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Biomedical subjects

J A Tucker

Publications and source records attributed to J A Tucker.

At least 19 recordsLinked to original sources

Loss of heterozygosity on chromosome 17q11-21 in cancers of women who have both breast and ovarian cancer.

OBJECTIVE: Our purpose was to determine the frequency of allele loss in the region of the BRCA1 gene in cancers of women who have both breast and ovarian cancer. STUDY DESIGN: Four polymorphic microsatellite markers on chromosome 17q11-21 were examined by the polymerase chain reaction in deoxyribonucleic acid from paraffin blocks of normal tissues, breast cancers, and ovarian cancers in 24 women who had primary cancers in both sites. RESULTS: Loss of heterozygosity was seen in one or more markers on chromosome 17q11-21 in 46% of breast cancers and 78% of ovarian cancers. In 38% of cases allele loss was seen in both cancers, and in all these cases the same allele was lost in both cancers. Significantly younger ages at diagnosis of both breast and ovarian cancer were noted among cases with allele loss in both cancers compared with cases in which allele loss was found only in the ovarian cancer (p < 0.05). CONCLUSIONS: Because cases in which 17q11-21 allele loss was seen in both cancers had a young age of onset and the same allele was always deleted in both cancers, hereditary alterations in BRCA1 may play a role in this subset. The older age of onset in cases in which allele loss was seen only in the ovarian cancer suggests that the development of these cancers is not related to an inherited defect in BRCA1.

Alleles

Predictors of help-seeking and the temporal relationship of help to recovery among treated and untreated recovered problem drinkers.

This study investigated variables predicting different help-seeking patterns (no treatment, AA participation only, or treatment plus AA participation) by problem drinkers who had maintained stable abstinence (n = 57). Collaterals verified subjects' help-seeking and drinking status. Help-seeking was predicted by greater alcohol-related psycho-social problems, especially in interpersonal relationships, but was not associated with heavier drinking practices or demographic characteristics. Subjects' belief that they could solve their own problem deterred help-seeking, whereas relationship problems and being unable to quit on one's own facilitated help-seeking. Additional incentives specific to AA were its privacy, anonymity, spiritual aspects, opportunities to help other problem drinkers, and the convenient meetings held at times typically spent drinking. Many subjects became abstinent before they sought help, especially from treatment programs. These findings implicate interpersonal factors as primary incentives for help-seeking and suggest that interventions often consolidate, rather than initiate, positive changes in drinking practices.

Adult

Fertility after cryptorchidism: a comparative analysis of early orchidopexy with and without concomitant hormonal therapy in the young male rat.

Infertility is common in patients with a history of bilateral cryptorchidism, even after successful prepubertal orchidopexy. Recent data suggest that this defect may be partially due to the existence of hormonal abnormalities in some forms of cryptorchidism. To analyze any potential benefit of hormonal therapy, we have evaluated the immediate and long-term effects of chronic hormonal therapy administered following surgical correction of cryptorchidism. First, using young male rats, we examined the effects of chronic human chorionic gonadotropin (HCG) and a luteinizing hormone-releasing hormone agonist (LHRH-A), alone or combined, on acute pituitary-gonadal axis responsiveness to LHRH administration. High doses of HCG and/or LHRH-A induced deleterious effects on the pituitary-testicular axis in terms of suppression of response to LHRH. Therefore, treatment with a low dose of HCG (50 U/kg/day) for 14 days was used, since it produced a significant increase in intratesticular testosterone (ITT). Second, we tested this hormonal regimen in a cryptorchid rat model. Bilateral cryptorchidism was produced by gubernaculum resection at 14 days of age. Early orchidopexy was performed at age 30 days, and HCG therapy was given from 31 to 44 days of age. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels were determined before and immediately after hormonal therapy, and at sacrifice. Animals were sacrificed at 61 days of age for determination of serum and testicular hormone levels, accessory sex organ weights and testis histology. Five or six animals from each group were retained for breeding studies at the age of 90 days. Hormonal alterations noted immediately following treatment of cryptorchid animals with HCG are not lasting. The data reveal that the fertility defect in bilateral cryptorchidism is partially prevented by early orchidopexy and that adjunctive hormonal therapy is probably of little additional benefit.

Analysis of Variance

Adequacy of recall of drinking patterns and event occurrences associated with natural recovery from alcohol problems.

