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Biomedical subjects

B M Newman

Publications and source records attributed to B M Newman.

At least 19 recordsLinked to original sources
PubMed1993

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.

Adolescent↗
PubMed1992

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.

Adult↗
PubMed1992

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.

Adult↗
PubMed1991

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.

Amino Acid Sequence↗
PubMed1991

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.

Antigens, CD↗
PubMed1990

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.

Child, Preschool↗
PubMed1989

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.

Adolescent↗
PubMed1989

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.

Adolescent↗
PubMed1988

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.

Adolescent↗
PubMed1988

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)

Animals↗
PubMed1987

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.

Achievement↗
PubMed1986

Presentation of congenital diaphragmatic hernia past the neonatal period.

Congenital diaphragmatic hernias (CDHs) presenting beyond the neonatal period are a rare and unusual problem; they occurred in 11 of 83 children at our institution. Two discrete clinical groups were apparent: (1) younger children, with mainly respiratory symptoms; and (2) older children with gastrointestinal (GI) complaints. Chest roentgenograms suggested CDHs, but GI contrast studies were necessary for confirmation in eight patients. The diagnosis was made preoperatively in ten of 11 children. At operation, no peritoneal sacs were found, the hernial contents were viable in all patients, and malrotation was present in six of 11 patients. None had evidence of pulmonary hypoplasia. Congenital diaphragmatic hernias do present beyond the neonatal age group in a significant number of cases (13% in our series), and a diagnosis of CDH should be considered in any child with persistent GI or respiratory problems and abnormal chest x-ray film findings. The mortality rate in these patients is small, but morbidity may be significant.

Child↗
PubMed1986

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.

Bacterial Infections↗
PubMed1986

Computed tomography of traumatic lung cyst: case report.

Blunt trauma to the chest may result in the formation of a traumatic lung cyst. The lesion itself is innocuous and requires no special treatment. Though it is important that traumatic lung cyst not be mistaken for a more serious complication of trauma requiring aggressive management, this distinction may be difficult to make on plain chest radiographs. However, in the setting of blunt chest trauma, the computed tomography appearance of a thin-walled cystic cavity completely surrounded by lung parenchyma is diagnostic of traumatic lung cyst.

Adolescent↗
PubMed1986

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)

Adolescent↗
PubMed1986

Pediatric trauma associated with all-terrain vehicles.

The frequency of injuries secondary to use of all-terrain vehicles (ATV) is increasing at an alarming rate, and these injuries are usually multiple and severe. Between January 1, 1983, and February 28, 1985, 415 pediatric patients were admitted to the University of Virginia Hospital for care of injuries secondary to trauma; 66 of these patients required intensive care. Of the 415 patients, 12 were injured secondary to ATV use, and four of these required intensive care. The average age was 12 years (range 2 to 16 years), and the average hospital stay was 20 days. Injuries included five closed head injuries, two associated with a basilar skull fracture requiring intracranial pressure monitoring; five long bone fractures, two requiring open reduction and internal fixation; two small bone fractures; two splenic ruptures; two liver lacerations, one of them requiring laparotomy; and one renal hematoma. One patient has required long-term rehabilitation for neurologic deficits. Physicians and the public should be aware of the injury potential of these vehicles and should advocate legislation promoting helmet laws and high safety standards for ATV users.

Abdominal Injuries↗
PubMed1986

Pancreaticobiliary factors in the modulation of small intestinal enterokinase in the rat.

Chronic pancreaticobiliary diversion was employed to study the modulation of enterokinase in the small intestine of adult rats. Diversion resulted in apparent trophic changes of the proximal bypassed portion of the intestinal mucosa. An almost complete loss of mucosal enterokinase activity in the proximal duodenum but no increase of enterokinase in the segments distal to reentry of the common duct was found in the pancreaticobiliary-diverted rats. The effect on the enterokinase activity in the proximal segment was specific in that no other brush-border enzymes measured in that segment were decreased. The decrease in enterokinase was partially prevented by dietary supplementation with pancreatic trypsinogen and completely avoided with the addition of a combination of bile acids and trypsinogen. Supplementation with bile acid alone did not preserve the enterokinase levels in the bypassed rats. The results suggested that trypsinogen is the primary factor responsible for modulating enterokinase levels in the proximal small intestine, with bile acids acting as a modifier.

Animals↗