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Biomedical subjects

T Griffin

Publications and source records attributed to T Griffin.

At least 55 records · Page 3Linked to original sources

Monensin in lipid emulsion for the potentiation of ricin A chain immunotoxins.

The utilization of carboxylic ionophores such as monensin for immunotoxin potentiation may be hampered by the poor solubility and short in vivo half-life of these highly lipophilic compounds. Therefore, the use of monensin formulated in a lipid/water emulsion was investigated for the in vitro and in vivo potentiation of immunotoxins. Monensin in emulsion or in buffer was equally effective for the in vitro potentiation of the cytotoxicity of both anti-human transferrin receptor and anti-carcinoembryonic antigen immunotoxins against target cells. In mice, buffer and lipid emulsion were compared as vehicles for the i.p. administration of monensin. The half-life of monensin in the peritoneal cavity of BALB/c x DBA/2 F1 (CD2F1) mice was increased 20-fold by inclusion in lipid emulsion (13 min versus 0.75 min). Treatment i.p. with anti-human transferrin receptor immunotoxin or anti-carcinoembryonic antigen immunotoxin and monensin emulsion prolonged the survival of mice with macroscopic i.p. tumor xenografts of H-Meso-1 mesothelioma and LS174T colorectal carcinoma (200-250% increased length of median survival). The in vivo antitumor effect of the cell-specific immunotoxin plus monensin emulsion was superior to immunotoxin alone or to immunotoxin plus monensin in buffer (P less than 0.03; Mann-Whitney U test). This indicates that delivery of monensin in preformed lipid emulsion may produce a reservoir effect of the ionophore in the peritoneal cavity of tumor-bearing mice. Nonspecific control immunotoxin plus monensin emulsion produced no increase in survival. Long-term tumor-free survival (greater than 150 days versus a median survival of 25 days for controls) of mice bearing microscopic LS174T xenografts was obtained by treatment with anti-human transferrin receptor immunotoxin plus monensin emulsion. Administration of either monensin in buffer or monensin in emulsion without immunotoxin had no significant effect on survival. Monensin in this pharmacologically available form significantly improved the in vivo efficacy of both anti-human transferrin receptor immunotoxin and anti-carcinoembryonic antigen immunotoxin when used as regional therapy.

Animals↗

The relationship of nasopharyngeal carcinomas and second independent malignancies based on the Radiation Therapy Oncology Group experience.

The authors sought to learn if the incidence of second independent malignancies after the irradiation of carcinomas of the nasopharynx is similar to that observed after treatment of tumors arising in other head and neck sites. One hundred twenty-one patients who had primary carcinomas of the nasopharynx who were treated solely by ionizing radiation (according to the specifications of a Radiation Therapy Oncology Group protocol) were identified and their subsequent well-being was reviewed. Overall there was a 4.1% incidence of second malignancies (2% after 3 years, 5% after 5 years, and 8% after 8 years) with most arising in the upper aerodigestive tract. This rate is significantly less than the rate associated with other head and neck sites. It is not significantly different from the rate of first malignancies observed in an age-matched and sex-matched population. When only those patients who were free of all evidence of neoplastic disease 6 months after the completion of radiotherapy are considered, similar analysis leads to similar outcomes. The authors conclude that the risk of second malignancies after the successful irradiation of carcinomas of the nasopharynx is substantially less than after treatment of tumors at other head and neck sites.

Adolescent↗

Coexistence of Lambert-Eaton myasthenic syndrome and subacute cerebellar degeneration: differential effects of treatment.

A 61-year-old woman presented with two paraneoplastic neurologic disorders--Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD)--that antedated the diagnosis of small-cell carcinoma of the lung by 15 months. Plasmapheresis initiated before the identification of the tumor had a beneficial effect on LEMS but did not affect the SCD. Chemotherapy administered for treatment of the primary tumor was also associated with improvement of LEMS but, like plasmapheresis, had no effect on SCD. While the pathogenesis of both LEMS and SCD is thought to be mediated predominantly by humoral immune factors, a differential therapeutic response indicates that mechanisms of tissue damage or susceptibility to tissue injury, or both, differ in these two disorders.

