scores and EndoPAT scores. Patients with preoperative ED were excluded. Statistical analysis using Student's t-test and Chi-squared analysis was performed to compare the two groups of men with respect to these variables. RESULTS: EndoPAT scores were not significantly different between men with general vs. postprostatectomy ED (1.97 vs. 2.08, p = 0.074). There was no relationship between EndoPAT and SHIM-5 scores in the general ED cohort. The prevalence of hypertension, hyperlipidaemia and cardiovascular (CV) disease was similar between the two groups, but diabetes and hypogonadism were more prevalent in men with general ED (21% vs. 9%, and 28% vs. 7%, p < 0.015). Overall, EndoPAT scores in postprostatectomy men with at least one risk factor were not significantly different compared with men with general ED with the same comorbidity, or a combination of two or more comorbidities. CONCLUSIONS: The value of EndoPAT testing in the clinical evaluation of ED patients is questionable.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Gender-based cardiometabolic risk evaluation in minority and non-minority men grading the evidence of non-traditional determinants of cardiovascular risk.

Evaluation of cardiometabolic risk has become vital in primary prevention of adverse vascular events (coronary artery disease, heart attack, stroke or congestive heart failure), particularly in younger middle-aged men (40-60 years old). To discern the prevalence of events in these men, clinicians often stratify cardiovascular risk and treat according to traditional Framingham risk criteria. Yet it is evident that the traditional Framingham risk assigned to intermediate- and low-risk men will miss several of these individuals deemed at high 'cardiometabolic risk', also known as residual cardiovascular risk. This review will elaborate the definition of cardiometabolic risk and apply the use of surrogate markers for cardiovascular risk stratification in men in addition to the traditional Framingham-based markers. It will utilise both gender non-specific and gender-specific determinants of cardiometabolic risk. Lastly, it will examine minority men's health and racial differences in these determinants of cardiovascular risk. This analysis includes an electronic literature search utilising PubMed, EMBASE and MEDLINE databases to clarify the level of evidence for the stepwise utility of novel biomarkers for cardiometabolic risk in the male patient. This manuscript generates discussion of the utility of markers of cardiometabolic risk stratification. The following questions are summarised: (i) Are there non-traditional tests that might define this risk better than traditional markers? (ii) Will treatment based on this risk assessment augment present risk stratification and lower cardiovascular risk? (iii) What is known regarding racial differences surrounding cardiometabolic risk assessment? Traditional risk factors including Framingham Risk Score underestimate the overall 10 year and lifetime risk for the intermediate-risk younger middle-aged men<60 years of age. This fact is especially true in the minority population. We have graded the evidence of non-gender specific and gender-specific markers of cardiometabolic risk, thereby, allowing greater clarification of risk in this population. The pragmatic use of these novel markers of cardiometabolic risk may help stratify those individuals at greater lifetime risk than that noted by the Framingham Risk Score.

Erectile dysfunction and testosterone screening with prostate specific antigen screening at age 40: are these three gender specific determinants additive for overall men's heath and do they improve traditional non-gender specific determinants to lessen cardiovascular risk and all-cause mortality?

AIMS: Assess support for a recommendation to add screening for both erectile dysfunction (ED) and hypogonadism to the initial medical evaluation of young-to-middle aged (≥ 40 years of age) men in light of recent guidelines suggesting prostate-specific antigen screening occur at that age. METHODS: A search of literature published from 1998 to 2009 was performed. Search terms included: ED combined with coronary artery disease (CAD), metabolic syndrome and hypogonadism, hypogonadism and ED, hypogonadism, ED and mortality. Articles were evaluated according to the Center of Evidence-Based Medicine. RESULTS: Both retrospective and prospective evaluations have demonstrated a strong relationship between ED, established cardiovascular risk factors, CAD and the potential occurrence of cardiovascular events. Low testosterone levels are associated with ED. Low serum total testosterone is an independent risk factor for both metabolic syndrome and type 2 diabetes and all-cause mortality. CONCLUSION: Traditionally, ED and testosterone levels have been considered mainly, if not exclusively, in the context of sexual health. The results briefly summarised herein and other recent reviews suggest that ED and hypogonadism are signals of future all-cause mortality and overall health status and thus move these evaluations into the broader arena of public health. Screening for ED and hypogonadism provide 'gender-specific determinants' to assess general metabolic and cardiovascular health risks in men. It is the opinion of the authors that this screening be performed in addition to the well-established non-gender-specific screening tests of lipids, blood pressure, obesity and serum glucose.

