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Biomedical subjects

A Fisher

Publications and source records attributed to A Fisher.

At least 163 records · Page 9Linked to original sources

Cardiac surgery: moving away from intensive care.

OBJECTIVE: To evaluate outcome in patients managed outside an intensive care unit after open heart surgery. BACKGROUND: The high cost of cardiac surgery is mainly due to the needs of traditional postoperative care. The requirements for intensive care and treatment has decreased with improvements in techniques of cardiac surgery and anaesthesia. In this setting the need to continue to depend on intensive care units for the recovery of cardiac surgical patients is questionable on clinical and economic grounds. DESIGN: Postoperative outcome in 245 patients over a four month period was studied prospectively. PATIENTS: Mean age of the patients was 63.2 years. They underwent a wide variety of operative procedures. Ninety percent of them recovered in a dedicated three bed cardiac surgical recovery area where the management protocol led to rapid extubation and step down in dependency care. RESULTS: Median time for ventilatory support was 90 minutes after transfer to the area. Only five patients were subsequently admitted to the general intensive care unit for prolonged respiratory and cardiac support. Ten patients were electively admitted to the general intensive care unit. Two deaths occurred in hospital in this group (0.8%). Four patients were ventilated for 24 hours in the recovery area itself and made an uncomplicated recovery. CONCLUSION: This study confirms that over 90% of patients undergoing cardiac surgery would recover safely and be treated effectively in a more economical area than intensive care.

Adult↗

Propofol to provide sedation after coronary artery bypass surgery. A comparison of two fixed rate infusion regimens.

Propofol (2,6, di-isopropylphenol) was given by continuous intravenous infusion to provide sedation following coronary artery bypass surgery. The need for additional sedation, analgesia and hypotensive agents was assessed at two propofol infusion rates (10 or 25 micrograms/kg/min). Both rates provided clinically satisfactory conditions. There were no differences in the requirements for analgesia or vasodilators between the groups. The higher infusion rate of 25 micrograms/kg/min was associated with a lower requirement for additional sedation but a more frequent need to stop the infusion temporarily to prevent hypotension.

Adult↗

Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family.

A new human cyclin, named cyclin E, was isolated by complementation of a triple cln deletion in S. cerevisiae. Cyclin E showed genetic interactions with the CDC28 gene, suggesting that it functioned at START by interacting with the CDC28 protein. Two human genes were identified that could interact with cyclin E to perform START in yeast containing a cdc28 mutation. One was CDC2-HS, and the second was the human homolog of Xenopus CDK2. Cyclin E produced in E. coli bound and activated the CDC2 protein in extracts from human G1 cells, and antibodies against cyclin E immunoprecipitated a histone H1 kinase from HeLa cells. The interactions between cyclin E and CDC2, or CDK2, may be important at the G1 to S transition in human cells.

Amino Acid Sequence↗

Culture conditions dictate whether mouse fetal thymus lobes generate predominantly gamma/delta or alpha/beta T cells.

Thymus lobes from 14 day-old mouse embryos cultured submerged in r-IL-2 generated a mixture of CD8 alpha+/CD4- and CD8-/CD4- gamma delta TcR expressing cells (Ceredig et. al. 1989). Based upon Northern analysis with TcR constant region probes, no alpha beta T cells could be identified in these cultures. Submerged lobes also showed responsiveness to IL-7. In contrast, when cultured at an air liquid interface as organ cultures (OC), most cells appeared to express alpha beta TcR (Ceredig 1988). Thus depending on the mode of culture, fetal thymus lobes generate predominantly gamma delta or alpha beta T cells; it is unclear how this difference is regulated. Previous phenotypic and functional experiments suggested that gamma delta T cells may be present in OC. In order to study gamma delta T cells in both submerged lobe and OC, we have carried out three colour flow microfluorimetric analysis of gamma delta TcR, abTcR, CD3, J11d and CD8 beta expression by subpopulations of CD8 alpha and CD4 defined thymocytes. In addition, using V gamma-specific oligonucleotides and the polymerase chain reaction, we have begun identifying and sequencing the V gamma repertoire of gamma delta T cells in these mouse fetal thymus cultures.

Animals↗

Evaluation of a "do not resuscitate" policy in intensive care.

