10 keys to quality care.
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Data Collection↗
Biomedical subjects
D Berry
Publications and source records attributed to D Berry.
Evidence against oppositional and pharmacokinetic mechanisms of tolerance to diazepam's sedative effects.
Acute administration of diazepam (2 mg/kg i.p.) to rats decreased the number of head-dips, locomotor activity and the number of rears made in the holeboard apparatus, indicating sedative effects. After daily treatment for 7 days with diazepam (2 mg/kg) tolerance developed to all these behavioural effects, despite serum concentrations of diazepam and N-desmethyldiazepam significantly higher than those following acute treatment. After 7 drug-free recovery days the rats were quite unresponsive to a probe dose of diazepam (2 mg/kg) and although there was a gradual recovery of responsiveness to diazepam, the reduction in rears still did not reach the level of the acute group even after 21 drug-free days. There was evidence for pharmacokinetic changes when probe doses of diazepam were given after 7, 14 or 21 recovery days. Lower levels of diazepam and higher levels of N-desmethyldiazepam than following an acute dose to the drug-naïve group were detected, indicating that the chronic treatment had resulted in a persistently enhanced rate of N-demethylation. It is argued that these changes do not fully account for the reduced responsiveness to the probe doses, and nor can they account for the gradual return of response over the 3-week recovery period. There were no detectable scrum concentrations of either compound 24 h after the end of the chronic treatment. However, no rebound increases in behavioural responses were detected at any time-point in withdrawal. Thus, the mechanism underlying this behavioural tolerance was not oppositional in nature. It is suggested that a situation-independent learned behavioural strategy is the most likely mechanism for the observed tolerance.
Animals↗
Where have all the nurses gone? Final results of our Patient Care Survey.
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Adult↗
Multiple small bowel perforations in a patient on treatment of tuberculosis.
Perforation and obstruction of the small intestine are well recognized in cases of ulcero-constrictive gastro-intestinal tuberculosis and at the commencement of anti-tuberculous chemotherapy. We present a case of two metachronous perforations in a patient despite established anti-tuberculous treatment.
Adult↗
Reverse transcription-polymerase chain reaction detection of collagen transcripts in healing human wounds.
The aim of this study was to analyse the expression of COl1A1, COl1A2 and COl3A1 in 6 mm diameter punch biopsies obtained from human wounds. Total RNA was isolated from biopsies taken from Sacrococcygeal pilonidal sinus excision cavities at weekly intervals between surgery and clinical closure. cDNAs were generated from the RNA using reverse transcriptase and polymerase chain reaction (PCR) amplifications performed with oligonucleotide primer pairs specific for regions of the COl1A1, COl1A2 and COl3A1 genes. The expression of these three genes was demonstrated throughout the course of healing on 36 biopsies taken from nine patients between surgery and clinical closure. Amplification bands demonstrated on cDNAs generated from 6 mm diameter biopsies were comparable in intensity and specificity with those generated from 50 mg excised scar tissue and cultured fibroblasts. The RT-PCR technique described here allows the rapid 'routine' detection of specific gene expression in 6 mm biopsies obtained from healing wounds.
Biopsy↗
Amonafide: An active agent in the treatment of previously untreated advanced breast cancer--a cancer and leukemia group B study (CALGB 8642).
Amonafide is a new imide derivative of naphthalic acid. The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials. The drug is extensively metabolized and detected in plasma and urine. Its toxicity has previously been correlated to the formation of an active metabolite, N-acetyl-amonafide. Amonafide was chosen for inclusion in the Cancer and Leukemia Group B (CALGB) master metastatic breast cancer protocol. CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil, or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil. The end point of CALGB 8642 is to assess the difference in survival, toxicity, and overall response when limited exposure to Phase II agents precedes standard chemotherapy. This report deals only with amonafide as a Phase II agent. Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed. Patients had to have histologically documented measurable breast cancer and a performance status of 0-1. Patients could not have had prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy was permitted. Patients could not have visceral crisis. Amonafide was given at 300 mg/m2/day i.v. for 5 days, and repeated at 21-day intervals for a maximum of four cycles. Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof. Toxicity was primarily hematological and bimodal: 32% had grade 3 or 4 leukopenia and 24% had grade 3 or 4 thrombocytopenia; 22% had no leukopenia and 44% had no thrombocytopenia. The response rate was 18%, including one complete response. When response was analyzed by hematological toxicity, there was a 35.7% response if patients had leukopenia grade 3/4 (versus 8.3%, P = 0.08). There was a 50% response if patients had thrombocytopenia grade 3/4 (versus 7.1%, P = <0.01). We conclude that amonafide is somewhat active in previously untreated breast cancer patients. There may be a steep dose-response curve, based on the significant correlation between myelosuppression and response. Rates of responses in patients adequately dosed (i.e., with significant hematotoxicity) with amonafide ranged from 35 to 50%. Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping.
