bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in burden and depression among informal caregivers of demented elders in the community
Authors: Gallicchio Lisa , Siddiqi Nauman , Langenberg Patricia , Baumgarten Mona
Published: October 2002

Background

Earlier studies have yielded inconsistent findings regarding gender differences with respect to burden and depression among informal community caregivers of dementia patients.

Objectives

The aim of the study was to determine whether or not there were gender differences in the prevalence of burden and depression among informal caregivers of community‐residing dementia patients.

Methods

Data from 259 female and 68 male caregivers who were part of the Canadian Study of Health and Aging were analyzed. Depressive symptoms were measured using the Center for Epidemiologic Studies—Depression Scale (CES‐D). Burden was assessed using Zarit's Burden Interview. Associations between the outcome variables (depressive symtoms and burden) and the independent variable, gender, were examined using logistic regression.

Results

In multivariable analysis, female caregivers were found to have significantly higher odds than male caregivers of having a score of 33 or higher on Zarit's Burden Interview (OR = 2.6; 95% CI 1.0, 6.7). The OR comparing women to men with respect to a high level of depressive symptoms (defined as a score of 16 or more on the CES‐D) was not significant (OR = 1.3; 95% CI 0.6, 2.9). Poor perceived caregivers health and more behavior disturbance in the patient were associated with significantly higher odds of high levels of caregiver burden and depression.

Conclusions

Adequate assistance must be given to women caregivers to ensure that they are not strained beyond what is clinically healthy. In addition, interventions should target caregivers of behaviorally disturbed patients as well as caregivers who report poor physical health to reduce the negative psychological impact of caregiving. Copyright © 2002 John Wiley & Sons, Ltd.
Gait performance in dementia: the effects of a 6‐week resistance training program in an adult day‐care setting
Authors: Hageman Patricia A. , Thomas Vince Salazar
Published: October 2002

Background

Age‐related declines in balance and muscle power are largely responsible for the changes in the various components of gait performance among elderly people. But these can often be remedied with strength training. People with cognitive impairment frequently demonstrate impaired gait, putting them at increased risks for falls and serious injury.

Objectives

This paper reports on the effects of a six‐week pilot study of moderate intensity strength training on the gait of elderly individuals with dementia who attend a day‐care center.

Methods

Twenty‐six adults (23 female, three male), age = 79.2 ± 6.6 years, completed the study. Each subject completed a baseline assessment of lower extremity strength and gait. Gait was evaluated using free‐ and fast‐gait speed over a 6‐meter course, the Tinetti‐Gait Assessment scale, the ‘Timed‐Up‐and‐Go’, and the Gait Assessment Rating Scale (GARS). The intervention consisted of moderate‐intensity progressive resistance lower extremity exercise using Theraband, for two to three sessions per week over the six weeks. Post‐intervention assessment of strength and gait was repeated at the completion of the sixth week. Multiple paired t‐tests were calculated for each outcome measure.

Results

The baseline assessment of gait suggests a high degree of frailty and risk for falls in the sample. Although post‐intervention scores reflected improvement on all gait measures, the only statistically significant change observed was in fast‐gait time.

Conclusion

A six‐week resistance training program proved to be of insufficient duration, intensity or specificity to produce significant change in gait outcome measures, with the exception of fast speed gait. Copyright © 2002 John Wiley & Sons, Ltd.
Physical disorders and causes of death in relatives of Alzheimer's disease patients
Authors: Kockler M. , Nitardy A. , Papassotiropoulos A. , Ptok U. , Maier W. , Heun R.
Published: October 2002

Background

Genetic risk factors are important in Alzheimer's disease (AD). These risk factors might also predispose for other disorders. This might lead to a familial coaggregation of AD and other disorders, e.g. Down's syndrome or Parkinson's disease. In the present study the risk of physical disorders in relatives of AD patients, of depressed patients and of control subjects were compared.

Methods

Family history and, if possible, interview information on physical disorders and causes of death in relatives of 146 patients with AD, 168 patients with major depression (MD) and 136 controls was collected. Statistical comparisons were performed using chi‐square tests and, if necessary, logistic regression analysis accounting for age, gender and interview status.