The decision to withhold cardiopulmonary resuscitation from a patient within an intensive care unit (ICU) may be a difficult but appropriate one for which there are few guidelines. We describe the formulation of a Do Not Resuscitate (DNR) policy in our multidisciplinary ICU. To evaluate the effect of implementation of the DNR policy on physician practice and on communication among physicians, nurses, patients and their families, we interviewed physicians and nurses caring for patients designated DNR before (n = 8) and after (n = 17) implementation of the DNR policy. We found that DNR orders in the ICU were not infrequent (2-3 per week). All patients designated DNR were either irreversibly ill or not responsive to maximal therapy, and 22 of 25 were not competent. The DNR order was not accompanied by withdrawal of other therapy in 50% of cases and one patient recovered and was discharged from hospital. The implementation of the DNR policy encouraged greater physician consultation with other physicians, patients and their families. Although there were differences in perception of communication between physicians and nurses, we believe that the DNR policy influenced physician practice and enhanced overall communication in the ICU.

Age Factors↗

Postoperative arrhythmias and risk factors after open heart surgery.

Cardiac arrhythmias were recorded during 24 hours in 40 consecutive patients requiring open-heart surgery, using continuous Holter monitoring. Most patients developed both supraventricular and ventricular arrhythmias. Complex ventricular arrhythmias were detected in 31 patients (78%) and 2 patients suffered an immediate postoperative myocardial infarction. The following risk factors were considered: age, sex, type of heart disease, preoperative left ventricular ejection fraction, cardiopulmonary bypass and aortic clamping duration, length of anesthesia, dopamine administration, and maximal level of CK and CK-MB. Only dopamine administration, even in low renal dose, was associated with the number and severity of ventricular arrhythmias.

Adult↗

Communicating the risk from radon.

A prominent television station developed a special series of newscasts and public service announcements about radon. This was combined with their advertising of the availability of reduced-price radon test kits in a local supermarket chain. The large number of test kits sold was a success from a marketing perspective, but not from a public health perspective--especially because of the very small share of high readings that were mitigated. In contrast, a study of housing sales showed a much higher testing rate and corresponding mitigation when risk communication accompanied the housing transaction, rather than being directed toward the general public. This paper examines the relative effectiveness of these alternative approaches to radon risk communication, emphasizing the implications for developing and implementing radon programs.

Communication↗

Human immunodeficiency virus infection in North American women: experience with 200 cases and a review of the literature.

This study was designed to define the epidemiology and natural history of human immunodeficiency virus (HIV) infection in women in Rhode Island. Two hundred women referred to Brown University physicians from 1986 through 1990 were evaluated at 3-to-6-month intervals for 12 to 60 months. All received antiretroviral therapy and prophylaxis against opportunistic infections when indicated on the basis of CD4 lymphocyte counts. Major findings included: 1) rapid shift of dominant mode of transmission from intravenous drug sharing to heterosexual route; 2) significant gender-specific differences in clinical presentation; 3) increased frequency of cervical dysplasia in women infected via intravenous needle sharing; 4) no definite gender-specific differences in progression of HIV infection; 5) enormous societal impact of HIV infection in women. Principal conclusions are: 1) rapid change to predominantly heterosexual HIV transmission can occur in North America, with serious societal impact; 2) gender-specific clinical features can lead to earlier diagnosis of HIV infection in women; 3) HIV infection in women does not pursue an inherently more rapid course than that observed in men.

Adolescent↗

Continuous postoperative regional analgesia by nerve sheath block for amputation surgery--a pilot study.

A pilot study of continuous postoperative regional analgesia by nerve sheath block for lower limb amputation is presented. At the time of exposure of sciatic or posterior tibial nerve trunks during above- or below-knee amputations in 11 patients with ASA physical status III or IV, a catheter was introduced directly into the transected nerve sheath for continuous infusion of 0.25% bupivacaine at a rate of 10 mL/h for 72 h. Effective amputation stump analgesia was obtained, significantly reducing the need for on-demand narcotic analgesics during this time to a mean dose equivalent of 1.4 mg of morphine compared with a retrospective control group who received the equivalent of a mean dose of 18.4 mg of morphine (P less than 0.0001). No complications related to the technique were observed. A follow-up of the group receiving continuous postoperative regional analgesia for up to 12 mo showed a total absence of phantom pain despite the presence of preoperative limb pain.

