Biomedical subjects
Publications and source records attributed to P Costello.
Spiral volumetric computed tomography (CT) was used prospectively in 20 patients with a suspected solitary pulmonary nodule less than 1 cm in diameter on plain chest radiographs. Four additional nodules were detected with spiral CT than were detected with conventional CT. This technique required a 12-second breath hold; patient cooperation was excellent.
CT scanning is used frequently to assess the condition of patients after liver transplantation. The CT records of 174 adult patients who underwent liver transplantation were studied retrospectively to determine the number and timing of CT studies as well as the frequency and significance of the findings. One-hundred seventy CT scans were obtained in 66 (38%) of the 174 patients, with a mean of 2.6 scans/patient. The interval between transplantation and scanning was 1 day to 24 months; in 59 (89%) of 66 patients, the first CT scan was obtained within 30 days. The acute indications for CT scanning were fever or leukocytosis in 54 (92%) of 59 patients and abnormal liver function tests in five (8%) of 59 patients. CT scans obtained more than 30 days after transplantation were repeat scans in all but seven patients. Indications in this latter group were the same as for the acute group, plus evaluation of hepatic neoplasia in three patients. CT findings included periportal low attenuation in 41 (62%) of 66 patients; ascites in 25 (38%); splenomegaly in 19 (29%); loculated intraperitoneal noninfected fluid collections in 13 (20%); intrahepatic, splenic, pancreatic, or perihepatic abscesses in seven (11%); hepatic infarction in six (9%); splenic infarction in three (4%); and hepatic calcification in two (3%). Other major abnormalities included inferior vena caval thrombosis (one patient), pseudoaneurysm of the hepatic artery with rupture (one patient), and recurrent hepatocellular carcinoma (one patient). CT scanning after liver transplantation is used predominantly in the acute setting to evaluate for liver infarction or intraabdominal abscess. In this setting, CT showed these abnormalities, in addition to tumor recurrence or vascular abnormalities, in 15 (23%) of 66 patients.
Human microvessels were isolated and cultured from non-neoplastic cerebral tissue specimens resected for the treatment of seizure disorders and from malignant glial tumors. After 1-2 weeks, cobblestone patterned plaques of cells were isolated and cultured from these microvessels. Cell lines positive for Factor VIII antigen and negative for glial fibrillary acidic protein were designated as endothelium. Endothelium from both tissue sources produced gamma-glutamyl transpeptidase in response to glial cell conditioned media. Tumor derived microvessel endothelium had decreased longevity in culture when compared to normal microvessel endothelium. Tumor derived endothelium also formed less extensive intercellular junctional complexes in vitro. The isolation and characterization of human cerebral microvessel endothelium derived from non-neoplastic tissue and glial tumors may lead to a further understanding of the role of endothelium in tumor growth and vascular permeability alterations.
Models for human cytomegalovirus (HCMV) brain infection have been developed in a variety of brain-derived cells in which the factors governing virus infectivity might be studied in vitro. Studies were initiated with brain endothelial cells, the likely portal of entry for virus into the central nervous system. Primary explant cultures of brain endothelial cells, derived from homogenates of healthy human brain, supported complete viral gene expression and cytopathic effect (CPE). Endothelial cells do not appear to be a barrier for HCMV passage into the central nervous system. Astroglial lines (primary explant or tumor-derived) varied in their ability to support HCMV replication. Some (T98G) supported incomplete (immediate-early) gene expression while others (A-172) did not support any detectable gene expression. Some astroglial lines (HS-683) supported extensive virus replication with minimal viral CPE. Neuronal cell lines (SK-N-MC) were fully permissive. The more differentiated glial lines (astrocytoma) were fully permissive to HCMV infection; however, the less differentiated glial lines (glioblastoma) were partly or nonpermissive.
The influence of disulfiram on theophylline metabolism was studied in 20 recovering alcoholics. Ten of the patients, who were selected at random, received 250 mg of disulfiram daily. The other 10 patients received 500 mg of disulfiram daily. Two single-dose studies of theophylline kinetics were performed--one as a baseline control and the other after 1 week of treatment with disulfiram. With disulfiram pretreatment, the plasma clearance of theophylline was decreased from 105.7 +/- 10.2 (mean +/- SEM) to 83.1 +/- 8.1 ml/kg per hour (p less than 0.001) in the 250 mg group and from 94.3 +/- 13.3 to 65.4 +/- 10.7 ml/mg per hour (p less than 0.001) in the 500 mg group. The elimination half-life was prolonged significantly in both groups. The percent reduction in theophylline clearance was greater in the 500 mg group (32.5 +/- 3.1; range, 21.6 to 49.6) than it was in the 250 mg group (21.2 +/- 1.7; range, 14.6 to 29.6; p less than 0.01). Disulfiram decreased the formation of all theophylline metabolites in smokers in both treatment groups. In each group, the hydroxylation pathway was affected more than the demethylation pathway. These data indicate that at therapeutic doses disulfiram exerts a dose-dependent inhibitory effect on theophylline metabolism. Depending on the dose of disulfiram, a dose reduction of theophylline by as much as 50% may be necessary to minimize the risk of toxicity.
