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Biomedical subjects

C Eng

Publications and source records attributed to C Eng.

At least 235 records · Page 13Linked to original sources
PubMed1993

Mortality from second tumors among long-term survivors of retinoblastoma.

BACKGROUND: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. PURPOSE: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. METHODS: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. RESULTS: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). CONCLUSIONS: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. IMPLICATIONS: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.

Adolescent↗
PubMed1993

Meningeal carcinomatosis from transitional cell carcinoma of the bladder.

Response rates of over 50% can be achieved in patients with metastatic transitional cell carcinoma of the bladder treated with cisplatin-based chemotherapy. With prolonged survival, intraparenchymal brain metastases may occur in as many as 12% of patients who received methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. Meningeal carcinomatosis from urothelial cancer is rare, however. A 71-year-old man, with metastatic, transitional cell carcinoma of the bladder, attained an excellent partial response to M-VAC chemotherapy. He subsequently presented with an acute confusional state 6 months after diagnosis. Head computed tomographic studies were nondiagnostic. Gadolinium-enhanced magnetic resonance images (MRI), however, demonstrated multifocal 1-cm nodules in the brain parenchyma and enhancement of the meninges. Meningeal carcinomatosis was confirmed by lumbar puncture. Records of 40 patients with advanced transitional cell carcinoma of the bladder treated with chemotherapy between 1977 and 1992 at a cancer center were reviewed retrospectively for the occurrence of documented meningeal carcinomatosis, intraparenchymal brain metastases, or both. Among 13 responders, only 1 other patient, a 64-year-old man, was identified who had minimal metastatic disease and attained a complete response to methotrexate and cisplatin. The patient relapsed 2 years after response, with cerebellar metastases and meningeal carcinomatosis. Central nervous system (CNS) metastases in patients with transitional cell carcinoma of the bladder are unusual. Although parenchymal brain metastases may be more common after prolonged remissions induced by combination chemotherapy, meningeal carcinomatosis remains uncommon. MRI may be a useful adjunct in the diagnosis of CNS metastases. A high index of clinical suspicion for the occurrence of CNS metastases from transitional cell carcinoma is encouraged.

Aged↗
PubMed1993

Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.

Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytoma. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10q11.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.

Amino Acid Sequence↗
PubMed1993

Ketamine alters calcium and magnesium in brain tissue following experimental head trauma in rats.

We previously reported that the N-methyl-D-aspartate receptor antagonists dizocilpine maleate and ketamine improved the neurological severity score (NSS) after head trauma in rats. Other investigators have reported increased calcium and decreased magnesium following head trauma in untreated rats. The present study was designed to determine whether ketamine influences the concentrations of calcium and magnesium in brain tissue following head trauma. Eighty-six male Sprague-Dawley rats (180 +/- 15 g) were divided into eight groups. Groups A (no head injury) and C (head injury) received no treatment. Groups B (no head injury) and D-H (head injury) received ketamine. In groups D, E, and F, ketamine, 180 mg/kg i.p., was given 1, 2, and 4 h after head trauma, respectively. In groups G and H, ketamine, 120 and 60 mg/kg, respectively, was given 1 h after head trauma. After we killed the rats at 48 h, cortical slices were taken to measure tissue calcium and magnesium content by the inductively coupled plasma atomic emission spectroscopy method. In the contused hemispheres, calcium increased and magnesium decreased (p < 0.0001). Among the head-injured groups, the increase in brain tissue calcium was smaller in groups receiving 60 mg/kg of ketamine at 1 h or 180 mg/kg of ketamine at 1, 2, or 4 h than in the group not receiving ketamine. The decrease in brain tissue magnesium was smaller in the groups receiving 180 mg/kg of ketamine at 1 and 2 h than in the group not receiving ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Post-ischaemic cardiac dilatation and remodelling: reperfusion injury of the interstitium.

