Search PubMed⌕ Search

Biomedical subjects

J R Jacobs

Publications and source records attributed to J R Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1988

Surgical considerations in maxillofacial prosthetic rehabilitation of the maxillectomy patient.

The radical maxillectomy performed for cancer of the paranasal sinuses has as its sequella some of the potentially most devastating functional losses in the field of head and neck oncology. The patient is left after surgical management with a defect that often prevents effective speech, deglutition, and mastication. This paper addresses the surgical considerations involved in the performance of a radical maxillectomy that can result in a favorable defect allowing subsequent optimal prosthetic rehabilitation of the patient.

Dentition↗
PubMed1988

Evaluation of high-dose cisplatin and 5-FU infusion as initial therapy in advanced head and neck cancer.

The combination of cisplatin and 5-fluorouracil (5-FU) infusion in head and neck cancer patients produces an overall response rate of 90% for advanced disease and 70% for recurrent disease. Whether or not escalating the platinum dose in combination with other agents, as has been done with refractory ovarian and testicular patients, would improve the response rates in patients with advanced head and neck cancer has not been evaluated. We undertook a study to determine the most efficacious dose of cisplatin that could be administered with 5-FU infusion in head and neck cancer patients. Eleven patients entered the study. Initial dose of cisplatin was 40 mg/m2 (in hypertonic saline) on days 1-5 plus 5-FU 1,000 mg/m2 on days 1-5 as a continuous infusion. Subsequent cisplatin doses were adjusted for the main toxicity, which was myelosuppression. The safest tolerable dose was 30 mg/m2 for 5 days. Overall response was 90% [45% complete response (CR) (5/11) plus 45% (5/11) partial response (PR)] which is comparable to that seen with cisplatin 100 mg/m2 and 5-FU in a 120-h infusion. Although patient numbers are small, there was no appreciable difference in response rate with higher dose cisplatin and there was a significant increase in serious toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Esmolol and left ventricular function in the awake dog.

Hypotension has been the most frequently reported adverse reaction associated with infusion of the beta 1-adrenergic receptor antagonist esmolol. In some patients, this hypotension has apparently occurred independent of reduction in heart rate or systemic vascular resistance, suggesting decreased stroke volume. In the present study, the preload recuitable stroke work area (PRSWA) model was used to evaluate the negative inotropic effects of esmolol in nine chronically instrumented awake dogs. Left ventricular (LV) transmural pressure and minor axis diameter were measured by micromanometers and sonomicrometry, respectively. Vena caval occlusions were performed so that an analog of stroke work (area within LV transmural pressure-diameter loop) could be measured over a range of preloading conditions during esmolol infusions of 0, 100, 300, 1000, and 3000 micrograms/kg-1.min-1 (n = 9), and at 15 and 30 min after termination of esmolol (n = 8). The linear relationship between stroke work and end-diastolic diameter was characterized for each caval occlusion by a slope and x-intercept. PRSWA was calculated for each caval occlusion as slope/two times the square of the difference between x-intercept and the largest end diastolic diameter observed in the study of a particular dog. Heart rate was different from control (91 +/- 4) only at the highest esmolol dose (127 +/- 4). LV peak positive dP/dt, minor axis ejection shortening, stroke work, and PRSWA were depressed from control at esmolol doses greater than or equal to 300 micrograms.kg-1.min-1. All parameters except dP/dt recovered within 30 min following termination of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Investigations into tracheal prosthetic reconstruction.

Reconstruction of circumferential tracheal defects may be necessary following trauma or oncologic surgery. For defects up to approximately 6 centimeters in an adult, an end-to-end anastomosis appears to be the method of choice. Larger defects may require utilization of a tracheal prosthesis. In dogs, a tracheal prosthesis constructed of Dacron polyurethane mesh (Osteomesh) was found to well tolerated following a two-stage implantation procedure. Normal confluent respiratory epithelium was identified in the lumen of the prosthesis. Previously reported difficulties with recurrent granulation tissue at the areas of anastomosis appear to have been successfully avoided.

Animals↗
PubMed1988

Radiation Therapy Oncology Group (RTOG) studies in head and neck cancer.