The adequacy of recall of drinking and events surrounding natural recovery from alcohol problems was investigated with 21 abstinent and 18 active untreated problem drinkers. During structured interviews, drinking was assessed for 6 years, and events were assessed for 1 year; both assessment periods ended about 6 years before data collection, which corresponded with the beginning of sobriety for abstinent subjects. The accuracy of subject reports of both variable classes was evaluated through comparisons with collateral reports, and the reliability of drinking reports was evaluated by reinterviewing a subset of subjects about 2 months after the first assessment. Reliability was generally high for subjects' drinking reports. Subject-collateral agreements were significant for drinking and event variables that collaterals could readily observe, but not for variables that were less observable. Current drinking status and the length of recall did not influence reporting accuracy. With some qualifications, these findings support the use of structured recall procedures to investigate drinking patterns and environmental circumstances related to natural recovery and highlight limitations in the use of collaterals as a verification method.

Adult

Relationships among tumor temperature, treatment time, and histopathological outcome using preoperative hyperthermia with radiation in soft tissue sarcomas.

The lack of an unambiguous thermal dosimetry continues to impede progress in clinical hyperthermia. In an attempt to define better this dosimetry, a model based on the cumulative minutes during which arbitrary percentages of measured tumor temperature points exceeded an index temperature was tested in patients with soft tissue sarcomas treated with preoperative hyperthermia and conventional radiation therapy. Patients received 5000-5040 cGy at 180-200 cGy per fraction. Hyperthermia was delivered 30-60 minutes after radiation therapy and given for 60 minutes. Patients were randomized between one and two hyperthermia treatments per week for a total of five or 10 treatments, respectively. Lesions were excised 4-6 weeks after completion of hyperthermia/radiation therapy. Successful treatment outcome was considered to be the finding of greater than 80% necrosis of the sarcoma upon histopathologic examination of the resected specimen. Forty-five patients were eligible with thermometry data available in 44 patients. An average of 19 interstitial sites were monitored each treatment per tumor. Sixty percent of tumors had a successful histopathologic outcome. Univariate analysis demonstrated that several descriptors of the temperature distribution were strongly related to treatment outcome; more strongly than nonthermometric factors, such as the number of treatments per week, tumor volume and patient age and more strongly than the commonly used temperature descriptors Tmin and Tmax. Descriptors that incorporated both temperature and time were also superior to the more commonly used descriptors Tmin and Tmax. Multivariate stepwise logistic regression analysis revealed that a descriptor of both the hyperthermia treatment time and the frequency distribution of intratumoral temperatures was the strongest predictor of histopathologic outcome and that the best predictive model combined this time/temperature descriptor and one versus two treatment per week grouping. The more conventional temperature descriptor, minimum measured tumor temperature, did not significantly enhance the predictive power of treatment group. Based on these results, we recommend that descriptors based on both the frequency distribution of intratumoral temperatures and hyperthermia treatment time be tested for relationships with treatment outcome in other clinical data bases. Furthermore, we recommend that temperature descriptors that are less sensitive to catheter placement and tumor boundary identification than Tmin and Tmax (such as T90, T50, and T10) be tested prospectively along with other important thermal variables in Phase II trials in further efforts to define a thermal dosimetry for spatially nonuniform temperature distributions.

Combined Modality Therapy

Interleukin-2-induced dermatotoxicity resembling toxic epidermal necrolysis.

Interleukin-2 is a promising new immunotherapeutic antineoplastic agent, but it can cause severe multiorgan toxicity. Although dermatologic toxicity is seen in most patients receiving IL-2 therapy, it is usually manifested as pruritus and an erythematous macular rash, which resolve quickly once infusion is terminated. We have described a patient who was allergic to multiple drugs and who had sloughing of large sheets of epidermis over 75% of body surface area during IL-2 therapy. Clinically, this was indistinguishable from toxic epidermal necrolysis, but the findings on skin biopsy were nonspecific for any dermatitides. The skin healed after cessation of IL-2 infusion, but the rash recurred upon resuming infusion at a lesser dose, indicting IL-2 as the probable causative agent. This unique dermatologic sensitivity to IL-2 suggests that IL-2 could act directly as a promoter in dermatologic disease. Patients with a history of allergic reactions to other unrelated drugs should be monitored carefully for unusual bullous dermatologic changes during IL-2 therapy.

