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Biomedical subjects

J Jacobs

Publications and source records attributed to J Jacobs.

At least 145 records · Page 8Linked to original sources

An intensive, five course, alternating combination chemotherapy induction regimen used in patients with advanced, unresectable head and neck cancer.

Progress in the treatment of advanced squamous cell cancer (SCC) of the head and neck (H & N) has included the development of combination chemotherapeutic regimens that achieve impressive complete response (CR) rates using two to three courses therapy with minimal toxicity and good patient tolerance. Further improvements in these results will require intensification of induction regimens. Therefore, a five course, alternating combination chemotherapy induction trial was initiated in an attempt to test the feasibility and toxicity of a prolonged, intensive induction regimen in patients with advanced SCC of H & N. Courses 1, 3, and 5 consisted of fluorouracil as a 120-hour infusion (5FU-I) with cisplatin (CACP) as an intravenous (IV) bolus. Courses 2 and 4 consisted of 3 weekly doses of high-dose methotrexate (HDMTX) followed by 5FU (5FU-b) and leucovorin rescue (LR). Forty-six stage IV patients with SCC of H & N (85% T4 and 58% N3) were entered. Thirty-one patients completed the study and 15 did not. Twenty-one of the 46 patients (46%) achieved a CR. Twenty-five of the 46 patients had N3 neck disease, ten of these 25 achieved a CR (40%), and eight did not complete therapy. Of the 15 patients not completing this study, one patient achieved a CR and eight achieved a partial response (PR). Eight of 46 (17%) were removed from study for reasons of toxicity (6% to 13%) or tumor progression (2% to 4%). The remaining seven were removed due to intercurrent medical conditions (four uncomplicated pneumonias and one gun shot wound) or lost to follow-up (2). Myelosuppression, mucositis, and skin toxicity increased in frequency by the end of the trial but were acceptable and reversible. The activity of this five-course regimen is promising given the advanced disease status of patients treated. Consideration of concurrent medical conditions, patient compliance, intensity of medical, nutritional and social support, and levels of acceptable toxicity will be necessary in the design of future, intensive induction trials.

Adult↗

Acute mercury poisoning and mercurial pneumonitis from gold ore purification.

We describe four men who had symptoms of acute mercury poisoning following exposure to mercury vapor. They were attempting home gold ore purification using a gold-mercury amalgam and sulfuric acid. Three of the four patients required treatment with penicillamine. The clinical and laboratory data are presented along with pulmonary function test results. Long-term follow-up of one patient indicates residual morbidity, with continued reduction in pulmonary diffusing capacity. This suggests permanent impairment of pulmonary function despite prompt chelation therapy.

Acute Disease↗

Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer.

In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5-fluorouracil (5-FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty-two of the chemotherapy-induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5-FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow-up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response.

Adult↗

Solid tumor preparation for clinical application of flow cytometry.

Intense interest in advanced squamous cell cancers of the head and neck (SCC of H&N) has resulted from the recent progress made in tumor responses with chemotherapy and radiotherapy. Unfortunately, the response patterns and clinical outcome of such patients are not adequately predicted on an individual patient basis using clinical parameters or conventional morphology. The study of flow cytometrically determined cellular parameters in such tumors is therefore of interest, but is hindered by inadequate tumor preparative technology. The previous article (10) in this journal describes the use of a murine SCC tumor, LC12, which was employed for comparative testing and determination of optimum techniques of preparation for this tumor. This report describes the application of these techniques to 144 specimens of human SCC of H&N. The mean total yield for these specimens is 7.4 X 10(7) cells/g of tissue. The mean viable enzymatic yield (3.3 X 10(7) cells/g) was higher than the mean viable mechanical yield (2.0 X 10(7) cells/g) except when lymph nodes were the source of the specimen (5.4 X 10(7) cells/g). The mean dye exclusion viability from enzymatically dissociated specimens were above 90%. Significant aneuploidal subpopulation losses were evident in mechanically dissociated and enucleated specimens. 65% of the enzymatically dissociated specimens were successfully cultured with a mean cloning efficiency of 2.1 X 10(-3). Preparative techniques derived from comparative testing with a murine standard tumor have been successfully applied to 144 specimens of SCC of H&N with resultant high yields and excellent viability. Technical problems detected during the preliminary testing with LC12 were confirmed in the human tumors.

