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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 181 records · Page 10Linked to original sources

Primary non-Hodgkins lymphoma of muscle.

A retrospective analysis was made of all patients with primary muscle non-Hodgkin's lymphomas registered with the Scotland and Newcastle Lymphoma Group over a 15-year period. Only eight patients were identified. The median age was 69 years (range 27-93). Five patients were male and six lymphomas were of high grade histology. The glutei and upper arm muscles were the main sites of origin, with the additional involvement of adjacent bone in four patients; only three had lymph node involvement at presentation. Most patients (6/8) received both chemotherapy and radiotherapy. The median survival was 33 months. The conclusion is that this is a small group of patients whose outlook is not as poor as has been suggested in previous reports.

Adult↗

Discontinuation, leaving reasons and course evaluation comments of students on the common foundation programme.

There is considerable financial incentive, at all levels, to reduce student nurse wastage and maintain recruitment to a workforce of professional nurses. This strategy is being pursued in a period following major educational change, when the attrition levels and leaving reasons of students need to be reassessed. Previous reports have identified a high voluntary loss of students on the common foundation programme (CFP) of the pre-registration nursing course. In order to achieve a better understanding of the basic problems faced by student nurses who consider leaving the CFP, questionnaires were distributed to three groups of students: current CFP students; students who had completed the CFP; and students who had discontinued training. The questionnaire responses show that course-based problems, identified as prime leaving reasons by the current and completed student groups, differ from the actual leaving reasons of discontinued students obtained by exit questionnaire. The attitudes of participating and discontinued students to theory, clinical and pastoral components of the CFP are not dissimilar. Some trends in attrition rate relate significantly to student category. Our results have implications for the management of student nurse attrition.

Adult↗

Preoperative visiting in Wales.

There is clear evidence in the nursing literature that preoperative visits conducted by theatre nurses have a therapeutic benefit for surgical patients. However, it would appear that the actual uptake of this practice is limited (Wicker 1995). The aim of this study is to investigate the prevalence of preoperative visiting in Wales and to identify factors associated with its occurrence or non-occurrence.

Attitude of Health Personnel↗

Expression and activity of vitamin D-metabolizing cytochrome P450s (CYP1alpha and CYP24) in human nonsmall cell lung carcinomas.

Extrarenal 25-hydroxyvitamin D3-1alpha-hydroxylase is believed to play a major role in the pathogenesis of hypercalcemia associated with various types of granulomatous and lymphoproliferative diseases and certain solid tumors. In this paper, we describe the cloning of the cytochrome P450 component of the extrarenal enzyme from a human nonsmall cell lung carcinoma, SW 900. The cytochrome P450 for the extrarenal 1alpha-hydroxylase has an amino acid sequence identical to that of the cytochrome P450 component of the CYP1alpha, the renal form of the enzyme, and appears to be a product of the same gene. CYP1alpha messenger RNA (mRNA) and 1alpha-hydroxylase enzyme activity were detected in two (SW 900, SK-Luci-6) of a series of five nonsmall cell lung carcinoma cell lines. All five lung cell lines were cultured with the same medium under the same conditions, but only two of the five expressed 1alpha-hydroxylase enzyme; two others (WT-E, Calu-1) expressed high levels of the reciprocally regulated enzyme, 25-hydroxyvitamin D3-24-hydroxylase, with its specific cytochrome P450 component, CYP24. Although under basal conditions the lung cell line SW 900 expressed only CYP1alpha and showed 1alpha-hydroxylase enzyme activity, when treated with small concentrations of 1alpha,25-dihydroxyvitamin D3 or high concentrations of 25-hydroxyvitamin D3, it began to express CYP24 and exhibit 24-hydroxylase enzyme activity. Somewhat surprisingly, SW 900 cells still had detectable CYP1alpha mRNA some 24 h after vitamin D treatment despite the fact that 1alpha-hydroxylase enzyme activity was unmeasurable. These data are consistent with the emerging hypothesis that vitamin D through its active form does not directly turn off CYP1alpha mRNA production but, rather, strongly stimulates CYP24, thereby masking CYP1alpha activity. The factor(s) responsible for the basal expression of CYP1alpha in SW 900 and SK-Luci-6 is currently unknown.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Targets and systems of health care cost control.