Female↗

Going the distance: rural health care in Texas.

Many doctors and hospitals are being squeezed out of rural and small-town Texas, and some of the population is beginning to suffer a lack of medical care comparable to that of underdeveloped countries. These articles consider the problem and present some options for improving health care delivery to rural Texans.

Delivery of Health Care↗

Comparison of abdominopelvic computed tomography results and findings at second-look laparotomy in ovarian carcinoma patients.

In 35 women with epithelial carcinoma of the ovary, the results of restaging laparotomy were compared with the preoperative abdominopelvic computed tomography (CT) findings to evaluate the accuracy of CT for determining tumor status. In the 36 studies performed, enhanced CT scans at 10-mm to 15-mm intervals had a sensitivity of 84% and a specificity of 88%; in addition, there was 86% agreement between the CT and surgical findings. These results suggest that although CT is not accurate enough to completely replace the restaging laparotomy, its high accuracy in determining residual disease after treatment is helpful for patient management.

Adenocarcinoma↗

Clinical expert systems versus linear models: do we really have to choose?

This article deals with decision subsystems at the level of the organism. In recent years there has been debate as to whether linear models or clinical expert systems make clinical decisions more effectively. Previous articles in this journal have favored linear models. This article argues the opposite case. We show that expert systems are not necessarily more expensive or less accurate than linear models and that, in theory at least, they can perform many tasks that are beyond the scope of linear models. Indeed, while a linear model may serve as a subsystem of a human or computer expert system, an expert system cannot be seen as a subsystem of a linear model. We conclude that clinical expert systems and linear models are not interchangeable and users should not be forced to choose between them.

Artificial Intelligence↗

Fast neutron teletherapy in advanced epidermoid head and neck cancer. A review.

An extensive review of clinical studies employing fast neutron teletherapy for advanced epidermoid carcinomas of the head and neck is presented. Head and neck tumors have represented an excellent study site because of their accessibility to physical examination for measurement of tumor response, and because early neutron beams have had poor depth dose characteristics, making the treatment of more deeply seated tumors technically difficult. A summary of the major trials comparing neutron and mixed-beam (combination neutron and photon) therapy with conventional therapy indicates no conclusive evidence of improvement in local control or survival rates for the experimental arms. Exceptions to this are the Hammersmith experience and the slightly higher lymph node control rates seen in two studies. An evaluation of toxicity indicates that with the new generation of cyclotrons, complication rates may approach parity with those of photon linear accelerators.

Carcinoma, Squamous Cell↗

Fast neutron radiation for inoperable and recurrent salivary gland cancers.

The current standard treatment of salivary gland cancers consists of surgical resection, with or without postoperative low linear energy transfer (LET) radiation, resulting in high locoregional control rates. However, tumor control prognosis is poor when conventional radiation is used alone for advanced, inoperable cases. An extensive review of the world's literature on fast neutron irradiation for inoperable, unresectable, or recurrent malignant salivary gland neoplasms is presented and compared with the experience using conventional low LET radiotherapy. The pooled data indicate a locoregional control rate of 67% for fast neutrons versus 25% for photons and/or electrons in the treatment of such advanced disease. The radiobiological rationale supporting this observed increase in tumor control is discussed. The overall significant late complication rate is 19%, but several suboptimal treatment factors were present that contributed substantially to the reported toxicity. With the modern machines and treatment techniques now available, the evidence overwhelmingly supports the role of fast neutron radiation as the treatment of choice for inoperable and recurrent salivary gland cancers.

Energy Transfer↗

Fast neutron radiotherapy for sarcomas of soft tissue, bone, and cartilage.

