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Biomedical subjects

W White

Publications and source records attributed to W White.

At least 37 records · Page 2Linked to original sources

Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.

The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.

Adult↗

The effect of glycopyrrolate premedication on postoperative sore throat.

Patients given general endotracheal anesthesia commonly experience postoperative sore throat and/or hoarseness. Our study examined whether the occurrence of postoperative sore throat was associated with the use of a glycopyrrolate premedication and found that it was. We randomly assigned 120 patients undergoing general endotracheal anesthesia for routine surgery to receive a preoperative mediation including or excluding glycopyrrolate. We controlled for factors known to increase the risk of a postoperative sore throat. After surgery, an interviewer, unaware of the subject's group assignment, questioned each subject about the presence of a sore throat and, if present, asked the patient to rate its severity. We found that patients who did not receive preoperative glycopyrrolate were significantly less likely to report having a sore throat or reported having a less severe sore throat than patients who did receive glycopyrrolate.

Adjuvants, Anesthesia↗

Clinical evaluation of continuous noninvasive blood pressure monitoring: accuracy and tracking capabilities.

A continuous, noninvasive device for blood pressure measurement using pulse transit time has been recently introduced. We compared blood pressure measurement determined using this device with simultaneous invasive blood pressure measurements in 35 patients undergoing general endotracheal anesthesia. Data were analyzed for accuracy and tracking ability of the noninvasive technique, and for frequency of unavailable pressure measurements by each method. A total of 25,133 measurements of systolic pressure, diastolic pressure, and mean arterial pressure (MAP) by each method were collected for comparison from 35 patients. Accuracy was expressed by reporting mean bias (invasive pressure minus noninvasive pressure) and limits of agreement between the two measurements. After correction for the offset found when measuring invasive and oscillometric methods of arterial pressure measurement, the mean biases for systolic, diastolic, and mean pressures by the pulse wave method were -0.37 mm Hg, -0.01 mm Hg, and -0.05 mm Hg, respectively (p < 0.001). The limits of agreement were: -29.0 to 28.2 mm Hg, -14.9 to 14.8 mm Hg, and -19.1 to 19.0 mm Hg, respectively (95% confidence intervals). When blood pressure measured invasively changed over time by more than 10 mm Hg, the noninvasive technique accurately tracked the direction of change 67% of the time. During the entire study, 3.2% of the invasive measurements were unavailable and 12.9% of the noninvasive measurements were unavailable. The continuous noninvasive monitoring technique is not of sufficient accuracy to replace direct invasive measurement of arterial blood pressure, owing to relatively wide limits of agreement between the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Determination↗

Two meals promote entrainment of rat food-anticipatory and rest-activity rhythms.

Ten female rats were fed early and late in the dark period of a 12-12 h light-dark cycle and then were fed at the same times in constant darkness. In both conditions rats were active prior to mealtimes and manifested no free-running components of activity. When the rats were placed in constant darkness and either were fed early and late in the inactive period, or had free access to food, six of the rats had rest-activity rhythms different from 24.0 h. Though a masking explanation could not be ruled out, two meals during the active period apparently entrained the rest-activity rhythms of these rats. The light-entrainable oscillator appears to integrate information from cycles of both illumination and food availability. Multiple sources of temporal information may promote more stable entrainment of the rest-activity rhythm than the light-dark cycle alone, especially in a burrow dwelling organism, like the rat, that can be exposed to inconsistent light-dark transitions.

Animals↗

The structure of the large subunit rRNA expressed in blood stages of Plasmodium falciparum.

Here we present the sequence of the large subunit (LSU) rRNA expressed in blood-stage forms (and therefore A-type) of the malaria parasite, Plasmodium falciparum, from two different isolates. We determined the genomic sequence of a rRNA unit of the CAMP parasite strain from within the internal transcribed spacer 1 (ITS1) through the 5.8S rRNA gene, the ITS2 and the entire large subunit rRNA gene. We have also determined the corresponding sequence of the gene of the FVO strain by sequencing cDNA clones derived from blood-stage asexual parasites. Differences between the two were due to scattered point mutations in expansion segments of the mature rRNA regions. In addition to the point mutations, the rRNA genes from the two strains could be distinguished by the presence of a more complex polymorphism near the 3' end of the molecule. The most complex polymorphic form was localized on a single chromosome and found in only a subset of geographically distinct isolates. The sequences of the 5.8S rRNA unit and the LSU rRNA unit reported here can be logically assembled into a complete secondary structure which conforms to the standard structure conserved in all eukaryotic ribosomes. The construction of a model of secondary structure for the LSU rRNA has allowed the identification of phylogenetically conserved sequences involved in drug interaction with the ribosome, as well as those sequences involved in tertiary interactions within the rRNA itself.

