Hepatic rupture caused by peliosis hepatis.

Peliosis hepatis is a rare entity that can affect children and cause fatal hepatic hemorrhage or hepatic failure. Radiographic findings are nonspecific and can resemble other hepatic pathologies such as cysts, abscesses, metastases, and hemangiomatosis. Peliosis hepatis can resolve spontaneously or by withdrawal of inciting medications. Certain cases may require surgical resection of the involved portions of the liver. Recently, fatal liver hemorrhage was reported in 2 pediatric patients with a rare congenital muscle disorder known as myotubular (centronuclear) myopathy. One of these patients was found at autopsy to have peliosis hepatis. The authors report the first successful treatment of life-threatening liver hemorrhage caused by peliosis hepatis in a child with myotubular myopathy. Awareness of this condition may reduce the catastrophic complications seen with peliosis hepatis.

Selective screening for cervical neoplasia: an approach for resource-poor settings.

BACKGROUND: Cervical malignancies are the leading cause of cancer-related morbidity and mortality among women in developing countries. Although early detection programmes using cytological methods, followed by aggressive treatment of precursor lesions are accepted as the main disease control strategy, fiscal limitations make this strategy unfeasible in many countries. METHODS: To screen selectively, we developed two risk scores using data from a population-based case-control study in Jamaica with 202 cases and 363 controls. Independent risk factors for cervical neoplasia were determined using logistic regression. An unweighted risk score for each subject was developed by a simple count of risk factors present and a weighted risk score was calculated by summing regression coefficients for each risk factor. RESULTS: Four patient characteristics were independently predictive of cervical neoplasia, older age (OR = 3.4, 95% CI : 1.8-6.7), > or = 4 pregnancies (OR = 5.6, 95% CI : 1.2-18.7), poverty (OR = 2.1, 95% CI : 1.3-3.3) and cigarette smoking (OR = 1.9, 95% CI : 1.2-3.2). Using cut-off points of > or = 20 for the weighted scores and > 3 for unweighted scores, the sensitivity and specificity were 65% and 69% for the unweighted score and 75% and 61%, respectively, for the weighted score. Areas under the receiver operating characteristic (ROC) curves for the weighted versus the unweighted scores were similar, suggesting similar overall accuracy. CONCLUSION: Selective screening using risk assessment strategies is potentially useful, particularly in resource-poor settings. However, whether weighting factors is essential is dependent on prevalence of factors in a given setting. Although this approach needs validation in other populations, women at highest risk for cervical neoplasia can be identified using demographic factors available during a regular clinic visit.

The transition to high school for academically promising, urban, low-income African American youth.

In nine urban Ohio school systems, low-income minority students identified as academically promising in sixth grade are eligible to participate in an intervention program. In the present study, twenty-two African American students in the program were asked to provide their perceptions of the transition to ninth grade. Specifically, the role of motivating factors, peers, school, teachers, parents, and neighborhood were examined. These students faced similar stressors, yet some were more able to achieve academic success. Results highlight the salience of mothers, the challenges of the ninth-grade curriculum, and adjustment to a bigger, more complex school environment for high and low performers. The implications for improving cooperation between school and family are discussed.

Phase I trial of intoplicine (RP 60475) administered as a 72 h infusion every 3 weeks in patients with solid tumors.

Intoplicine (RP 60475) was selected for a phase I evaluation because it inhibits topoisomerase I and II, and has exhibited antitumor activity against a variety of preclinical solid tumor models. Intoplicine is a 7H-benzo[e]pyrido[4,3-b]indole that inhibits DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA. Twenty-eight patients with refractory advanced malignancies who met standard phase I eligibility criteria were enrolled in a dose-escalation study of intoplicine, ranging from 7 to 420 mg/m2/day administered as a continuous 72 h i.v. infusion. Fifty-three courses were administered and evaluated. Myelosuppression (four patients, grade 3; two patients, grade 4) and hepatic toxicity (one patient, grade 3) were dose limiting at 336 mg/m2/day. No objective antitumor responses were observed. The pharmacokinetic parameters of intoplicine were investigated in 11 patients at dose levels of 112 (n=1), 224 (n=3), 336 (n=6) and 420 (n=1) mg/m2/day. Both the area under the plasma concentration versus time curves and the maximum plasma concentrations increased linearly within the dose range studied. Intoplicine content measured in whole blood exceeded that found in plasma by 3- to 7-fold, indicating that red blood cells may serve as a drug reservoir. Preclinical cytotoxic concentrations were not achieved at the dose levels studied.