Aged↗

Pyocin typing of Pseudomonas aeruginosa isolates from children with cystic fibrosis.

Pyocin typing and serotyping of 433 strains of Pseudomonas aeruginosa from children with cystic fibrosis (CF) showed that pyocin type 9 was predominant, particularly in association with polyagglutinating serotype. The common pyocin groups, 1, 5 and 10, made up only 20% of these isolates in contrast to reported rates of up to 89% in other studies using non-CF strains. No strains of pyocin type 3 were found. Polyagglutinating strains made up 72% of strains from patients colonized with P. aeruginosa for more than 12 mths. Pyocin type 9 was associated with 93% of polyagglutinating strains. The parallel between pyocin type 9 and polyagglutinating serotype suggests that these may both be characteristics acquired by P. aeruginosa colonizing patients with CF. Because of confounding between duration of colonization and exposure to cross-infection, this study does not allow definition of the role of cross-infection in determining the characteristics of these strains in most patients. In siblings, however, evidence supports a role for cross-infection either between siblings or from a common source. In 6 pairs of siblings studied, each pair had at least 1 pyocin group in common concurrently, either at entry to the study or after an interval of several months. Identical and unusual pyocin groups were recognized in samples obtained on the same day from pairs of siblings. More studies are needed to compare results of pyocin typing with methods such as genome fingerprinting to characterize these strains and determine whether the observed distribution of pyocin groups in CF isolates is related to cross-infection or whether the combination of pyocin type 9 with polyagglutinating serotype is a characteristic of CF strains.

Adolescent↗

Evidence of paired M2 muscarinic receptors.

Binding assays involving various antagonists, including N-[3H] methylscopolamine, [3H]quinuclidinyl benzilate, AFDX-116, pirenzepine, and propylbenzilylcholine mustard, disclosed only a single population of M2 muscarinic receptors in membranes from the rat "brainstem" (medulla, pons, and colliculi). However, competition curves between N-[3H]methylscopolamine and various agonists, including oxotremorine, cis-dioxolane, and acetylethylcholine mustard, showed approximately equal numbers of guanine nucleotide-sensitive high affinity (H) sites and guanine nucleotide-insensitive low affinity (L) sites. This 50% H phenomenon persisted in different buffers, at different temperatures, after the number of receptors was halved (and, thus, the remaining receptor to guanine nucleotide-binding protein ratio was doubled), after membrane solubilization with digitonin, and when rabbit cardiac membranes were used instead of rat brainstem membranes. Preferential occupation of H sites with acetylethylcholine mustard, and of L sites with quinuclidinyl benzilate or either mustard, yielded residual free receptor populations showing predominantly L and H sites, respectively. Low concentrations of [3H]-oxotremorine-M labeled only H sites, and the Bmax for these sites was 49% of the Bmax found with [3H]quinuclidinyl benzilate plus guanine nucleotide. These and other results are most consistent with the idea that H and L receptor sites exist on separate but dimeric receptor molecules and with the hypothesis that only the H receptors cycle between high and low affinity, depending upon interactions between this receptor molecule and a guanine nucleotide-binding protein.

Animals↗

Appendectomy in primary and secondary staging operations for ovarian malignancy.

Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures.

Appendectomy↗

(+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine, an M1 selective cholinergic agonist, attenuates cognitive dysfunctions in an animal model of Alzheimer's disease.

