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Biomedical subjects

J R Clark

Publications and source records attributed to J R Clark.

At least 19 recordsLinked to original sources
PubMed1994

The utility of electronic mail as a medium for patient-physician communication.

OBJECTIVE: To examine patients' knowledge, use, and attitudes regarding electronic mail communication with their family physicians. DESIGN: Mail survey. SETTING: A university-based family practice center. PARTICIPANTS: Adult patients (18 years and older) of full-time faculty physicians at a university-based family practice center who had seen their physicians at lease once in the 10-month period between July 1, 1992, and April 30, 1993 (N = 4094). Subjects were eligible for participation if both they and their physicians had an electronic mail address at the University of Kentucky, Lexington (n = 117). INTERVENTION: None. MAIN OUTCOME MEASURES: Patient-reported knowledge, use, and attitudes regarding the utility of electronic mail as a means of patient-physician communication. RESULTS: The response rate to the survey was 74% (n = 87). Patient-physician communication via electronic mail was positively perceived by patients for whom electronic mail was accessible Patient-physician communication via electronic mail was perceived to increase speed, convenience, and access to medical care. Electronic mail communication was perceived to be good for simple and nonurgent problems, such as refilling prescriptions, communicating laboratory results, and making appointments. Ninety percent of the patients who had corresponded with their physicians via electronic mail used the medium to discuss a medical problem. CONCLUSIONS: Although electronic mail is not presently in wide use for patient-physician communication, there is great potential for its widespread acceptance.

Attitude↗
PubMed1994

Response of serum cytokines in patients undergoing laparoscopic cholecystectomy.

The clinical observation that a laparoscopic cholecystectomy is a minimally invasive operation has not been demonstrated on a biochemical basis. Interleukin-6, a known endogenous pyrogen and hepatocyte-stimulating protein, correlates with the significance of surgical trauma. Utilizing the IL-6 immunoassay, we studied this biochemical parameter of trauma to compare its response in laparoscopic vs open cholecystectomy. Sixteen patients who underwent only laparoscopic cholecystectomy showed peak IL-6 concentrations of 51 pg/ml (22-86) vs a peak IL-6 concentration of 124 pg/ml (56-225) for open cholecystectomy. Six additional patients who underwent an ERCP followed by laparoscopic cholecystectomy showed a dramatic rise in peak IL-6 concentration to 315 pg/ml (15-634). These results biochemically confirm the true minimal invasiveness of laparoscopic cholecystectomy. The findings in the ERCP-followed-by-laparoscopic-cholecystectomy group support the theory that two invasive procedures in close proximity may prime the cytokine system in its response to surgical trauma.

Blood Loss, Surgical↗
PubMed1993

Mutagenesis after cancer therapy.

A subset of Hodgkin's disease (HD) and breast cancer patients have been reported to have elevated hprt mutant frequencies in peripheral blood lymphocytes after cessation of therapy. A subset of these patients are also known to develop second therapy-related malignancies. Therefore, it is clearly important to determine if these elevations in mutant frequency represent true, persistently elevated mutation frequencies. As a follow-up to our study of patients previously treated for HD, we recruited for a prospective study six previously treated HD patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7 months. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single strand conformation polymorphisms at the T-cell receptor-gamma locus of individual mutant clones. This analysis showed that 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients were siblings. The sibling mutants generally did not persist over time. However, one patient had one mutant clone that persisted, but slowly decreased in prevalence over a 7 month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Downwind drift and deposition of malathion on human targets from ground ultra-low volume mosquito sprays.

