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Biomedical subjects

D C Smith

Publications and source records attributed to D C Smith.

At least 37 records · Page 2Linked to original sources

The auditory evoked response as an awareness monitor during anaesthesia.

We investigated the relationship between the latency of the Nb wave of the auditory evoked response (AER) and periods of awareness during propofol anaesthesia. In the anaesthetic room before cardiac surgery the AER was recorded continuously in 14 patients. Awareness was measured by the ability of the patient to respond to command using the isolated forearm technique (IFT). The Nb latencies were shorter when the patients were able to respond than at loss of response (P<0.001). In six patients who repeated this transition from response to loss of response, there was a high and significant correlation between Nb latencies. None of the patients had any recollection of events after the initial induction of anaesthesia as measured by explicit and implicit memory tests. These results suggest that the Nb latency of the AER may represent an indication of awareness in individual patients, but wide inter-patient variability limits its practical usefulness. In addition, because no evidence of memory was demonstrated, even when patients were known to be awake, the relationship between AER and memory processing remains unclear.

Aged↗

Aspiration of an oropharyngeal airway during nasotracheal intubation.

The oropharyngeal airway (OPA) has been a remarkably safe device since its invention by Guedel in 1933. This plastic device is easily placed in the mouth and used for aiding in mask ventilation. We report a case of the aspiration of an OPA causing near total upper airway obstruction.

Adult↗

Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study.

PURPOSE: Patients with locally advanced bladder cancer or who are not medically fit for surgery are a therapeutic dilemma. Radiotherapy with or without single agent cisplatin has been the major therapeutic modality. A phase II Southwest Oncology Group trial investigated the efficacy and feasibility of 5-fluorouracil, cisplatin and radiation in this patient subset. MATERIALS AND METHODS: Eligible patients had muscle invasive bladder cancer (clinical stages T2-T4) with nodal involvement at or below the level of bifurcation of the iliac vessels, were medically or surgically inoperable, or refused cystectomy. Patients underwent pretreatment cystoscopy and detailed tumor mapping, and were treated with 75 mg. /m.2 cisplatin on day 1 and 1 gm./m.2 daily, 5-fluorouracil on days 1 to 4 and definitive radiotherapy. Chemotherapy was repeated every 28 days, twice during and twice after radiation. RESULTS: From October 1993 to April 1998, 60 patients were enrolled in study. Of the 56 eligible patients 34% had unresectable tumors, 21% were not medically fit for surgery and 45% refused cystectomy. Overall, 68% of the patients had clinical T3 tumors or greater and 22% had nodal metastasis. Treatment was completed as planned in 32 of 56 (57%) patients. The most frequent grade 3 or 4 toxicities were neutropenia, stomatitis or mucositis, diarrhea, neuropathy and nausea. There were 53 patients who were evaluable for response, although response was not determined for 18. The overall response rate was 51% (95% confidence interval [CI] 37 to 65) based on intent to treat with a complete response rate of 49% (95% CI 35 to 63). Estimated median survival of the 56 patients was 27 months (95% CI 21 to 40 months) with an overall 5-year survival of 32%. The 5-year survival of the 25 patients who refused surgery was 45%. CONCLUSIONS: Concurrent 5-fluorouracil, cisplatin and radiation therapy is feasible. Despite a promising complete response rate, the overall 5-year survival suggests the need for more effective systemic therapy. The 5-year survival of patients who refused cystectomy suggests that this combined modality may provide another alternative to cystectomy for these patients.

Aged↗

Pelvic recurrences post cystectomy: current treatment strategies.

Pelvic recurrence following cystectomy is a devastating problem for both physician and patient. Patients who recur locally usually do so within the first 2 years following surgery. Stage, grade, and possibly p53 status of the tumor are prognostic indicators for local failure. Patients with extensive disease at the time of diagnosis may benefit from adjuvant or neoadjuvant treatment to attempt to decrease the rate of recurrence. Treatment of patients with local failure should use a multimodality approach that includes systemic chemotherapy with or without local radiation therapy or surgery. Although rare, long-term survival can be achieved in selected patients.

Abdominal Neoplasms↗

Elective removal of an intramyocardial bullet.

A 26-year-old man had a gunshot wound in the right posterolateral aspect of the chest. A chest radiograph showed the bullet in the region of the cardiac silhouette. The patient was hemodynamically stable and had no complaints of dyspnea or abdominal pain. Echocardiography and computed tomography identified the bullet in the wall of the right ventricle. The surgical management of the injury is discussed in detail.

Adult↗

A trial of etomidate for rapid sequence intubation in the emergency department.