Cardiac size and geometry have an important influence on clinical prognosis in heart disease. The cardiac interstitium would appear to play a major role in modulating muscle configuration after ischaemic insults. Ischaemic reperfusion injury of the heart should not be viewed as confined to the myocyte compartment. There are major events occurring in the interstitial compartment which could ultimately determine the long-term configuration and topography of the heart. Thus, permanent plastic changes in cardiac dimensions appear to evolve after initial alterations in the collagen matrix. The physiological, cellular, biochemical, and molecular considerations in the cardiac interstitium are quite different from those of the myocyte compartment. Accordingly, therapeutic interventions to modulate cardiac geometry and remodelling may differ.

Animals↗
PubMed1993

The role of gene mutations in the genesis of familial cancers.

The simplest molecular mechanism of hereditary tumorigenesis is represented by retinoblastoma (RB). Knudson's model specifies that, in hereditary RB, the first mutation in an allele of the RB gene exists in the germline. A subsequent somatic mutation in the second normal RB allele releases RB formation in the eye. This mechanism of loss of function of both normal tumor suppressor gene copies applies to other hereditary cancer syndromes as well, including multiple endocrine neoplasia type 1, neurofibromatosis type 2, Li-Fraumeni syndrome, and probably familial breast/ovarian syndrome. In some syndromes, e.g. familial adenomatous polyposis and multiple endocrine neoplasia type 2, the mechanism may be slightly different. Loss of function of only one allele of the susceptibility locus appears to be sufficient to promote a proliferative advantage in target tissues. In many of these inherited cancer syndromes, variable expression and variable penetrance of phenotypes exist. Allelism, existence of a multigene complex, or modulation of expression by modifier genes may explain the phenomena.

Animals↗
PubMed1993

Effect of captopril on postischemic myocardial expansion.

The effects of captopril on systolic function and diastolic myocardial expansion were assessed in an open-chest multiple occlusion model of myocardial stunning. Captopril was given as a 0.25 mg/kg bolus followed by a continuous infusion at 0.25 mg/kg/h for the duration of the stunning protocol, which was initiated 30 min after the bolus dose was given. The coronary artery was occluded for 5 min and reperfused for 10 min. This procedure was performed 12 times. Regional systolic function and end-diastolic length (EDL) in both the stunned region and normal zone were measured by sonomicrometry. Heart rate (HR) and left ventricular diastolic blood pressure (LVDP) were not significantly different between untreated (n = 11) and captopril-treated (n = 10) groups. The mean aortic pressure (MAP) in the captopril-treated group was approximately 10 mm Hg lower than in the untreated group, p < 0.05. Systolic function as determined by the percentage systolic shortening was significantly decreased to approximately 20% of baseline (preocclusion) function in both untreated and captopril treated groups as a result of the stunning procedure, p < 0.001. However, there was an important treatment effect on diastolic expansion of stunned myocardium. In the untreated group, the stunned myocardium underwent a 5-7% relative increase in end-diastolic length (expansion), p < 0.05. In the captopril-treated group, this expansion process was abolished. We conclude that in a multiple occlusion model of myocardial stunning, captopril had no effects in preserving systolic function but had favorable attributes in dilation and expansion of postischemic myocardium.

Animals↗
PubMed1992

Increase in myofilament separation in the "stunned" myocardium.

This study explores the effects of ischemic reperfusion injury on the radial separation distance between thick and thin myofilaments. The left anterior descending coronary artery was occluded for 5 mins and reperfused for 10 mins twelve times repetitively in 6 dogs. At the end of a final 90 min reperfusion period, the hearts were fixed by perfusion with glutaraldehyde, and subepicardial and subendocardial tissue from both normal and ischemic areas were prepared for transmission electron microscopy. Quantitative analysis of inter-filament distance (IFD) was performed on micrographs of transverse sections. The center-to-center IFD was calculated from the numerical density of thick filaments at the A band level using a hexagonal array conversion formula. Sarcomere length was measured on micrographs of longitudinal sections. The results showed that center-to-center thick IFD in the stunned subendocardium was 43.9 +/- 0.8 nm which was significantly greater than the control distance of 40.6 +/- 0.4 nm (P less than 0.001) from normal zone tissue. Thick IFD in the subepicardium was also significantly different: 43.4 +/- 0.6 nm in the stunned tissue as compared with 39.0 +/- 0.7 nm in the non-ischemic tissue (P less than 0.001). Sarcomere length in the normally perfused subendocardium was 2.01 +/- 0.07 micron and was increased to 2.20 +/- 0.08 micron in the stunned subendocardium (P less than 0.005). Sarcomere length in the normal and the stunned subepicardium was also different: 2.02 +/- 0.04 vs. 2.10 +/- 0.09 micron (P less than 0.005). The significant increase in spatial separation between the contractile filaments may affect optimal cross-bridge force generation at the molecular level.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗
PubMed1992