Results

In contrast to our hypotheses, there was no increased risk of cerebrovascular disease, Down's syndrome, haematological malignancies or Parkinson's disease in relatives of AD patients compared with relatives of patients with MD and of controls. The explorative analysis revealed that congenital malformations, i.e. malformations of the heart or of the extremities, were slightly increased in relatives of AD patients. Relatives of patients with AD or MD were at increased risk of dying as a result of accidents, in most cases falls in advanced age, and relatives of patients with MD were at slightly increased risk of dying from gastroenterologic diseases, in most cases complications of peptic ulcers.

Conclusion

The results do not support a major overlap between the genetic risk of AD and the genetic risk of cerebrovascular disease, Down's syndrome, haematological malignancies or Parkinson's disease. The finding of an increased risk of congenital malformations in relatives of AD patients needs further replication before it can be stated. The increased risk of dementia or depression with cognitive impairment in elderly relatives of patients with AD or MD increases the risk of accidents like falls. The genetic risk of depression in relatives of patients with MD could have a negative influence on the prognosis of peptic ulcera. Copyright © 2002 John Wiley & Sons, Ltd.
Service contact and psychopathology in very‐late‐onset schizophrenia‐like psychosis: the effects of gender and ethnicity
Authors: Reeves S. , Stewart R. , Howard R.
Published: October 2002

Background

Epidemiological data on very‐late‐onset (>60 years) schizophrenia‐like psychosis (SLP) are scarce. There are only two published follow‐up studies.

Objective

To examine the associations of gender and ethnicity with health service contact and psychopathology in SLP.

Method

We identified all new referrals of SLP to the Maudsley hospital between 1995–2000. Demographic details and information on the course of the illness were obtained from case notes. Those patients who agreed to take part were seen at home and assessed with respect to psychopathology and neurological side effects.

Results

The median duration of illness at the time of assessment was 3 years (range 1–6 years). Male patients were more likely to be admitted to hospital compulsorily and to be lost to follow‐up than female patients. Caribbean‐born patients were more likely to refuse to take part than British‐born patients. Of the 26 (48%) patients who were interviewed, 38% were experiencing paranoid symptoms, 94% of patients receiving medication were in regular contact with a community psychiatric nurse (CPN). Treatment response was dose related and was not increased by the use of a depot.

Conclusion

The effects of gender and ethnicity on outcome need to be further investigated through larger studies. High loss to follow‐up amongst male patients may be indicative of a poor prognosis. Regular contact with a CPN may be more important than the use of a depot in maintaining treatment response. Copyright © 2002 John Wiley & Sons, Ltd.
Trends in suicide from drug overdose in the elderly in England and Wales, 1993–1999
Authors: Shah Rajen , Uren Zoë , Baker Allan , Majeed Azeem
Published: October 2002

Background

Drug overdose is a common method of suicide in the elderly. Hence, an understanding of current trends in epidemiology of these deaths is important when considering measures to decrease suicide rates.

Methods

Analysis of the Office for National Statistics (ONS) database of deaths from overdose and poisoning. Suicide and undetermined deaths from drug overdose between 1993–1999 in the over 65 year olds were studied. Socio‐demographic data from the four drug groups most commonly used in overdose were extracted, and age and sex specific mortality rates calculated. Enumeration districts were ranked into five quintiles based on their Carstairs scores, and death rates in each quintile for men and women calculated.

Results

There were 1864 deaths from drug overdose during the study period. Suicide and undetermined death rates from drug overdose remained stable between 1993–1999. Drugs most commonly used in overdose were (in order) paracetamol (and related compounds), benzodiazepines, antidepressants, and opiates. Women comprised 62% of deaths. Death rates increased with age, with highest rates in men over 75 (37.7 deaths per million). Benzodiazepines showed the most marked increase with age. Co‐proxamol comprised 32% of deaths from paracetamol compounds, and 95% of antidepressant deaths were due to tricyclic antidepressants. There was no association in women between Carstairs area deprivation and suicide rates; in men rates were highest in the most deprived areas.