Since its foundation in 1971, the RTOG has conducted a successful clinical research program in head and neck mucosal squamous cell carcinoma with 22 treatment protocols and one registry study which combined have accumulated data on over 5,500 patients. The RTOG was the first multicenter group to evaluate neoadjuvant chemotherapy before definitive radiation with its methotrexate study. Although the study was negative, RTOG has since conducted five pilot or phase II studies of neoinduction or concurrent chemotherapy with radiation therapy in patients with inoperable tumors. The last study showed that radiation concurrent with cisplatinum was tolerable with a suggestion of increased antitumor effect. In patients with potentially resectable tumors, RTOG has completed a pilot study of combination chemotherapy administered either before or after the surgery with radiotherapy. Based upon its findings, the treatment sequence, surgery-chemotherapy-radiotherapy, was chosen as the experimental arm for a new phase III study. This study was subsequently adopted by the head and neck intergroup mechanism as its study (INT 0034/RTOG 8503). RTOG has investigated the optimal timing of radiotherapy with surgery. The 7303 study established that postoperative radiotherapy achieved significantly better locoregional control but not improved absolute survival. Approximately 30% of the patients on each arm failed to complete both modalities. Even when comparison is restricted to patients who completed both modalities, postoperative radiotherapy still produced the better locoregional control. Efforts to overcome the limitations imposed by tumor hypoxia through use of carbogen (95% O2 and 5% CO2) breathing or the radiosensitizer misonidazole during radiotherapy have been unsuccessful. In a phase I study, RTOG showed that 15 to 18 sessions of sensitized radiation can be safely delivered with the new radiosensitizer SR 2508 in contrast to only six such sessions with misonidazole. This promising radiosensitizer is now being tested in a phase III trial. RTOG has also investigated variations in fraction size, fraction number, and total radiation dose. In the 7102 study, split-course irradiation achieved equivalent antitumor results as compared to continuous daily irradiation but with less social alteration and cost to the patient. In the hyperfraction pilot study 7703, twice a day irradiation with 120 cGys up to 6,000 cGys proved to be tolerable.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1987

Induction chemotherapy in advanced head and neck cancer. A Radiation Therapy Oncology Group Study.

Cisplatin (cis-platinum, 100 mg/m2) and fluorouracil (1000 mg/m2/d), for 120 hours' infusion every three weeks for three courses, produced a 93% overall response rate and a 54% complete clinical response at the single-institution level. The same combination was tested in the Radiation Therapy Oncology Group to evaluate the effectiveness and feasibility of this combination. An overall response rate of 86% was obtained, with a 38% complete clinical response. Only 27 of 42 patients completed planned surgery. Compliance with chemotherapy and radiation therapy was substantially better. No additional morbidity after surgical resection or postoperative radiation therapy was identified as secondary to the induction chemotherapy. We conclude that the combination of cisplatin and fluorouracil infusion is effective, with high complete clinical response rate in patients with advanced, previously untreated head and neck carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Dynamics of behaviour during neuronal morphogenesis in culture.

We report a developmental sequence in the type and frequency of behaviours of neurons differentiating in vitro. We characterised these changes with extensive analysis of time-lapse sequences from both the continuing cell line pheochromocytoma PC12 and primary mixed cell culture of cat and mouse central nervous system. PC12 cells activated by nerve growth factor (NGF) differentiate in a uniform and synchronous manner. This allowed the first quantification of changes in different neuron behaviours during morphogenesis. Shortly after NGF activation, PC12 cells are highly labile in morphology and exhibit a large variety of morphological behaviours. During the first week of differentiation, the frequency of these behaviours declines, and gross morphology becomes more stable. The frequency of neurite initiation after 1 week in NGF is one-seventh what it was after 2 days in NGF. Over the same period, neurite retraction declines to one-third, and somal migration ceases altogether. Growth-cone activity does not decline during development. These behaviour changes correlate with published data on the differentiation of the neurite cytoskeleton. A qualitatively similar ontogeny was noted in the differentiation of CNS neurons in mixed cell culture. Major differences occur in the relative timing of changes in behaviours. Mature, stable morphology is not detected in these cultures until 7 weeks in vitro.

Adrenal Gland Neoplasms↗
PubMed1987

Sufentanil disposition during cardiopulmonary bypass.