Thoracic epidural anesthesia via the caudal approach in children.

We investigated the feasibility of performing thoracic epidural anesthesia via the caudal approach in 20 children (age 62 +/- 38 months and weight 18.5 +/- 7.3 kg; mean +/- standard deviation). Based on external landmarks, a predetermined length of 24-G epidural catheter (Concord Portex 20/24 microcatheter system) with stylet was passed into the epidural space through a 20-G intravenous catheter inserted through the sacrococcygeal ligament, and a radiograph of the abdomen and chest was obtained. The radiographically determined catheter tip position was within two vertebrae of the target position in 17 of 20 subjects. In one subject, it was impossible to advance the catheter more than 10 cm. The other two malpositioned catheters were successfully reinserted. Intraoperative caudal anesthesia and postoperative pain relief were satisfactory in all 20 subjects. We have found it possible to use the caudal approach to thoracic epidural anesthesia in children as old as 10 yr. Ease of removal of the stylet, ease of injection, and negative aspiration and test doses predict successful placement and obviate the need for routine radiographic confirmation of catheter position.

Anesthesia, Caudal↗
PubMed1992

The influence of propofol with and without nitrous oxide on cerebral blood flow velocity and CO2 reactivity in humans.

The cerebrovascular response to CO2 has been reported to be preserved during propofol anesthesia, but no comparison with awake control values has been made, and the additional influence of N2O has not been investigated. Using the noninvasive technique of transcranial Doppler ultrasonography, this study investigated the cerebrovascular response to varying levels of PaCO2 while awake and during anesthesia with propofol and propofol/N2O. Seven adults without systemic diseases undergoing nonneurologic surgery were studied. A pulsed-wave Doppler monitor was used to measure the mean middle cerebral artery flow velocity (Vmca) during varying levels of PaCO2 (25-55 mmHg) under the following conditions: 1) awake; 2) propofol 2.5 mg.kg-1 bolus followed by continuous infusion of 150 micrograms.kg-1.min-1; and 3) propofol as in the condition above plus 70% N2O. During the awake study condition, hypocapnia was induced by voluntary hyperventilation, and hypercapnia was induced with rebreathing of 7% CO2 in a closed circuit. During the anesthetized study conditions, hypocapnia and hypercapnia were induced by adjustment of minute ventilation. A minimum of five to six simultaneous Vmca and PaCO2 measurements were obtained under each of the study conditions. Systemic blood pressure was monitored via a radial arterial catheter, and phenylephrine was administered if mean arterial blood pressure decreased below 60 mmHg (phenylephrine was used in three of five patients in the propofol-N2O group). Linear regression and analysis of covariance were used for statistical analysis of Vmca-PaCO2 relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Collagen loss in the stunned myocardium.