Diagnosis, Differential

Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.

PURPOSE: Hypercalcemia is a rare complication of prostate cancer, and no definite association with any histologic subtype of prostatic malignancy has been documented. We have recently seen three patients who developed hypercalcemia in the setting of prostate cancer. All had neuroendocrine carcinoma of the prostate (NCPs), which prompted an exploration of the potential association of hypercalcemia with NCP. DESIGN: An extensive review of literature published in the English-language was conducted to identify cases of hypercalcemia associated with prostate cancer and well-documented cases of NCP. RESULTS: We found 17 reported cases of hypercalcemia clearly associated with prostate cancer and a total of 61 cases of well-documented NCP. Including our cases, 11 of the 20 reported cases of hypercalcemia associated with prostate carcinoma were in patients with neuroendocrine carcinomas. CONCLUSION: Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies.

Adenocarcinoma

Infant botulism: considerations for airway management.

Infant botulism is a national problem with over 1000 confirmed cases in the United States since it was first recognized as a distinct clinical entity in 1976. The disease is characterized by a progressive, symmetrical descending paralysis of cranial nerves with eventual involvement of axial and trunk muscle innervation. Most infants progress to complete respiratory failure. An initial report in 1979 recommended early tracheotomy for avoidance of long-term intubation complications. However, over the past 10 years at St. Christopher's Hospital for Children, analysis of airway management in 11 patients with infant botulism revealed a median intubation time of 16 days. Following extubation, all patients progressed to complete respiratory recovery without adverse laryngotracheal sequelae. Otolaryngologists consulted for the airway management of infants with botulism should adopt a conservative approach with meticulous monitoring of endotracheal tube sizes and leak pressures. Tracheotomy is rarely required.

Botulism

Isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma.

Two women developed apparently isolated recurrences of ovarian carcinoma involving prior incisions after receiving intraperitoneal radioactive chromic phosphate (P-32) adjuvant therapy for early epithelial ovarian carcinoma. Both are alive without evidence of disease at second-look laparotomy after surgical resection of the abdominal wall metastases and cisplatin-based combination chemotherapy. Mechanisms of cutaneous and incisional implantation metastases are discussed. Adjuvant therapy with intraperitoneal P-32 is unable to provide systemic therapy for occult metastatic disease. The favorable outcome in these cases probably reflects limited tumor burden at the time of recurrence and stands in stark contrast to other cases of soft tissue recurrences of ovarian carcinoma reported previously.

Abdominal Muscles

Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1).

A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer.

Adenocarcinoma

Neonatal and pediatric microsubglottiscope set.

A microsubglottiscope for infants and children has been developed for microlaryngeal surgery in the glottic and subglottic regions of the larynx. The universal handle allows selection of several sizes of blades to be used according to the patient's anatomic limitations. The tips of these blades have been designed specifically to give exposure to the subglottis and upper trachea under microscopic magnification. A needle adapter for jet ventilation has been included. The authors have used this instrument in young infants and children for diagnosis and for laser resection of subglottic stenosis, hemangioma, and suprastomal granuloma, and have found the exposure to be superior to that obtained with conventional microlaryngoscopes.

Child

Agreement between subject and collateral verbal reports of alcohol consumption in older adults.

The accurate measurement of alcohol consumption in natural environments is a focal empirical issue in studies of the determinants of drinking. Four studies investigated agreement between subject and collateral questionnaire reports of drinking by adults over age 60 years (N = 83), and three of these studies also assessed agreement between daily subject and collateral prospective reports of subject drinking over 4 (Study 2) or 12 (Studies 3 and 4) week intervals. Subject and collateral questionnaire reports were significantly correlated. Excellent agreement was found for the group of subjects for self-monitoring reports of the number of drinking days and quantity of alcohol consumption per day, including reports of the temporal patterning of consumption, but variability in agreement existed across subject-collateral pairs. The discussion focuses on the conditions conductive to accurate measurement and on the importance of investigating predictor variables of individual differences in the accuracy of verbal reports of alcohol consumption.

Aged

Characterization of a new model of human prostatic cancer: the multicellular tumor spheroid.

