Assessment of oncolytic HSV efficacy following increased entry-receptor expression in malignant peripheral nerve sheath tumor cell lines.

Limited expression and distribution of nectin-1, the major herpes simplex virus (HSV) type-1 entry-receptor, within tumors has been proposed as an impediment to oncolytic HSV (oHSV) therapy. To determine whether resistance to oHSVs in malignant peripheral nerve sheath tumors (MPNSTs) was explained by this hypothesis, nectin-1 expression and oHSV viral yields were assessed in a panel of MPNST cell lines using γ134.5-attenuated (Δγ134.5) oHSVs and a γ134.5 wild-type (wt) virus for comparison. Although there was a correlation between nectin-1 levels and viral yields with the wt virus (R=0.75, P =0.03), there was no correlation for Δγ134.5 viruses (G207, R7020 or C101) and a modest trend for the second-generation oHSV C134 (R=0.62, P=0.10). Nectin-1 overexpression in resistant MPNST cell lines did not improve Δγ134.5 oHSV output. While multistep replication assays showed that nectin-1 overexpression improved Δγ134.5 oHSV cell-to-cell spread, it did not confer a sensitive phenotype to resistant cells. Finally, oHSV yields were not improved with increased nectin-1 in vivo. We conclude that nectin-1 expression is not the primary obstacle of productive infection for Δγ134.5 oHSVs in MPNST cell lines. In contrast, viruses that are competent in their ability to counter the antiviral response may derive benefit with higher nectin-1 expression.

River delta morphology: wave climate and the role of the subaqueous proffile.

Application of a comprehensive wave climate program to seven major deltas indicates that deltaic configurations and coastal landform combinations depend to a considerable degree on the wave power adjacent to the shore and on the river discharge relative to wave forces. Nearshore wave power is not correlative with deepwater wave power but, owing to frictional attenuation, is a function of the subaqueous slope. The subaqueous slope, in turn, depends partially on the slope and width of the continental shelf but primarily on the rate at which the river can supply sediments to the nearshore zone. River-dominated configurations result only when the river is able to build flat offshore profiles, which reduce nearshore wave power; where the subaqueous slope is steep, waves reach the shore comparatively undiminished and wave-built forms prevail.

Antiquity of the continental slope along the middle-atlantic margin of the United States.

A detailed high-resolution geophysical study of part of the continental slope along the mid-Atlantic margin of the United States indicates that it is an ancient, relict landscape largely unmodified by modern slope processes. The slope morphology is heavily influenced by bedrock outcrops, including joints and bedding planes, rather than by any single degradational process. A pelagic drape averaging 3 to 5 meters in thickness blankets the slope. Carbon-14 dates from eight drop cores show that the drape was deposited in late Pleistocene and Holocene times. The Holocene part of the drape, comprising the uppermost 1 meter, was deposited at a continuous rate of 10 centimeters per 1000 years. Most features on the slope predate the drape cover.

Neonatal high-frequency jet ventilation: four years' experience.

During a 4-year period, 34 neonates were treated with high-frequency jet ventilation (HFJV) using two different HFJV systems. Twenty-three of the neonates had severe pulmonary air leaks, five had congenital left-sided diaphragmatic hernias, and six had end-stage respiratory failure without pulmonary air leaks. The two HFJV systems performed similarly in all pathologic conditions. Following HFJV, arterial blood gas values improved in 28 of the 34 patients (82%). Eleven patients (32%) ultimately survived. Of 23 patients with pulmonary air leaks, 17 (74%) improved, nine (39%) survived. One infant with diaphragmatic hernia and one with end-stage respiratory failure survived. Ten of 12 patients (85%) who died following eight or more hours of HFJV had significant tracheal histopathology in the region of the endotracheal tube tip. The lesions ranged from moderate erythema to severe necrotizing tracheobronchitis with total tracheal obstruction. HFJV can be useful in the treatment of severe pulmonary air leaks in neonates and may prove useful in the treatment of congenital diaphragmatic hernias. However, HFJV produces inflammatory injuries in the proximal trachea. More clinical and laboratory studies are needed to define the relative risks and benefits of this new therapy.