BACKGROUND: This study was performed to biochemically assess and quantify the previously observed ultrastructural alterations in the collagen matrix of stunned myocardium. METHODS AND RESULTS: The stunned myocardium was produced in 13 mongrel dogs by a series of 12 coronary artery occlusions of 5 minutes followed by 10-minute reperfusion periods, with a final reperfusion period of 90 minutes. Regional systolic function in the stunned myocardium was 17% of control. Relative end-diastolic length in the stunned region increased up to 8%. There was a nonuniform transmural loss of collagen. Hydroxyproline in the stunned endocardium was not different from control. The stunned midwall and epicardium demonstrated 12.5% (p less than 0.05) and 14.6% (p less than 0.005) decreases, respectively. All transmural layers in the stunned myocardium had significant increases in collagenase activity before procollagenase activation, averaging a 73.6% increase (p less than 0.025). Complete activation of all procollagenase forms with aminophenylmercuric acetate revealed no differences in fully activated collagenase between the stunned and normal regions. The lysosomal enzymes, elastase and cathepsin G, were not different between stunned and normal zone tissue. These results would tend to exclude exogenous sources of protease in the stunned myocardium at the 90-minute final reperfusion time frame. Collagen fibers were isolated from the stunned and normal zone tissue and underwent dansyl chloride reaction. Stunned collagen fibers had 9% greater dansyl labeling, suggesting greater numbers of exposed N-terminal amino acid residues on the fiber and compatible with greater enzymatic cleavage activity on the stunned collagen matrix. Tissue water content was consistently greater in the stunned region compared to the normal: a uniform transmural increase of approximately 1.7%. CONCLUSIONS: The stunned myocardium is characterized by both systolic dysfunction and diastolic expansion or dilatation. Endogenous procollagenase is activated by the ischemic process leading to degradation of the extracellular matrix. The underlying mechanisms may be relevant in ischemic enlargement of the heart and cardiomyopathy.

Animals↗
PubMed1991

Reciprocal strains in the normal and ischemic myocardium and their relation to the size of the ischemic region.

Previous studies have reported "bulging" of the ischemic zone and reciprocal shortening of the normal zone during the isovolumetric contraction period. This study examines the interaction and relation of these reciprocal strains during the isovolumetric contraction period. Normal zone and ischemic zone segment length data were acquired at 1 ms intervals during acute ischemia in 10 open chest dogs. The relation of ischemic zone and normal zone segment length was inversely linear in the isovolumetric contraction period during steady state ischemia and during preload reduction (mean correlation coefficient 0.92). The slope derived from the regression analysis was the same as that determined from the first and last data points of the isovolumetric contraction period (correlation coefficient between the regression versus two-point slope 0.96). This slope was used to calculate the size of the ischemic area based on the hypothesis that the isovolumetric normal zone shortening quantitatively accounted for the ischemic zone bulging during the isovolumetric contraction period, with the percent risk region serving as a weighing factor. The calculated risk region correlated with the anatomic risk region (r = 0.83, p less than 0.01; n = 9) and was independent of preload. During the isovolumetric contraction period, left ventricular short-axis diameter shortened approximately 0.2%; 80% of the ischemic zone lengthening occurred during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Isolation and characterization of insoluble collagen of dog hearts.

A procedure for isolating insoluble heart collagen has been developed. The method involves the use of defined optimal conditions of sonication that yield no thermal denaturation of the triple-helical structure nor disruption of the primary structure of the collagen molecules; this is followed by extraction of isolates with nondenaturing agents. The amino acid residues of the isolates are then reacted with dansyl chloride to allow determination of amino-terminal residues and quantification of the collagen. The method has several advantages over existing procedures: (i) There is no other method available for isolation of undenatured insoluble heart collagen in almost pure form (consists of 96% of type I collagen) and in a good yield. Sonication of tissue at or below 4 degrees C for a total of 120 s (15 s sonication repeated 8 times at 120-s intervals) yielded insoluble collagen fibers with 90% yield and a 20-fold purification as determined by the increase in Hyp content of the isolates. Extraction of these isolates with 0.6 M KCl and 1 M NaCl at 4 degrees C resulted in a 22-fold purification with 70% yield, while the classical extraction method with nondenaturing reagents yielded only 5-fold purification. (ii) There has been little study of the derivatization of an insoluble protein (collagen) with dansyl chloride. The Lys residues of collagen could be recovered as epsilon-Dns-Lys in 84% yield from a reverse-phase C-18 column by high-performance liquid chromatography. This assay allows measurement of 0.1-100 nmol epsilon-Dns-Lys. (iii) The method generates direct information concerning the quantity of collagen and its nature with respect to amino groups.

Animals↗
PubMed1990

Elevated creatine kinase and malignancy.

Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumors with poor prognosis.

Biomarkers, Tumor↗