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Biomedical subjects

A Fried

Publications and source records attributed to A Fried.

At least 37 records · Page 2Linked to original sources
PubMed1993

A morphology index based on sonographic findings in ovarian cancer.

A morphology index based on morphologic characteristics of ovarian tumors was developed. Specific categories included tumor volume, wall structure, and septal structure. A point scale (0-4) was developed within each category with the total points per evaluation varying from 0-12. Sonograms on 121 patients undergoing exploratory laparotomy for ovarian masses were evaluated using this index. Eighty ovarian tumors had a morphology index score < 5, and all were benign (negative predictive value, 1.000). In postmenopausal patients, a morphology index score > or = 5 had a positive predictive value for malignancy of 0.45. All ovarian malignancies had significant abnormalities in wall structure and all had a total volume in excess of 10 cm3. The findings of the present investigation indicate that the morphology index is a cost effective adjuvant method which significantly increases the specificity and positive predictive value of transvaginal sonography. The routine application of a morphology index to screening sonography should decrease the amount of diagnostic surgery performed in order to detect each case of ovarian cancer.

Adolescent↗
PubMed1993

Diagnosis and treatment of the slit ventricle syndrome.

Slit ventricles are a complication of a functioning shunt. This article examines the diagnosis and treatment of slit ventricles and slit ventricle syndrome, the pathophysiology involved, a rationale for treatment, and the direction of therapy in the near future. The authors conclude that determining which type of SVS is present is the first step in treatment and that the best treatment is a strategy aimed at the specific type of SVS that is responsible for the symptoms.

Brain Diseases↗
PubMed1993

An abnormal gallbladder presenting as a huge, rounded photon-deficient area in radionuclide hepatobiliary imaging.

Tc-99m DISIDA hepatobiliary imaging was used to evaluate a hemophiliac patient presenting with symptoms of acute cholecystitis and gastrointestinal bleeding. There was nonvisualization of this abnormal gallbladder even on 6 1/2-hour delayed DISIDA images. Instead, a huge photon-deficient area was seen in the gallbladder fossa. Ultrasound and computed tomography findings were consistent with an enlarged gallbladder filled with blood.

Adult↗
PubMed1992

Progressive vision loss. A rare manifestation of familial cavernous angiomas.

We studied four generations of a family in which the index case had progressive loss of vision secondary to a cavernous angioma of the optic nerve and chiasm. Magnetic resonance imaging of the brain revealed multiple, asymptomatic intracerebral cavernous angiomas. Brain magnetic resonance imaging scans of the family members revealed multiple cavernous angiomas in the brother and paternal grandfather, but none in the father or his siblings. Autopsy reports of the paternal great grandfather noted multiple cavernous angiomas in the brain and abdominal viscera. We believe our patient to be the sixth reported case in which a cavernous angioma involved the optic chiasm and optic nerve. Magnetic resonance imaging is a sensitive and specific method of detecting cavernous angiomas. Cavernous angiomas have an autosomal dominant pattern of inheritance with variable penetrance. Surgical intervention in patients with symptomatic cavernous angiomas depends on the location and size of the lesion and associated surgical risks.

Adolescent↗
PubMed1991

Subpopulations of marrow stromal cells share a variety of osteoblastic markers.

A series of stromal cell lines derived from mouse bone marrow, representing subpopulations of putative stromal cell types, were examined for the expression of osteoblastic properties. The effects of dexamethasone and specific inhibitors on alkaline phosphatase activity, cAMP response to bone-seeking hormones, and the ability to mineralize extracellular matrix in vitro as well as collagen typing were used as osteoblastic markers. We found that all stromal cell types examined possess some osteoblastic features but differ in the degree of expression. The data provide support to the hypothesis of a common stem cell for marrow stromal cells.

Alkaline Phosphatase↗
PubMed1991

Fusiform dilatations of the carotid artery following radical surgery of childhood craniopharyngiomas.

Between 1982 and 1990, a series of 31 children with craniopharyngiomas underwent initial surgery at the Children's Hospital of Philadelphia with an attempt at total tumor removal. Nine (29%) of them were found to have fusiform dilatation of the supraclinoid carotid artery either at the time of surgery for recurrence (one patient) or on routine surveillance with enhanced computerized tomography 6 to 18 months postoperatively (eight patients). The finding of carotid enlargement was confirmed in seven cases with magnetic resonance angiography and in one case with a formal arteriogram. Eight of the nine patients remain alive at a mean of 3.7 years after diagnosis. None have experienced hemorrhage or other symptoms referrable to fusiform dilatation of the carotid artery, which is believed to result from surgical manipulation of the carotid artery.

Adolescent↗
PubMed1991

Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies.