Neonatal apnea associated with maternal clonazepam therapy: a case report.

A 2750-g female infant was born at 36 weeks' gestation to a 40-year-old woman treated with clonazepam throughout her pregnancy. The infant developed apnea, cyanosis, and hypotonia within a few hours of birth. The mother's serum clonazepam level at delivery was 32 ng/mL; the cord blood level was 19 ng/mL. The infant had no congenital malformations, evidence of infection, or seizures. Clinical episodes ceased by ten days of age. The woman elected to breastfeed; breast milk clonazepam levels were between 11 and 13 ng/mL. She was discharged with a cardiorespiratory monitor. The authors suggest that infants of mothers receiving this agent during pregnancy or while nursing have serum levels measured. Additionally, these infants should be monitored for central nervous system depression or apnea.

MR of the spinal cord in a patient with herpes zoster.

Increased signal intensity on initial magnetic resonance images of the spinal cord in a patient with herpes zoster demonstrated that this virus caused inflammation of the cervical spinal cord. This pathology corresponded well with neurologic deficits seen clinically, but the extent of the neurologic deficits ultimately could not be determined by magnetic resonance of the spinal cord alone because the nerve roots were also affected.

Invasive central nervous system aspergillosis: cure with liposomal amphotericin B, itraconazole, and radical surgery--case report and review of the literature.

Invasive aspergillosis of the central nervous system is a rare but well-described disease. There have been only a few reported survivors, and mortality exceeds 95% in the immunosuppressed host. We present a 2-year-old boy with acute lymphatic leukemia and multiple Aspergillus brain abscesses who was successfully treated with liposomal amphotericin B, itraconazole, and surgical excision of the abscesses. Liposomal amphotericin B is a new preparation that safely allows the attainment of significantly higher tissue levels with less toxicity than standard amphotericin B. The treatment of patients with invasive central nervous system aspergillosis is reviewed.

Hypercarbic ventilatory responses of infants at risk for SIDS.

We examined the hypercarbic ventilatory responses (HVR) of 143 infants at risk for sudden infant death syndrome (SIDS) and 34 normal control infants. Sixty-five of the at-risk infants had experienced apparent life-threatening events (ALTE), and 78 were siblings of SIDS victims. Twenty-three (35%) of the ALTE infants experienced subsequent apnea; one died of SIDS. Seven (9%) of the SIDS siblings experienced subsequent apnea; two ultimately died of SIDS. In the HVR studies, we measured tidal volume (VT), minute ventilation (VE), frequency of breathing (f), and end-tidal PCO2 (PETCO2) at rest and while breathing 2% and 4% CO2. Mean HVR vales for the ALTE, sibling, and control groups were all similar. The mean HVR values for those at-risk infants who experienced subsequent apnea were not different from those who did not experience subsequent apnea. However, those infants experiencing subsequent apnea had higher mean VT/kg values (P less than 0.01) and lower mean PETCO2 values (P less than 0.001) than those who did not. The SIDS siblings had significantly lower resting VT/kg values than either the near-miss infants or normal controls (P less than 0.01). We did not find depressed HVR values in infants at risk for SIDS. On the contrary, those infants who experienced subsequent apnea had evidence suggesting relative hyperventilation. SIDS siblings had evidence suggesting relative hypoventilation. These findings are interesting and thought-provoking. However, HVR studies do not appear to be sensitive, specific, or appropriate for the general screening of infants at risk for SIDS.

Identifying lung overdistention during mechanical ventilation by using volume-pressure loops.