What does it take to have a positive impact on minority students' college retention?

This paper describes the Young Scholars Program (YSP), which seeks to expand the pool of African American and other underrepresented minority youth who aspire to attend college, and to help them meet entrance requirements and successfully obtain a college degree. Quarter-by-quarter data for the first two groups of YSP students entering The Ohio State University were promising. Their retention rates approximated university averages, while comparison groups showed lower levels of retention. It was concluded that the many facets of the Young Scholars Program, as well as the students' positive reputation among family members, peers, and teachers, produced strong motivation, ability, and determination to succeed.

Incidence of hypercalcemia in patients with malignancy referred to a comprehensive cancer center.

BACKGROUND: Hypercalcemia is a serious and not infrequent complication of malignant diseases; precise information about the incidence of hypercalcemia is not readily available. The study was designed to determine the incidence of hypercalcemia in patients with cancer. METHODS: Retrospective analysis was done of laboratory data from 7667 patients registered at M.D. Anderson Cancer Center for the first time during 1989 for whom serum calcium levels were determined during the first 2 months after registration. RESULTS: Severe hypercalcemia (serum calcium level of more than 12.0 mg/100 ml) was present in 40 patients (0.52%); it occurred most often in patients with renal cell cancer (1.42%) and non-small cell lung cancer (1.03%). Less frequent diagnoses were multiple myeloma (0.79%), leukemia (0.63%), non-Hodgkin lymphoma (0.26%), and cancer of the gastrointestinal tract (0.20%). Moderate hypercalcemia (calcium levels of 10.8-12.0 mg/100 ml) was present in 48 patients (0.63%); it occurred most often in patients with renal cell cancer (3.30%) and multiple myeloma (2.38%). Less frequent diagnoses were non-small cell lung cancer (0.89%), non-Hodgkin lymphoma (0.79%), leukemia (0.63%), and cancer of the gastrointestinal tract (0.51%). The presence of hypercalcemia was associated with increased frequency of distant metastases, bone metastases, and increased mortality consistent with other studies of the prognostic effect of this complication. CONCLUSIONS: Hypercalcemia may appear as a frequent complication in patients with cancer at some time during the course of their disease, but its incidence is relatively low.

Phase I trial of Taxotere: five-day schedule.

BACKGROUND: Taxotere, a semisynthetic compound structurally related to taxol, has a broad spectrum of activity in murine transplantable tumors; in the B16 melanoma model, it caused a total log cell kill 2.5 times greater than that caused by taxol at equitoxic doses. PURPOSE: We conducted a phase I study of Taxotere (a) to determine its qualitative and quantitative toxic effects and a starting dose for phase II trials, (b) to investigate its clinical pharmacology, and (c) to document its antitumor activity. METHODS: Taxotere was given as a 1-hour infusion at a starting dose of 1 mg/m2 per day for 5 consecutive days. The 5-day course of therapy was repeated every 21 days. Thirty-nine cancer patients with advanced disease were entered in the study; at least three patients were entered at each dose level. Initial dose escalations were planned at 100% increments until biologic activity was observed; subsequent escalations were planned at 50% increments until grade 2 toxicity (the National Cancer Institute's Common Toxicity Criteria) occurred and then at 25% increments until the maximum tolerated dose was established. RESULTS: Thirty-nine patients were entered in the study. Successive dose levels used were 1, 4, 8, 16, 12, and 14 mg/m2 per day. The dose-limiting toxic effects were granulocytopenia and concurrent mucositis. Grade 4 granulocytopenia associated with grade 3 mucositis developed in six of 12 patients treated at a dose of 16 mg/m2 per day, two of 10 treated at 12 mg/m2 per day, and two of eight treated at 14 mg/m2 per day. Because these toxic effects occurred concurrently, all patients so affected developed neutropenic fevers and required hospitalization. Neither cardiac nor neurologic toxic effects were noted. Anti-tumor activity was observed in six patients with ovarian cancer and in one with breast carcinoma. Although pharmacokinetic parameters were consistent between day 1 and day 5 for individual patients, considerable variation existed among those treated at the same dose level. A relationship was observed between the area under the curve for plasma concentration of drug x time (AUC) on day 1 and the percentage decrease in absolute granulocyte counts. CONCLUSION: Granulocytopenia associated with oral mucositis is the dose-limiting toxicity of this schedule. We recommended a starting dose of 14 mg/m2 per day for phase II studies of this 5-day schedule. Dose modifications on days 2-5 based on the day-1 AUC may allow individualized dosing.