Adenine↗
Charnley low-friction arthroplasty of the hip. Twenty-year results with cement.
The first 333 Charnley (Thackray, United Kingdom) total hip arthroplasties performed at the Mayo Clinic between 1969 and 1970 have been followed since that time. One hundred twelve patients (112 hips) remain alive at 20 years. Clinical results remain excellent. The Mayo clinical and roentgenographic hip scoring system rates the results as good to excellent in 39 of 69 hips (with all necessary data to calculate the entire score), fair in 13 hips, and poor in 17 hips. The clinical score alone showed satisfactory results in 77 of 112 hips. Some clinical deterioration was attributed to the advancing age of the patients (mean age at final follow-up evaluation, 84 years). Probable roentgenographic loosening (component migration, complete bone-cement interface, radiolucent line greater than 1 mm, cement fracture) was noted in 12 of 69 acetabular components (17%) and 28 of 69 femoral components (36%). Two patients had required revision since the last report at 15 years for a total of 38 patients (32 revised, 4 Girdlestone arthroplasties, 2 stem fractures not yet revised). The probability of surviving 20 years without revision of the components was 84% (83% for men, 85% for women). The rates of loosening, revision, and failure (revision, Girdlestone, or symptomatic loosening) remain linear over 20 years of follow-up evaluation. If the probability of revision is based on patient age at the time of the initial total hip arthroplasty, there is a significantly increased probability of revision in those patients less than 59 years of age (27%) compared to those 59-65 years of age (13%), 65-70 years (7.5%), and over 70 years (12%).
Aged↗
Analysis of vocal disorders with methods from nonlinear dynamics.
Several authors have recently demonstrated the intimate relationship between nonlinear dynamics and observations in vocal fold vibration (Herzel, 1993; Mende, Herzel, & Wermke, 1990; Titze, Baken, & Herzel, 1993). The aim of this paper is to analyze vocal disorders from a nonlinear dynamics point of view. Basic concepts and analysis techniques from nonlinear dynamics are reviewed and related to voice. The voices of several patients with vocal disorders are analyzed using traditional voice analysis techniques and methods from nonlinear dynamics. The two methods are shown to complement each other in many ways. Likely physiological mechanisms of the observed nonlinear phenomena are presented, and it is shown how much of the terminology in the literature describing rough voice can be unified within the framework of nonlinear dynamics.
Electroencephalography↗
Overexpression of p53 and HER-2/neu proteins as prognostic markers in early stage breast cancer.
OBJECTIVE: Overexpression of the p53 and HER-2/neu oncogenes are the two most common genetic abnormalities associated with breast cancer. Shorter survival time has been reported in patients with tumors with p53 or HER-2/neu. This report analyzes a retrospective cohort of early stage breast cancers for both oncogenes and relates overexpression to clinicopathologic parameters and survival. METHODS: Immunostaining for p53 and HER-2/neu was performed on 230 paraffin-embedded specimens of stage I and II breast cancers diagnosed and treated at Duke University Medical Center between 1984 and 1987. Positive staining for both p53 and HER-2/neu in paraffin-embedded tissues indicates an underlying genetic abnormality: point mutations in the p53 gene and amplification of the HER-2/neu gene. RESULTS: In this cohort of patients, 24% were positive for p53 and 17% for HER-2/neu. Four per cent were positive for both oncogenes. Significant correlations were found between p53 immunostaining and increasing tumor size, stage, and low estrogen and progesterone receptor contents. Univariate analysis showed that p53 and HER-2/neu were indicators of overall and failure-free survival. An additive effect on survival was observed in patients with both oncogene abnormalities. Nodal status, HER-2/neu, and p53 all attained independent prognostic value in a multivariate analysis. CONCLUSIONS: The p53 and HER-2/neu oncogenes have proven but limited prognostic value. An approach that combines several molecular genetic markers with established pathologic criteria may help physicians to make more accurate predictions of prognosis in patients with early stage breast cancer.
