Biomedical subjects
Publications and source records attributed to J L Freeman.
Metastatic papillary carcinoma to the sinuses and skull base is a rare occurrence. A case report of aggressive papillary carcinoma is reported. The tumor contained areas of insular and anaplastic degeneration with strong positive staining for p53 oncogene. Management included primary surgery, administration of radioactive iodine, and external beam radiation.
Although modern imaging techniques become more accurate for the assessment of lymph node metastases in the neck as criteria and technology evolve, micrometastases remain occult with any technique. Even the routine histopathological examination of neck dissection specimens is unable to detect all micrometastases. Because knowledge on the incidence of micrometastases in the clinically NO neck might be of importance for decision making regarding elective treatment, a retrospective study on 96 elective neck dissections was conducted. Meticulous histopathological examination of the neck dissection specimens yielded 3092 lymph nodes of which 67 (2.2%) were tumor-positive. Twenty-six of these 67 lymph node metastases were micrometastases. Of the 36 tumor-positive neck dissection specimens, 21 contained micrometastases. In 9 tumor-positive specimens only micrometastases were found. This high incidence of micrometastases has important implications for the diagnostic work-up, the treatment, and histopathological examination of the NO neck.
A 47-item Paranoia/Suspiciousness Questionnaire was developed on a non-psychiatric sample using modified items from several established scales of paranoia and related concepts. Factor analysis of the questionnaire identified five moderately correlated subscales labelled Interpersonal Suspiciousness/Hostility, Negative Mood/Withdrawal, Anger/Impulsiveness, Mistrust/Wariness and Perceived Hardship/Resentment. There were no significant difference between males and females on the questionnaire or any of the subscales. The full questionnaire and the subscales showed satisfactory internal consistency and test-retest reliability. Further research is needed to establish the scale as a useful diagnostic tool.
The ret/PTC oncogene is unique to papillary thyroid cancer. Three forms of this oncogene, formed by translocation of three different genes to the tyrosine kinase domain of the ret protooncogene, result in constitutive kinase activation. Correlation with clinical outcome is controversial; ret/PTC-1 has been suggested to predict aggressive behavior. There is no morphological description of ret/PTC-positive tumors. We analyzed 60 thyroid carcinomas for ret/PTC expression to determine correlation with clinical history, disease stage, or tumor morphology. Ribonucleic acid extracted from frozen tissue was reverse transcribed; PCR was performed to amplify ret/PTC-1, 2, and -3. The TPC-1 cell line was the positive control for ret/PTC-1. All tumors were characterized morphologically. Clinical data were collected. The 57 papillary and 3 follicular carcinomas were resected from 44 female patients and 15 males. The average age at diagnosis was 46.2 yr (range. 24-83 yr). Three patients had a history of neck irradiation. At diagnosis, 11 patients had extrathyroidal tumor extension, 20 had lymph node metastases, and 1 had lung metastasis. Thirteen patients had tall cell papillary carcinomas; 3 tumors had focal insular or anaplastic dedifferentiation. The average follow-up was 13.4 months, during which 4 patients had recurrent disease. No deaths occurred. One papillary carcinoma (1.7%) was positive for ret/PTC-1, none was positive for ret/PTC-2, and 2(3.4%) were positive for ret/PTC-3. Although all 3 patients who had tumors containing ret/PTC rearrangements were under the age of 45 yr (range, 26-44 yr) and had small tumors (< 1.2 cm), 2 of these 3 patients presented with lymph node metastases, and the third had lymphatic invasion. ret/PTC oncogene expression did not correlate with radiation history. In summary, ret/PTC oncogene rearrangements were found in 3 of 60 (5%) thyroid carcinomas and were not present in tumors with aggressive morphological features. However, we found ret/PTC rearrangements in young patients (< 45 yr of age) with small thyroid carcinomas showing a predisposition for lymphatic involvement, suggesting a possible role in the development of this subgroup of tumors.
OBJECTIVES: This study examined the association between community rates of iron deficiency in children and sociodemographic characteristics of Massachusetts communities. METHODS: Between April 1990 and March 1991, 238 273 Mssachusetts children 6 through 59 months of age were screened; iron deficiency was defined as an erythrocyte protopophyrin concentration of 0.62 micromol/L or higher and a blood lead level of less than 1.2 micromol/L. Sociodemographic data were obtained from the 1990 US Census. RESULTS: Five percent of communities had iron deficiency rates greater than 13.9 per 100 children screened. Iron deficiency rate was positively associated with proportion of Southeast Asians (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.08, 1.12), proportion of Hispanics (OR = 1.008, 95% CI = 1.002, 1.013), and high school incompletion (OR = 1.028, 95% CI = 1.020, 1.035). Similarly, an examination of three Massachusetts cities indicated that the iron deficiency rate was higher for children with Southeast Asian (relative risk [RR] = 3.6, 95% CI = 3.3, 3.8) and Hispanic (RR = 1.6, 95% CI = 1.5, 1.8) surnames than for all other children. CONCLUSIONS: Wide variation exists in iron deficiency rates for children in Massachusetts communities. Community iron deficiency was associated with low socioeconomic status and high proportions of Southeast Asians and Hispanics.