Animals↗

Acute regional myocardial ischemia and recovery after cardiopulmonary bypass: effects of intensity of antecedent ischemia.

Aortic cross-clamping with inadequate myocardial preservation has been shown to cause postoperative decreases in myocardial performance following coronary artery bypass graft surgery. We have demonstrated a mild decrement in myocardial beta-receptor function associated with cold cardioplegia in a normal animal model; in normal human hearts, however, response to beta-adrenergic inotropic stimulation was diminished significantly. Beta-receptor dysfunction also is associated with chronic myocardial ischemia that is associated with severe ischemic heart disease. Although the change in beta-receptor function with acute regional myocardial ischemia associated with severe ischemic heart disease is not understood fully, we found that the intensity of regional ischemia significantly affects functional recovery after cardiopulmonary bypass (CPB). Myocardial stunning does not appear to be significant in this dysfunction; however, alterations in beta-receptor density and function may play a critical role in post-CPB ventricular function.

Animals↗

Depression in male and female patients undergoing cardiac surgery.

The present longitudinal study was designed to determine the prevalence of depression in male and female patients undergoing cardiac surgery, and to examine what factors are associated with depression before and after surgery. One day prior to surgery (T1), and one day prior to discharge from the hospital (T2), 141 patients completed a psychometric test battery including the Center for Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety Inventory (STAI), and the Perceived Social Support Scale (PSSS). Data were also collected on 13 physiological measures. Forty-seven per cent of patients were depressed (defined as a score of 16 or above on the CES-D) at T1. Scores on the CES-D significantly increased from T1 (M = 15) to T2 (M = 20), with 61 per cent of patients classified as depressed at T2. Factors associated with depression at T1 were female gender, higher state anxiety, and less social support. Depressed patients at T2 were characterized by higher scores on the STAI at T2 and higher scores on the CES-D at T1. The prevalence of depression in cardiac surgery patients, particularly women, may be underrecognized and warrants increased attention.

Adult↗

The Mini Mental State Exam as a predictor of neuropsychological functioning after cardiac surgery.

OBJECTIVE: The present longitudinal study was designed to: 1) determine the ability of the Mini Mental State Exam (MMSE) to predict neuropsychologic impairment based on neuropsychologic testing five to seven days and six weeks after cardiac surgery; and 2) to determine whether the traditional or the education-related MMSE norms are more appropriate to use for this purpose. METHOD: The day before surgery (T1), before hospital discharge (T2), and six weeks after surgery (T3), 247 subjects completed a battery of five neuropsychologic tests. Subjects also completed the Center for Epidemiological Studies Depression Scale and the Speilberger State-Trait Anxiety Inventory. Subjects completed the MMSE two to three days after surgery. RESULTS: Stepwise regression analyses revealed that the MMSE significantly predicted only a small portion of the variance in neuropsychologic test performance at T2, and to an even lesser extent at T3, over and above the demographic variables. In assessing the association between an impairment score (derived from the neuropsychologic test battery) and the MMSE, we found that the traditional MMSE cut-off score maximized specificity (number of true negatives) while the education-adjusted MMSE cut-off scores maximized sensitivity (number of true positives). CONCLUSIONS: These results suggest that although the MMSE is widely used to assess cognitive mental status, it may have limited value in identifying patients with cognitive impairment post-cardiac surgery, and special attention must be paid to the cut-off scores used in interpreting the MMSE.

Adult↗

Possible mechanisms accounting for the growth factor independence of hematopoietic progenitors from umbilical cord blood.

