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Biomedical subjects

L Buchanan

Publications and source records attributed to L Buchanan.

16 recordsLinked to original sources

A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy.

High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7 h 30 min post the initial dose of emetogenic chemotherapy was compared to high-dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min prior to chemotherapy in a randomised, double-blind, parallel subjects design study. On the prochlorperazine arm intravenous dextrose placebos every 2 h maintained blinding. Complete suppression of vomiting occurred in 42% on metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52% with non-cisplatin-containing regimens) while major responses (2 or less vomits) occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who vomited after cisplatin, prochlorperazine achieved a significantly shorter duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P = 0.03). The response rate to prochlorperazine for cisplatin-induced emesis between 12 and 24 h was significantly better than for metoclopramide (prochlorperazine = 0.02). Toxicities were equivalent except for significantly greater sedation and dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on both arms but were only severe enough to stop treatment on metoclopramide. The metoclopramide regimen was five times as expensive as prochlorperazine. High-dose prochlorperazine is an active and cost-effective antiemetic.

Adolescent

A randomised trial of dexamethasone, lorazepam and prochlorperazine for emesis in patients receiving chemotherapy.

To define further the place of dexamethasone in antiemetic combinations, lorazepam, prochlorperazine and placebo (LP) were compared with lorazepam, prochlorperazine and dexamethasone (DLP) in a randomised, double-blind, crossover study. Both patient and observer assessments were documented in 84 patients receiving both cisplatin and non-cisplatin chemotherapy. The addition of dexamethasone significantly reduced the severity of nausea (P = 0.002) and vomiting (P less than 0.0001), duration of nausea (P = 0.01) and vomiting (P = 0.002) and the number of vomiting episodes (P = 0.003). DLP was the superior regimen in subsets of patients receiving cisplatin and the non-cisplatin chemotherapy. The improvements produced by the dexamethasone regimen were large and of major benefit to our patients. Patients documented significantly improved tolerance to chemotherapy with DLP courses (P = 0.0006). Overall, significantly more patients preferred DLP (P less than 0.0001). Patient assessments produced results similar to observer assessments but gave a broader understanding of their experience. The addition of dexamethasone to prochlorperazine and lorazepam significantly improved our patients' experience while receiving chemotherapy.

Adult

Ontogenesis of the murine hepatic extracellular matrix: an immunohistochemical study.

To define the role of the extracellular matrix (ECM) in hepatogenesis, we examined the temporal and spatial deposition of fibronectin, laminin and collagen types I and IV in 12.5-21.5 day fetal and 1, 7 and 14 day postnatal rat livers. In early fetal liver, discontinuous deposits of the four ECM components studied were present in the perisinusoidal space, with laminin being the most prevalent. All basement membrane zones contained collagen type IV and laminin, including those of the capsule (mesothelial), portal vein radicles and bile ductules. Fibronectin had a distribution similar to that of collagen type IV early in gestation. However, at later gestational dates, fibronectin distribution in the portal triads approached that of collagen type I, being present in the interstitial connective tissues; whereas, collagen type IV and laminin were restricted to vascular and biliary basement membrane zones in those regions. The cytoplasm of some sinusoidal lining cells and hepatocytes reacted with antibodies to extracellular matrix components. By electron microscopy the immunoreactive material was localized in the endoplasmic reticulum, indicating the ability of these cells to synthesize these ECM proteins. Biliary ductular cells had prominent intracytoplasmic staining for laminin and collagen type IV from day 19.5 gestation until 7 days of postnatal life, but lacked demonstrable fibronectin or collagen type I. These results demonstrate that by 12.5 days of gestation the rat liver anlage has deposited a complex extracellular matrix in the perisinusoidal space. The prevalence of laminin in the developing hepatic lobules suggests a possible role for this glycoprotein in hepatic morphogenesis. In view of the intimate association of the hepatic lobular extracellular matrix with the developing vasculature, we hypothesize that laminin provides a scaffold of the developing liver, but once the ontogenesis is complete, intrahepatic perisinusoidal laminin expression is suppressed.