Conclusion

Suicides in the over 65 year olds may be decreased by changes in prescription practice. Paracetamol, co‐proxamol, tricyclic antidepressants and benzodiazepines should be prescribed with caution to the elderly with depression or at high risk of depression. Copyright © 2002 John Wiley & Sons, Ltd.
Using larger dimensional signal subspaces to increase sensitivity in fMRI time series analyses
Authors: Zarahn Eric
Published: October 2002

It has been explained previously how using large dimensional signal‐subspaces can reduce/eliminate bias in the estimated fMRI response (Burock and Dale [2000]: Hum Brain Mapp 11:249–260). It has also been explained how one can project this less biased estimate onto a one‐dimensional subspace of interest (Burock and Dale [2000]: Hum Brain Mapp 11:249–260). In cases where there are multiple, correlated characterized response components per event type, separately projecting the full hemodynamic response onto one‐dimensional subspaces of interest can lead to bias. We present an approach for both estimating the full hemodynamic response and obtaining from it unbiased estimates of effects of theoretical interest (in the context of ordinary least‐squares estimation). The latter estimates are identical to those obtained by projecting the original data into the space defined by the (possibly multi‐dimensional) effects of theoretical interest, but the ensuing statistical inference can be more sensitive. Hum. Brain Mapping 17:13–16, 2002. © 2002 Wiley‐Liss, Inc.
Heteroatom chemistry of cyclic benzopolychalcogenides: Synthesis and characterization
Authors: Sato Ryu
Published: October 2002

Many benzopolychalcogenides, for example benzotrithioles, benzotetrathiins, and benzopentathiepins were synthesized from corresponding 1,2‐benzenedichalcogenols as starting compounds. The stability of the pentathiepin ring toward functional groups was confirmed by use of amino and sulfide groups as substituents in the molecule of benzopentathiepin. Furthermore, the intramolecular interaction between two polysulfide rings was also studied by synthesis of bisbenzotrithiole, 7,7′‐diethyl‐4,4′‐ethylenedioxybis (benzo[1,2‐d][1,2,3]trithiole). © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:419–423, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10069
Kaposiform hemangioendothelioma of the external auditory canal in an adult
Authors: Hardisson David , Prim Mariá Pilar , De Diego Juan Ignacio , Patrón Mercedes , Escribano Anne , Rabanal Ignacio
Published: October 2002

Background

Kaposiform hemangioendothelioma is an uncommon vascular tumor initially reported to occur exclusively in children.

Methods

The presentation, pathologic evaluation, and management of an unusual case of kaposiform hemangioendothelioma is presented and discussed.

Results

A 27‐year‐old HIV‐negative man was initially seen with a reddish nodule located in the outer third of the external auditory canal. Histologically, the tumor was composed of spindle‐shaped cells arranged in short fascicles associated with small endothelial‐like vascular spaces, similar in appearance to Kaposi's sarcoma. The lesion was locally excised but recurred 1 month later; then radiation therapy was performed. The patient remains well at 5‐year follow‐up.

Conclusions

Recognition of kaposiform hemangioendothelioma is important to avoid possible confusion with a variety of vascular neoplasms with different biologic potential. This case presented some diagnostic difficulty because of the age of the patient and the unusual location of the lesion and had to be mainly distinguished from Kaposi's sarcoma. © 2002 Wiley Periodicals, Inc. Head Neck 24: 614–617, 2002
Somatostatin analog treatment of a cervical thoracic duct fistula
Authors: Valentine Carl N. , Barresi Roberto , Prinz Richard A.
Published: October 2002

Background

Reoperation for recurrent thyroid cancer poses an increased risk of complications, including thoracic duct fistula. Treatment of this complication is controversial. A survey of thoracic literature reports the use of somatostatin analog, whereas no cases have reported the use of this therapy in cases arising from neck dissection.

Methods

We report a 16‐year‐old girl with recurrent papillary thyroid cancer who had a persistent lymphatic‐cutaneous fistula develop after repeat modified left neck dissection. Despite conservative management, drainage persisted for 2 months. A regimen was begun that included TPN and injections of a somatostatin analog.

Results

Treatment with a somatostatin analog resulted in an immediate attenuation of drainage and subsequent closure of the fistula after 16 days of treatment.

