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Biomedical subjects

T J Hall

Publications and source records attributed to T J Hall.

At least 55 records · Page 3Linked to original sources

Familial juvenile polyposis. Study of a kindred: evolution of polyps and relationship to gastrointestinal carcinoma.

Familial juvenile polyposis is a rare intestinal polyposis that has recently been associated with gastric and colonic adenocarcinoma. The authors report a kindred of 41 members, 11 of whom have familial juvenile polyposis. In these patients, random sections of otherwise grossly normal-appearing colonic mucosa showed a dense population of mixed inflammatory cell infiltrates in the superficial third of the lamina propria. Fine nodular mucosa was noted focally and diffusely in six of eight colons resected. These consisted of foci of dense inflammatory cell infiltrates in the mucosa with slight crypt architectural abnormalities. The majority of lesions were typical juvenile polyps. Dysplastic changes were noted in the polyps that were 1-2.9 cm or larger. The largest polyps contained foci of villous adenoma and juvenile polyp. A focus of adenocarcinoma of the colon was noted at the base of the villous adenoma portion of the largest polyp. The gastric polyps were histologically identical to hyperplastic polyps of the stomach. This report represents the largest number of patients (eight) in a single family with familial juvenile polyposis studied histologically. This is also the first time that the changes in the nonpolypoid colonic and gastric mucosa have been reported. The pattern of inheritance in this family suggests that the trait for familial juvenile polyposis segregates as an autosomal dominant.

Adenocarcinoma↗

Quantitative ultrasonic detection of parenchymal structural change in diffuse renal disease.

OBJECTIVE: The authors determined whether quantitative ultrasound could be useful in the evaluation of diffuse renal disease. METHODS: Digitized radiofrequency ultrasound data were acquired from the kidneys of patients with biopsy-proven diffuse renal disease and transplant rejection (37 patients plus 18 normal volunteers). The results of the quantitative analysis were compared with histology results to determine if microscopic renal structure could be correlated with quantitative features such as scatterer size and scatterer spacing. The results also were analyzed using receiver operating characteristic analysis to determine if diffuse disease could be detected reliably using quantitative methods. RESULTS: The three most useful features in the native kidneys were mean scatterer spacing (MSS), sigma's, and average scatterer size (D). Using these features, it was possible to detect diffuse renal disease causing a decrease in renal function with an area under the ROC curve (Az) of 0.93. The feature D corresponded closely to histologically measured average glomerular diameters. For normals, D = 216 microns and glomerular diameter = 211 microns. No histologic correlate was found for scatterer spacing. In transplants, MSS and integrated backscatter were most useful for detecting rejection (Az = 0.87), and D in rejection was similar to the values for normal kidney and normally functioning transplants. CONCLUSIONS: The D value corresponds to glomerular diameter, and glomerular enlargement can be detected readily using quantitative ultrasound. Combinations of two to four quantitative features can detect diffuse renal disease and transplant rejection reliably.

Humans↗

Comparison of the low-contrast detectability of a screen-film system and third generation computed radiography.

Contrast-detail (CD) analysis was used to compare the low-contrast detectability of computed radiography (CR) and screen-film (SF) as applied to the task of adult chest radiography. A phantom was constructed and imaged using the same exposure factors throughout all experiments. Within-observer variance, between-observer variance, and image sample variance were calculated and used to estimate the standard error for each experiment. The results of these CD experiments agreed with the predictions of the Rose model. Observers performed equally well for low-contrast target detection using CR and SF.

Adult↗

Diagnosis and natural history of extramammary tumors metastatic to the breast.