We measured the pulmonary mechanics of 23 mechanically ventilated neonates. Airway pressures, inspiratory and expiratory flows were simultaneously measured. Values for respiratory system mechanics were then derived from these data by using a personal computer and a special software program. Volume-pressure (V-P) loops and respiratory system compliance values were determined for representative mechanical breaths. Twelve infants had normal-appearing V-P loops. Eleven had V-P loops characteristic of lung overdistention, showing decreasing changes in volume with progressive increases in pressure. To quantify this visual observation, we determined the change in compliance during the last 20% of inspiration (C20). We then compared this value to the total compliance value for the entire breath (C) using the ratio C20/C. Mean values for C, C20, and C20/C were compared for the two patient groups. Total respiratory system compliance values were similar. C20 values were decreased in those patients with V-P loops showing overdistention. C20/C values were significantly decreased in those patients with V-P loop evidence of overdistention. Patients with V-P loop evidence of overdistention all had C20/C values less than 0.8. Those with normal-appearing V-P loops all had C20/C values greater than 1.0. The C20/C ratio appears to effectively quantitate visual V-P loop evidence of lung overdistention during mechanical ventilation.

The effects of bedside pulmonary mechanics testing during infant mechanical ventilation: a retrospective analysis.

We examined the effects of regular bedside testing of pulmonary mechanics (PM) on the outcome of 468 acutely ill, mechanically ventilated neonates. During the first of two 18-month study periods, 217 infants were mechanically ventilated without the assistance of PM measurements. During the second 18-month period, 251 infants were ventilated with the assistance of at least daily PM measurements. Using data obtained from the PM tests, we adjusted the infants' ventilators to maintain tidal volume, inspiratory time, and pressure-volume loops within predetermined limits. With the exception of the PM measurements, given the limitations of retrospective analyses, both groups of infants received identical medical and nursing care. The infants ventilated with the assistance of PM testing developed fewer pneumothoraces (4.0%; 10/251) vs. no PM testing, 10.1% (22/217); P < 0.05 by Chi-square analysis]. Infants weighing less than 1,500 g ventilated with the assistance of PM measurements had less intraventricular hemorrhage (IVH) overall, most notably, less grades I and II IVH (total IVH-PM testing, 39.1% vs. no PM testing, 65.7%; P < 0.01; Grades I-II IVH-PM testing, 30.4% vs. no PM testing, 54.9%; P < 0.01). IVH incidence was decreased independent of pneumothorax occurrence. Survival rates, incidences of bronchopulmonary dysplasia, and durations of mechanical ventilation and hospitalization were similar. This retrospective analysis suggests that PM testing during infant mechanical ventilation reduces common acute ventilator-associated complications.

Comparison of high-frequency oscillatory ventilation and high-frequency jet ventilation in cats with normal lungs.

Four adult cats received alternating high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) at equivalent proximal airway pressures. Physiologic measurements were made before and after each ventilator change. Proximal airway pressures were then adjusted as necessary to reestablish normal pH and PaCO2 values. Aortic, pulmonary artery, and central venous pressures were monitored. Cardiac outputs were measured. Pulmonary and systemic vascular resistance, intrapulmonary shunt, and alveolar-arterial oxygen gradient were determined. Following the change from HFOV to HFJV at similar proximal airway pressures, HFJV always produced higher pH values (P less than 0.0001), higher PaO2 values (P less than 0.05), lower PaCO2 values (P less than 0.0001), as well as higher cardiac outputs (P less than 0.01), lower pulmonary artery pressures (P less than 0.001), and lower pulmonary vascular resistances (P less than 0.001). Following the reciprocal crossover, from HFJV to HFOV, HFJV pH values were again higher (P less than 0.001), and PaCO2 values were again lower (P less than 0.001). A comparison of HFOV and HFJV at similar pH and PaCO2 values showed that HFOV consistently required higher peak inspiratory pressures (P less than 0.001), higher mean airway pressure (P less than 0.001), and higher pressure wave amplitudes (P less than 0.001). Under the circumstances of this study, HFJV produced better gas exchange at lower proximal airway pressures.

Urinary excretion of aminohydroxypropylidene bisphosphonate in cancer patients after single intravenous infusions.