Conclusion

The use of somatostatin analog can increase the success of conservative management of thoracic duct fistulae. © 2002 Wiley Periodicals, Inc. Head Neck 24: 810–813, 2002
Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations
Authors: Zugaro Michaël B. , Berthoz Alain , Wiener Sidney I.
Published: October 2002

Head direction cells discharge selectively when the head of the animal is oriented in a specific direction. The goal of this study was to determine how sensory signals arising from passive rotations (e.g., triggered by vestibular stimulation and dynamic visual inputs) influence the responses of anterodorsal thalamic head direction cells in the absence of voluntary movement cues (e.g., motor command, efference copy, and associated kinesthetic signals). Three unrestrained rats consumed water from a reservoir at the center of a circular platform while passively subjected to sinusoidal rotatory oscillations at fast (153 ± 27°/s, sd) and slow (38 ± 15°/s) peak velocities. In 14 anterodorsal thalamic head direction cells, the preferred directions, angular response ranges and baseline firing rates remained stable, but the peak firing rates were, on average, 36% higher during the fast rotations (Wilcoxon matched‐pairs test, p < 0.001; variation range: +11%∼+100%). No cell changed its peak firing rate by less than 10%, while three cells (21%) increased their peak firing rates by more than 50%. The velocity‐dependent increase in peak firing rates was similar for left and right rotations, and the skewness of the directional response curves were not significantly different between left and right turns (Wilcoxon matched‐pairs tests, n = 14, ns). These results show that sensory signals concerning self‐movements modulate the responses of the head direction cells in the absence of active locomotion. Hippocampus 2002;12:481–486. © 2002 Wiley‐Liss, Inc.
Entorhinal axons exhibit sprouting in CA1 subfield of the adult hippocampus in a rat model of temporal lobe epilepsy
Authors: Shetty Ashok K.
Published: October 2002

Intracerebroventricular kainic acid administration in rat, a model of temporal lobe epilepsy, results in CA3 pyramidal neuron degeneration leading to deafferentation of CA1 pyramidal neurons. Denervation in CA1 shows a near‐complete recovery of synaptic density over 2–3 months, but the source of axons participating in the reinnervation is not clear. This study investigated the contribution of the entorhinal cortex in this reinnervation by comparing the distribution of the entorhinal axons in the CA1 subfield between the intact hippocampus and the CA3‐lesioned hippocampus at 3 months after administration of kainic acid. Entorhinal axons were visualized by anterograde tracing using injections of the biotinylated dextran amine into the entorhinal cortex. In the CA1 subfield of the intact hippocampus, entorhinal axons were conspicuous in the alveus and the stratum lacunosum moleculare. The distribution in the strata oriens, pyramidale, and radiatum was sparse and was characterized by isolated entorhinal fibers of the alvear pathway crossing these strata to the stratum lacunosum moleculare. However, after kainic acid‐induced CA3 lesion, the density of entorhinal axons increased significantly in the CA1 stratum radiatum (375% of the intact hippocampus), as a large number of axons emanating from the entorhinal fiber plexus in the stratum lacunosum moleculare invaded the stratum radiatum. The stratum radiatum also exhibited wavy entorhinal axons filled with boutons and oriented parallel to the stratum pyramidale, suggesting collateral sprouting from entorhinal axons traversing the stratum radiatum. Thus, a significant aberrant sprouting of entorhinal axons occurs into the CA1 stratum radiatum after CA3 lesion. The sprouted fibers appear to come from both entorhinal fiber plexus in the stratum lacunosum moleculare (translaminar sprouting) and entorhinal axons traversing the stratum radiatum (intralaminar sprouting). However, the major contribution appears to be from the entorhinal plexus in the stratum lacunosum moleculare. This aberrant sprouting may lead to altered afferent excitatory connectivity in the CA1 subfield and contribute to the persistent CA1 hyperexcitability that occurs after the CA3 lesion. Hippocampus 2002;12:534–542. © 2002 Wiley‐Liss, Inc.
Decentralization, health care and policy process in the Punjab, Pakistan in the 1990s
Authors: Collins C. D. , Omar Mayeh , Tarin Ehsanullah
Published: October 2002

The Province of the Punjab underwent a number of attempts to decentralize the health sector in the 1990s. Among the most important were the decentralization of financial management within the district, the Sheikhupura PHC Pilot Project, the establishment of the District Health Authorities and District Health Management Teams, the creation of semi‐autonomous hospitals and the programme of District Health Government (DHG). These usually received donor support and promotion, and emerged from within the provincial Department of Health, and more specifically the Secretariat and the internationally supported Second Family Health Project (FH2). Of particular significance was the DHG change, which involved a decentralization to the district, the appointment of powerful Chief Executives, the formation of District Management Committees and purchaser–provider separation. The paper reviews these proposals, focusing on the need to build on experiences and learning lessons from pilot projects, reform continuity, developing consultation and involvement and policy analysis. The latter indicates the importance of developing more in‐depth policy analysis around the role of the central organization, the form of decentralization and the purchaser–provider separation. The paper concludes by underlining the need to ensure that political strategy and in‐depth policy are appropriately coordinated in the policy process. Copyright © 2002 John Wiley & Sons, Ltd.
Analysis of surface roughness in relation to soil loss and runoff at high rainfall intensities
Authors: Idowu O. J. , Rickson R. J. , Godwin R. J.
Published: October 2002

The decay of roughness is an important factor governing surface processes such as infiltration and soil erosion. Thus the decay of surface roughness under different surface conditions was investigated and related to quantitative amounts of soil loss, runoff and sediment concentration in a laboratory experiment.