Forty-two difficult-to-cultivate group A coxsackieviruses (i.e., group A types other than A7, A9, and A16), collected primarily from throat swab specimens of patients suffering from fever, pharyngitis, lymphadenopathy, and cough during the 1986 enterovirus season, were isolated in less than 24-h-old suckling mice. Thirty-six moribund mice were sacrificed and autopsied, and then their brains and back musculature were inoculated into rhabdomyosarcoma (RD), guinea pig embryo (GPE), rhesus monkey kidney (RhMk) and human carcinoma of the larynx (HEp-2) cell cultures. Twelve of the 36 suckling mice isolates were adapted to grow in RD and GPE cells after two passes and have been identified in RD cells by type-specific antisera as group A coxsackievirus types A2, A4, and A8. Three passes in RhMk or HEp-2 cell cultures were insufficient to affect a discernible cytopathic effect. Coxsackievirus types A1, A19, and A22, unable to grow in any of the four cell cultures tested, were identified by virus neutralization in suckling mice. These data denote the efficacy of suckling mice for the isolation of difficult-to-cultivate group A coxsackieviruses.
Forty computed tomography (CT)-assisted aspirations performed with only hand guidance were prospectively compared with 40 performed with a CT body-stereotaxic system. Although there was no statistically significant difference in lesion size and path length between the two groups, use of stereotaxis compared with hand guidance decreased by 75% the number of needle manipulations required to place a needle within a lesion. With the stereotaxic method, only 43 needle manipulations were required to confirm a needle placement in 40 lesions, with no lesion requiring more than two attempts. Use of stereotaxis decreased the number of localization scans by 80% and biopsy time by 50%. It is concluded that CT-guided needle placements with hand guidance are often inaccurate and, unless the lesion is large, require multiple needle manipulations to place a needle within the lesion. Stereotaxis-guided biopsies, on the other hand, decrease radiation exposure, biopsy time, and trauma from multiple needle punctures.
We report a patient with absence of the external carotid artery. The major external branches originate from the internal carotid artery which is really a common arterial trunk. The embryology and clinical significance of this rare vascular anomaly are discussed.
Microvessels were isolated from non-neoplastic human cerebral cortical fragments resected for treatment of intractable seizure disorder. The microvessels were incubated in modified Lewis medium with 20 or 30% fetal bovine serum. Within 1-2 weeks, two cell populations emerged from the isolates. One type of cells had polygonal morphology, showed density-dependent contact inhibition at confluence in vitro, showed lectin-binding characteristics of endothelium (but only moderate positivity for factor VIII antigen), demonstrated induction of gamma-glutamyl transpeptidase when exposed to astrocyte-conditioned media, and responded to insulin by a pronounced increase in DNA synthesis. The other variety of cells grew in vitro more slowly in irregular strands separated by clear zones, showed ultrastructural features of smooth muscle, and isoelectric focusing of cell proteins revealed the presence of smooth-muscle-specific alpha-isoactin. Both types of cells could be serially subcultured. The ability to isolate and grow the two cell types, tentatively identified as human cerebral microvascular endothelium and smooth muscle, may facilitate studies of human blood-brain barrier function as well as the pathogenesis of cerebral microangiopathies unique to the human brain.
A new CT body stereotaxic system that is particularly suited to multiple placements of needles precisely in parallel is described. By scanning through a right triangle placed on the patient's skin, the stereotaxic method defines an entry point for the first needle placement. An articulating arm is then used to aim the needle at the entry point and hold the needle at the correct angle. The arm can be angled so that the complex approaches from one scan plane to another can be made to place needle arrays through inaccessible lesions, for instance, beneath the diaphragm. Animal and phantom studies have shown that placement of multiple needle arrays in parallel from CT scan data is possible.
A stereotaxic guidance system has been used in conjunction with a conventional CT unit to biopsy 26 consecutive thoracic lesions. Accurate needle placement with a single manipulation occurred in 24 instances and two lesions required second passes. The technique provided adequate pathologic material with an acceptable complication rate. System advantages include the ability to approach lesions along oblique paths, controlled approach in difficult locations (mediastinal, peripheral, subscapular), capacity to biopsy small nonfluoroscopically visualized lesions, and increased speed over manual techniques.
