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Biomedical subjects

J R Clark

Publications and source records attributed to J R Clark.

At least 37 records · Page 2Linked to original sources
PubMed1997

Late developing supernumerary teeth in the mandible.

This paper presents two cases in which supplemental premolars were an incidental finding. Although anomalies of tooth number and form are quite common, both cases demonstrate late forming supernumeraries with one case illustrating their development in a more unusual site. It is not routine practice to screen for late development of teeth during orthodontic treatment. Therefore the possibility of their interference with occlusal development or orthodontic mechanics such as space closure, should always be kept in mind.

Bicuspid↗
PubMed1997

Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for squamous cell carcinoma of the head and neck: long-term results.

PURPOSE: A phase II trial of cisplatin, fluorouracil, and leucovorin (PFL) induction chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck region (HNCA). PATIENTS AND METHODS: One hundred two patients (stage III/IV, previously untreated) were treated with induction PFL. Patients with resectable primary tumor site lesions and clinical complete response (CR) were offered radiotherapy (RT) without surgery to the primary tumor site. Response, toxicity, local-regional therapy, survival, and preservation of the primary tumor site were assessed. RESULTS: Among 279 courses, the overall response rate was 81%. Nineteen (19%) failed to respond, including three who died during therapy. Sixty-seven (69%) of 97 with assessable primary lesions had a clinical CR at the primary tumor site. Pathologic CR was recorded in 46 of 55 (84%) clinical CR patients who had biopsies performed on the primary tumor site. Toxicities resulted in unexpected hospitalizations in 19% of cases. After definitive local-regional therapy, 84 (82%) were disease-free including 71 (69%) with preserved primary tumor site anatomy. With a median follow-up time of 63 months, the cause-specific, overall (OS), and failure-free survival (FFS) rates at 5 years are 58%, 52%, and 51%. Local failure occurred in 29 of 102 (29%) and the local control rate at 5 years was 68%. CONCLUSION: PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status. Preservation of the primary tumor site could be achieved without apparent loss of local control or survival. Management of neck disease by surgery or RT must be individualized and separate from management of primary tumor. Survival compares favorably with similar trials of induction chemotherapy or chemoradiotherapy.

Adolescent↗
PubMed1997

Pathogenesis and prevention of doxorubicin cardiomyopathy.

A review is presented of the various types of cardiotoxicity associated with the clinical use of doxorubicin, a highly effective antineoplastic agent of the anthracycline family. Acute toxicity is related to rapid intravenous administration of the drug and is manifested by vasodilatation, hypotension and cardiac arrhythmias. Subacute toxicity is very uncommon. It develops early in the course of therapy and is characterized by myocarditis and pericarditis. Chronic toxicity is the most common form of doxorubicin-induced cardiac toxicity. It is manifested by chronic dilated cardiomyopathy, which develops late in the course of therapy or shortly after its termination. Morphologic changes are characteristic and consist of myofibrillar loss and cytoplasmic vacuolization (which is due to dilatation of the sarcoplasmic reticulum) of the myocytes. The damaging effects of reactive oxygen species, generated by the interaction of doxorubicin with iron, play a critically important role in the pathogenesis of the chronic cardiotoxicity. Other factors related to this toxicity include inhibition of DNA topoisomerase II, stimulation of certain immune responses and a diversity of other biochemical effects on various cellular organelles. Doxorubicin induces apoptosis in a variety of cell types, but not in cardiac myocytes. The chronic cardiotoxicity of doxorubicin is significantly attenuated by chelation of iron by ICRF-187 (dexrazoxane). A greatly delayed type of doxorubicin cardiotoxicity has been recently found to occur in survivors of childhood cancers who were treated with doxorubicin without any immediate adverse effects, but develop chronic cardiomyopathy at periods of time ranging up to 15 years later. The pathogenesis of this type of toxicity remains to be determined.

Antibiotics, Antineoplastic↗
PubMed1996

Doxorubicin-induced apoptosis in spontaneously hypertensive rats: differential effects in heart, kidney and intestine, and inhibition by ICRF-187.

The occurrence of apoptosis in heart, kidney and small intestine was investigated in spontaneously hypertensive rats (SHR) treated with doxorubicin (1 mg/kg/week for 6, 9 and 12 weeks) with and without pretreatment with the iron chelator ICRF-187 [(+)1.2-bis(3.5-dioxopiperazinyl-l-yl)propane] (25 mg/kg, i.p., given 30 min before doxorubicin). Animals receiving either ICRF-187 alone or saline were used as controls. Cells undergoing apoptosis were identified ultrastructurally and by staining using the nick-end labeling method. The results obtained by counting cells with positive nick-end labeling showed that, when given in cumulative doses of 9 and 12 (but not 6) mg/kg, doxorubicin induced significant toxicity in the heart, kidneys and intestine in association with apoptosis in epithelial cells of the intestinal mucosa and renal tubules but not in cardiac myocytes. At these doses nick end labeling in the heart was confined to occasional endothelial cells, interstitial dendritic cells and macrophages. The frequency of doxorubicin-induced apoptosis in renal and intestinal epithelial cells was decreased by pretreatment of the SHR with ICRF-187. Our data support the concept that the chronic cardiomyopathy induced by doxorubicin is not mediated by apoptosis of the cardiac myocytes.