Biology and natural history of prostate cancer and the role of chemoprevention.

Androgens not only play an important role in the development and function of the prostate but they are also intimately involved in the development and progression of prostate cancer (PCa). Within the prostate, testosterone is converted to the more potent androgen dihydrotestosterone (DHT) via the action of 5α-reductase enzymes. DHT is the primary prostatic androgen and promotes the growth and survival of normal, hyperplastic and malignant prostate tissues. Throughout the different stages of PCa [prostatic intraepithelial neoplasia (PIN), localised, recurrent, and metastatic] there is an increase in expression of 5α-reductase enzymes, particularly in localised high-grade carcinoma. Specifically inhibiting 5α-reductase may reduce the production of DHT in the prostate while maintaining other endogenous hormone levels. Clinical studies have shown significant PCa risk reduction by blocking this pathway with 5α-reductase inhibitors (5ARIs). However, this comes at a risk, albeit low, with sexual side effects, gynaecomastia and cardiac failure. In addition, one study has shown a slight, but significant, risk of high-grade PCa. The currently available evidence does not support the routine use of 5α-reductase inhibitors to prevent PCa in the general population. It could, however, be considered as an individual option for high-risk or concerned patients with appropriate education from the prescribing provider.

STEP: simplified treatment of the enlarged prostate.

We propose a simple and practical approach to the identification, evaluation and treatment of lower urinary tract symptoms (LUTS) resulting from an enlarging and obstructive prostate. The proposed Simplified Treatment for Enlarged Prostate (STEP) plan is a logical guide to patient management by the primary care provider (PCP). Symptoms of enlarged prostate (EP) are common and may frequently progress into a condition with profound adverse effects on quality of life. Despite the high prevalence, EP is underdiagnosed and undertreated. This situation may result from patient- and provider-related issues. Assessment of symptoms of EP should be initiated with a discussion of LUTS. Evaluation includes a focused history, physical examination and selected laboratory tests. Certain factors put the symptomatic patient at risk for disease progression; however, not all factors can be readily evaluated in the PCP setting. The serum prostate-specific antigen (PSA) level acts both as an indicator of prostatic size and a screening tool for prostatic cancer, and thereby provides an important tool for PCPs. The STEP plan is a logical guide to patient management. Step 1, watchful waiting, is appropriate in patients with symptoms that are not bothersome. If symptoms cause bother, the initiation of an alpha-blocker (AB) in step 2, provides relatively rapid symptom improvement. Patients with bothersome symptoms and a PSA > or = 1.5 ng/ml are at risk for progression and consideration should be given to combination treatment with an AB and a 5alpha-reductase inhibitor (step 3). Patients with refractory symptoms should be referred to a urologist (step 4). Identification, evaluation and management of EP are within the domain of the primary care setting. The STEP approach provides a simple and practical framework for PCPs to manage most men with symptoms of EP.

Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus.

* A significant proportion of men with erectile dysfunction (ED) exhibit early signs of coronary artery disease (CAD), and this group may develop more severe CAD than men without ED (Level 1, Grade A). * The time interval among the onset of ED symptoms and the occurrence of CAD symptoms and cardiovascular events is estimated at 2-3 years and 3-5 years respectively; this interval allows for risk factor reduction (Level 2, Grade B). * ED is associated with increased all-cause mortality primarily due to increased cardiovascular mortality (Level 1, Grade A). * All men with ED should undergo a thorough medical assessment, including testosterone, fasting lipids, fasting glucose and blood pressure measurement. Following assessment, patients should be stratified according to the risk of future cardiovascular events. Those at high risk of cardiovascular disease should be evaluated by stress testing with selective use of computed tomography (CT) or coronary angiography (Level 1, Grade A). * Improvement in cardiovascular risk factors such as weight loss and increased physical activity has been reported to improve erectile function (Level 1, Grade A). * In men with ED, hypertension, diabetes and hyperlipidaemia should be treated aggressively, bearing in mind the potential side effects (Level 1, Grade A). * Management of ED is secondary to stabilising cardiovascular function, and controlling cardiovascular symptoms and exercise tolerance should be established prior to initiation of ED therapy (Level 1, Grade A). * Clinical evidence supports the use of phosphodiesterase 5 (PDE5) inhibitors as first-line therapy in men with CAD and comorbid ED and those with diabetes and ED (Level 1, Grade A). * Total testosterone and selectively free testosterone levels should be measured in all men with ED in accordance with contemporary guidelines and particularly in those who fail to respond to PDE5 inhibitors or have a chronic illness associated with low testosterone (Level 1, Grade A). * Testosterone replacement therapy may lead to symptomatic improvement (improved wellbeing) and enhance the effectiveness of PDE5 inhibitors (Level 1, Grade A). * Review of cardiovascular status and response to ED therapy should be performed at regular intervals (Level 1, Grade A).