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Neutral endopeptidase (EC 3.4.24.11) is highly expressed on osteoblastic cells and other marrow stromal cell types.

A series of cultured mouse marrow stromal cell lines of different phenotype characteristics were examined for their neutral endopeptidase (NEP) activity using the highly selective chromophoric substrate of enzyme, 3-carboxypropanoyl-alanyl-alanyl-leucine 4-nitroanilide. All the cell lines tested contained appreciable amounts of NEP activity, but the cells expressing an osteoblastic phenotype, MBA-15, showed the high levels. Other non-stromal osteoblastic cell lines, MC-3T3-E1, ROS 17/2.8 cells derived from mouse long bone explants, were also rich in NEP. A four-fold stimulation of NEP activity was observed when certain MBA-15 clones were cultured in the presence of 1 alpha,25-dihydroxyvitamin D3. Since NEP is an effective cell-surface endopeptidase, it may play a role in the dynamics of bone formation, via interaction with biologically active polypeptides.

Amino Acid Sequence↗
PubMed1989

Treatment of renal cell carcinoma with daily low-dose alpha-interferon.

While alpha-interferon has yielded objective tumor regressions in patients with metastatic renal cell carcinoma, such therapy is usually associated with significant toxicity often requiring dose modifications and/or cessation of therapy. In the absence of a clearly defined optimal dose and schedule for alpha-interferon, it appears reasonable to seek a means for improving the therapeutic index for this drug. We report the results of a pilot trial in which patients with renal cell carcinoma were treated with a daily low dose of alpha-interferon. Seventeen patients were treated with alpha-interferon (Roferon-A) at a dose of 1 million U subcutaneously daily. There were no exclusionary criteria for this pilot trial. Sixteen patients were evaluable for response and toxicity. Therapy was well-tolerated with no interruption of therapy for toxicity. No patient experienced the "flu-like" syndrome that is associated with higher doses, and there was no episode of granulocytopenia or thrombocytopenia. Four patients achieved a partial response (PR), with one PR persisting at 20 months. Sites of response included lung (two patients), liver (one patient), and bone (one patient). These results indicate that this regimen is well tolerated and can be expected to render objective responses. Formal Phase II trials are warranted in order to define the response rate for this regimen.

Aged↗
PubMed1988

Delineation of bacterial luciferase aldehyde site by bifunctional labeling reagents.

Previously we have established that a highly reactive cysteinyl group on the alpha subunit is at the aldehyde site of the (alpha beta) dimeric Vibrio harveyi luciferase. Three isomeric bifunctional reagents have been synthesized and used to further delineate the luciferase aldehyde site. These probes differ in their relative positions of and distances between the two functional groups active in chemical and photochemical labelings, respectively. Each of the probes can effectively and reversibly inactivate luciferase by forming a disulfide linkage primarily to the reactive cysteinyl residue. Upon subsequent photolysis, a diazoacetate arm in each probe was activated for photochemical labeling of amino acid residues within reach. After reductive regeneration of the reactive cysteinyl residue, 0.35-0.40 probe per dimeric luciferase was found to have been photochemically incorporated, correlating well with the degree of irreversible enzyme inactivation. Low but significant amounts of the three isomeric probes initially attached to the alpha reactive cysteine through a disulfide have been found to photochemically tag certain residues on beta. The latter residues are estimated to be no more than 8-11 A away from the alpha reactive cysteine. Thus the reactive cysteinyl residue, and hence the aldehyde site, must be at or near the alpha beta subunit interface. Furthermore, the structural integrity of the microenvironment surrounding this reactive cysteinyl residue is crucial to luciferase activity. An HPLC method for the isolation of luciferase alpha and beta subunits has also been developed.

Affinity Labels↗
PubMed1988

The theoretical requirements of shunt design as determined by biomechanical testing in pediatric hydrocephalus.

This paper reviews the mechanics of shunts currently used to treat hydrocephalus and contrasts these devices with the normal mechanism of CSF circulation. These differences are examined with reference to the biomechanical testing performed in hydrocephalus children. These studies show that in most untreated hydrocephalics, enhanced volume storage accompanies a partial absorptive defect. After treatment, volume storage changes in most children but persists in a minority. Using these tests, it is possible to describe the requirements for successful shunting of hydrocephalic children at all stages of the process. This discussion elaborates the theoretical requirements for revising current shunt design.

Absorption↗
PubMed1987

Fatal aplastic anemia in a child with Down's syndrome.