Malathion was sprayed using a truck-mounted ultra-low volume (ULV) aerosol generator. The generator was operated at 41.4 kPa (6 psi) at flow rate of 128 ml (4.3 fl. oz.) per min. Malathion concentrations were measured at selected positions on live, stationary human subjects wearing protective clothing and placed along a transect at right angles to the path of the truck. Two standing subjects were exposed downwind to the malathion spray at 7.6 and 15.2 m. A third subject was exposed while jogging in the same direction as the spray vehicle and 1.5 m from the spray path. No significant differences (P > 0.05) in total amount of malathion deposited on subjects was demonstrated. During the last 4 sprays, average amounts of malathion deposited on ground level at 15.2, 30.4 and 91.2 m were not significantly different (P > 0.05). Malathion dermal residues were compared with the acute LD50 value (4,100 mg/kg) for a 70 kg adult male. Calculated malathion dermal exposures were less than the acute lethal dose for a human subject by 4 orders-of-magnitude or more.

Adult↗
PubMed1992

Lipid-associated sialic acid, squamous cell carcinoma antigen, carcinoembryonic antigen, and lactic dehydrogenase levels as tumor markers in squamous cell carcinoma of the head and neck.

BACKGROUND: Circulating tumor markers are valuable adjuncts in the management of several malignant lesions, including germ cell tumors and adenocarcinomas of the breast, colon, prostate, and ovary. However (to the authors' knowledge), currently, no serologic markers have been shown to have prognostic value for patients with squamous cell carcinomas of the head and neck (SCCHN). METHODS: Novel and existing markers were evaluated prospectively in patients with SCCHN: The levels of lipid-associated sialic acids (LASA), squamous cell carcinoma circulating antigen (SCC-Ag), carcinoembryonic antigen (CEA), and lactic dehydrogenase (LDH) were evaluated in 52 patients: 42 with active measurable SCCHN and 10 with no clinical evidence of active disease after treatment (NED). RESULTS: In patients with active disease, LASA, SCC-Ag, CEA, and LDH were elevated in 71%, 33%, 27%, and 18%, respectively, and in seven patients with distant metastasis (M1) in 100%, 86%, 57%, and 33%, respectively. None of the markers were elevated in the NED group. The incidence and magnitude of LASA and SCC-Ag elevations correlated with the extent of disease (active disease versus NED, Stage III versus IV, T0-3 versus T4 primary lesions, M0 versus M1). LDH and CEA elevations correlated primarily with the presence of distant metastases. CONCLUSIONS: LASA appears to be a promising sensitive marker of SCCHN, followed in decreasing order of sensitivity by SCC-Ag, CEA, and LDH. Additional study to evaluate the specificity of LASA and its correlation with tumor response to therapy is warranted.

Antigens, Neoplasm↗
PubMed1992

Continuous-infusion cisplatin, 5-fluorouracil, and bolus methotrexate in the treatment of advanced non-small cell lung cancer.

BACKGROUND: Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC: METHODS: Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen). RESULTS: Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2. CONCLUSIONS: PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy.

Adult↗
PubMed1991

Analysis of prognostic factors in squamous cell carcinomas of the head and neck.

It appears that prognostic factors of proven value in the management of other malignancies have marginal value in the treatment of patients with squamous cell carcinomas of the head and neck (SCCHN). For example, age, sex, and performance status do not correlate with treatment outcome. Similarly, histologic differentiation has little predictive value, with undifferentiated carcinomas of nasopharyngeal origin being a possible exception. On the other hand, primary tumor site may be an important prognostic factor, with tumors arising from the nasopharynx, oral cavity, and possibly the oropharynx having a more favorable outcome, whereas tumors of the hypopharynx appear to be the least favorable. A tumor's TNM stage is also highly predictive of response to treatment and survival. Overall stage of disease is an effective predictor of relapse and survival only for patients with limited disease and only after the primary site is specified. Independent of primary tumor site, an inverse correlation clearly exists between T and N stage and either response to treatment or overall survival. Flow cytometry, a relatively new test, appears to be one of the most significant predictors of response to chemotherapy, relapse, and survival in patients with SCCHN. As a prognostic factor, DNA tumor content may be independent of all other known clinical and pathologic factors. Patients with diploid tumors have a superior relapse-free and overall survival as compared with patients whose tumors are aneuploid. Another parameter of significant value is the patient's response to induction chemotherapy, with responding patients demonstrating a far superior relapse-free and overall survival compared with nonresponders. In summary, the site of the primary tumor, its T stage, N stage, and DNA content, and the magnitude of its response to induction chemotherapy are the most valuable prognostic factors in SCCHN. It is assumed, however, that as new and more effective therapies are developed for patients with SCCHN, previously significant prognostic factors will cease to have clinical or scientific value. Similarly, as new diagnostic tests and staging tools are developed, a new generation of prognostic factors with greater biologic and clinical relevance is likely to emerge. In the evolution of new therapies for patients with SCCHN, prognostic factors such as those mentioned here or ones yet to be evaluated will be central to the design of clinical studies and the identification of specific patients for specific therapies. Once treatment is initiated, treatment-related prognostic factors may further identify patients for whom modifications of the initial therapeutic plan would be appropriate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