Hematopoietic progenitors obtained from the bone marrow of healthy adults fail to undergo clonogenic maturation in vitro if a source of hematopoietic growth factors is not included in the culture dishes. In contrast, a fraction of similarly purified progenitors obtained from umbilical cord blood undergo clonogenic maturation even in the absence of added growth factors. We postulated that production of hematopoietic growth factors within the culture dishes containing the progenitors of umbilical cord blood origin might be responsible. We postulated further, that this production might be by non-progenitor cells co-plated along with the progenitors, or alternatively by CD34+ cells themselves, or by cells clonally derived from CD34+ cells. To test these possibilities we first assessed the effect of including in the cultures neutralizing antibody directed against various growth factors. Inclusion of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) and anti-interleukin-3 (IL-3) (but not anti-IL-2) significantly reduced the growth factor independence of cord blood progenitors (P < .005 and P < .01). Inclusion of both anti-GM-CSF and anti-IL-3 almost completely ablated the spontaneous colony growth (P < .001). Inclusion of IL-10 also reduced, in a concentration-dependent fashion, the spontaneous generation of umbilical cord blood-derived colonies. Transcripts for GM-CSF and IL-3 were detected, by reverse transcriptase-polymerase chain reaction (RT-PCR), in the CD34+ cells from cord blood and from adult marrow. When plated without added growth factors, however, the CD34+ cells of adult marrow origin failed to produce colonies, whereas 6% of cord blood CD34+ cells similarly cultured did so. When these growth factor independent colonies were plucked from culture, transcripts for GM-CSF and IL-3 were identified in all. We conclude that production of GM-CSF and IL-3 occurs within culture dishes containing hematopoietic progenitors of umbilical cord origin, and that this explains some of their apparently unique features of in vitro growth.

Adult↗

Measurement of long-term hemodynamic changes and the use of 24-hour blood pressure monitoring to evaluate treatment.

Hemodynamic studies at rest as well as during exercise are useful for profiling the hemodynamic derangements in essential hypertension and for evaluating the changes produced by antihypertensive therapy. Modern, lightweight, 24-hour ambulatory blood pressure monitoring devices can provide useful information in understanding circadian variation of blood pressure, and also in evaluating blood pressure control over 24 hours. We have studied in > 400 patients the hemodynamic profiles of most of the commonly used antihypertensive agents. Results from our study of amlodipine, a novel calcium antagonist, are presented as an example. Nineteen patients with mild-to-moderate essential hypertension underwent invasive hemodynamic studies while at rest, supine, and sitting, and during 50, 100, and 150 W bicycle exercise in the sitting position. Systolic, diastolic, and mean arterial blood pressure decreased 16% (p < 0.01) at rest and during exercise, and total peripheral resistance was reduced 18%. Blood pressure during the daytime and during sleep was reduced approximately 16%. The reductions in systolic and diastolic pressures were similar. There were no significant changes in heart rate or cardiac output. Amlodipine was well tolerated. Two patients developed ankle edema, which disappeared when the dose was reduced, and in 1 patient the drug was withdrawn because of nondrug-related side effects.

Adult↗

Neuronal activity in rabbit neostriatum during classical eyelid conditioning.

Extracellular multiple- and single-unit recordings were made from the neostriatum of rabbits during classical eyelid conditioning. Neostriatal neurons processed information regarding the conditioned auditory stimulus (CS) and conditioned eyelid response (CR) as well as the unconditioned stimulus/response (US/UR). These data are consistent with previous reports that neostriatal neurons respond to movement and movement-related sensory stimuli. In most cases, neostriatal neurons increased activity to the US during the early phase of training, but to the CR as training progressed. A close temporal correlation was found between neuronal activity and CR onset with unit discharges typically preceding CR onset by 10-50 ms. The activity of some multiple and single units was monitored after injection of haloperidol, a neuroleptic and dopamine antagonist known to disrupt neostriatal function. Interestingly, haloperidol caused a greater disruption of CRs at low-intensity than at high-intensity CSs, but conditioning-related neuronal activity was disrupted equally at both intensities. These data are discussed in terms of a possible role for the neostriatum in eyelid conditioning.

Animals↗

Two meals in the active period of the rat both entrain food-anticipatory activity.

We examined the effect of presenting two meals at fixed times on the activity of six intact female rats. Rats maintained on a 12-12 h light-dark cycle were fed: ad lib, at two randomly chosen times during the active period, and at 3 and 9 h, 1 and 7 h, and 5 and 11 h after light offset. During ad lib and random feeding conditions, wheel turning primarily occurred during the first half of the active period. During fixed-time feeding conditions, wheel turning was concentrated around the times of meal availability. To determine whether anticipatory wheel turning during fixed-time feeding conditions was based on a circadian mechanism, each condition was followed by a test: light cues omitted and rats were deprived of food for 2 consecutive days. Wheel turning patterns observed while a feeding condition was in effect persisted during meal omission. Nest and food/water compartment visits were not as sensitive to feeding times. Meals may have modified bouts of activity that are also synchronized by light-dark cycles.

Animals↗

Sclerosing sweat duct carcinoma in an 11-year-old boy.