Adult↗

Embolization in cataclysmal hemorrhage caused by squamous cell carcinomas of the head and neck.

Cataclysmal hemorrhage occurred in eight patients with known aggressive squamous cell tumors of the head and neck. Angiography showed neovascularity, narrowing, beading of affected arteries, and pseudoaneurysms. Postembolization residual stump formation was seen in a few patients. A total of 11 embolization procedures were performed in these eight patients. Embolization materials included polyvinyl alcohol, isobutyl-2-cyanoacrylate, and detachable balloons. Survival times ranged from 5 to 274 days, with no deaths as a direct result of hemorrhage. Only one severe complication following embolization was noted.

Adult↗

Economic examination of cefoperazone therapy.

Medical records of 1137 patients from 35 hospitals were reviewed to examine the total cost of care for patients receiving cefoperazone as initial therapy compared to a control group receiving alternative agents. The direct costs of care measurable through a retrospective review of patient records were examined, including the cost of antibiotic acquisition, drug administration, laboratory testing, and room and board. Results of a regression analysis show that cefoperazone as initial therapy is associated with lower costs for all factors studied except acquisition cost. Antibiotic acquisition averaged $24 per patient more for the cefoperazone group (p less than 0.01). However, for cefoperazone patients drug administration was $63 less (p less than 0.0001), laboratory testing costs averaged $9 less (p = 0.22), and costs associated with room and board charges were $80 less (p = 0.40). Total costs averaged $3073 per cefoperazone patient and $3228 per control patient (p = 0.20). These data suggest that the previously accepted definitions of antimicrobial costs (i.e., cost per gram, cost per dose, cost per day) may no longer be adequate in this era of cost containment. In order to make sound clinical decisions with lowest total costs, practitioners should identify how and where costs are incurred.

Anti-Bacterial Agents↗

The impact of conventional morphologic analysis on response rates and survival in patients with advanced head and neck cancers treated initially with cisplatin-containing combination chemotherapy.

The response to initial treatment with cisplatin-containing combination chemotherapy as well as survival, were correlated with tumor differentiation (well, moderate or poorly differentiated) in 164 patients with advanced, untreated squamous cell carcinoma of the head and neck. Thirty-three percent of the tumors were graded as poorly differentiated, 59% moderately differentiated, and 8% were well differentiated. The overall clinical response rates were nearly equal for the three grades of differentiation: 79% for well differentiated, 86% for moderately differentiated, and 89% for poorly differentiated. The complete response rate was somewhat higher for poorly differentiated tumors: 46% as compared to 32% and 29% for moderately and well differentiated respectively, but the differences were not statistically significant. The median survival for each morphologic group was 22, 16, and 12 months for well differentiated, moderately differentiated and poorly differentiated tumor, respectively (P = 0.097). For patients achieving a complete clinical response to chemotherapy, there was a difference in survival when stratified according to degree of histologic differentiation. Patients who were complete responders and had well or moderately differentiated tumors attained 75% and 38% survival at 36 months, respectively, versus 19% for patients with complete response and poorly differentiated tumors (P = 0.064). The degree of differentiation of previously untreated squamous cell cancers of the head and neck does not conclusively predict tumor response to combination chemotherapy, but may reflect differences in natural history. Survival is improved in patients with differentiated tumors as compared to those with poorly differentiated tumors. Morphologic grading in patients achieving a complete response reveals a decrease in survival for patients with poorly differentiated tumors.