BACKGROUND: In patients with known extramammary malignancies, metastatic disease should be considered in the differential diagnosis of a breast mass. STUDY DESIGN: Retrospective review. RESULTS: From January 1, 1980 to December 31, 1992, nine women (ages 25 to 67 years) were identified with breast masses, the biopsies of which proved to be metastatic from other sites. All patients presented with palpable breast masses. Mammograms were obtained in five patients; all demonstrated the palpable abnormality. Two of three mammograms showing multiple nodules were evaluated as suggestive of benign disease. In three patients, breast metastases were the presenting symptom of an occult primary tumor. The remaining six patients were diagnosed with metastatic disease in the breast from ten months to 15 years after the initial diagnosis (mean of 5.5 years) of an extramammary malignancy. One-half of the patients presented five or more years after the initial diagnosis. Breast metastases were associated with disseminated metastatic disease in eight of the nine patients. Six patients died after a mean interval of 8.2 months (range of 3.5 to 35 months) from diagnosis of breast metastases. One patient was unavailable for follow-up evaluation and is presumed dead. CONCLUSIONS: Metastatic disease should be considered in the differential diagnosis of a palpable breast mass, particularly if there is a history of extramammary malignancy. The presence of multiple or bilateral well-circumscribed nodules may suggest a benign process on mammography. Breast metastasis is usually indicative of diffuse metastatic disease and a poor prognosis. Biopsy and careful review of previous pathologic material assures prompt treatment and avoids an unnecessary radical operation.

Adult↗

Laparoscopic appendectomy: is it worth it?

Data on all laparoscopic appendectomies (LA) were collected prospectively from June 1990 through July 1992 and compared retrospectively with all open appendectomies (OA) done at the same hospital during the same time period. Laparoscopic appendectomies were performed in 29 patients (ages 15-47, mean 25.3 years) and OA in 77 patients (ages 18-71, mean 31.9 years, P < 0.01). Preoperative findings were similar in the two groups. Acute appendicitis was confirmed in 22 (76%) LA and in 57 (74%) OA; of these, 9/22 (41%) LA and 23/57 (40%) OA were gangrenous or perforated. A normal appendix was removed in seven (24%) LA and in 20 (26%) OA. Three patients (10%) required conversion of LA to an open procedure. Operative time was significantly longer for LA (mean 105 minutes) compared with OA (mean 69 minutes; P < 0.001). Postoperative complications requiring further intervention (wound infection or intraabdominal abscess) occurred in three LA (10%) and in 23 OA (30%, P < 0.05). Wound morbidity as measured by number of wounds left open at surgery or opened for infection was significantly less after LA (14% LA, 39% OA, P < 0.001). Hospital stay was significantly shorter after LA (mean 4.2 days) compared with OA (mean 6.3 days; P < 0.05). Hospital charges and professional fees were not significantly different between the two groups. In selected patients, LA is a safe, effective alternative to OA, with fewer complications and shorter hospital stay. In addition, hospital charges are similar, making an investment of more time in the operating yield an outcome equal or superior to OA.

Acute Disease↗

The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro.

Mithramycin is an mRNA synthesis inhibitor that has been used to decrease bone resorption in patients with humoral hypercalcemia and Paget's disease. During studies on the mechanism of action of mithramycin it became clear that the compound has a direct inhibitory effect on osteoclastic bone resorption in the in vitro bone slice assay. At concentrations of 0.1-100 nM mithramycin directly inhibited osteoclastic bone resorption dose-dependently up to 66 +/- 5% at 100 nM (mean +/- SEM, 3 expts.). Another mRNA synthesis inhibitor, actinomycin D (0.1-100 nM) and the protein synthesis inhibitor, cycloheximide (0.1-10 microM), also dose-dependently inhibited osteoclastic bone resorption by 78 +/- 7% at 100 nM and 76 +/- 7% at 10 microM, respectively. Mithramycin and actinomycin D at 100 nM did not affect osteoclast survival on bone slices and were therefore not cytotoxic at the concentrations used. Mithramycin (100 nM) and cycloheximide (10 microM) both slightly decreased osteoclast cytoplasmic spreading. Addition of 100 nM mithramycin 6 hr after osteoclast adhesion to bone slices still inhibited subsequent resorption by 50%, indicating a continued but lesser requirement for mRNA synthesis during bone resorption. These results show that approximately 75% of osteoclasts obtained from neonatal rat long bones are activated by adhesion to mineralized bone surfaces and require mRNA and protein synthesis in order to resorb bone in vitro.

Animals↗

Renal ultrasound using parametric imaging techniques to detect changes in microstructure and function.