Rainfall with an intensity of 128 mm/h was applied to a bare or mulched surfaces of a sandy loam soil with known surface roughness at specified time intervals. The decay of roughness as expressed by roughness ratio, in this experiment, was better predicted when related to an exponential function of the square root of cumulative kinetic energy of rainfall rather than with the cumulative rainfall. The roughness decay equations in literature did not predict breakdown under mulched surfaces accurately. Thus the exponent parameters of the roughness decay equations were adjusted to reflect the reduced decay occurring under mulched surfaces.

In a bare soil, regression equations expressing the dependent variables as a function of initial roughness index were significant, but with low coefficients of determination, being 0·39 for soil loss, 0·12 for runoff and 0·36 for sediment concentration. In addition to initial roughness index, cumulative kinetic energy of rainfall was further included in the regressions. This led to an increase in coefficients of determination, which was 0·81 for soil loss, 0·74 for runoff and 0·49 for sediment concentration.

The coefficients of determination (0·87 for soil loss, 0·85 for runoff and 0·51 for sediment concentration) were further increased when the final roughness index was included in addition to initial roughness index and cumulative kinetic energy in the regressions.

This work shows that soil loss and runoff could be predicted from bare soil surface provided the initial roughness and the energy of rainfall is known. However, field verifications of these relationships are needed under different tillage tools and under natural rainfall. Copyright © 2002 John Wiley & Sons, Ltd.
Short‐term inflow forecasting using an artificial neural network model
Authors: Xu Z. X. , Li J. Y.
Published: October 2002

The primary objective of this study is to investigate the possibility of including more temporal and spatial information on short‐term inflow forecasting, which is not easily attained in the traditional time‐series models or conceptual hydrological models. In order to achieve this objective, an artificial neural network (ANN) model for short‐term inflow forecasting is developed and several issues associated with the use of an ANN model are examined in this study. The formulated ANN model is used to forecast 1‐ to 7‐h ahead inflows into a hydropower reservoir. The root‐mean‐squared error (RMSE), the Nash–Sutcliffe coefficient (NSC), the A information criterion (AIC), B information criterion (BIC) of the 1‐ to 7‐h ahead forecasts, and the cross‐correlation coefficient between the forecast and observed inflows are estimated. Model performance is analysed and some quantitative analysis is presented. The results obtained are satisfactory. Perceived strengths of the ANN model are the capability for representing complex and non‐linear relationships as well as being able to include more information in the model easily. Although the results obtained may not be universal, they are expected to reveal some possible problems in ANN models and provide some helpful insights in the development and application of ANN models in the field of hydrology and water resources. Copyright © 2002 John Wiley & Sons, Ltd.
Assimilating remote sensing data in a surface flux–soil moisture model
Authors: Crosson William L. , Laymon Charles A. , Inguva Ramarao , Schamschula Marius P.
Published: October 2002

A key state variable in land surface–atmosphere interactions is soil moisture, which affects surface energy fluxes, runoff and the radiation balance. Soil moisture modelling relies on parameter estimates that are inadequately measured at the necessarily fine model scales. Hence, model soil moisture estimates are imperfect and often drift away from reality through simulation time. Because of its spatial and temporal nature, remote sensing holds great promise for soil moisture estimation. Much success has been attained in recent years in soil moisture estimation using passive and active microwave sensors, but progress has been slow. One reason for this is the scale disparity between remote sensing data resolution and the hydrologic process scale. Other impediments include vegetation cover and microwave penetration depth. As a result, currently there is no comprehensive method for assimilating remote soil moisture observations within a surface hydrology model at watershed or larger scales.