The effect of the rate of infusion of disodium aminohydroxypropylidene bisphosphonate (APD; CGP 23339A), an inhibitor of bone resorption, on urinary excretion of this agent was studied in a randomized open-label study in 20 cancer patients. Ten patients received 60 mg of APD over 4 h, and the remaining 10 patients received the same dose over 24 h. Urine collected during specified intervals for 72 h after the start of the infusion was analyzed by high-performance liquid chromatography for unchanged APD. Mild and transient adverse experiences were observed in 12 (60%) patients; the most common were headache, fever, and phlebitis at the infusion site. No clinically significant laboratory abnormalities were observed, and none of the experiences were serious enough to require discontinuation of treatment. Cumulative urinary excretion of APD was a linear function of time, increasing rapidly after both the 4- and 24-h infusions were started. The mean (+/- standard deviation) cumulative urinary excretion of APD was 51.1 +/- 13.0% of the dose in the 20 patients, 55.0 +/- 15.0% in the 10 patients given the 4-h infusion, and 47.2 +/- 9.9% in the 10 patients receiving the 24-h infusion. Thus, the rate of infusion of the 60-mg dose did not influence retention of APD at 72 h after the start of therapy. Similarly, the presence or absence of bone metastases did not influence cumulative urinary excretion or the retention of APD.

Otitis media. Incidence, duration, and hearing status.

The middle ear status and hearing sensitivity in 483 normal infants have been closely monitored as part of the Dallas Cooperative Project, University of Texas at Dallas, effort to assess the effect of early otitis media with effusion on speech and language development. At least one episode of otitis media with effusion occurred in 73.5% of the children between the ages of 6 and 18 months. Almost a quarter of these were discovered at "well-baby" checkups and were appropriately classified as "silent." The hearing levels, the methods of hearing assessment, and the implications of these data are described.

The management and clinical course of testicular seminoma: 15 years' experience at a single institution.

Testicular seminoma is one of the most curable solid neoplasms, with 5-year survival rates in excess of 90%. However, controversy persists around its optimum management, particularly for Stage I disease. The outcome of 314 patients with testicular seminoma who were treated at a single institution is reported. A comparison of adjuvant radiotherapy and surveillance for Stage I is presented, and the possible prognostic influence of an elevated serum beta-human chorionic gonadotrophin (beta hCG) is assessed. The 5-year disease-free survival for all stages of presentation was 95.5%. There were more relapses in Stage I patients undergoing surveillance (14/94, 15%) than postorchidectomy radiotherapy (6/144, 4%; P = < 0.05). However, survival was identical irrespective of treatment policy, with no disease-related deaths in either group of Stage I patients. There were eight tumour-related deaths from advanced disease and 14 deaths from non-tumour causes. Three were due to cardiorespiratory disease, four to an unrelated second malignancy, two from infection and one from suicide; in four patients, the cause was unknown. Preoperative beta hCG was elevated in 29 (18%) of Stage I patients and in 24 (62%) of those presenting with Stage II disease. Patients were more likely to have advanced disease (> or = Stage II) if beta hCG was elevated (P < 0.001). Neither disease-free nor overall survival were influenced by the preoperative level of beta hCG. Surveillance appears to be a safe alternative to postorchidectomy radiotherapy for Stage I disease, provided the patient is prepared for intensive long term follow-up. An increased risk of relapse, but not of tumour death, can be expected and unnecessary treatments avoided.

The management and survival of patients with advanced germ-cell tumours: improving outcome in intermediate and poor prognosis patients.