RATIONALE AND OBJECTIVES: Signal processing techniques have been used to generate parametric ultrasound images that describe properties of tissue microstructure. METHODS: Images of the average scatterer size (D) and integrated backscatter coefficient (IBC) for normal dog kidneys were examined. RESULTS: With parametric ultrasound the authors identified sources of cortical backscatter and observed microanatomical changes corresponding to ischemia. In particular, scatterer size images acquired in vitro and in vivo show it is possible to rapidly assess changes and differences in the average glomerular diameter and the average arteriolar cross-sectional diameter. CONCLUSIONS: A more direct interpretation of sonographic image data is possible with this new type of imaging. Parametric imaging may have a diagnostic role as a means to differentiate among conditions producing increased cortical echogenicity and to detect important structural indicators such as glomerular hypertrophy.

Animals↗

Gastric carcinoma among younger individuals in Mississippi.

During a time when gastric cancer in the United States appears to be decreasing in incidence and occurring primarily in older individuals, a 12-year review of our experience (1977 to 1989) has identified a disproportionate number of gastric cancers in the young black population. In this series of 97 patients with gastric adenocarcinoma, the mean age at diagnosis was 58 years (range, 22 to 84 years). There were 54 men (56%) and 43 women; 78 (80%) were black, 17 (18%) were white, one was American Indian, and one was Mexican. Fifty-two patients (54%) had stage IV disease at the time of presentation. Fifty-two patients (54%) were less than 60 years old at diagnosis; 45 (86%) of these were black men. We do not know the reason for this unusual age distribution, but a combination of environmental factors or an unusually susceptible population may be involved. Identification of a gastric ulcer in this cohort warrants careful follow-up and appropriate treatment.

Academic Medical Centers↗

Development of an in vitro hepatotoxicity assay for assessing the effects of chronic drug exposure.

We have used the human hepatoma cell line HepG2 to compare the hepatotoxic effects of acute (24 hr) and chronic (up to 10 days) exposure to amitriptyline, paracetamol and ondansetron. In acute exposure studies, hepatotoxicity was assessed by the sulforhodamine B protein staining method, where amitriptyline and paracetamol produced 50% hepatotoxicity at concentration of 30 microM and 7 mM, respectively, while ondansetron was non-hepatotoxic at 100 microM, the highest concentration used. In chronic exposure studies, the morphology of HepG2 cells was assessed by phase microscopy every 2 days and the compounds, at concentrations determined from the acute assay, were added fresh every 2 days. Chronic exposure to amitriptyline and paracetamol produced significant morphological changes in HepG2 cells at 3 microM and 1 mM respectively, concentrations which had no significant effect in the acute assay. Ondansetron (100 microM) produced only slight morphological changes in the cells after 10 days of culture. The combination of acute and chronic drug exposure assays with HepG2 cells represents novel in vitro systems for the hepatotoxicological assessment of drugs intended for human use.

Acetaminophen↗

Na+/H(+)-antiporter activity is essential for the induction, but not the maintenance of osteoclastic bone resorption and cytoplasmic spreading.

We have examined the kinetics of the effects of inhibitors of the Na+/H(+)-antiporter (dimethylamiloride) and the vacuolar H(+)-ATPase (bafilomycin A1) on bone resorption by disaggregated rat osteoclasts in the bone slice assay. Bafilomycin A1 (100 nM) inhibited resorption by approximately 95%, 75%, 80% and 60% respectively, when added at t = 0, 1, 3 or 6 hr after osteoclast adherence to bone slices, during a 24 hr culture period. The incomplete inhibition by bafilomycin A1 when added after the start of incubation was presumably accounted for by resorption that had occurred prior to addition of the compound. Dimethylamiloride (100 microM) inhibited bone resorption by 80% and 65% when added at t = 0 or 1 hr after osteoclast adherence, but was without effect when added at t = 3 or 6 hr. In addition, dimethylamiloride but not bafilomycin A1 strongly inhibited osteoclast cytoplasmic spreading. The results indicate that Na+/H(+)-antiporter activity is essential for controlling intracellular pH during early activation events stimulated by the adherence of osteoclasts to mineralized bone surfaces, which lead to cytoskeletal activation, cell spreading and bone resorption.