An infant with Down's syndrome developed severe persistent neutropenia at the age of 9 months and fluctuating anemia and thrombocytopenia at one year of age which terminated as full-blown aplastic anemia at 26 months of age. Immunological evaluation revealed increased peripheral and bone marrow lymphocytes and impaired blood OKT4: OKT8 ratio. Bone marrow granulocyte-macrophage colony forming cells (GM-CFC) were markedly increased, while peripheral blood mononuclear cells (PBMN) produced normal numbers of colonies. The patient's PBMN and serum were both somewhat inhibitory to normal bone marrow derived GM-CFC, suggesting the existence of a suppressor activity both in his serum and PBMN. This unusual course of aplastic anemia and the abnormalities in T-cells and hematopoiesis in Down's syndrome are discussed.

Anemia, Aplastic↗
PubMed1987

A laboratory model of shunt-dependent hydrocephalus. Development and biomechanical characterization.

This study was designed to determine whether implanting shunts in hydrocephalic cats produced the same biomechanical changes as have previously been found in children with shunts. Neuraxis volume-buffering capacity (pressure-volume index: PVI) and the resistance to the absorption of cerebrospinal fluid (CSF) were determined before and 3 weeks after placing shunts in 16 hydrocephalic cats. Intracranial pressure (ICP) was monitored for at least 6 hours after the shunts were occluded. The brains were perfused in vivo and removed to assess the size of the ventricles. The mean PVI of the hydrocephalic cats was 3.6 +/- 0.2 ml (+/- standard error of the mean) before the shunts were placed. Three weeks after adequate shunt function was first established, the mean PVI decreased to 1.1 +/- 0.1 ml and was similar to values determined in control animals. Prior to shunt placement, the resistance to the absorption of CSF was 28.4 +/- 4.5 mm Hg/ml/min and did not vary with ICP. This parameter changed after shunting and increased as a function of ICP (r = 0.87, p less than 0.001). At ICP's below 20 mm Hg, the resistance to the absorption of CSF was 65.0 +/- 18.0 mm Hg/ml/min but increased to 220.0 +/- 40.5 mm Hg/ml/min when determined at ICP's above 20 mm Hg. Corroborating evidence for this linkage of resistance to the absorption of CSF to ICP was found in the inexorable rise of ICP during the 6 hours of monitoring after the shunts were occluded. After shunt placement, the ventricles were normal in size in 12 cats and slightly enlarged in four. The biomechanical profile and pressure response to shunt occlusion in this laboratory model resembles that previously described in shunt-dependent children. As in humans, shunt placement in hydrocephalic cats results in normalization of the PVI and a linkage of the resistance to the absorption of CSF to ICP. The significance of these changes as they relate to shunt dependency is discussed.

Animals↗
PubMed1986

Pressure-volume relationships in shunt-dependent childhood hydrocephalus. The zone of pressure instability in children with acute deterioration.

The pressure-volume index (PVI) technique of bolus manipulation of cerebrospinal fluid (CSF) was used to measure neural axis volume buffering capacity and resistance to absorption of CSF (Ro) in 20 shunt-dependent hydrocephalic children acutely ill from shunt malfunction. All children had had ventricles that were near normal or subnormal in size when the shunts were functioning. The mean intracranial pressure (ICP, +/- standard deviation (SD] at the time of revision was 10.6 +/- 6.4 mm Hg. The mean measured PVI (+/- standard error of the mean) was 18.4 +/- 1.1 ml compared to the normal PVI of 17.5 +/- 4.4 ml (+/- SD) predicted for these children. According to paired t-tests, these measured values were similar to those predicted on the basis of neural axis volume for each child, indicating that these children had normal neural axis volume buffering capacity. While the study was in progress, abrupt increases of ICP were documented in all children. These waves were observed spontaneously as well as in response to the addition of volume to the neural axis. In each child a specific threshold pressure along the pressure-volume curve corresponded to the appearance of unstable ICP. The threshold pressures at which this occurred corresponded to a mean neural axis compliance of 0.32 +/- 0.07 ml/mm Hg (+/- SD). The Ro varied as a function of ICP. The Ro measured at ICP's below 15 mm Hg ranged from 2 to 7.5 mm Hg/ml/min and rose to 12 to 30 mm Hg/ml/min at pressures in the 20 to 25 mm Hg range. The results of this study indicate that neural axis volume buffering capacity is normal in shunt-dependent children who respond to shunting by reconstitution of the cortical mantle. This study indicates that the proximate cause of their abrupt clinical deterioration is unstable ICP, which occurred at a similar point on the pressure-volume curve of all children studied. The correlation of Ro to ICP suggests that CSF absorption does not increase in these children as ICP rises, resulting in movement along relatively normal pressure-volume curves. The functional implications of these parameters are discussed.

Adolescent↗
PubMed1986

Subtle deterioration in shunted childhood hydrocephalus. A biomechanical and clinical profile.