A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men.

Erectile dysfunction (ED) is associated with clinical atherosclerosis and several atherosclerotic risk factors including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity and sedentary lifestyle. Clinical atherosclerosis is also associated with these same risk factors and with biomarkers of inflammation, thrombosis, endothelial cell activation. We evaluated the cross-sectional association between the degree of ED and levels of atherosclerotic biomarkers. A subcohort of 988 US male health professionals between the ages 46 and 81 years as part of an ongoing epidemiologic study had atherosclerotic biomarkers measured from blood collected in 1994-1995. These same men had in 2000, been retrospectively asked about erectile function in 1995 and in 2000. Biennial questionnaires since 1986 assessed medical conditions, medications, smoking, physical activity, body mass index, alcohol intake. The retrospective assessment of erectile function in 2000 for 1995 in these 988 men ranged from very good - 28.2%, good - 25.1%, fair - 19.2%, poor - 13.6%, to very poor - 13.9%. Men with poor to very poor erectile function compared to men with good and very good erectile function had 2.9 the odds of having elevated Factor VII levels (P=0.03), 1.9 times the odds of having elevated vascular cell adhesion molecule (P=0.13) and 2.0 times the odds of having elevated intracellular adhesion molecule (P=0.06) and 2.1 times the odds of having elevated total cholesterol/high-density lipoprotein ratio (P=0.02) comparing the top to bottom quintiles for each atherosclerotic biomarker after multivariate adjustment. Lipoprotein(a), homocysteine, interleukin-6 and tumor necrosis factor receptor, C-reactive protein and fibrinogen were not associated with the degree of erectile function after adjustment. We conclude that selected biomarkers for endothelial function, thrombosis and dyslipidemia but not inflammation are associated with the degree of ED in this cross-sectional analysis. Future studies evaluating the prospective association of ED, endothelial function and cardiovascular disease appear warranted.

Multiple sclerosis and alcohol use disorders: In-hospital mortality, extended hospital stays, and overexpenditures. / Esclerosis múltiple y trastornos asociados al consumo de alcohol: mortalidad atribuible, prolongación de estancias y exceso de costes hospitalarios.

INTRODUCTION: The objective of this study was to analyse the impact of alcohol use disorders (AUD) in patients with multiple sclerosis (MS) in terms of in-hospital mortality, extended hospital stays, and overexpenditures. METHODS: We conducted a retrospective observational study in a sample of MS patients obtained from minimal basic data sets from 87 Spanish hospitals recorded between 2008 and 2010. Mortality, length of hospital stays, and overexpenditures attributable to AUD were calculated. We used a multivariate analysis of covariance to control for such variables as age and sex, type of hospital, type of admission, other addictions, and comorbidities. RESULTS: The 10,249 patients admitted for MS and aged 18-74 years included 215 patients with AUD. Patients with both MS and AUD were predominantly male, with more emergency admissions, a higher prevalence of tobacco or substance use disorders, and higher scores on the Charlson comorbidity index. Patients with MS and AUD had a very high in-hospital mortality rate (94.1%) and unusually lengthy stays (2.4 days), and they generated overexpenditures (1,116.9euros per patient). CONCLUSIONS: According to the results of this study, AUD in patients with MS results in significant increases in-hospital mortality and the length of the hospital stay and results in overexpenditures.