The role of cisplatin in treatment regimens for squamous cell carcinoma of the head and neck.

Advanced squamous cell carcinoma of the head and neck (SCCHN) is both a local-regional and a systemic disease that is ineffectively managed by conventional surgery and radiotherapy. For patients with advanced but potentially curable (Mo) disease, the morbidity associated with conventional surgery or radiotherapy may be significant whereas the probability of lasting disease control is low. For those with recurrent or metastatic lesions, surgery or radiotherapy are rarely effective options. In this setting, chemotherapy has been evaluated as primary therapy for patients with recurrent or metastatic disease and as an adjunct to surgery or radiotherapy for those with potentially curable lesions. As palliative therapy, methotrexate remains the single agent of choice. Combination chemotherapy has been associated with a higher response rate but not improved survival when compared with methotrexate alone. Cisplatin, both as a single agent and in combination with 5-fluorouracil, is active against SCCHN, and may be superior to methotrexate in antitumor activity. The impact of induction and adjuvant chemotherapy or concurrent chemotherapy and radiotherapy in patients with potentially curable lesions remains controversial. A specific role for chemotherapy has not been confirmed by prospective randomized trial, but effective therapies have been achieved: Regimens with increased activity against squamous carcinomas have been reported, clinical trials with sufficient power to reach significant conclusions have been published, and organ preservation has been confirmed as an appropriate end point for studies of induction chemotherapy or concurrent chemotherapy and radiation. The clinical experience with chemotherapy for patients with recurrent or metastatic SCCHN as well as induction and adjuvant chemotherapy and concurrent chemotherapy and radiotherapy for those with potentially curable disease is reviewed, with particular emphasis given to trials involving cisplatin and to avenues for continued clinical investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.

Adult↗
PubMed1990

Surgery for pulmonary metastases from renal cell carcinoma. Army experience from 1977-1987.

The Army Medical Centers' combined ten-year experience (1977-1987) with renal cell carcinoma metastatic to the lung is presented. Those patients who underwent resection of the lung metastases were compared with those who did not. Certain factors within the two groups were analyzed mainly for effect on survival: number and location of pulmonary metastases, disease-free interval from nephrectomy, extent of lung resection, and synchronous vs asynchronous metastases. Comparisons were made with reports from the literature, and conclusions were made in reference to indications for resection and other modes of therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Detection of B- and T-cells in paraffin-embedded tissue sections. Diagnostic utility of commercially obtained 4KB5 and UCHL-1.