Discussion of health care cost control policy and politics tends to focus on terms such as "market," "government," and "managed care" that are either too general or too value laden to encourage sound analysis. This article proposes an alternative framework for classifying cost control policies. It first distinguishes targets from systems of control. Targets can then be divided into categories of service (e.g., hospital care, pharmaceutical treatment) and components of cost (e.g., price and volume). Systems can be classified in terms of the degree of pooling of finance, ranging from no insurance to a single pool of funds, and how payment of providers is organized, ranging from all payers paying all providers on the same terms to extensive selective contracting among payers and providers. The article analyzes examples of target policy and politics, system policy and politics, and how system choices can influence which targets are targeted how well, so as to show that both policy consequences and political alignments become clearer by using these terms. As one instance, discussions of "managed care" are often confused because the term has two meanings, one referring to target policy and one to system policy.

Cost Control↗

Dual-color visualization of trans-Golgi network to plasma membrane traffic along microtubules in living cells.

The mechanisms and carriers responsible for exocytic protein trafficking between the trans-Golgi network (TGN) and the plasma membrane remain unclear. To investigate the dynamics of TGN-to-plasma membrane traffic and role of the cytoskeleton in these processes we transfected cells with a GFP-fusion protein, vesicular stomatitis virus G protein tagged with GFP (VSVG3-GFP). After using temperature shifts to block VSVG3-GFP in the endoplasmic reticulum and subsequently accumulate it in the TGN, dynamics of TGN-to-plasma membrane transport were visualized in real time by confocal and video microscopy. Both small vesicles (<250 nm) and larger vesicular-tubular structures (>1.5 microm long) are used as transport containers (TCs). These TCs rapidly moved out of the Golgi along curvilinear paths with average speeds of approximately 0.7 micrometer/second. Automatic computer tracking objectively determined the dynamics of different carriers. Fission and fusion of TCs were observed, suggesting that these late exocytic processes are highly interactive. To directly determine the role of microtubules in post-Golgi traffic, rhodamine-tubulin was microinjected and both labeled cargo and microtubules were simultaneously visualized in living cells. These studies demonstrated that exocytic cargo moves along microtubule tracks and reveals that carriers are capable of switching between tracks.

Animals↗

Attentional bias for emotional faces in generalized anxiety disorder.

OBJECTIVES: Recent cognitive theories propose that attentional biases cause or maintain anxiety disorders. This study had several aims: (i) to investigate such biases in generalized anxiety disorder (GAD) using naturalistic, ecologically valid stimuli, namely, emotional facial expressions; (ii) to test the emotionality hypothesis by examining biases for happy as well as threat faces; and (iii) to assess the time course of the attentional bias. DESIGN: The dependent variable was an index of attentional bias derived from manual RTs to probe stimuli. There were four independent variables: one between-subjects variable of group (2: GAD, control), and three within-subjects variables: Type of emotional face (2: threat, happy), Stimulus duration (2: 500 ms, 1250 ms) and Half of task (2: first, second). METHOD: Attentional bias was assessed with a dot probe task. The stimuli comprised photographs of threatening, happy and neutral faces, presented using two exposure durations: 500 ms and 1250 ms. RESULTS: Anxious patients showed greater vigilance for threatening faces relative to neutral faces, compared with normal controls. This effect did not significantly vary as a function of stimulus duration. Anxious patients also showed enhanced vigilance for happy faces, but this was only significant in the second half of the task. CONCLUSIONS: The study confirmed not only that GAD patients show a bias in selective attention to threat, relative to controls, but also that this bias operates for naturalistic, non-verbal stimuli. As the attentional biases for threat and happy faces appeared to develop over a different time frame, different underlying mechanisms may be responsible.

Adult↗

Chronic drinking, binge drinking, and drunk driving II.

Data from the Rhode Island Behavioral Risk Factor Survey on self-reported alcohol consumption and drunk driving were examined. Driving while intoxicated was significantly associated with both binge drinking and chronic drinking, but the measures of drinking were not significantly associated.

Alcohol Drinking↗

Laparoscopic repair of bilateral and recurrent hernias.

The optimal inguinal hernia repair has been controversial for decades. Since the advent of minimally invasive surgery, laparoscopic techniques have added to the controversy. Laparoscopic hernia repair has been advocated by many experts for the repair of bilateral and recurrent inguinal hernias. This study reviews the experience of a single community-based teaching hospital using the total extraperitoneal (TEP)-approach laparoscopic hernia repair for treating patients with bilateral and/or recurrent inguinal hernias. Since the TEP approach was adopted in June 1993, a total of 457 patients were treated for bilateral (322 patients) and/or recurrent (175) inguinal hernias (40 patients had recurrent and bilateral hernias). A total of 779 hernias were repaired with this technique. The average age of this patient group was 47 years, and there were 413 males and 44 females. Operative time averaged 68.3 minutes per patient, and there were 26 (5.7%) minor complications. There were 2 (0.4%) major complications, an enterotomy and a cystotomy, both early in the series and both in patients with previous lower abdominal surgery. There have been no deaths. With an average follow-up of 30 months (range, 1-60 months), there have been three (0.2%) recurrences. These recurrences were due to technical problems (inadequate mesh coverage), and each was repaired with a laparoscopic transabdominal approach or an anterior open approach. The use of the TEP-approach laparoscopic hernia repair is safe and effective in patients with recurrent and/or bilateral inguinal hernias.