Do baseline estrogen and testosterone affect lower urinary tract symptoms (LUTS) prior to or after pharmacologic treatment with tadalafil?

Little is known about how total testosterone and estradiol-17ß influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17ß, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17ß and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17ß was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17ß versus those with higher baseline estradiol-17ß. Lower baseline estradiol-17ß was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17ß levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17ß levels when responsiveness was measured using total IPSS and IPSS-V.

Psychiatric comorbidity in pedophilic sex offenders.

OBJECTIVE: The primary purpose of this research was to assess the rates of axis I and axis II psychiatric disorders, as defined in DSM-IV, in a group of pedophilic sex offenders. METHOD: Forty-five male subjects with pedophilia who were participating in residential or outpatient sex offender treatment programs were recruited to participate. Subjects were interviewed by using the Structured Clinical Interview for DSM-IV. RESULTS: Ninety-three percent of the subjects (N = 42) met the criteria for an axis I disorder other than pedophilia. The lifetime prevalence of mood disorder in this group was 67%. Sixty-four percent of the subjects met the criteria for an anxiety disorder, 60% for psychoactive substance use disorder, 53% for another paraphilia diagnosis, and 24% for a sexual dysfunction diagnosis. CONCLUSIONS: Axis I and II comorbidity rates are high in this population. Untreated comorbid psychiatric disorders may play a role in treatment failure and recidivism.

Cerebral white matter and cognition in hydrocephalic children.

Although children with hydrocephalus frequently show poor development of nonverbal cognitive skills relative to verbal skills, little is known about the neuropathologic correlates of these discrepancies. In this study, cerebral white-matter structures and lateral ventricles were measured from the magnetic resonance images of age-matched children with meningomyelocele, meningocele, and aqueductal stenosis and normal subjects. The volume of each lateral ventricle and the cross-sectional area of the corpus callosum and internal capsules were correlated with concurrent measures of verbal and nonverbal cognitive skills. The corpus callosum in the meningomyelocele and aqueductal stenosis groups was smaller. The lateral ventricles were larger, and the internal capsules were smaller, in all patient groups than in normal subjects. There were no differences in the size of the centra semiovale. Although verbal and nonverbal measures correlated positively with the size of the corpus callosum, the correlation was higher for nonverbal measures. Nonverbal measures correlated with the right, but not the left, lateral ventricle and with the area of the right and left internal capsules. Verbal measures correlated with the left, but not right, lateral ventricle and with the left, but not right, internal capsule. These results show a relationship between the corpus callosum and cognitive skills that is also influenced by hydrocephalus-related changes in the lateral ventricles and other cerebral white-matter tracts.

Adaptation to metastatic cancer pain, regional/local cancer pain and non-cancer pain: role of psychological and behavioral factors.

The present study compared the adaptation of cancer pain patients and chronic non-cancer pain patients. Differences between samples of cancer pain patients with and without metastatic disease were also examined. Cancer pain patients reported comparable levels of pain severity to non-cancer chronic pain patients; however, pain due to cancer was associated with higher levels of perceived disability (t(250) = 2.97, P < 0.004) and lower degree of activity (t(286) = 2.45, P < 0.04). The patients with cancer pain, particularly those with metastatic disease, reported significantly higher levels of support and solicitous behaviors from significant others, compared to non-cancer chronic pain patients. The majority of the cancer patients, both with (81%) and without (84%) metastatic disease as well as non-cancer chronic pain patients (85%), could be classified into one of three psychosocial subgroups that had been previously identified with non-cancer chronic pain patients: 'dysfunctional' (high levels of pain, perceived interference, affective distress and low levels of perceived control and activity), 'interpersonally distressed' (high levels of affective distress, negative responses from significant others and low levels of perceived support) and 'adaptive copers' (low levels of interference and affective distress, high levels of perceived control and activity). The distribution of the profiles was significantly different across groups (chi2(4) = 12.79, P < 0.02). However, within each profile. the response patterns were highly comparable across groups. Thus, contrary to the suggestions of some authors, cancer pain and non-cancer chronic pain patients share many features in common. Furthermore, the heterogeneity of psychosocial adaptation to pain within each patient group suggests the importance of psychological assessment in determining the pain management plan.