Chemotherapy resistant sarcoma treated with whole body hyperthermia (WBH) combined with 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

Seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with 1-3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Two patients (12%) experienced partial responses (PR). In addition, four objective tumour responses (OR) lasting more than 4 months were documented. One patient with previously rapidly growing chondrosarcoma pulmonary metastases experienced stable disease (SD) for 38 months from the onset of treatment. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. Cumulative thrombocytopenia was a therapy-limiting toxicity of the combined treatment, and occurred in six of seven patients. Acute toxicities attributable to WBH alone included transient thrombocytopenia in all patients, non-cardiogenic pulmonary oedema in two patients, and mild hypotension in five patients. Acute granulocytosis was observed in all patients. No treatment related deaths occurred. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases.

Phase I trial and clinical pharmacology of elsamitrucin.

Elsamitrucin (BMY-28090) is an antitumor antibiotic first described in 1985 that has significant oncolytic activity against a number of murine tumors including P388, L1210, B16 and M5076, as well as against MX1 and HCT116 xenografts. Preclinical toxicology studies of elsamitrucin revealed edema of multiple organs associated with hypoproteinemia and, at lethal doses, severe multiorgan toxicity. We conducted a phase I clinical trial (31 patients) of elsamitrucin administered as a 10-min i.v. infusion every 3 weeks. The starting dose (0.6 mg/m2) was 1/3 of the dog low toxic dose. The maximum tolerated dose was 30 mg/m2. Dose-limiting toxicity was reversible hepatic dysfunction manifested by elevated transaminase levels not associated with bilirubin, alkaline phosphatase, or lactate dehydrogenase elevations. Other toxicities included nausea, vomiting, malaise, and phlebitis. Because the hepatic toxicity was brief and reversible, a subsequent study (18 patients) was conducted with elsamitrucin administered every 2 weeks. Reversible grade 3 hepatotoxicity was again observed at 30 mg/m2. Plasma and urine samples from patients receiving doses of 0.6-36 mg/m2 were analyzed for drug content. The maximum plasma concentration and area under the plasma concentration versus time curve values increased linearly with doses up to 25 mg/m2 but not at higher doses. The terminal half-lives, total body clearances, and volume of distribution were 36-60 h, 10-19 liters/h/m2, and 400-1100 liters/m2, respectively. Less than 5% was excreted in the urine in 24 h as parent compound. Bile was collected from one patient with an indwelling biliary catheter. Approximately 22% of the dose was excreted in 48 h, suggesting that biliary excretion of elsamitrucin may be an important route of drug elimination. Based on reversible hepatic toxicity, the phase II recommended dose of elsamitrucin is 25 mg/m2 every 2 weeks.

Signaling by vascular cell adhesion molecule-1 (VCAM-1) through VLA-4 promotes CD3-dependent T cell proliferation.

Vascular cell adhesion molecule, VCAM-1, is an adhesion molecule expressed on activated endothelium thought to play a role in leukocyte migration to sites of inflammation. VCAM-1 adheres to leukocytes through the VLA-4 integrin. Recombinant soluble VCAM-1 (rsVCAM) and anti-CD3 mAb OKT3 were utilized to address the role of the VCAM-1/VLA-4 pathway in antigen-dependent T cell activation. Monocyte-depleted T cells proliferated upon exposure to co-immobilized OKT3 and rsVCAM but to neither alone. In contrast, an anti-VLA-4 mAb HP1/2 failed to co-activate with OKT3, despite the fact that both rsVCAM and HP1/2 support T cell adhesion comparably. These data indicate that adhesive function is not sufficient for co-stimulatory activity. They also reveal that VCAM-1 may play a role in regulating T cell immune responses as well as migration in vivo.

Expression and functional characterization of a soluble form of endothelial-leukocyte adhesion molecule 1.

Endothelial leukocyte adhesion molecule 1 (ELAM1) is a leukocyte adhesion molecule induced on human venular endothelium in vitro and in vivo by inflammatory stimuli. A truncated cDNA for ELAM1 has been constructed, stably expressed in Chinese hamster ovary cells, and the secreted recombinant soluble form of ELAM1 (rsELAM1) purified to homogeneity by immunoaffinity chromatography. rsELAM1, when immobilized on plastic, is fully functional as an adhesion protein, and selectively binds only cells known to bind cell-surface ELAM1 expressed on human endothelial cells, including the myelomonocytic cell line HL60 and the colon carcinoma cell line HT29. Immobilized rsELAM1 also binds human PMN, monocytes, NK cells, and T cells. T cell subset analyses indicate preferential binding of CD4+ T memory cells. However, rsELAM1 is only a weak inhibitor of ELAM1-mediated adhesion. rsELAM1 should prove valuable for the further study of the role of ELAM1 expressed on the vascular wall during the inflammatory response.