A number of pharmacologic agents have been used for induction during rapid sequence intubation (RSI). Some of these agents may have adverse effects that can limit their use in certain clinical settings. This study was undertaken to determine the safety and utility of etomidate in patients with a range of underlying clinical conditions. Thirty-four patients underwent RSI in the emergency department (ED). Hemodynamic measurements and clinical assessments were recorded before and after intubation. The results suggest that etomidate is a safe and effective agent for use in a range of patients undergoing RSI in the ED.

Aged↗

Analysis of silicon in human tissues with special reference to silicone breast implants.

The increase, in the last two decades, in the application of silicones (polysiloxanes) and inorganic silicon compounds in medicine and the food industry, has exposed the human body to extensive contacts with these substances. Most silicone breast implants contain a gel consisting of a crosslinked silicone elastomer swollen by silicone oil (PDMS). Diffusion of PDMS through the silicone elastomer envelope and rupture of the envelope with release of the gel contents both occur clinically. The amount and distribution of silicone compounds in various tissues are key issues in the assessment of health problems connected with silicone implants. We have measured by GFAAS the Si content of tissues from normal and implant patients and the organic solvent extractable Si levels (assumed to be silicone), using careful control of sample collection and preparation. Whole blood levels were: implant patients mean 38.8 (SD 25.6) (microg/kg), controls mean 24.2 (SD 26.7) (microg/kg) in one study and subsequently 103.8 (SD 112.1) and 74.3 (SD 86.5) (microg/kg) in another study. Capsular tissue levels were: gel implants 25047 (SD 39313) (mg/kg of dry tissue), saline implants 20.0 (SD 27.3) (mg/kg of dry tissue) and controls 0.24 (SD 0.39) (mg/kg of dry tissue). Breast milk levels were: implant patients mean 58.7 (SD 33.8) (microg/kg), controls mean 51.1 (SD 31.0) (microg/kg); infant formula mean was 4.40 (mg/kg). Various precautions were undertaken to avoid Si contamination in this work, the most important being a) the use of a Class 100 laboratory for sample preparation and b) application of strict and elaborate washing procedure for specimen collection tools and laboratory plasticware. This data demonstrated that to properly interpret the importance of these numbers for human health, a larger study of "normal" levels of Si in human tissues should be undertaken and factors such as diet, water, race and geographical location should be considered.

Breast Implants↗

One stop breast clinics--victims of their own success? A prospective audit of referrals to a specialist breast clinic.

AIMS: We aimed to assess the number of unnecessary referrals to a specialist breast clinic, with special reference to urgent referrals, and to compare referrals with published guidelines for referral to these clinics. METHODS: We carried out a prospective audit of new patient referrals from primary care to a specialist breast clinic. We assessed the total number of referrals, proportion of urgent and non-urgent referrals, proportion of unnecessary referrals according to published guidelines, waiting times for outpatient appointments and outcomes for these patients. RESULTS: Of the total of 321 referrals, 35% were urgent. Twenty-eight per cent of urgent referrals and 37% of non-urgent were inappropriate according to published guidelines. Ten per cent of referrals had breast cancer while 90% had benign disease or no pathology. CONCLUSIONS: There is a proliferation of guidelines (NHS, SIGN, BASO, Patients' Charter) for the organization of specialist breast clinics with the aim of providing rapid diagnosis for patients with malignant disease, or reassurance for symptomatic patients that they do not have breast cancer. However increasing numbers of patients are being referred to these clinics with minimal or no pathology, and this is not acknowledged by these guidelines. In this prospective study of referrals from primary care to a specialist breast clinic, one-third of referrals were inappropriate and this inevitably reduced the efficiency of the service provided for patients with significant symptoms.

Adolescent↗

Rapid ("warm") autopsy study for procurement of metastatic prostate cancer.

In this report, we describe the distribution of metastases from 14 patients who had hormone-refractory adenocarcinoma of the prostate and agreed while alive to undergo directed autopsies after their deaths. These autopsies were undertaken specifically to document the distribution of metastases, characterize tumors phenotypically and immunohistochemically, harvest fresh and snap frozen tumor and normal control tissues suitable for molecular examination, and establish cell lines via passages through generations of severe combined immunodeficient and athymic mice. Achievement of these goals was obtained through the development of a multidisciplinary team approach. Team members included a medical oncologist, pathologists, urologists, and researchers. The autopsy and tissue procurement teams were available on a round-the-clock basis. The tissues harvested from these autopsies yielded high-quality tumor samples, as evidenced by excellent preservation seen by light microscopy, strong prostate-specific antigen immunostaining, and the successful development of xenografts. The development and expansion of this program represent a valuable resource for molecular and clinical researchers.