Animals

Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states.

Adult

Power spectral analysis of heart rate variability after biofeedback training.

This study investigated the effects of biofeedback/self-management training on heart rate variability (HRV) in six sudden cardiac arrest survivors. The physiological-theoretical basis of the training was cognitively inducing respiratory sinus arrhythmia. Power spectral analyses and nonspectral analyses (Kleiger, Magid, SCANN, BB50 measures) of HRV measured before and after 5 weeks of biofeedback training are described. The posttraining Kleiger measure of mean HRV increased compared to the pretraining mean HRV (159 +/- 37 ms vs 147 +/- 38 ms). After training, the high frequency components (0.27-0.30 Hz) of the power density spectra were markedly increased, suggesting an increase of respiratory-driven parasympathetic activity. After training, the low frequency components (0.05 Hz) were slightly decreased, suggesting a decrease in sympathetic activity. The increases noted in the high frequency components were more striking during 9 hours at night than during the day. These data indicate that subjects who have had sudden cardiac arrest can, through biofeedback/self-management, cognitively increase their HRV over a 5-week period, consequently increasing parasympathetic activity.

Arrhythmia, Sinus

Value of screening thyroid function in acute medical admissions to hospital.

During a 4-month period an audit was performed to assess the value of thyroid function test (TFT) screening of all medical admissions, without known thyroid disease, to a single hospital. Abnormal TFTs were found in 125 of the 630 patients admitted (20%). Carbimazole or thyroxine was started in 13 patients (2.1%) discovered to have thyrotoxicosis (n = 4) or hypothyroidism (n = 9). In only four of these patients was the diagnosis of thyroid disease apparent clinically. The sick euthyroid state was found in 73 patients (11.6%), while the TSH compensated hypothyroid state was detected in 39 patients (6.2%). The low detection rate of new thyroid disease would suggest that unselective screening of all admissions is unjustified. However, the problem of diagnosing thyroid disease and the morbidity of untreated thyroid disease suggests that biochemical screening of TFTs in a selective group of medical patients admitted to hospital may be justified.

Acute Disease

Pain reduction in local anesthetic administration through pH buffering.

The effects of pH buffering on the pain of administration and efficacy of three local anesthetics (1% lidocaine, 1% lidocaine with 1:100,000 epinephrine, and 1% mepivacaine) were investigated in a randomized, prospective, double-blind study of 25 adult volunteers. Plain and buffered solutions of the three local anesthetics were prepared, and a 0.5 intradermal injection of each was administered. Pain of anesthetic infiltration was rated from zero to ten. The area of anesthetized skin surrounding each injection site was measured at time intervals following each injection. Buffering the local anesthetics significantly reduced the mean quantitative pain estimates compared to the nonbuffered controls: 1) 1% lidocaine compared with buffered 1% lidocaine, 4.9 +/- 0.4 versus 1.1 +/- 0.2 (P less than 10(-6)); 2) 1% lidocaine with epinephrine compared with buffered 1% lidocaine with epinephrine, 5.1 +/- 0.4 versus 1.8 +/- 0.4 (P less than 10(-6)); and 3) 1% mepivacaine compared with buffered 1% mepivacaine, 5.1 +/- 0.4 versus 0.9 +/- 0.2 (P less than 10(-6)). Onset, extent, and duration of skin anesthesia were not statistically altered by pH buffering. The pain of local anesthetic administration can be dramatically reduced by buffering the local anesthetic prior to its infiltration. Anesthetic efficacy is not compromised, and patient acceptance may be significantly increased.

Adult

Ganglioside composition in human cataractous nuclei.