Adult↗

Value of the lateral radiologic view of the chest in children with acute pulmonary illness.

Although expert committees have questioned the usefulness of lateral radiologic views of the chest without specific indications, many physicians commonly order both posteroanterior and lateral views in assessing pediatric patients who have signs and symptoms of acute chest disease. To investigate the usefulness of lateral view in children, three experienced physicians independently reviewed and interpreted the posteroanterior view alone and the posteroanterior and lateral views for 179 children 1 to 10 years of age. The films were made between 1980 and 1982 at McMaster University Medical Centre, Hamilton, Ont. A high level of agreement was found between the interpretations based on the posteroanterior view alone and those based on both views. Addition of the lateral view did not improve agreement between the interpretations and the final hospital chart radiologic diagnosis in a clinically significant manner, nor did the lateral view improve the accuracy of localization of radiologic abnormalities. Obtaining a lateral view whenever radiologic examination of the chest is indicated but when specific indications are lacking is unlikely to prove useful to experienced physicians in diagnosing and managing acute pulmonary illness in children.

Acute Disease↗

Purification and characterization of heparin-binding endothelial cell growth factors.

Thirteen endothelial cell growth factors have been purified to homogeneity by heparin affinity and reversed-phase high performance liquid chromatography, and their chromatographic and electrophoretic properties were compared. The amino acid compositions of 10 of these mitogens have also been determined. The results indicate that these heparin-binding growth factors (HBGFs) can be subdivided into two classes. Class 1 HBGFs are anionic mitogens of molecular weight 15,000-17,000 found in high levels in neural tissue and include acidic brain fibroblast growth factor and retina-derived growth factor. Class 2 HBGFs are cationic mitogens of molecular weight 18,000-20,000 found in a variety of normal tissues and are typified by pituitary fibroblast growth factor and cartilage-derived growth factor. Typical class 2 HBGFs have also been isolated from a rat chondrosarcoma, a human melanoma, and a human hepatoma, suggesting that tumors do not make a structurally distinct HBGF class. These results provide a sound basis for the evaluation of the HBGFs purified from a variety of tissues and species and for the delineation of their normal and pathological functions in vivo.

Amino Acids↗

Evaluation of two adaptive sodium nitroprusside control algorithms.

Computer control of sodium nitroprusside infusion may be safer and provide better control of arterial blood pressure than is achieved with manual control. In a series of test maneuvers in 20 mongrel dogs, the performance of two adaptive control algorithms (controllers) was compared and their safety tested. The controllers were set to infuse sodium nitroprusside to decrease mean arterial pressure and maintain it 20 to 30 mm Hg below the control pressure. Then, sequentially, the right atrium was paced to simulate a supraventricular tachydysrhythmia, the right ventricle was intermittently paced to simulate ventricular extrasystoles, large tidal volumes were given to simulate a respiratory-therapy maneuver, the catheter was clamped to simulate clotting, an air bubble was introduced, and the infused sodium nitroprusside concentrations were either doubled or halved. Next, 500 ml of blood was drawn. Then, in sequence, positive end-expiratory pressure was applied, the right atrium was paced, and large tidal volume breaths were given to cause the blood pressure to fluctuate. When the controllers were turned on, mean arterial pressure reached the set point and remained within 5 mm Hg of the target pressure after 8.6 +/- 0.9 minutes (mean +/- SEM). The controllers properly handled the differences in sodium nitroprusside sensitivity and the catastrophic challenges presented in the experiments. When the animals were not being disturbed, stability was maintained and the blood pressure was kept well within 5 mm Hg of the desired pressure. The controllers rejected all invalid pressure signals during testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Homodyne interferometer for basilar membrane vibration measurements. II. Hardware and techniques.