Gene therapy has now become a standard experimental approach for treating cancers that have failed conventional therapies. As the understanding of the molecular nature of carcinogenesis develops, new approaches are being taken to directly target tumor cells, thus bypassing the difficulties of killing cells that are resistant to chemotherapy and radiation. One emerging gene therapy approach has been through the genetic modification of tumor cells with a suicide gene such as the herpes simplex virus thymidine kinase gene (HSV-TK) and ganciclovir (GCV) therapy. Death of tumor cells modified with the HSV-TK gene leads to killing of unmodified in situ tumor cells in a phenomenon termed the "bystander effect." The basis both for this effect and other gene therapy trials underway for the treatment of cancer will be discussed.
Surgically resected thyroids from 425 patients with thyroid disease other than carcinoma of follicular cell derivation were thoroughly examined for occult micropapillary carcinoma (MPC). There were 317 cases of nodular hyperplasia, 36 of thyroiditis, 44 follicular adenomas, and 28 others. Glands were sectioned at 2- to 3-mm intervals and fixed in formalin. Every section was examined histologically. There were 71 cases (16.7%) of MPC containing 118 tumors. Among 343 women, 51 (14.9%) had MPC; among 82 men, 20 (24.4%) had MPC. The average age of all of the patients was 46.9 years and of those with MPC, 50.5 years. The occurrence of MPC peaked between 40 and 70 years and declined in older patients. MPC was found in 8.9% of patients who underwent lobectomies, 10.8% who had hemithyroidectomies, and 24.1% of those who had total thyroidectomies. Logistic regression analysis revealed significant associations between the presence of MPC and the patient sex, age, and extent of surgery; in contrast, there was no association between the occurrence of MPC and the underlying thyroid disease. These data indicate that MPC is present in up to 24.1% of thyroids removed for unrelated thyroid disease. The predominance of this lesion in men is in striking contrast to the occurrence of clinically significant thyroid cancer. This suggests that the initiation of carcinogenesis is not sexually dimorphic, whereas promoters of tumor growth are. A rational management of this common disease awaits the results of careful controlled trials.
Between 1991 and 1994, 600 thyroidectomies were performed at the Beilinson Medical Center in Israel, 120 of which were due to malignancies. Routine preoperative and follow-up ultrasound examinations were performed in 100 cases. A prospective study comparing preoperative ultrasonic and operative findings revealed that ultrasound offered significant preoperative information that could alter operative decisions. Ultrasound also proved to be a valuable tool in follow-up. Based on ultrasound findings, patients were salvaged at an early stage of recurrent disease.
OBJECTIVE: To describe claviculotomy and claviculectomy for access to lesions of the lower part of the neck, with simultaneous reconstruction. METHODS AND MATERIALS: A retrospective review of 15 patients who underwent claviculotomy for access to the lower part of the neck. RESULTS: Eight patients underwent plate reconstruction, and one patient required subsequent removal. Three patients underwent total claviculectomy, and four patients underwent partial claviculectomy. Ten patients are alive and free of disease, three have died of disease, and two are alive with disease. All but two patients are satisfied with shoulder function, and one patient is dissatisfied with the cosmetic result. CONCLUSIONS: The claviculotomy and claviculectomy technique for tumors that transgress the neck, thoracic inlet, and axilla offers maximal exposure for excision, vascular control, and preservation of vital structures. Modern plating techniques have allowed clavicular reconstruction with improved cosmesis and preservation of shoulder stability.