The basic radiobiological rationale for the use of fast neutron radiotherapy in the treatment of classically radioresistant tumors such as soft tissue sarcomas, osteogenic sarcomas, and chondrosarcomas is reviewed. There are no definitive randomized studies comparing high and low linear energy transfer radiotherapy for these tumor systems, but a review of published series is highly suggestive of a therapeutic advantage for fast neutrons. For soft tissue sarcomas, the local control rate is 53% (158 of 297) with fast neutrons, compared with 38% (49 of 128) with photons/electrons; for osteogenic sarcomas, the local control rate is 55% (40 of 73) with fast neutrons, compared with 21% (15 of 73) with photons/electrons; and for chondrosarcomas, the local control rate is 49% (25 of 51) with fast neutrons, compared with 33% (10 of 30) with photons/electrons. An ongoing clinical trial for these tumors is also described.

Bone Neoplasms↗

The marginal mandibular nerve in rhytidectomy and liposuction surgery.

A concern in the current trend toward more aggressive undermining in rhytidectomy and liposuction surgery has been the potential for damage to the marginal mandibular nerve. This study was undertaken in an attempt to clarify the exact peripheral pathway of the marginal mandibular nerve. A series of 22 fresh cadaver heads were studied bilaterally by gross dissection and histologic studies. It was found that dissection superficial to the platysma up to a point 2 cm lateral to the lower lip can be done safely. Medial to this point, dissection is hazardous and is not indicated because the marginal mandibular nerve becomes more superficial as it travels to innervate its effector muscles. Additionally, dissection in this area is technically difficult because of the tight adherence of the skin to the underlying muscles. This adherence generally permits only the formation of fine superficial rhytids that are best treated by chemical peel or dermabrasion.

Adipose Tissue↗

Implementation of an outpatient prescription drug formulary in a managed-care system.

The development and implementation of an outpatient prescription formulary in an independent-practice model health maintenance organization (HMO) and the role of the pharmacy and therapeutics (P&T) committee in the process are described. Approximately 600 physicians provide medical care and control the operation of this independent practice association (IPA); of approximately 45,000 members, 95% are eligible for outpatient prescription services provided by one of 188 local pharmacies. The formulary, which is restricted to noninjectable medications, was developed by a P&T committee composed of eight IPA physicians, a representative of the local pharmaceutical association, and three staff members of the IPA's pharmacy department. The printed version of the formulary indexed almost 1800 items and included only commonly used medications to limit its size. Requests for additions or deletions of drugs were evaluated monthly. After a four-month period during which physicians were asked to comply with the formulary, mandatory compliance was imposed, with a limit of 16 nonformulary prescriptions per physician per month being allowed. Based on the results of an informal survey, the physicians indicated that the formulary was relatively easy to adjust to (44.1%), somewhat difficult to work with (43.6%), and somewhat disruptive to their prescribing practices (55.3%). When asked about quality of patient care, 74.3% indicated there was no change. Physician compliance with the formulary system increased from 88.0% to 96.1% after the formulary was mandated by the IPA. Under the direction of the P&T committee, a formulary was implemented effectively in this HMO outpatient prescription drug program.

Delivery of Health Care↗

Patient biodistribution of intraperitoneally administered yttrium-90-labeled antibody.

Although 90Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicates the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of 90Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')2 fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with 90Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chromatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabel instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of 90Y, the dose to tumor for a 1-mCi administration would be approximately 50 rad with normal tissues receiving approximately 8 rad.

Animals↗

Familial pancreatic adenocarcinoma in three generations. A case report and a review of the literature.

Although scattered case reports of familial clustering of pancreatic cancer have appeared in the literature, hereditary factors have not been clearly associated with increased risk for this malignancy. The current report documents the familial occurrence of pancreatic adenocarcinoma in three women of consecutive generations who died of their disease at progressively younger ages. The diagnoses are histologically confirmed in all three cases. Although two of the women carried a single known risk factor for pancreatic carcinoma (cigarette smoking), a familial predisposition to this disease is strongly implicated. The case suggests that the role of inheritance in pancreatic carcinoma may merit further exploration.

Adenocarcinoma↗