Abdominal Muscles↗

Chloroquine sensitivity of Plasmodium vivax in Thailand.

Chloroquine has been the standard treatment for Plasmodium vivax malaria for more than 40 years in most regions of the world. Recently, however, chloroquine-resistant P. vivax has been reported from Oceania, several parts of Asia, and South America. In order to assess the situation in Thailand, 886 patients with vivax malaria who were admitted to the Bangkok Hospital for Tropical Diseases from 1992 to 1997 were followed prospectively. Most of the patients had been infected on the western border of Thailand and were experiencing their first malarial infection when admitted. All received oral chloroquine (approximately 25 mg base/kg body weight, administered over 3 days) and then were randomized to receive primaquine (15 mg daily for 14 days) or no further treatment. All the patients were initially responsive to chloroquine, clearing their parasitaemias within 7 days, and there were no significant differences in the clinical or parasitological responses between those treated with primaquine and those given no further treatment. Plasmodium vivax parasitaemias re-appeared within 28 days of chloroquine treatment in just four patients. In each of these four cases, re-treatment with the same regimen of chloroquine resulted in eradication of the parasitaemia, with no further appearance of parasitaemia during the next, 28-day, follow-up period. These data indicate that virtually all acute (i.e. blood-stage) P. vivax infections acquired in Thailand can still be successfully treated with chloroquine.

Adolescent↗

The use of imaging studies in the diagnosis and management of thyroid cancer and hyperparathyroidism.

With the variety of radiopharmaceutical agents and refined imaging techniques, thyroid and parathyroid imaging provides much valuable clinical information. The use of imaging is most important in the follow-up of differentiated (DTC) and medullary thyroid cancer (MTC). Patients with DTC are followed with serum thyroidglobulin and 131I whole body scintigraphy when the serum thyroglobulin level is elevated. When the 131I scintigram is negative, 201Tl scintigraphy may best identify the site of recurrent DTC. Alternative radioisotopes, ultrasound, CT, and FDG PET are also useful in localizing the site of DTC metastases. MTC recurrences and metastases are more difficult to image. Selective venous catheterization is the most sensitive and specific method for detecting areas of recurrent MTC. High-resolution ultrasound, CT, MR imaging, and scintigraphy are all capable of, and useful in, detecting macroscopic foci of metastatic tumor. Somatostatin receptor scintigraphy and 99mTc DMSA have been the most frequently used nuclear imaging agents in patients with recurrent MTC. Imaging for hyperparathyroidism remains controversial. Sestambi has become the preferred isotope for parathyroid scintigraphy; whereas high-resolution ultrasound is also frequently used. Preoperative imaging is being used as a method to allow a unilateral neck exploration, more recently, in conjunction with intraoperative 1-84 PTH assay and with intraoperative use of the gamma probe. Most often, parathyroid imaging is performed before reoperation for persistent hyperparathyroidism.

Carcinoma↗

Structural studies of fibrinolysis by electron microscopy.

Fibrin is degraded by the fibrinolytic system in which a plasminogen activator converts plasminogen to plasmin, a serine protease that cleaves specific bonds in fibrin leading to solubilization. To elucidate further the biophysical processes involved in conversion of insoluble fibers to soluble fragments, fibrin was treated with either plasmin or the combination of plasminogen and plasminogen activator, and morphologic changes were observed using scanning electron microscopy. These changes were correlated with biochemical analysis and with characterization of released, soluble fragments by transmission electron microscopy. Initial changes in the fibrin matrix included creation of many free fiber ends and gaps in the continuity of fibers. With more extensive digestion, free fiber segments associated laterally, resulting in formation of thick fiber bundles. Supernatants of digesting clots, containing soluble derivatives, were negatively contrasted and examined by transmission electron microscopy. Large, complex fragments containing portions of multiple fibers were observed, as were pieces of individual fibers and smaller fragments previously identified. Some large fragments had sharply defined ends, indicating that they had been cleaved perpendicularly to the fiber direction. Other fibers showed splayed ends or a lacy meshwork of surrounding protofibrils. Longer times generated more small fragments whose molecular composition could be inferred from their appearance. These results indicate that fibrinolytic degradation results in larger pieces than previously identified and that plasmin digestion proceeds locally by transverse cutting across fibers rather than by progressive cleavage uniformly around the fiber.