A number of growth factors have been implicated as stimuli of thyroid cell proliferation; overexpression of these growth factors and/or their receptors may play a role in the growth of thyroid tumors. To determine if immunohistochemical detection of growth factors and/or their receptors correlates with morphological alterations in proliferative lesions of thyroid, we examined the localization of epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and their common receptor, EGF-receptor (EGF-R), insulin-like growth factor-1 (IGF-1), IGF-1-receptor (IGF-R) and IGF binding proteins (IGFBP)-1, -2, -3, and -4, nerve growth factor (NGF), and its receptor NGF-receptor (NGF-R), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF), in normal thyroid tissue and various thyroid tumors. We applied the streptavidin-biotin technique to formalin-fixed, paraffin-embedded tissues. We studied 8-16 different cases of each of the following: normal human thyroid, multinodular hyperplasia, follicular adenoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, and anaplastic carcinoma. EGF, TGF-alpha, and their receptor EGF-R were widely expressed in normal thyroid and in all the thyroid lesions examined. IGF-1 and IGFBP-1 were diffusely present in all different thyroid tissues as well. There was no difference in staining intensity or distribution that correlated with the pathological process. IGFBP-4 seemed to have a variable expression. IGFBP-2 and -3 were detected only in medullary carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Adequate hemostasis during lacrimal drainage surgery affects the success of the operation. Nasal decongestants, which are sympathomimetric agents including sympathomimetic amines and imidazoline derivatives, help to decrease bleeding. Certain of the imidazoline derivatives--oxymetazoline and xylometazoline--are potent and long-acting agents that have many of the same adrenergic effects as cocaine. Their use as an alternative to cocaine provide adequate hemostasis with less adverse reactions than cocaine. The authors recommend premedication of the nasal mucosa with oxymetazoline or xylometazoline before lacrimal drainage surgery for obtaining maximal nasal mucosal decongestion.
Diagnosis-related groups have been revised through more refined uses of secondary diagnoses. Under the refined diagnosis-related groups, patients are distinguished with respect to classes of secondary diagnoses that are disease- and procedure-specific. Each class represents a different level of utilization for a given principal diagnosis or surgical procedure. The refined system was evaluated with national data from the Medicare program. Estimates of hospital costs and utilization based on refined diagnosis-related groups were more precise than those based on unrefined diagnosis-related groups. This approach to diagnosis-related group refinement does not represent a radical departure from the current diagnosis-related group framework and does not require new data collection efforts. Moreover, a payment system based on the refined model is less affected by the ordering of the diagnoses than under the existing diagnosis-related group system. How the refined diagnosis-related group framework can accommodate future refinements at all levels of the classification scheme is also discussed.
OBJECTIVES: The purpose of the study was to examine the relationship between communities' sociodemographic and housing characteristics and incidence of lead poisoning. METHODS: This was a population-based correlational study of 238,275 Massachusetts children from birth through 4 years of age who were screened for lead poisoning in 1991-1992. A logistic regression model was developed with the community as the unit of analysis, the case identification rate for lead poisoning (newly identified children with venous blood lead > or = 25 micrograms/dL per 1000 children) as the dependent variable, and US census variables as independent variables. RESULTS: A significant independent relationship with the community case identification rate of lead poisoning was found for seven variables: median per capita income, percentage of housing built before 1950, percentage of the population who were Black, percentage of children screened, and a "poverty index." Rates of iron deficiency and percentage of Hispanics were not associated with the case identification rate of lead poisoning. CONCLUSIONS: Massachusetts communities' incidence of lead poisoning is correlated with sociodemographic and housing characteristics. In states similar to Massachusetts and without screening data, this model may help target screening programs.
Acute tracheal obstruction by a mediastinal mass is uncommon in otolaryngologic practice. Choosing techniques for securing the airway, induction of anaesthesia, and the surgical approach require careful deliberation. We report our experience in a patient with acute respiratory distress due to external compression of the trachea in the mediastinum by metastatic carcinoma. We used a fibre-optic bronchoscope ensheathed by an endotracheal tube to secure the airway. Standard tracheotomy tubes were too short to splint open the obstruction in the distal trachea, whereas the long Montgomery T-tube was effective.
Rac, a small molecular weight GTPase in the Ras superfamily, participates in the activation of the multicomponent superoxide-generating NADPH oxidase of human neutrophils. Rac is 30% identical to Ras overall, but is 75% identical within the sequence corresponding to the effector region of Ras, which regulates mitogenesis through interactions with the protein kinase Raf1. We investigated the role of this region in Rac1 using site-directed mutagenesis. In a cell-free semirecombinant NADPH oxidase system, mutants in the 26, 33, 38, and 45 amino acids showed 20-110-fold reduced binding to the oxidase complex as judged by EC50 values and reduced (44-80%) maximal activities in superoxide generation. Only the GTP gamma S-bound form associated, since the GDP-bound form of Rac neither activated alone nor competed with GTP gamma S-Rac. EC50 values for neither p47-phox nor p67-phox were affected when mutant Racs were used in place of Rac. Data indicate direct binding of the Rac effector region to one or more components of the respiratory burst oxidase. Results indicate a general role for conserved effector-equivalent regions in small GTPases in the regulation of protein-protein interactions.