Animals↗
PubMed1996

Docetaxel: an active drug for squamous cell carcinoma of the head and neck.

PURPOSE: We conducted a phase II study designed to evaluate the activity, safety, and tolerability of docetaxel (Taxotere: Rhône-Poulenc Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who had not received prior palliative chemotherapy. PATIENTS AND METHODS: Thirty-one patients with measurable, locoregional, or metastatic SCCHN were treated with docetaxel, administered at a dose of 100 mg/m2 as a 1-hour intravenous (i.v.) infusion once every 21 days on an outpatient basis. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic administration of growth factors or antiemetics was not permitted. RESULTS: Thirty-one patients were treated. Twenty-nine patients were assessable for response and 30 for toxicity. Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response had stable disease (SD) and seven (23%) experienced progression of disease (PD). The major response rate was 42% (95% confidence interval [CI], 24% to 60%). The median duration of responses was 5 months (range, 2 to 14). The principal toxicity was leukopenia, which occurred with rapid onset and brief duration. Sixteen patients (53%) experienced nadir fever, and 13 required dose reduction. Hypersensitivity reactions occurred in four patients. Grade 3 peripheral neuropathy occurred in two patients; grade 2 or 3 fatigue occurred in six (20%) and 10 (33%), respectively. Minimal edema (grade 1) occurred in five patients (17%). Clinically significant mucositis, diarrhea, or dermatitis were not observed. CONCLUSION: Docetaxel has major activity against SCCHN. It appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis. Premedication with dexamethasone, cimetidine, and diphenhydramine is associated with a reduced incidence of significant edema, hypersensitivity reactions, and dermatologic toxicities.

Adult↗
PubMed1996

Antibiotics and upper respiratory infection: do some folks think there is a cure for the common cold.

BACKGROUND: Symptomatic treatment is the only recommended therapy for the uncomplicated "common cold." The purpose of this study was to examine the use of antibiotics and other prescription medications for the common cold in a Medicaid population seen in ambulatory care settings. METHODS: A cross-sectional sample of Kentucky Medicaid claims from July 1, 1993, through June 30, 1994, was analyzed. Subjects were patients seen in an ambulatory setting for the common cold, defined as acute nasopharyngitis. A total of 1439 individuals were seen for 2171 separate outpatient and emergency department encounters for the common cold. Outpatient visits accounted for 99% (2144) of the encounters. RESULTS: Patients in 35% (752) of the encounters did not fill a prescription for medication, 6% (129) filled a prescription for an antihistamine or other symptomatic medication, and 60% (1290) filled a prescription for an antibiotic for the common cold. Nineteen different antibiotics, 54% of which were amoxicillin, were prescribed for the common cold. Less than 2% of the encounters had a secondary diagnosis of either acute sinusitis or otitis media. These encounters were not more likely than the total sample to receive antibiotics. Adults were more likely than children to receive an antibiotic (P<.001), and urban physicians were more likely than rural physicians to prescribe antibiotics (P=.02). A conservative estimate of the annual cost of antibiotic prescribing for the common cold in the United States was $37.5 million. CONCLUSIONS: A majority of persons receiving medical care for the common cold are given prescriptions for an unnecessary antibiotic. Unchecked, this practice may lead to greater antibiotic resistance and unnecessary use of health care resources. Future research should focus on the ability to institute behavioral changes for treatment of the common cold in both closed systems (eg, managed care) and open systems (eg, general community of physicians).

Adolescent↗
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↗
PubMed1993

Failure of cimetidine to reduce postoperative hypocalcemia in patients with primary hyperparathyroidism undergoing neck exploratory operation.

BACKGROUND: Although use of histamine H2 antagonists for chronic treatment of primary hyperparathyroidism (PHP) is ineffective, pretreatment with cimetidine has been reported to reduce the incidence of postoperative hypocalcemia in patients with PHP undergoing neck exploratory operation. The current investigation was conducted to determine the validity of this assertion. METHODS: In a randomized, double-blind, placebo-controlled trial, 20 patients with PHP were treated with either cimetidine or placebo for 10 to 14 days before neck exploratory operation. Clinical outcome and biochemical indexes before and after drug treatment in both groups were compared. RESULTS: Cimetidine treatment resulted in a modest increase in preoperative parathyroid hormone level but did not affect any other parameter, including serum calcium level or renal tubular reabsorption of phosphate. Intraoperative time was similar in both groups. Mean postoperative calcium nadir was identical regardless of therapy (8.3 mg/dl), and seven (70%) patients from each group had at least one serum calcium measurement less than 8.5 mg/dl. CONCLUSIONS: Cimetidine treatment before neck exploratory operation for PHP does not diminish the frequency or severity of postoperative hypocalcemia.

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↗