Amiloride↗

Computers in ultrasonic imaging.

This article describes the role of computers and digital electronics in state-of-the-art diagnostic ultrasound scanners. An overview of the computational requirements is provided, and limits on color flow image frame rates are discussed. The new scanner architectures emerging may be used to extend current limitations of ultrasonography, making features such as automatic phase aberration correction, speckle reduction, and tissue characterization available.

Humans↗

Identifying acoustic scattering sources in normal renal parenchyma in vivo by varying arterial and ureteral pressures.

Ultrasonic backscatter properties of normal dog kidney parenchyma are examined in vivo to determine sources of acoustic scattering. We systematically varied the renal perfusion and ureteral pressures to obtain detailed information about scattering sources that could not be seen under in vitro conditions. These data suggest that in normal parenchyma the principal sources of backscatter are Bowman's capsule at low frequencies (2.5-5.0 MHz) and glomerular arterioles at high frequencies (5.0-15.0 MHz). We found that the integrated backscatter coefficient (IBC) in normally perfused kidney cortex is approximately half that measured in the ischemic organ at all frequencies. Ischemia was found to reduce scatterer size estimates (D) by 10% at low frequencies and increase D54% at high frequencies. Acute obstruction of the kidney, under diuresis, produced an 11% increase in D at low frequencies, and no significant change in D at high frequencies. These variations in backscatter measurements are explained in terms of changes in the microscopic anatomy of the kidney.

Animals↗

Laparoscopic appendectomy. Initial experience in a teaching program.

From February 1990 to December 1991, 16 laparoscopic procedures were performed for right lower quadrant pain. There were nine men and seven women, aged 16 to 47 years (mean, 27.2 years). All procedures were performed by surgical chief residents with prior experience in laparoscopic cholecystectomy, first-assisted by an attending surgeon. The appendix was visualized and a definitive diagnosis was made in all patients. One patient with acute salpingitis underwent diagnostic laparoscopy only; two patients underwent laparotomy (perforated appendicitis, perforated diverticulitis). A fourth patient had an acute torsion of an ovarian cyst managed laparoscopically. Laparoscopic appendectomy was successfully performed in 12 patients (acute appendicitis, 9; fibrosis or chronic inflammation, 2; normal appendix, 1). Mean operative time for laparoscopic appendectomy was 95.7 minutes, and mean postoperative stay was 2.5 days. The authors conclude that operative time, diagnostic accuracy, and complication rates for laparoscopic appendectomy are acceptable. Within the context of a training program, laparoscopic appendectomy provides an opportunity for surgical residents to expand laparoscopic skills.

Adolescent↗

Specific inhibition of IgE antibody production by an antisense oligodeoxynucleotide oligomer (Oligostick).

We have investigated the ability of an antisense oligonucleotide (ASE-1) to specifically inhibit IgE synthesis by a human myeloma cell line, U266. ASE-1 inhibited IgE production in a concentration-dependent manner, as assessed by isotype-specific ELISA measurement of immunoglobulin in myeloma cell supernatants. Inhibition of IgE production was specific and not due to cytotoxicity since IgG1 and IgM production by human myeloma cell lines ARH-77 and RPMI-1788 respectively, was not significantly affected by up to 20 microM ASE-1 whereas IgE production was inhibited by approximately 70% at this concentration. These results indicate that antisense oligonucleotides represent a potential therapeutic approach to the treatment of IgE-mediated allergic diseases.

Antibodies, Neoplasm↗

Regulation of calcitonin release from the 6.23 rat C-cell line by cyclic nucleotide analogues and pharmacological mediators.

Calcitonin release from 6.23 rat medullary thyroid carcinoma C-cells was stimulated by dibutyryl cyclic AMP and inhibited by dibutyryl cyclic GMP in concentration dependent fashion. Histamine, isoproterenol, prostaglandin E2 and Bay K 8644 stimulated calcitonin release, while acetylcholine and serotonin had no significant effect on CT release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