OBJECTIVE: To explore the reasons for underutilization of beta blocker treatment after acute myocardial infarction. DESIGN: A retrospective chart review. SETTING: Two large community hospitals in Milwaukee, Wisconsin. PATIENTS/PARTICIPANTS: All subjects (n = 694) discharged alive from July 1, 1990, to June 30, 1991, who had a diagnosis of acute myocardial infarction were eligible. Of these, 250 had missing data, resulting in a final sample of 444. RESULTS: Twenty-nine percent of the 444 patients were prescribed beta blocker therapy on discharge. Characteristics of the patients and their treatment associated with receipt of beta blocker therapy were identified with a logistic regression model. The adjusted odds ratios were 0.52 for female gender, 0.34 for no health insurance, 0.21 for chronic obstructive pulmonary disease, 0.46 for congestive heart failure, 0.28 for atrioventricular block, 1.86 for hypertension, 1.93 for chest pain during acute myocardial infarction, and 4.65 for prehospital beta blocker use. Prescription of beta blocker therapy was also influenced by receipt of other treatment modalities. The adjusted odds ratios were 0.23 for receipt of beta blocker therapy associated with myocardial revascularization, 0.18 for prescription on discharge of calcium channel blockers, and 0.22 for receipt of angiotensin-converting enzyme inhibitors. CONCLUSION: A minority of patients discharged after acute myocardial infarction receive beta blocker therapy, and women are only half as likely as men to receive it, after controlling for other factors. Though there are no data relating to whether calcium channel blockers or angiotensin-converting enzyme inhibitors lessen the protective effect of beta blocker therapy post-acute myocardial infarction, it would appear that these agents are frequently being used in lieu of beta blocker therapy for post-acute myocardial infarction patients.
BACKGROUND: Epithelioid sarcoma is a rare and aggressive malignancy commonly occurring in the tendon sheaths of the distal extremities of young adults. This article presents the clinical and pathologic details of two patients with epithelioid sarcoma in the orbit, the first to be reported as occurring in this location. METHODS: The clinical history, results of physical and radiologic examination, surgical procedures, pathologic specimens, and clinical course of each patient were reviewed and recorded. RESULTS: Biopsies were performed of the masses that were found in the superotemporal orbit of both patients. Results of pathologic examination in each patient caused considerable difficulty, and the correct diagnosis was reached only after extensive consultation. The first patient underwent wide soft tissue and bone exenteration and is alive without recurrence at 3 years. The second patient had multiple recurrences and died of recurrent and metastatic disease at 29 months. CONCLUSIONS: Epithelioid sarcoma must be added to the differential diagnosis of orbital sarcomas. The histology is nodular with a pseudogranulomatous appearance. Based on our limited experience, epithelioid sarcoma of the orbit may have a course similar to that which occurs elsewhere in the body, requiring aggressive surgical treatment at the outset.
Through-and-through oral cancer (T4+) involving contiguous mucosa, mandible, and skin is a devastating disease with poor prognosis and represents one of the most difficult reconstructive challenges in head and neck surgery. Thirty-eight patients underwent immediate microvascular reconstruction following surgical tumor ablation. The purpose of the present review was to assess the value of microvascular reconstruction in these essentially palliative reconstructive efforts. The iliac crest osteocutaneous flap was used in the majority of patients and was found to be ideal for the reconstruction of large bony and soft-tissue defects present in this group of patients. Other methods, including pectoralis major, forehead, and latissimus dorsi flaps, also were used in the soft-tissue reconstruction. The mean follow-up was 16 +/- 2 months, and the mean hospitalization was 43 +/- 22 days. The majority of patients succumbed to recurrent or related diseases, yet a few went on to survival despite the initial advanced stage of disease. A number of complications were observed. However, most patients developed normal or easily intelligible speech (65 percent), and most (78 percent) had their tracheostomies closed and sustained themselves on an oral soft diet (84 percent). Bony union was noted in the majority of patients (73 percent). Although the prognosis in full-thickness oral carcinoma is grim, it appears that palliative surgery in these cases is well justified. The goals are to shorten the duration of hospitalization, reduce morbidity, and improve the remaining quality of life. Microvascular tissue transfer offers a means to achieve these goals in a single, reliable procedure. We feel that immediate one-stage bone and soft-tissue reconstruction restores dignity and relieves suffering in this unfortunate group of individuals.