Hepatobiliary cystadenoma: a rare hepatic tumor in a child.

This report describes a 3-year-old child with a hepatobiliary cystadenoma. Cystadenomas are benign, multilocular, cystic neoplasms that usually occur in middle-aged women. The patients may be asymptomatic, but often there are vague abdominal complaints related to extrinsic compression of the stomach, duodenum, or biliary tree. Recurrence following incomplete excision and the presence of carcinoma within otherwise benign cysts has been documented. Complete resection is the therapy of choice, and thorough histopathologic evaluation is imperative.

Pleuroperitoneal shunts in the management of persistent chylothorax.

Between June 1981 and June 1988, we placed pleuroperitoneal shunts in 16 patients for the management of refractory chylothorax on the Pediatric Surgical Service, University of Virginia. The cause of the chylothorax was caval thrombosis from central venous catheters in 5 patients, idiopathic in 3, and mediastinal lymphangioma in 2, and in 6, it developed after a cardiac procedure. Chylothorax in each patient was unresponsive to thoracentesis, tube thoracostomy, and dietary manipulations. A Denver double-valved shunt system is currently employed and is implanted using general anesthesia. Manual pumping is required postoperatively for several months. Twelve (75%) of the 16 patients had excellent results with complete elimination of the chylothorax and resolution of symptoms. In 10 of these 12, the shunt has been removed. Four had an unsatisfactory result: 3 had inferior vena cava hypertension, and 3 were low-birth-weight premature infants. Four patients seen early in this series required revision of the position of the pleural catheter, with successful drainage in each instance. Pleuroperitoneal shunting is a safe, simple, and effective treatment of chylothorax in infants and children. In view of our success in treating chylothorax with these shunts, we recommend early shunting before the development of nutritional or immunological depletion.

The changing nature of the parent-adolescent relationship from early to late adolescence.

This research analyzes changes in the parent-child relationship that help clarify the balance between individuation and cohesiveness over the period from age 11 to 17. Data were collected from mothers, fathers, and oldest children in 110 families whose oldest child was 11, 14 or 17. Three methods were involved: a survey of attitudes about family decision making, independence, love, understanding, and satisfaction with parenting; Loevinger's measure of ego level for parents and children; and an open-ended assessment of qualities family members admired in one another. The results provide insight into expectations and processes involved in revising the quality of parent-child relationships during early adolescence.

Patient-controlled analgesia in pediatric surgery.

Patient-controlled analgesia (PCA) with a microprocessor-operated infusion syringe was first suggested for human use in 1965. Clinical studies from the United States and Europe have shown this form of analgesia to be well accepted by adults, but the use of this technology for children has not been studied. We evaluated PCA in 15 consecutive pediatric surgical patients between the ages of 11 and 18 years undergoing major thoracic or abdominal surgery. The patients and their parents were instructed in the use of the equipment prior to surgery and PCA was initiated after the patients left the recovery room. The mean duration of PCA was 2.6 days. No serious mechanical difficulties with the infusion apparatus were encountered. The acceptance of PCA was excellent with only two patients preferring some other method of analgesia. Pain relief was assessed twice daily by a registered nurse using a verbal-visual pain scale. On a 1 to 10 scale average pain relief was 7.2. Eight of the patients had had a previous operation, and seven of these reported that PCA was a better method of achieving pain control. A comparison of the 15 study patients with 15 previous patients with similar procedures indicated that PCA patients used less analgesia in the postoperative period, although they tended to use more in the first 24 hours. PCA is found to be a safe and effective means of analgesia in pediatric patients. Adequate pain relief was achieved with less analgesia and with less nursing attention. This technology is recommended for postoperative pediatric patients.

Long-term pancreatic-biliary diversion in the rat: persistent loss of mucosal enterokinase, with reinduction by delayed oral pancreatic biliary supplementation.