Aged↗

Determination of intermediate biomarker expression levels by quantitative reverse transcription-polymerase chain reaction in oral mucosa of cancer patients treated with liarozole.

Liarozole is a 1-substituted imidazole derivative that inhibits cytochrome P450 activity and increases endogenous plasma concentrations of retinoid acid (RA). We have previously demonstrated that RA down-modulates transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) levels in head and neck squamous cell carcinoma by decreasing the transcription rate of these two genes. Previous reports suggest that RA receptor (RAR)-beta levels are down-modulated in head and neck cancer and are restored by RA therapy. Cellular RA-binding protein (CRABP)-II is up-regulated by RA and appears to modulate intracellular RA metabolism. In conjunction with a Phase I clinical trial, total intact RNA was extracted from oral cavity mucosa biopsied from 17 patients with advanced malignancies, before and after treatment with a 4-week course of liarozole. To analyze these limited quantities of total RNA (as little as 0.6 microg/sample), a quantitative reverse transcription-PCR assay was developed using delayed dropping of the 5' beta-actin primer to amplify the highly abundant beta-actin gene as an internal control. We used this method to determine the expression levels of TGF-alpha, EGFR, RAR-beta, and CRABP-II before and after treatment. There was a trend toward elevation of RAR-beta levels in oral mucosa after liarozole therapy (P = 0.107), whereas TGF-alpha, EGFR, and CRABP-II were not modulated by systemic liarozole treatment. These results suggest that liarozole may up-regulate RAR-beta in tissues from cancer patients and that expression levels of potential intermediate biomarkers may be determined in small tissue biopsies using a quantitative reverse transcription-PCR assay.

Actins↗

A phase II trial of CI-958 in patients with hormone-refractory prostate cancer.

PURPOSE: To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks. PATIENTS AND METHODS: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria. RESULTS: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions. CONCLUSIONS: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.

Adult↗

Recombinant vaccinia-PSA (PROSTVAC) can induce a prostate-specific immune response in androgen-modulated human prostate cancer.

OBJECTIVES: Prostate cancer recurrence, evidenced by rising prostate-specific antigen (PSA) levels after radical prostatectomy, is an increasingly prevalent clinical problem in need of new treatment options. Preclinical studies have suggested that for tumors in general, settings of minimal cancer volume may be uniquely suitable for recombinant vaccine therapy targeting tumor-associated antigens. A clinical study was undertaken to evaluate the safety and biologic effects of vaccinia-PSA (PROSTVAC) administered to subjects with postprostatectomy recurrence of prostate cancer and to assess the feasibility of interrupted androgen deprivation as a tool for modulating expression of the vaccine target antigen, as well as detecting vaccine bioactivity in vivo. METHODS: A limited Phase I clinical trial was conducted to evaluate the safety and biologic effects of vaccinia-PSA administered in 6 patients with androgen-modulated recurrence of prostate cancer after radical prostatectomy. End points included toxicity, serum PSA rise related to serum testosterone restoration, and immunologic effects measured by Western blot analysis for anti-PSA antibody induction. RESULTS: Toxicity was minimal, and dose-limiting toxicity was not observed. Noteworthy variability in time required for testosterone restoration (after interruption of androgen deprivation therapy) was observed. One subject showed continued undetectable serum PSA (less than 0.2 ng/mL) for over 8 months after testosterone restoration, an interval longer than those reported in previous androgen deprivation interruption studies. Primary anti-PSA IgG antibody activity was induced after vaccinia-PSA immunization in 1 subject, although such antibodies were detectable in several subjects at baseline. CONCLUSIONS: Interrupted androgen deprivation may be a useful tool for modulating prostate cancer bioactivity in clinical trials developing novel biologic therapies. Immune responses against PSA may be present among some patients with prostate cancer at baseline and may be induced in others through vaccinia-PSA immunization.

Androgen Antagonists↗

Relationship of components of an alcohol interoceptive stimulus to induction of desire for alcohol in social drinkers.