BACKGROUND: Sclerosing sweat duct carcinoma, or microcystic adnexal carcinoma, is a rare neoplasm of the skin with both pilar and eccrine differentiation. Previously this neoplasm has been reported only in adults. We describe a case of sclerosing sweat duct carcinoma in an 11-year-old white male. OBJECTIVE: Description of Mohs surgical procedure for successful management of sclerosing sweat duct carcinoma in a child. METHODS: Mohs micrographic surgery was performed on this rare neoplasm. RESULTS: The described procedure resulted in successful excision of this uncommon neoplasm. CONCLUSION: We present a case of sclerosing sweat duct carcinoma, an unusual cutaneous neoplasm, in an 11-year-old male that was successfully managed using Mohs micrographic surgery.

Carcinoma, Skin Appendage↗

met and HGF-SF in normal melanocytes and melanoma cells.

HGF-SF stimulates the proliferation of normal human melanocytes in the presence of synergistic factors, one of which is bFGF, and promotes motility and expression of high levels of tyrosinase activity and melanin content. Melanocytes from a recurrent blue nevus were also stimulated by HGF-SF, whereas cells from advanced primary and metastatic lesions either did not respond, were only slightly stimulated or, in one case, were inhibited. Signal transduction was mediated by tyrosyl-phosphorylation of met and several other proteins, including MAP kinase/ERK2. Met expression and phosphorylation in response to HGF-SF was normal in human melanoma cells, and HGF-SF-transduced mouse melanocytes were not tumorigenic. Taken together, the results show that met is not constitutively active in human melanomas and that its activation by an autocrine loop is not sufficient to confer the tumorigenic phenotype. They raise the possibility that exogenous HGF-SF may play a role at early stages of malignant conversion by acting synergistically with bFGF and by promoting the dispersion of factor-dependent cells to ectopic sites.

Animals↗

Decay-accelerating factor expression on either effector or target cells inhibits cytotoxicity by human natural killer cells.

Previous studies have shown that freshly isolated CD16+ NK cells are deficient in the expression of decay-accelerating factor (DAF), or CD55, a membrane regulator of C3 activation. In this study we investigated the significance, for NK cell-mediated lysis, of DAF expression on the target and effector cells. The effect of DAF expression on the susceptibility of NK cell targets was investigated by several means: first, DAF- cell lines were cloned from K562; second, the cloned DAF- cells were reconstituted with exogenous purified DAF; and third, anti-DAF F(ab')2 was used to block DAF function on the DAF+ K562 cells. Consistently, the presence of DAF in the target cell membrane, either naturally occurring or experimentally incorporated, afforded the target cell protection against lysis, and this protection could be blocked with anti-DAF. Similarly, targets for antibody-dependent cell-mediated cytotoxicity with exogenous DAF incorporated in their plasma membrane became less sensitive to antibody-dependent cell-mediated cytotoxicity by NK cells compared with the same target cells without incorporated DAF in their membranes. DAF incorporated in the plasma membranes of the effector NK cells made the NK cells less effective at killing K562 targets. The known function of DAF is to regulate C3 activation, and we were able to demonstrate that the isolated NK cell is capable of releasing C3. It is also possible that the participation of DAF in NK cell function represents a new, noncomplement-dependent function for DAF.

Antibody-Dependent Cell Cytotoxicity↗

Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

Haemodynamic responses at rest and during exercise were studied in 18 patients with essential hypertension following long-term treatment with amlodipine. Patients underwent a 2-week placebo run-in period followed by a mean duration of 11 months' treatment with amlodipine 5-10 mg (mean dose 9 mg) once daily. Blood pressure was measured intra-arterially, cardiac output by dye dilution and heart rate by electrocardiogram. Amlodipine produced a mean reduction in systolic and diastolic arterial pressure of 27 and 16 mm Hg, respectively, at rest and after exercise. At rest sitting, mean systolic and diastolic arterial pressures were reduced by 16 and 14% (p less than 0.01), respectively, from initial mean values of 182.4/111.2 mm Hg. This reduction in blood pressure was associated with a marked reduction in the total peripheral resistance index of 19% (p less than 0.001). Similar responses were observed at rest supine and during exercise. No significant changes were seen in heart rate. Stroke index showed a small increase at rest and during exercise together with a trend towards an increase in cardiac index after treatment with amlodipine. Ambulatory blood pressure monitoring was carried out in 10 patients after the placebo run-in and at the end of the study. Amlodipine showed effective blood pressure control throughout the 24 h after one daily dose. The incidence of side effects was low (ankle oedema in 2 patients).

Adult↗