In order to investigate the ability of a computer-assisted continuous infusion (CACI) system to maintain constant plasma levels of sufentanil during cardiopulmonary bypass (CPB) using pharmacokinetic data derived from healthy surgical patients to determine the infusion rate, ten patients were anaesthetized with diazepam, enflurane and oxygen until ten minutes prior to the expected time of initiation of CPB. At that point, an infusion of sufentanil, aimed to reach a central compartment concentration of 5 ng.ml-1, was started via CACI. Plasma concentrations of sufentanil, haematocrit, total protein and albumin concentrations, and nasopharyngeal and CPB inflow temperatures were obtained at predetermined intervals before and up to 90 min after the initiation of CPB. Plasma concentrations of sufentanil reached 3.8 +/- 0.4 ng.ml-1 before CPB and approached the 5.0 ng.ml-1 set point (4.7 +/- 0.4 ng.ml-1) over the 90 min of CPB. In conclusion, our results show that it is possible to obtain stable plasma levels of sufentanil on CPB using a pharmacokinetically driven infusion scheme; however, our data suggest that use of such a system may lead to accumulation of drug during CPB.

Aged↗
PubMed1987

Distribution of basement membrane in squamous cell carcinoma of the head and neck.

The immunohistologic distribution of the basement membrane components, type IV collagen and laminin, was evaluated in 57 alcohol-fixed, paraffin-embedded tissue sections which demonstrated immunostaining patterns with antigen preservation similar to that of frozen tissue sections. Normal and hyperplastic squamous mucosa, a spectrum of intraepithelial neoplasia, and invasive squamous cell carcinomas of the upper aerodigestive tract were evaluated by this technique. Prominent and continuous basement membrane staining characterized normal and reactive hyperplastic squamous mucosa. The basement membrane varied greatly with epithelial dysplasia and was usually prominent and continuous in mild to moderate dysplasias. In severe dysplasia/carcinoma in situ, the basement membrane was often thinned and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas was also varied. Basement membrane was usually present in invasive tumors with well-defined tumor host borders and cohesive patterns of stromal invasion which were interpreted as foci of histologic differentiation. In contrast, invasive carcinomas with irregular cords or single tumor cells distributed through the host stroma invariably lacked basement membrane at the tumor-stromal interface; this was interpreted as a decreased expression of histologic differentiation. We conclude that 1) severe intraepithelial neoplasia is often associated with irregularities of basement membrane and that the absence of basement membrane does not necessarily define invasive cancer; 2) immunolocalization of basement membrane in invasive carcinomas is common in areas displaying histologic differentiation; and 3) the association of basement membrane distribution and histologic pattern of tumor invasion suggests that squamous cell carcinomas are capable of undergoing focal histologic differentiation after invasion has occurred.

Basement Membrane↗
PubMed1986

Malignant fibrous histiocytoma of the larynx.

Malignant fibrous histiocytomas of the upper respiratory tract are rare, aggressive, mesenchymal neoplasms. There have been sporadic cases reported in the English language literature. This paper reports the case of a subglottic malignant fibrous histiocytoma in a 26-year-old female. A review of the important clinical-pathological features of this type of tumor is presented. The treatment of choice appears to be wide surgical resection of the tumor. Although the published experience is small, it appears that tumors of the subglottic space are characterized by a younger patient population and a better prognosis than those of the larynx.

Adult↗
PubMed1986

Combined modality therapy utilizing a cisplatin combination for effective chemotherapy in patients with previously untreated head and neck cancer.

In patients with locally advanced head and neck cancer, the results of standard definitive treatments of surgery, radiotherapy, or both were disappointing. The local and regional recurrence rates were high, despite adequate surgical resection with negative margins and postoperative radiotherapy to all known or possible disease areas. Combination cisplatin chemotherapy given initially before definitive treatments produced a high overall antitumor response and up to 50 percent clinical complete response. Before answering the question of value of chemotherapy as part of the multimodality treatment, it is important to identify the safest and most form of chemotherapy. The degre of chemotherapy effectiveness is defined by the incidence of clinical and, most important, histologic complete response. To assess this effectiveness, chemotherapy was given before definitive treatments to patients with measurable disease. From our 10 year experience we have concluded that continuing the development of induction chemotherapy, including investigating the timing of such effective treatment and assessing the value of such therapy, is of the utmost importance.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Cisplatin and nifedipine: synergistic cytotoxicity against murine solid tumors and their metastases.