Selected mechanical features of the design of the homodyne interferometer are described. This interferometer was utilized for basilar membrane vibration measurements. The massive construction necessary to minimize mechanical vibration and noise is described. In order to measure basilar membrane vibrations, it was necessary to increase its reflectivity. Gold crystals were utilized as microscopic mirrors. The technique for fabrication of gold crystals is described. These crystals are small and fragile and required special handling. The method of picking up the crystals and placing them on a preselected location is described. In order to minimize the effect of the involuntary animal movements a reference mirror system is cemented to the skull. The design of the reference mirror system and the method of cementing it to the skull are described.

Animals↗

Atrial demand pacing to protect against vagal overactivity in sympathetic autonomic neuropathy.

The clinical features, investigation and management of a patient with a subacute autonomic neuropathy are described. A series of physiological and biochemical studies indicated severe but selective sympathetic cardiovascular dysfunction, associated with bradycardia. The bradycardia was enhanced by raising blood pressure but there was no other evidence either of cardiac vagal impairment or hyperreactivity. Oral atropine prevented the bradycardia but had to be withdrawn because of intolerable side effects. An atrial demand pacemaker was implanted to elevate basal heart rate and prevent bradycardia. The pacemaker alone did not improve postural hypotension but it enabled the blood pressure to be readily and safely controlled by a combination of drugs.

Autonomic Nervous System↗

Oncocytic adenoma of the parotid gland with psammoma bodies.

An unusual slow-growing tumor was found in the superficial lobe of the right parotid gland. It was multilobulated and encapsulated and consisted of sheets of epithelial oncocytes and minor foci of myoepithelium and ducts. Psammoma bodies were abundant. An antibody directed against keratin protein was localized in all tumor cells and in ductal but not acinar elements of adjacent parotid tissue. Ultrastructurally, the neoplastic cells proved to be ductal epithelial and myoepithelial oncocytes.

Adenoma↗

A randomized trial of cisplatin (CACP) + 5-fluorouracil (5-FU) infusion and CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck.

One of the most active chemotherapeutic regimens for treatment of advanced and recurrent head and neck cancer is cisplatin (CACP) + 5-fluorouracil (5-FU) infusion with a response rate of 90% in advanced, previously untreated patients and 70% in patients with recurrent disease. Forty-four patients from two Wayne State University-affiliated hospitals were entered into a randomized trial of CACP (100 mg/m2) day 1 and 24-hour infusion of 5-FU (1000 mg/m2) days 1 through 4 versus CACP (100 mg/m2) day 1 and bolus 5-FU (600 mg/m2) day 1 and day 8. Thirty-eight patients were evaluable for three induction courses. Response for the infusion arm was 72% (4/18 complete response [CR] + 9/18 partial response [PR]). Response for the bolus arm was 20% (2/20 CR + 2/20 PR). The difference in response was statistically significant by chi-square analysis (P less than 0.01). Seventy percent of the patients on the bolus arm experienced leukopenia with several episodes of grades 3 and 4 leukopenia. In addition, 50% of the patients on the bolus arm experienced thrombocytopenia. Stomatitis was more frequent on the infusion arm but it was mild and reversible. The complete responders on either arm have a median survival of 120+ weeks; partial responders, 30 weeks. Cisplatin + 5-FU infusion produces a superior response as initial chemotherapy for three courses compared with CACP and 5-FU bolus.

Antineoplastic Combined Chemotherapy Protocols↗

Genes for insulin I and II, parathyroid hormone, and calcitonin are on rat chromosome 1.

Insulin, parathyroid hormone, and calcitonin are polypeptide hormones that regulate important physiological processes in target tissues. Rat genes encoding each hormone were chromosomally assigned to rat chromosome 1. Both rats and mice have two insulin genes (I and II). However, in contrast to mice in which insulin I and II are asyntenic, rat insulin I and II were both localized to chromosome 1. This study identifies a conserved syntenic group on rat chromosome 1, and implies that mouse insulin I and II genes were chromosomally separated after rats and mice diverged 20-35 million years ago.

Animals↗