Gangliosides were isolated from human cataractous nuclei by solvent extraction, dialysis, and thin-layer chromatography and compared to gangliosides present in human whole normal and cataractous lenses. Three predominant gangliosides were tentatively identified as GM1, GM3, and GD1a, and several other resorcinol-positive components were observed in each of the sets of lens tissue. Thin-layer chromatographic patterns were similar, although some minor and possibly significant differences in band intensities were observed when chromatograms of gangliosides from cataractous nuclei and cataractous whole lenses were visually compared with those of whole normal lenses. Total ganglioside extracts were methanolyzed and the fatty acid methyl esters extracted with hexane and resolved by gas chromatography. Nervonic acid (C-24:1) content was increased in cataractous nuclei as compared to normal and cataractous whole lenses.

Cataract

A prospective study of topical dimethyl sulfoxide for treating anthracycline extravasation.

Twenty patients with extravasation of anthracyclines were treated on a single-arm pilot study with topical 99% dimethyl sulfoxide (DMSO) and observed for 3 months with regular examinations and photographs. DMSO was applied to approximately twice the area affected by the extravasation and allowed to air dry. This was repeated every six hours for 14 days. The initial signs of extravasation included swelling in 17 patients, erythema in 15, and pain in 12. The median area of damage was 8.25 cm2 and a median of 25 minutes elapsed between extravasation and application of DMSO with one patient not treated until seven days postextravasation. Sixteen patients were observed for 3 months, two died of disease earlier after receiving 2 weeks of DMSO and three days of DMSO, respectively, and two were lost to follow-up having received one day and five days of DMSO. In no patient did extravasation progress to ulceration or require surgical intervention, suggesting with 95% confidence a true ulceration rate of between 1% and 17%. At 3 months there was no sign of residual damage in six patients, while a pigmented indurated area remained in ten. Two patients had a recall reaction with increased pain at the extravasation site when further intravenous (IV) doxorubicin was administered. The only toxicities of DMSO included a burning feeling on application subsequently associated with itch, erythema, and mild scaling. Blisters occurred in four patients. Six patients reported a characteristic breath odor associated with DMSO. Topical DMSO appears to be a safe and effective treatment for anthracycline extravasation.

Administration, Topical

A new device for delayed hypersensitivity skin testing.

A new device for assessment of delayed cutaneous hypersensitivity using seven standardized antigens (Multitest CMI) was compared to conventional intradermal testing with two recall antigens in 83 patients referred for nutritional support. Sixteen patients (19.3%) were anergic to Multitest CMI while four (4.8%) were anergic to conventional testing. Patients anergic to Multitest CMI had a higher complication (intraabdominal abscess, prolonged ileus, sepsis, pneumonia) than those who were immunocompetent by this test suggesting a group at greater risk. This interpretation is consistent with an increased specificity of Multitest CMI over conventional testing in the identification of clinically important anergy.

Adult

A disposable emergency wound treatment kit.

Biomechanical studies in our laboratory have provided a scientific basis for selecting surgical gloves and instruments, drugs, and dressings for traumatic wound treatment. This armamentarium has been incorporated into a disposable emergency wound treatment kit for use in the emergency department. Its upper tray is for wound cleansing, while its lower tray is used for wound closure. A clinical evaluation of the kit by emergency physicians was very favorable because it saved time, eliminating the need to search for and assemble the gloves, instruments, drugs, and dressings for wound treatment.

Disposable Equipment

Guidelines for supervised wound care by emergency nurse practitioners.

Nearly 10 million patients with traumatic lacerations are treated annually in Emergency Departments in the United States. Since these wounds do not usually pose a threat to the patient's life, they assume a lower level of priority than emergent conditions. Consequently, treatment of patients with lacerations is often delayed until the emergent patient is resuscitated. In the event that wound care is inadvertently delayed, bacteria may proliferate to levels that result in infection. In selected patients, supervised wound care by an emergency nurse practitioner (ENP) can safely eliminate this delay in treatment. During their graduate training in the University of Virginia Nursing School, the ENPs are instructed to treat traumatic wounds with physician supervision. The criteria for patient selection and care are outlined in comprehensive guidelines reported herein. The bases for these treatment guidelines were clinical and experimental studies conducted at our medical center which examined the influence of various therapeutic decisions on the ultimate fate of the wound.

Asepsis