Electrophoresis, Polyacrylamide Gel↗

Recycling of golgi-resident glycosyltransferases through the ER reveals a novel pathway and provides an explanation for nocodazole-induced Golgi scattering.

During microtubule depolymerization, the central, juxtanuclear Golgi apparatus scatters to multiple peripheral sites. We have tested here whether such scattering is due to a fragmentation process and subsequent outward tracking of Golgi units or if peripheral Golgi elements reform through a novel recycling pathway. To mark the Golgi in HeLa cells, we stably expressed the Golgi stack enzyme N-acetylgalactosaminyltransferase-2 (GalNAc-T2) fused to the green fluorescent protein (GFP) or to an 11-amino acid epitope, VSV-G (VSV), and the trans/TGN enzyme beta1,4-galactosyltransferase (GalT) fused to GFP. After nocodazole addition, time-lapse microscopy of GalNAc-T2-GFP and GalT-GFP revealed that scattered Golgi elements appeared abruptly and that no Golgi fragments tracked outward from the compact, juxtanuclear Golgi complex. Once formed, the scattered structures were relatively stable in fluorescence intensity for tens of minutes. During the entire process of dispersal, immunogold labeling for GalNAc-T2-VSV and GalT showed that these were continuously concentrated over stacked Golgi cisternae and tubulovesicular Golgi structures similar to untreated cells, suggesting that polarized Golgi stacks reform rapidly at scattered sites. In fluorescence recovery after photobleaching over a narrow (FRAP) or wide area (FRAP-W) experiments, peripheral Golgi stacks continuously exchanged resident proteins with each other through what appeared to be an ER intermediate. That Golgi enzymes cycle through the ER was confirmed by microinjecting the dominant-negative mutant of Sar1 (Sar1pdn) blocking ER export. Sar1pdn was either microinjected into untreated or nocodazole-treated cells in the presence of protein synthesis inhibitors. In both cases, this caused a gradual accumulation of GalNAc-T2-VSV in the ER. Few to no peripheral Golgi elements were seen in the nocodazole-treated cells microinjected with Sar1pdn. In conclusion, we have shown that Golgi-resident glycosylation enzymes recycle through the ER and that this novel pathway is the likely explanation for the nocodazole-induced Golgi scattering observed in interphase cells.

Endoplasmic Reticulum↗

Role of xklp3, a subunit of the Xenopus kinesin II heterotrimeric complex, in membrane transport between the endoplasmic reticulum and the Golgi apparatus.

The function of the Golgi apparatus is to modify proteins and lipids synthesized in the ER and sort them to their final destination. The steady-state size and function of the Golgi apparatus is maintained through the recycling of some components back to the ER. Several lines of evidence indicate that the spatial segregation between the ER and the Golgi apparatus as well as trafficking between these two compartments require both microtubules and motors. We have cloned and characterized a new Xenopus kinesin like protein, Xklp3, a subunit of the heterotrimeric Kinesin II. By immunofluorescence it is found in the Golgi region. A more detailed analysis by EM shows that it is associated with a subset of membranes that contain the KDEL receptor and are localized between the ER and Golgi apparatus. An association of Xklp3 with the recycling compartment is further supported by a biochemical analysis and the behavior of Xklp3 in BFA-treated cells. The function of Xklp3 was analyzed by transfecting cells with a dominant-negative form lacking the motor domain. In these cells, the normal delivery of newly synthesized proteins to the Golgi apparatus is blocked. Taken together, these results indicate that Xklp3 is involved in the transport of tubular-vesicular elements between the ER and the Golgi apparatus.

Amino Acid Sequence↗

Protein kinase C-zeta activity but not level is decreased in Alzheimer's disease microvessels.

While there is considerable evidence demonstrating altered activity of the major isoforms of protein kinase C (PKC) in the vasculature and neurons of Alzheimer disease (AD) brains, little is known about the activity and/or levels of the atypical PKC isoforms. The objective of this study is to compare PKC-zeta activity and level in cerebral microvessels isolated from AD brains with microvessels from the brains of nondemented age-matched controls. Measurements of the kinase activity reveals that the PKC-zeta activity is significantly (P < 0.01) lower in AD brain microvessels compared with vessels from control brain. Despite this decrease in enzyme activity, the level of PKC-zeta, assessed by Western blot, is significantly (P < 0.01) elevated in AD microvessels. These data demonstrate significant and divergent changes in the PKC-zeta activity and level in the microcirculation of the AD brain and suggest that aberrant regulation of microvascular PKC-zeta could contribute to the abnormal signaling mechanisms at the blood-brain barrier in the AD brain.

Aged↗