Tortuosity as an index of the age and diameter increase of coronary collateral vessels in patients after acute myocardial infarction.

A possible correlation among increase in diameter, lengthening or tortuosity and age of bypassed obstruction was investigated in coronary arterial collateral vessels. In 35 autopsy patients with a myocardial infarct of known age, as determined from clinical history and pathologic demonstration of an infarct of consistent age in the distribution of an obstructed vessel, 140 collateral vessels were identified in postmortem arteriograms and measurements made of their diameter and tortuosity. Multivariable regression analyses showed that collateral diameter and tortuosity increase with greater time after the infarction. It is suggested that identification of tortuosity in a coronary vessel may provide an indication that it functions as a collateral channel and of the degree of its dilatation and the time it has been a collateral channel. The lengthening that produces tortuosity probably arises from the same relaxation of medial tension that induces dilatation as a result of increased blood flow.

Carbon fiber implants in osteochondral defects of the rabbit patella.

Carbon fiber implants were used to fill osteochondral defects created on the articular surface of the patella of 36 rabbits, for the purpose of studying the long-term histological changes of the repair process. Six months after surgery the defect was filled by fibrous tissue, where the superficial area was organized parallel to the joint surface. Fibrocartilage developed after 9 months and, after 12 months, the defects were covered by hyaline cartilage tissue.

Unusual cervical spinal cord toxicity associated with intra-arterial carboplatin, intra-arterial or intravenous etoposide phosphate, and intravenous cyclophosphamide in conjunction with osmotic blood brain-barrier disruption in the vertebral artery.

BACKGROUND AND PURPOSE: When the clinical and radiologic characteristics of an unusual cervical spinal cord complication of intra-arterial (IA) chemotherapy with blood brain-barrier (BBB) disruption in the vertebral circulation are documented. Seven cases are reported and analyzed in search of a pathophysiologic explanation. METHODS: We retrospectively identified 94 patients who received a total of 380 standardized regimens of IA carboplatin, IA or IV etoposide phosphate, and IV cyclophosphamide infusion in conjunction with osmotic BBB disruption of the vertebral artery. We describe seven of those patients in whom unexpected neck pain developed followed by neurologic symptoms primarily in the upper extremities. RESULTS: The symptoms correlated with MR abnormalities (T1 hypointensity, T2 hyperintensity, and unusual contrast enhancement) in the cervical spinal cord, usually involving the gray matter. The neurologic deficits and MR changes were generally transient. One patient who received a flu vaccination 48 hours before the chemotherapy incurred progressive myelitis and expired. CONCLUSION: The pathophysiology of this complication is probably multifactorial but may be related to vascular streaming and an atypical inflammatory toxic reaction to carboplatin and etoposide. The complication has not recurred during a 6-month period following modification of the protocol.

Behavioral changes after closed head injury in children.

This study provides a longitudinal follow-up of the behavioral adjustment of 45 children with mild, moderate, and severe closed head injuries. Two measures of behavioral adjustment, the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales (VABS), were obtained from a parent at the time of injury and at 6 and 12 months postinjury. The severely injured children obtained significantly poorer VABS scores than children with mild and moderate injuries over the year-long follow-up. In addition, on the CBCL, severely injured children had more school problems and engaged in fewer social activities than mild and moderately injured children. These results show that severe head injury in children was associated with declines in adaptive functioning, whereas scores for children with mild and moderate injuries did not differ, nor did they deviate from average levels at any follow-up interval.

Posthemorrhagic hemispheric cysts in neonates: treatment by cystoventriculostomy.

Two premature infants developed enlarging symptomatic hemispheric cysts secondary to intraparenchymal hemorrhages. Computed tomographic scans obtained after metrizamide was injected into the cysts demonstrated that they were isolated from the ventricular system. The cysts were treated by biopsy of the common cyst-ventricular wall through a ventriculoscope. Both patients have been followed for over 1 year. Repeat scans have demonstrated resolution of the cysts, a return to midline of the ventricular system, and an increase in the volume of cerebral tissue. The original abnormal neurological signs have disappeared, and the developmental progress has been excellent.