Diversion of pancreatic-biliary (PB) secretions in rats for 23 days led to loss of enterokinase (EK) activity in bypassed segments of the small intestine. Simultaneous oral trypsinogen and bile salt (TB) supplements prevented the loss of EK activity. To study the temporal course of events after PB diversion and to determine if the loss of EK is reversible, PB diversion was performed in rats by surgical transposition of the 4-cm segment of duodenum including the ampulla of Vater to a point 30 cm distal to its original site. Bypassed and control (sham- and nonoperated) rats fed standard rat chow were sacrificed at 10, 23, and 45 days after surgery. One bypassed group was fed standard chow for 23 days and then chow supplemented with TB until sacrifice at 45 days. At sacrifice, the intestines were divided into segment 1 (the bypassed proximal 30 cm) and segment 2 (the 30 cm distal to the bypass). In segment 1, EK disappeared almost completely by 10 days and remained at the same low levels at both 23 and 45 days (p less than 0.05). No significant changes in EK levels were found at any time in segment 2 distal to the bypass. Mucosal disaccharidase activity in segment 1 increased or showed no change. In rats with delayed TB supplementation, EK activity in segment 1 returned almost to control levels at the time of sacrifice. The results confirm the importance of PB secretions in the maintenance of EK activity. The effects of bypass on EK are both enzyme- and site-specific.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of high school on social development.

In reviewing the literature on the social impact of high school, six themes were identified: (1) students perceive strong norms for conformity to school rules, (2) the emphasis on conformity and control influences the quality of student/teacher relations which tend to be role bound and inflexible, (3) paths to social status continue to emphasize athletic competence, (4) peer group identification has an impact on social relations within the larger community as well as in the school setting, (5) powerlessness is felt as a result of the authoritarian approach to decision making, and (6) the overall high school environment does not enhance students' beliefs in the Bill of Rights. It was concluded that high school students have limited opportunities for flexible self-definition. As a result of the way they are treated by authority figures and the strong pressures toward conformity, many adolescents fail to learn the extent of their rights or effective strategies for the exercise of power.

Advances in the management of infected urachal cysts.

Persistent urachal remnants are uncommon congenital anomalies. Unless an umbilical fistula exists, infection may be the first indication of this abnormality. Five children received initial treatment for this problem at the Children's Hospital of Buffalo during a 20-year period, 1964 to 1984, and a sixth was seen secondarily. There were four boys and two girls; their ages ranged from 8 months to 9 years. Lower abdominal mass with fever and local tenderness were the most common presenting signs. Ultrasound was the most accurate study, correctly diagnosing the cyst in both patients so examined. Incision and drainage alone was performed in one patient. The other five were managed with antibiotic therapy and complete excision as the primary procedure. Cultures were obtained in five patients and were positive in four, growing Staphylococcus aureus in three and Escherichia coli in one. Significant genitourinary abnormalities were discovered in four of the five patients evaluated. It is concluded that the previously recommended therapy of incision and drainage followed by delayed resection was developed in the preantibiotic era to minimize the mortality from sepsis and the morbidity from recurrence. Our experience indicates that the use of appropriate antibiotics followed promptly by complete cyst excision as a primary procedure is both possible and safe in most cases. Furthermore, the large number of associated genitourinary abnormalities suggests that a complete work-up for these conditions should be performed.

Percutaneous central venous catheterization in children: first line choice for venous access.

Percutaneous central venous (CV) catheters using the jugular and subclavian veins have been widely used for hemodynamic monitoring and for venous access in difficult clinical situations. However, peripheral venous cutdowns (PVC) still remain the primary mode of short-term venous access in children. To evaluate percutaneous CV line insertion as a routine procedure, a prospective study of 115 patients (75 CV and 40 PVC) was performed. Ages ranged from 1 day to 17 years; age and weight were similar in both groups. Eighty-three CV lines were attempted, with a success rate of 93%, while 82% of 49 PVC insertions were successful. Complications occurred in 11 (14%) patients with CV access and 31 (78%) with PVC lines. In the latter group, poor flow was a problem in 65%, infiltration in 37.5%, and phlebitis in 27.5%. In the CV group, arterial puncture occurred during insertion in 2 (3%) patients with no adverse sequelae, catheter slippage occurred in 4 (5%), and poor flow in 2 (3%). A large majority (79.2%) of CV lines functioned successfully until no longer needed, as compared with 15% of PVC catheters. The latter were removed before completion of treatment because of poor flow (40%), phlebitis (20%), or catheter problems (10%). Catheter sepsis was documented in only one CV line. Two cutdowns had major local infections. The average catheter longevity was 10.2 days for CV lines, 4.1 days for PVC.(ABSTRACT TRUNCATED AT 250 WORDS)