Calcium channel blockers of 3 chemical classes and calmodulin antagonists have recently been shown to enhance the cytotoxicity of conventional cancer chemotherapeutic agents. We tested the ability of nifedipine, a dihydropyridine class calcium channel blocker, to enhance the cytotoxicity of cisplatin, the current chemotherapeutic of choice against human head and neck tumors and testicular carcinoma. Both in vitro and in vivo, combination therapy with nifedipine and cisplatin resulted in synergistic inhibition of tumor cell proliferation, primary tumor growth and appearance of spontaneous pulmonary metastases. This combination also significantly increased the survival of mice bearing cisplatin-resistant tumors. This is the first indication that calcium channel blockers can enhance the cytotoxicity of cisplatin as well as the first demonstration that calcium channel blockers can enhance cytotoxicity of chemo-therapeutic agent against a solid tumor and its metastases.

Animals↗
PubMed1986

Arterial embolization for control of bleeding in advanced head and neck carcinoma.

There are a number of patients with unresectable recurrent carcinoma of the head and neck who continue to lead a relatively functional life despite advanced local disease. For these patients bleeding from tumor represents a devastating complication that can abruptly terminate the course of an otherwise chronic disease, albeit a uniformly fatal one. The technique we describe renders a relatively safe and effective treatment that seems to control this problem. We report on our experience with three patients whose tumor bleeding was controlled by permanent intra-arterial embolization with Ivalon, a polyvinyl alcohol-based foam. The technique, indications, and complications are discussed.

Adult↗
PubMed1986

Changes in the organization of the neuritic cytoskeleton during nerve growth factor-activated differentiation of PC12 cells: a serial electron microscopic study of the development and control of neurite shape.

After exposure to nerve growth factor, PC12 cells differentiate within a period of only a few days into cholinergic sympathetic neurons. Using computer-assisted three-dimensional serial electron microscopic reconstruction, we describe the progressive cytoskeletal and structural changes of PC12 neurites at different stages in their differentiation. Developmental changes in these neurites can be characterized by two major transitions. First, microtubules (MTs), which define the longitudinal axis of the neurite, increase in number leading to a more cylindrical and uniform neurite shape. Second, there are major changes in the relative numbers of other organelle types, which reflect the functional specialization of the neurite. These changes do not in themselves seriously affect shape change of the neurite during development, however the presence of these organelles and their associated obligatory volumes (volumes surrounding organelle) account for well over 50% of the neurite's volume at all stages of development. The MT-MT distances and obligatory volumes associated with the organelles remain constant throughout development. Thus, we can conclude that many of the observed changes seen in developing PC12 neurites are due simply to the production of a greater number of MTs in the cell, and that many of the other important parameters that can be measured and contribute to neurite shape remain constant during development.

Animals↗
PubMed1986

Experimental modification of PC12 neurite shape with the microtubule-depolymerizing drug Nocodazole: a serial electron microscopic study of neurite shape control.

The microtubule-depolymerizing drug Nocodazole has been used to experimentally manipulate the form of PC12 neurites. Both time-lapse photography and serial electron microscopy demonstrate that microtubule depolymerization leads to varicosity formation due to a clustering of membranous organelles in young neurites (nerve growth factor activated within 7 d). Neurites that have been nerve growth factor activated 7 or more d before Nocodazole application are resistant to microtubule depolymerization. These data and data from previous papers has been combined in an attempt to predict quantitatively the volume and the shape of a neurite. The relationship is described mathematically by Vn = 4.52 Vo + 0.0054 MTl, where Vn is local neurite volume, Vo is organelle volume, and MTl is MT length (the constant, 0.0054 is micron2), and 4.52 is the obligatory volume constant derived from serial electron microscopic studies. The equation predicts the total volume of neurites despite alterations of morphology due to Nocodazole and despite changes in morphology during development.

Animals↗
PubMed1986

Effects of nasal and laryngeal stimulation upon peripheral lung function.

Arterial hypoxemia and sudden death have been associated with the placement of posterior packs for control of severe epistaxis. There exists some controversy as to the mechanism underlying the clinically observed hypoxemia; some authors postulate a nasal pulmonary reflex as the basis for the hypoxemia. In an attempt to further investigate this theory, collateral ventilation was measured in the dog model during nasal and laryngeal stimulation. Collateral ventilation is thought to be one of the most sensitive techniques available to assess the resistive and elastic properties of the lung periphery. In the dog, with respiratory rate controlled (i.e., anesthetized and paralyzed), nasal stimulation with mechanical, thermal, and chemical stimuli failed to affect collateral ventilation. This finding suggests that the reflex may be acting either in larger lung segments or on the pulmonary vascular bed itself.

Airway Resistance↗