AIMS: The survival of germ-cell tumours (GCT) was transformed after the introduction of cisplatin-based therapy. Previous trials have indicated BEP (bleomycin, etoposide and cisplatin) as the optimum treatment, although some centres including our own advocate the use of the alternating regimen POMB-ACE (cisplatin, vincristine, methotrexate, bleomycin and dactinomycin, cyclophosphamide and etoposide) for men with intermediate or poor prognosis disease. We analysed the survival and management of GCT patients treated at a specialist cancer centre in relation to internationally recognised prognostic groupings. MATERIALS AND METHODS: We retrieved patient information using the Trent Testicular Tumour Registry and supplemented it with information from patient notes. This included all patients with Royal Marsden Hospital Stage II, III and IV disease and patients with stage I disease at diagnosis with raised markers or subsequent relapse. We compared the efficacy and toxicity of the BEP and POMB-ACE chemotherapy regimens, and assessed relapse-free and overall survival. RESULTS: We identified 178 non-seminomatous germ cell tumours (NSGCT) and 71 seminoma patients. Overall survival was similar to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification for the good (95% vs 92%) and intermediate groups (82% vs 80%). The outcome for the poor prognosis group was better than expected in our series (57% vs 48%). There was a higher proportion of both immediate and late side-effects with POMB-ACE. CONCLUSION: Survival and disease progression rates at this single institution were at least as good as reported by the IGCCCG and somewhat better for the poor-prognosis group. This may reflect use of the POMB-ACE chemotherapy regimen as opposed to standard BEP regimen. However, a randomised comparison of BEP and POMB-ACE would be required to validate this.

Neonatal transcutaneous arterial oxygen saturation monitoring.

Transcutaneous arterial oxygen saturation (TcSaO2) and directly measured oxygen saturation values from 25 neonates with a variety of respiratory problems were compared. At arterial oxygen saturations above 60 per cent, TcSaO2 measurements were accurate and reliable. However, SaO2 values less than 60 per cent were significantly overestimated by TcSaO2, so careful laboratory confirmation of low SaO2 values is necessary. The use, accuracy, and limitations of this noninvasive transcutaneous technique for measuring arterial hemoglobin-oxygen saturation are discussed.

Synovial fluid lactic acid in septic arthritis.

Lactic acid concentrations in the synovial fluid of 71 patients with inflammatory arthritis were determined by an enzyme method. In 63 samples from 54 patients with a variety of non-septic arthritides, including rheumatoid arthritis, reactive arthritis and gout, the concentration of lactic acid was never greater than 10.2 mmol/l, whereas all twelve patients with septic arthritis had concentrations of 11 mmol/l or greater. Two patients with gonococcal arthritis did not have raised lactic acid concentrations. The enzyme method of lactic acid estimation is an accurate reproducible means of differentiating septic from nonseptic arthritis prior to the isolation of the infecting organism. However, caution is necessary when interpreting the results in those patients who have recently received antibiotic therapy, or in whom gonococcal arthritis is suspected.

Similarities in the social competencies of learning disabled and low achieving elementary school children.

This study sought to examine distinctions in social competencies between children with learning disabilities (LD) and other children who also experience academic difficulties. Eighty-five children with LD (54 male, 31 female) in Grades 3 through 6 from a large urban school district were compared to a group of low achieving (LA) peers matched on achievement as well as sex, race, and grade. The samples were 42% black, 39% Hispanic, and 19% Anglo. Both groups completed two self-concept questionnaires, a loneliness scale, and a measure of their social relationships outside of school. In addition, their classmates completed a peer rating scale and their teachers completed two ratings of the child's social skills. The results indicated that children with LD and LA children were comparable on most measures, although children with LD reported themselves as being less lonely than LA children. In addition, regular-class children rated children with LD as more likable than LA children. The results highlight similarities in the social competencies of children with LD and LA children and suggest that special education classes may offer some social advantages to children with mild handicaps.

Learning disabilities and social competence: a social ecological perspective.

To explore the relationship between learning disabilities (LD) and social competence, various indexes of social and academic competence were collected from a sample of students with LD, as well as a matched sample of children without disabilities, in Grades 3-6. Measures included academic grades, teacher perceptions, peer perceptions, self-perceptions, social network outside of school, and direct observation of social interactions. Results suggest that children with LD differ from children without disabilities on virtually all indexes of academic competence, regardless of social status. In the social domain, children with LD had higher self-concept scores than did children without disabilities. Most social differences were linked to the child's peer status, independent of disability.