A study of 23 patients undergoing orthotopic liver transplantation revealed that 80% of patients developed a clinically significant chest radiographic abnormality. Localized chest radiographic abnormalities generally occurred within the initial postoperative weeks and appeared to be related to the surgical procedure. Diffusely abnormal chest radiographs were most often associated with an infectious pneumonitis and rarely occurred prior to the third postoperative week. Two patients developed unusual pulmonary calcifications demonstrable by computed tomography and radionuclide bone scan.
Pulmonary complications following orthotopic liver transplantation (OLT) were prospectively evaluated in 18 individuals transplanted at the New England Deaconess Hospital. Of sixteen patients who survived the immediate postoperative period, 12 (75%) sustained a pulmonary complication. Of these complications, 64% were noninfectious--whereas 22% were infectious, and 14% probably infectious. Six of eight documented infections were caused by viruses of the herpes group. In four cases of viral pneumonitis other pulmonary pathogens were isolated (fungi-3, protozoan-1, bacteria-1). Unlike noninfectious complications, pulmonary infections were associated with a fatal outcome in five of six patients who died after OLT. Pulmonary complications are frequent and serious occurrences after OLT, and contribute to both the morbidity and mortality of this procedure. Compared with pulmonary complications seen after transplantation of other organs, OLT was associated with a higher proportion of noninfectious complications but a similar spectrum of pulmonary infections.
In a group of 61 patients admitted to New England Deaconess Hospital, Boston, with a diagnosis of acquired immune deficiency syndrome (AIDS), 25 were found to have Kaposi's sarcoma involving the skin and mucous membranes. Of these 25 patients, eight had lesions involving the respiratory system. Radiographically, patients with Kaposi's sarcoma had hilar and mediastinal adenopathy with perihilar parenchymal infiltration which progressed to diffuse bilateral infiltrates over a period of months. This pattern and the tempo of its evolution were distinctly different from the diffuse infiltrates seen in patients with Pneumocystis carinii pneumonia. Bronchoscopy was performed in seven of the eight patients, revealing characteristic lesions of Kaposi's sarcoma in the airways. We propose that parenchymal pulmonary Kaposi's sarcoma can be strongly suspected in a patient with AIDS who has the following features: a characteristic radiologic pattern; endobronchial Kaposi's sarcoma at bronchoscopy; and no evidence of opportunistic infection. In this subset of patients, further diagnostic intervention such as open lung biopsy, a procedure with potential morbidity in these ill individuals, may be unnecessary.
A new body stereotaxic system used to facilitate CT-guided biopsies is described. By scanning through a triangle placed on the patient's skin, the method defines an entry point for the biopsy. An articulating arm is then used to aim the needle at the entry point and hold the needle at the correct angle. The arm can be angled so that complex approaches from one scan plane to another can be made in order to take biopsies of lesions beneath the diaphragm. Using the system, 23 of 25 lesions were hit on the first needle manipulation; two manipulations were needed for each of the other two lesions. In comparison with previous experience, procedure time was decreased and the numbers of needle manipulations and localization scans were decreased 75% and 90%, respectively.
Seven cases of hepatocellular carcinoma (hepatoma) (HCC) presenting as primary extrahepatic masses on CT are reported. All cases were diagnosed at the time of percutaneous biopsy, surgical resection, or autopsy. In none of the cases was the final diagnosis of HCC prospectively suspected on the basis of clinical and radiologic findings. Although three of the patients were at higher risk for development of HCC because of their medical histories, the absence of an elevated serum alpha-fetoprotein level and the extrahepatic location of the masses by CT suggested other disease. This variable pattern of radiologic presentation of HCC should be kept in mind during the evaluation of patients with suspected HCC, or when the findings on abdominal/pelvic CT of mass and presumed hepatic metastases are at variance with the clinical presentation.
An analysis of the sonograms of 60 patients with a surgically confirmed diagnosis of ectopic pregnancy was performed. In 36 examinations, both real-time and static images were compared, and real-time was judged superior in 22 based on a correlation between the original report and surgical pathology. The appearance of the endometrial canal and the adnexa was characterized in a total of 65 scans. The endometrial canal appearance was variable, with the most common finding being a linear echo (39%). The adnexal changes were less diverse, with an adnexal ring suggestive of an extrauterine gestational sac identified in 60%. In 10 cases, the adnexal ring contained a distinct fetus with a measurable crown-rump length, and cardiac activity was evident in six. Our results indicate that real-time ultrasound coupled with serum beta-hCG RIA should be the procedure of choice when ectopic pregnancy is suspected.
Endometriosis in the subcutaneous tissue is an uncommon finding, but one reported in association with surgical incisions and scars. The use of ultrasound, but not computed tomography, has been reported in the diagnosis of such lesions. Reported here is a case of abdominal subcutaneous endometrioma detected by CT in a patient with confusing symptoms.