Biomarkers, Tumor↗
Mechanical lithotripsy.
Endoscopic lithotripsy is a procedure used for the removal of large stones in the common bile duct that cannot be removed after sphincterotomy. This procedure causes fragmentation of large stones, which allows easier retrieval of stones by other instruments such as balloons or baskets. There are currently two types of mechanical lithotripsy: one type uses an instrument called a mechanical lithotriptor, and the second type uses an electrohydraulic lithotriptor. This article focuses on mechanical lithotripsy. Since it is vital for the operator of this equipment to understand its function, assembly, disassembly, and maintenance, specific guidelines are provided.
Gallstones↗
Isolation and pharmacological characterization of a hamster urinary bladder neurokinin A receptor cDNA.
Functional cDNA clones for hamster neurokinin-2 receptor (NK-2R) were isolated from hamster urinary bladder using a polymerase chain reaction-based methodology. The hamster NK-2R consists of 384 amino acids with a relative molecular weight of 43,418. Hamster NK-2R shares significant amino acid sequence homology with other tachykinin receptors, particularly with rat, bovine, and human NK-2R (94.3, 84.4, and 86.5%, respectively). To examine the pharmacology of cloned hamster NK-2R, we transfected mouse erythroleukemia cells with this receptor, prepared high speed membranes, and studied the receptor properties utilizing the ligand [4,5-3H-Leu9]NKA in a receptor-binding assay. For pharmacological comparison, we also transfected the human NK-2R into mouse erythroleukemia cells. [3H]NKA bound to hamster NK-2R receptor in a protein-dependent, high affinity (Kd1 = 4.14 +/- 0.31 nM), saturable (Bmax1 = 679 +/- 26 fmol/mg of protein), and highly specific manner (89 +/- 2%). A smaller population (10% density) of lower affinity receptors (Kd2 = 150 +/- 92 nM), was also observed in competition experiments. [3H]NKA bound to the human receptor with significantly higher affinity and overall greater receptor density (Kd1 = 0.37 +/- 0.11 nM, Bmax1 = 234 +/- 175 fmol/mg of protein; Kd2 = 9.0 +/- 2 nM, Bmax2 = 1989 + 990 fmol/mg of protein). [3H]NKA binding to both hamster and human receptors was enhanced greatly by divalent cations, whereas GTP analogs weakly inhibited binding to hamster receptor, but potently inhibited binding to the human receptor. Competition experiments with agonists demonstrated binding to high and low affinity states of NK-2 receptors, with identical order of potency in hamster or human NK-2R; NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) >> substance P >>> Senktide. However, remarkable differences were observed in studies with selective NK-2 antagonists (hamster, SR48,968 > L659,877 > R396 >> MEN10,376 versus human, SR48,968 > MEN10,376 > L659,877 > R396). The rank order of antagonist affinity is consistent with the observations of NK-2 receptor pharmacology in the native tissues.
Amino Acid Sequence↗
A diterpene epoxide from the marine brown alga Dictyota sp.: possible vasopressin V1 receptor antagonist.
A novel epoxide, in addition to eight known diterpenes, has been isolated from a marine brown alga of the genus Dictyota. The structures of these compounds were established by the interpretation and comparison of spectral data with literature data. Most of the isolates demonstrated vasopressin receptor antagonist activity in vitro with the new epoxide being the most active of the diterpenes tested.
Animals↗
Conioidines A and B, novel DNA-interacting pyrrolidines from Chamaesaracha conioides.
Two novel pyrrolidine compounds, conioidines A [1] and B [2], have been isolated from the Texas plant, Chamaesaracha conioides (Solanaceae). Their structures were determined by spectroscopic methods and hydrolysis studies. Both natural products, like doxorubicin, showed DNA-specific KB cell cytotoxicity. Dose-response data indicated a Kd value of 2.8 microM for binding of conioidine A [1] to calf thymus DNA.
Animals↗
Psychosocial and toxicological profile of drug misuse in male army conscripts in Kuwait.