Eighteen hydrocephalic children who presented with subtle deterioration when their shunts malfunctioned were studied during shunt revision by means of the pressure-volume index (PVI) technique. Bolus manipulation of cerebrospinal fluid (CSF) was used to determine the PVI and the resistance to the absorption of CSF (Ro). Ventricular size was moderately to severely enlarged in all the children. Steady-state intracranial pressure (ICP) at the time of shunt revision was 17.5 +/- 7.3 mm Hg (range 8 to 35 mm Hg). Pressure waves could not be induced by bolus injections in the 8- to 35-mm Hg range of ICP tested. The mean +/- standard deviation (SD) of the predicted normal PVI for this group was 18.5 +/- 2.7 ml. The mean +/- standard error of the mean of the measured PVI was 35.5 +/- 2.1 ml, which represented a 187% +/- 33% (+/- SD) increase in volume-buffering capacity (p less than 0.001). The ICP did not fall after bolus injections in three children, so that the Ro could not be measured. In the remaining 15 patients, Ro increased linearly as a function of ICP (r = 0.74, p less than 0.001). At ICP's below 20 mm Hg, Ro ranged from 2.0 to 5.0 mm Hg/ml/min, but increased to as high as 21 mm Hg/ml/min when ICP was above 20 mm Hg. This study documents that subtle deterioration in shunted hydrocephalic children is accompanied by abnormally compliant pressure-volume curves. These children develop ventricular enlargement and neurological deterioration without acute episodic pressure waves. The biomechanical profile of this group differs from other children with CSF shunts.

Absorption↗
PubMed1985

Biomechanical and hydrodynamic characterization of the hydrocephalic infant.

The pressure-volume index (PVI) technique of bolus manipulation of cerebrospinal fluid (CSF) was used to measure neural axis volume-buffering capacity and resistance to the absorption of CSF in 16 hydrocephalic infants prior to shunting. The mean steady-state intracranial pressure (ICP) was 11.7 +/- 5.7 mm Hg (+/- standard deviation (SD], representing a modest elevation of ICP in infants. The mean measured PVI was 28.1 +/- 1.5 ml (+/- standard error of the mean (SEM] compared to the predicted normal level for these infants of 12.1 +/- 2.7 ml (+/- SD) (p less than 0.001). This resulted from an enhanced volume storage capacity in the hydrocephalic infants. The PVI was not related to ventricular size in these hydrocephalic infants. Although absorption of the additional bolus of fluid did not occur at steady-state ICP, it was readily absorbed once ICP was raised above a mean threshold pressure of 16.0 +/- 5.0 mm Hg (+/- SD) in 13 of the 16 infants. Above this pressure, the mean CSF absorption resistance was 7.2 +/- 1.3 mm Hg/ml/min (+/- SEM) which is twice the normal values as measured by the bolus injection technique. The biomechanical profile of infantile hydrocephalus described in this study indicates that two factors are required for progression of ventricular volume. While an absorptive defect may initiate the hydrocephalic process, progressive volume storage requires an alteration in the mechanical properties of the intracranial compartment.

Absorption↗
PubMed1985

Effect of the skull and dura on neural axis pressure-volume relationships and CSF hydrodynamics.

The pressure-volume index (PVI) technique of bolus manipulation of cerebrospinal fluid (CSF) was used to measure changes of neural axis volume buffering-capacity and CSF dynamics produced by different conditions of the skull and dura. Twenty-eight cats were studied in the intact state, after bilateral craniectomy, and with the dura opened. At each stage of altering the container of the brain, the following parameters were obtained: steady-state intracranial pressure (ICP), sagittal sinus venous pressure, PVI, and the resistance to the absorption of CSF. The resistance to absorption of CSF was determined using both the bolus injection and the continuous infusion of fluid. After craniectomy, PVI increased from 0.76 +/- 0.04 to 1.3 +/- 0.07 ml (+/- standard error of the mean) (p less than 0.001) and increased further to 3.6 +/- 0.17 ml (p less than 0.001) after opening the dura. The resistance to absorption of CSF (Ro), determined by bolus injection, decreased after craniectomy from 91.3 +/- 7.5 to 56.3 +/- 6.2 mm Hg/ml/min (p less than 0.001) and decreased further to 8.9 +/- 0.66 mm Hg/ml/min (p less than 0.001) after opening the dura. Although resistance determined by constant infusion was similar, results were dependent on the rate of infusion. Despite these changes of resistance and PVI, steady-state ICP and sagittal sinus venous pressure were similar in all three conditions of the skull and dura. These studies indicate that changes of the container of the brain affect pressure-volume relationships within the neural axis. However, the changes of resistance to absorption of CSF are in a direction that preserves a steady-state hydrodynamic equilibrium.

Absorption↗