Although many recent studies have begun exploring the diagnostic utility of anti-B- and anti-T-cell antibodies that work on paraffin-embedded tissue sections, the most optimal panel to use remains uncertain. In addition, many of the published reports have used antibodies obtained before their commercial formulation and distribution. For these reasons, B5-fixed paraffin-embedded tissue samples from 174 reactive or neoplastic lymphoid and hematopoietic proliferations were immunostained with the commercially obtained antibodies 4KB5, UCHL-1, and, in selected cases, L26. In reactive nodes, 4KB5 stained B-cell areas and UCHL-1 T-cell areas. Seventy-nine percent of the B-cell neoplasms were 4KB5 positive, and only 2% were UCHL-1 positive. Two cases of myeloma were 4KB5 and UCHL-1 negative. The 4KB5-negative B-cell lymphomas (ML-B) were all L-26 positive. UCHL-1 stained 78% of the T-cell lymphomas (ML-T), and 4KB5 stained 14%. In the five 4KB5-positive putative T-cell lymphomas, immunoglobulin and T-cell receptor gene rearrangement studies were performed. In Hodgkin's disease (HD), Reed-Sternberg (RS) cells were UCHL-1 negative in 75% of cases and occasionally positive in 25%. Definite 4KB5 positivity of RS cells was identified in both cases of lymphocyte predominant HD and in one case of nodular sclerosing HD with monomorphic large cell areas. With the exception of 1 of 15 acute nonlymphocytic leukemias that was UCHL-1 positive, all acute leukemias were 4KB5 and UCHL-1 negative. In summary, commercially obtained 4KB5 and UCHL-1 form a useful but not absolutely specific or sensitive paraffin section immunoperoxidase panel for the categorization of B- and T-cell lymphoid neoplasms. Addition of L26 appears to add to the sensitivity and specificity of the panel. Definite immunophenotypic distinction of HD from non-Hodgkin's lymphomas, particularly of T-cell type, often was not possible.

Antibodies, Monoclonal↗
PubMed1990

Oral complications following neoadjuvant chemotherapy in patients with head and neck cancer.

Oral complications from cancer chemotherapy are well documented for the hematologic malignancies but are less well defined for cancers of the head and neck. This prospective study examined 82 patients with stage III or IV disease to determine the incidence and severity of oral sequelae following a total of 141 cycles of neoadjuvant chemotherapy. Taste alteration (37%) was the most frequent problem, followed by mucositis (30%) and ulceration (22%). Xerostomia, increased salivary flow, loss of appetite, weight loss, dysphagia, bleeding, and infection were also encountered. We conclude that oral problems are common following chemotherapy for head and neck tumors and that more aggressive investigational protocols will result in a much higher incidence and severity of problems. Prevention of these sequelae by conventional as well as investigational means is important to keep them from becoming dose-limiting problems.

Antineoplastic Agents↗
PubMed1989

A phase I-II trial of cisplatin, hyperthermia and radiation in patients with locally advanced malignancies.

A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m2 (4 patients), 30 mg/m2 (8 patients), and 40 mg/m2 (12 patients) was given rapidly (over 5-10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min; the target minimum tumor temperature was 43 degrees C. Following hyperthermia, a 400 cGy fraction of radiation was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000-6600 cGy in patients with full radiation tolerance or 2400-3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m2 dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m2 required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with small tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43 degrees C in CR versus 2.0 min in PR patients). Local toxicities included second degree burns in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4-12 weeks without surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Abdominal aortic aneurysm repair in patients with pelvic kidney. Technical considerations and literature review.

Effective methods for performing abdominal aortic aneurysmectomy associated with congenital pelvic kidney are presented. The embryology and surgical anatomy of these lesions are reviewed. Ordinarily, successful aortic reconstruction can be performed with low risk to the pelvic kidney by use of readily available in situ cold perfusion. Two illustrative case reports applying this method are presented. The recently reported technique of double proximal clamping of the aorta was also employed in one case. This technique allows lumbar collaterals within the aneurysm to perfuse the kidney during construction of the proximal aortic anastomosis, thereby minimizing absolute renal ischemic time. Both in situ cold perfusion and double proximal clamping are effective methods for renal preservation that do not rely on complex extraanatomic techniques. A review of the literature with a discussion of the advantages and disadvantages of previously reported methods of renal preservation is presented.

Aged↗