Multicellular tumor spheroids (MTS) provide a closer in vitro correlate to in vivo malignancy than do conventional monolayer cultures; while simulating many parameters of in vivo growth, MTS systems provide those perquisites (i.e., experimental control, economy, expediency) associated with in vitro evaluation of preclinical therapeutic strategies. For these reasons, we exploited the proclivity of the highly metastatic human prostatic carcinoma subline I-LN-PC3-IA to spontaneously assume a spheroid morphology under routine culture conditions. I-LN spheroids demonstrate salient features described in other spheroid systems and exhibit histologic characteristics of human prostate carcinoma. Cells encompassed in the I-LN spheroid format demonstrated functional divergence from their monolayer counterparts with respect to immunoreactivity for prostatic acid phosphatase, positional dependence of prostate-restricted p40 antigen expression, and chemotherapeutic drug response. This new in vitro-in vivo transition model of human prostatic carcinoma should provide a valuable in vitro context to expediently evaluate in vivo correlates of oncolytic protocols on a malignancy that remains refractive to therapy.

Antineoplastic Agents

Compositional analysis of Biomer.

Biomer, a segmented polyether polyurethane, has been analyzed via hydrolysis/gas chromatography to determine its composition. In addition to the previously reported 4,4'-methylene bis(phenyl isocyanate) (MDI), polytetramethylene glycol (PTMO), and ethylenediamine, we now report the presence of diethylamine, 1,3-diaminocyclohexane and poly(diisopropylaminoethyl methacrylate-co-decyl methacrylate), Biomer's cloudy insoluble phase. In addition, a method is presented to characterize the methacrylate additive by molecular weight based on GPC. Also found by chromatography were the antioxidants Santowhite Powder and BHT. XPS shows no Si (silicone) on the Biomer surface, and a total chloride analysis reports no chloride (less than 0.03%). Time-of-flight SIMS data suggest evidence for the methacrylate additive at the surface, and mass spectroscopy can be interpreted as evidence for a diaminocyclohexane.

Antioxidants

Soft-tissue sarcomas: MR imaging and MR spectroscopy for prognosis and therapy monitoring. Work in progress.

The authors studied the usefulness of hydrogen-1 T2 measurements and phosphorus-31 magnetic resonance (MR) spectroscopy as indicators of prognosis and monitors of response to therapy in a group of patients with soft-tissue sarcomas. All eight patients were treated with combined local hyperthermia and fractionated radiation therapy, followed by surgical resection of the tumor. Each patient underwent T2 measurements and five patients underwent MR spectroscopy (phase encoded in one dimension) before treatment, after the first hyperthermia treatment, at the end of the therapy course, and just before surgery. Catheter thermometry was performed at each hyperthermia treatment. The T2 and MR spectroscopic variables were compared with thermometric data and the histologic findings from the complete surgical specimen. Changes in T2 correlated with histologic grade of tumor and thermometric data. The pretherapy tumor pH correlated positively, and changes during therapy in pH, ratio of phosphocreatine to inorganic phosphate (Pi), ratio of nucleoside triphosphate to Pi, and the phosphomonoester signal-to-noise ratio correlated negatively, with the percentage of tumor necrosis on the surgical specimen. These preliminary data suggest MR imaging and MR spectroscopy may be useful in the evaluation of such patients before and during therapy.

Adult

Laser supraarytenoidectomy for laryngomalacia with apnea.

Laryngomalacia, the most common congenital abnormality of the larynx, is a mild self-limiting disorder in the vast majority of cases. Severely obstructive cases do occur. In the past, these have required treatment with a tracheotomy. At St. Christopher's Hospital for Children, laryngomalacia was diagnosed in one-hundred and fifty-three infants during the three-year period from 1986 through 1988. Patients who had unusually severe symptoms, such as apneic spells, impaired ability to eat and severe choking episodes, were evaluated with four channel nasal thermister pneumocardiograms (sleep studies). Four infants with severe laryngomalacia had sleep studies which demonstrated obstructive apnea. In these infants, the carbon dioxide laser was used to vaporize excess floppy supraarytenoid tissue, a supraarytenoidectomy.

Apnea

Primary leiomyoma of the liver.

A 30-yr-old woman with right upper quadrant abdominal pain was found to have a hepatic leiomyoma. This is the youngest patient in whom this rare tumor has been found. The diagnostic approach toward gastrointestinal leiomyomata is emphasized, including the role of immunohistochemistry.

Adult