The ability of a low (0.2 g/kg) oral dose of ethanol to provide a drug discriminative stimulus was studied in young healthy human volunteers, who were social drinkers. Seventeen of 24 subjects acquired the discrimination following 10 trials in which they received aliquots of ethanol or of placebo drink (tonic water mixed with Tabasco sauce). In generalization studies, in which the dose of ethanol was varied, discrimination performance was dose dependent; doses greater than 0.05 g/kg gave rise to significant ethanol-appropriate responding. Concurrent estimates of the subjective effects of doses administered as discriminative stimuli revealed that two factors--taste and light-headedness--were associated with discrimination: at the training dose, 0.2 g/kg, although both the factors taste and light-headedness were significantly increased, only taste predicted discrimination performance. At lower doses, taste did not contribute to discrimination, but the subjective rating light-headedness correlated significantly with discrimination accuracy. Post hoc analyses of the influence of the amount of alcohol regularly drunk by the volunteers, on discrimination performance suggested light-headedness correlated with discriminative performance only in social drinkers drinking more than 20 units per week. In a second experiment, groups of "high" (mean 40 units per week) and "low" (mean 10 units per week) social drinkers were prospectively identified. Discrimination performance of 0.2 g/kg ethanol in orange juice vs. orange juice vehicle indicated that both groups were able to perform the discrimination following a single training trial, and that generalization curves over the range 0.05-0.2 g/kg were dose dependent, and not different between the groups. At the lowest dose, discrimination performance was predicted by taste, stimulation, and light-headedness in the "high" group, but not in the "low" group. The ability of these ethanol doses to induce feelings of craving for ethanol were assessed in parallel, using the Desire for Alcohol Questionnaire (DAQ). "High" drinkers showed higher desire for ethanol on all factors of the DAQ except the "positive negative reinforcement" factor, and sampling ethanol tended to increase desire in these measures. However, at each dose, the induction of feelings of desire for ethanol showed a negative correlation with discrimination performance. These findings are discussed in the context of the ability of animals and humans to use several components of drug-induced stimuli in the performance of drug discrimination, and the role of such discriminative stimuli in priming of ethanol drinking.

Alcohol Drinking↗

Chemotherapy for hormone refractory prostate cancer.

New combinations have been developed that show significant activity in therapy for hormone refractory prostate cancer. Several of these are designed to address specific cellular targets unique to prostate cancer. To date, the major benefits of these therapies have been palliative in nature, resulting in an improvement in quality of life, particularly with the combination of mitoxantrone and prednisone. None of these agents or regimens have been shown to affect survival significantly, and none can be considered to be standard therapy for this disease. Nonetheless, the success of these regimens in inducing response has challenged the skepticism concerning the appropriateness of chemotherapy for patients with advanced prostate cancer. The ability to slow and even reverse the growth of far advanced disease raises the possibility that the application of these regimens earlier in the course of the disease will have a more significant impact on the morbidity and, in the long run, on the mortality of prostate cancer. It is hoped that the enrollment of patients into properly designed clinical trials of new agents and combinations will result in the development of therapy with proven efficacy in the near future.

Anthracyclines↗

Oral chemotherapy for hormone refractory prostate cancer. The University of Michigan experience.

The use of oral chemotherapy for the treatment of malignant disease is expanding. The authors' experience with oral chemotherapy for hormone-refractory prostate cancer continues to grow. These therapies are well-tolerated and effective. Already, these regimens are being improved by hybridizing them with intravenous agents such as paclitaxel. Also, oral novel agents are being tested that may offer new options for the treatment of hormone-refractory prostate cancer.

Administration, Oral↗

Irrigation of soil with synthetic landfill leachate--speciation and distribution of selected pollutants.

The fates and toxicities of selected landfill leachate pollutants in a soil with a low attenuation potential were investigated. Soil columns consisting of a loamy sand which had been irrigated with synthetic landfill leachates were dissected and analysed for pH, electrical conductivity, copper and zinc species, iron and phenol concentrations and microbial activity. Copper was found to be least mobile and accumulated in the top 4 cm of the soil columns. Sequential extraction of the soil revealed that at least two-thirds of the total copper was in the EDTA-, NaOH-extractable and residual fractions. Approximately 2% of the copper was water soluble and between 1 and 22% was in the MgCl(2)-extractable fraction. Zinc and phenol were relatively mobile and were detected throughout the soil-column profile as well as in the column effluents. The greatest zinc fraction (55-71%) was MgCl(2)-extractable. Zinc solubility in water was again low (1-4%). Phenol was partially adsorbed by the soil but its main attenuation occurred by biodegradation. Microbial activity was affected by the availability of the carbon source as well as the presence of copper and zinc. Copper was more inhibitory to microbial activity than zinc. In the presence of phenol, the simultaneous application of zinc and copper distinctly reduced microbial activity. No inhibitory effect of copper and zinc was observed in the absence of phenol when the microorganisms were severely carbon limited.

Journal Article↗