AF102B [(+-)-cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine], a structurally rigid analog of acetylcholine, was investigated in a number of neurochemical, pharmacological and behavioral tests related to cholinergic functions. AF102B induced atropine-sensitive contractions of isolated guinea pig ilea and trachea preparations with EC50 values of 3.5 and 3 microM being 87- and 1.3-fold less potent than acetylcholine, respectively. Binding studies using the radioligands pirenzepine, cis-dioxolane and quinuclidinyl benzilate in rat cerebral cortex and quinuclidinyl benzilate in cerebellar homogenates indicated that AF102B was a potent and highly selective M1-type muscarinic probe, being more selective for M1 receptors than oxotremorine, carbachol and AF102A (the trans-isomer of AF102B). AF102B had a 3-fold higher apparent affinity for M1 receptors than the prototype M1 agonist, McN-A-343, cis- and trans-AF30 (other rigid analogs of acetylcholine). Treatment of rat cortical homogenates with Cu++ ions did not modify the affinity observed for the muscarinic antagonists atropine, scopolamine and pirenzepine, whereas increasing the proportion of high affinity sites for the agonists oxotremorine-M, carbachol and McN-A-343. The apparent affinity of AF102B also increased by Cu++ treatment suggesting that this compound interacts with rat cerebral cortex muscarinic receptors as an agonist. AF102B did not affect high affinity choline transport, choline acetyltransferase and acetylcholinesterase activities in rat brain preparations. In rats treated with AF64A (the cholinotoxin ethylcholine aziridinium ion; 3 nmol/2 microliters/side i.c.v.), AF102B (1 mg/kg p.o. or i.p.), AF102A (1 mg/kg i.p.), cis-AF30 (1 mg/kg, i.p.) and physostigmine (0.06 mg/kg i.p.), each reversed cognitive impairments in a step-through passive avoidance task. Both AF102B and AF102A (1 mg/kg i.p.), but not physostigmine (0.1 mg/kg i.p.), were effective also in reversing reference memory impairments in a Morris water maze test. Repetitive administrations of AF102B (0.2 mg/kg/day i.p.) improved AF64A-induced working memory deficits in the Morris water maze test, but did not affect open field behavior. The data show that the selective M1 agonist AF102B can restore AF64A-induced cognitive impairments, without producing adverse central and peripheral side effects at the effective doses and this can indicate its potential use for the treatment of Alzheimer's disease.

Alzheimer Disease↗

Hierarchical pattern of mucosal candida infections in HIV-seropositive women.

PURPOSE: Candida is the most common cause of opportunistic mucosal infections in human immunodeficiency virus (HIV)-positive women. We had observed an apparent correlation between the severity of immunodeficiency and the site of mucosal candida infection. The current study was designed to determine whether significant correlations existed between the sites of mucosal candida infection and the degree of immunodeficiency, as determined by subsets of lymphocyte populations. PATIENTS AND METHODS: The subjects in this study are 66 HIV-seropositive women evaluated by members of the Brown University Acquired Immunodeficiency Syndrome (AIDS) Program during the 3-year period, September 1, 1986, through August 30, 1989. All patients had thorough clinical evaluations and relevant laboratory studies at defined intervals. All patients with CD4 lymphocyte counts below 0.2 X 10(9)/L received zidovudine therapy as soon as it became available. After July 1988, all patients with CD4 counts below 0.2 X 10(9)/L received prophylaxis against Pneumocystis carinii pneumonia. All patients were counseled about HIV infection, its modes of transmission, and the early symptoms of opportunistic infections. RESULTS: The longitudinal data demonstrated that candida often infected vaginal mucosa when there was no significant reduction in CD4 lymphocyte counts. Candida infection of the oropharyngeal mucosa was associated with highly significant reductions in CD4 lymphocyte counts. Esophageal candidiasis occurred only with advanced immunodeficiency associated with CD4 counts below 0.1 X 10(9)/L. CONCLUSIONS: Candida mucosal infections occur in a hierarchical pattern in women with HIV infection. Determination of the basis for the differences in susceptibility to candida of the vaginal, oropharyngeal, and esophageal mucosal surfaces will require further studies.

Adolescent↗

Reversal of age-related cognitive impairments by an M1 cholinergic agonist, AF102B.

This study examined the effect of a specific M1 cholinergic agonist, AF102B, on place learning of aged and young rats. Spatial reference memory was tested in the Morris Water Maze task, while spatial working memory was tested on an 8-arm radial maze. Both memory functions were impaired in aged rats compared to young animals. However, the administration of AF102B significantly reduced the age-related cognitive impairments observed in both tasks. This data supports the assertion of the "cholinergic hypothesis," namely that specific enhancement of cholinergic function may reverse geriatric cognitive deficits.

Aging↗

Radon risk communication research: practical lessons.

Those responsible for state and local radon programs often express frustration about the small share of homes that have been tested for radon, and the small share of those with high readings that have been mitigated. There are now a number of completed studies that have examined how well alternative ways of communicating about radon risk have accomplished the goals of motivating appropriate testing and mitigation. This paper summarizes the research results that are most crucial for planning and implementing effective radon risk communication programs. We identify six reasons why people do not respond to radon as a serious threat and provide some remedies suggested by radon studies.

Communication↗