The pattern of drug use among 2183 young Kuwaiti conscripts was studied using the Drug Abuse Screening Test (DAST) and urine analysis. Drug misuse rates were low, compared with similar set-ups elsewhere as independently confirmed by urine test (0.7% amphetamine and 2.8% other street drugs; alcohol was not detected in this sample) and self-report (7.9% on DAST). This may be attributed to the influence of the Islamic traditions on lifestyles. Significant correlations were seen between self-report of multiple drug use and positive urine results for both amphetamine and other street drugs, while positive urine amphetamine was associated with families seeking help for treatment, problems with family and/or work and having or being hospitalized for drug-related medical problems. Amphetamine as the major identified individual misused drug was significantly associated with older age group but negatively correlated with marital status, higher education and employment. The discrepancy between self-report of drug misuse-related problems and objective proof of this may reflect the inappropriateness of some of DAST items to this sample, culturally desired responses or both.
Adolescent↗
Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides.
To better define thrombin-receptor interactions, we synthesized human thrombin peptides and identified binding-domain peptides that bind thrombin receptors and activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H. Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with a single topical application of thrombin receptor-activating peptide (TRAP-508) or human alpha-thrombin in saline enhances 7-d incisional breaking strength in normal rats up to 82% or 55% over saline-treated controls, respectively. Control wounds require approximately 11.5 d to achieve breaking strength equivalent to TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates healing, shifting the time course forward by up to 4.5 d. Histological comparisons at day 7 show more type I collagen, less evidence of prolonged inflammation, and an increase in number and maturity of capillaries in TRAP- and thrombin-treated incisions. Angiograms also show 50-65% more functional vascularization going across thrombin- and TRAP-treated surgical incisions. Thus, alpha-thrombin and thrombin peptides, such as those released following injury, appear to initiate or enhance signals required for neovascularization and wound healing. The ability to accelerate normal wound healing events with synthetic peptides representing receptor binding domains of human thrombin may offer new options for management of wound healing in man.
Amino Acid Sequence↗
Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro.
The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575 -Arg-Gly-Asp-Ser- and Fg-gamma 400-411 -HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1 microM [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, Ki 2.9 +/- 1.9 microM (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, Ki 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S-[Cys-(N alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (Ki 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4 microM dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists.
Amino Acid Sequence↗
Implicit and explicit knowledge bases in artificial grammar learning.
Two experiments examined the claim for distinct implicit and explicit learning modes in the artificial grammar-learning task (Reber, 1967, 1989). Subjects initially attempted to memorize strings of letters generated by a finite-state grammar and then classified new grammatical and nongrammatical strings. Experiment 1 showed that subjects' assessment of isolated parts of strings was sufficient to account for their classification performance but that the rules elicited in free report were not sufficient. Experiment 2 showed that performing a concurrent random number generation task under different priorities interfered with free report and classification performance equally. Furthermore, giving different groups of subjects incidental or intentional learning instructions did not affect classification or free report.
Adult↗
Leakage of macromolecules in ventilated and unventilated segments of preterm lamb lungs.
The movement of macromolecules into and out of unventilated lung segments was evaluated in prematurely delivered and ventilated lambs. Seven lambs at 130 days gestational age had a bronchial balloon placed at birth before the first breath to obstruct the left lower lobe. Surfactant and 131I-albumin were instilled into the left lower lobe while surfactant and 125I-albumin were instilled into the remaining lung, and 70,000 molecular weight [3H]dextran was given into the vascular space at birth. Twenty-five percent of the lung by weight was not ventilated, and 24% of the total leak of dextran from the vascular space was recovered in the unventilated lungs at 3 h. An epithelial leak of protein from the two lung regions was documented by the loss of 11.4 and 18.4% of the labeled albumins in the nonventilated and ventilated lung regions, the appearance of 4.9 and 7.5% of the airway-instilled albumin in the vascular space from the nonventilated and ventilated lung regions, and the recovery of the labeled albumins in the carcasses of the lambs. The bidirectional flux of macromolecules was larger in the ventilated than in the nonventilated lung regions, indicating that ventilation can increase the leak of protein in the preterm lung. The lung areas that were never exposed to ventilation or oxygen also demonstrated a large bidirectional flux of macromolecules, a finding not present in the fetus, fullterm newborn, or adult. These findings indicate that ventilation is not solely responsible for the increased protein leak found in preterm lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
Albumins↗