This paper describes a measurement–modelling system for estimating the three‐dimensional soil moisture distribution, incorporating remote microwave observations, a surface flux–soil moisture model, a radiative transfer model and Kalman filtering. The surface model, driven by meteorological observations, estimates the vertical and lateral distribution of water. Based on the model soil moisture profiles, microwave brightness temperatures are estimated using the radiative transfer model. A Kalman filter is then applied using modelled and observed brightness temperatures to update the model soil moisture profile.

The modelling system has been applied using data from the Southern Great Plains 1997 field experiment. In the presence of highly inaccurate rainfall input, assimilation of remote microwave data results in better agreement with observed soil moisture. Without assimilation, it was seen that the model near‐surface soil moisture reached a minimum that was higher than observed, resulting in substantial errors during very dry conditions. Updating moisture profiles daily with remotely sensed brightness temperatures reduced but did not eliminate this bias. Copyright © 2002 John Wiley & Sons, Ltd.
Episodic stream water pH decline during autumn storms following a summer drought in northern Sweden
Authors: Laudon Hjalmar , Bishop Kevin
Published: October 2002

The sources of episodic pH decline in four streams from northern Sweden during the autumn of 1996 were quantified. The events, in which pH dropped by between 1·0 and 2·4 units, were preceded by an extensive summer drought. Total organic carbon, which increased 100% to 160% during peak flow, was the most important driving mechanism of the episodic pH decline. Sulphate, however, was relatively more important during these autumn events than during spring flood. In the sites where past and present anthropogenic deposition were believed to be the main source of sulphate in stream water, sulphate contributed less than 0·3 pH units to the pH decline. In catchments where natural sources of sulphate are known to be important, sulphate contributed up to 0·6 units of pH decline. The export of sulphate during the episodes was two to nine times higher than what was expected from deposition only. The drought preceding the study episodes resulted in some of the lowest ground water levels during the 1990s in that region. The large export of sulphate was probably due to oxidation of natural sulphate bearing minerals in the soil and/or previously deposited sulphate driven by the low ground water level preceding the episodes. Copyright © 2002 John Wiley & Sons, Ltd.
Determination of longitudinal dispersivity in an unconfined sandy aquifer
Authors: Kim Dong‐Ju , Kim Joung‐Souk , Yun Seong‐Taek , Lee Sang‐Hoon
Published: October 2002

Study of the mobility of contaminants in an aquifer is an important issue for the proper remediation of contaminated groundwater. Determination of associated solute transport parameters therefore is essential for investigation of the extent to which groundwater can be contaminated. This study aimed at determining solute transport parameters for an unconfined sandy aquifer at a laboratory scale through various tracer tests using a conservative solute as a tracer. Tracer tests consisted of both well‐tracer tests (single and double wells) and an aquifer tracer test using a plume‐capturing device such as time domain reflectometry (TDR). The results showed that longitudinal dispersivities estimated from the single and double well‐tracer tests were 2·2 cm and 13·5 cm for a travel distance of 9·3 cm and 13·5 cm from the injection point respectively. These results agreed reasonably well with the results of the aquifer tracer test. The solute transport parameters obtained at multiple points in the aquifer through the aquifer tracer test revealed that the dispersivity length was proportional to the travel distance by a factor of 0·3, which was moderately higher than the value of 0·1 given in the literature. Copyright © 2002 John Wiley & Sons, Ltd.
Supra‐additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro
Authors: Raitanen Misa , Rantanen Virpi , Kulmala Jarmo , Helenius Hans , Grénman Reidar , Grénman Seija
Published: October 2002

The effect of concurrent paclitaxel and cisplatin was tested in vitro in 5 vulvar squamous cell carcinoma (SCC) cell lines (UM‐SCV‐1A, ‐2, ‐4 and ‐7 and UT‐SCV‐3). Chemosensitivity was tested using the 96‐well plate clonogenic assay. Paclitaxel concentrations used varied between 0.4 and 1.6 nM, and cisplatin concentrations varied between 0.1 and 0.9 μg/ml. These drug concentrations are clinically achievable. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the 2 drugs with the survival fraction (SF) of paclitaxel alone. With all cell lines tested the growth‐inhibitory effect of simultaneous paclitaxel and cisplatin was at least additive. The effect of the tested combination on the UM‐SCV‐1A and UT‐SCV‐3 cell lines was clearly supra‐additive with all paclitaxel concentrations tested, and the UM‐SCV‐4 and UM‐SCV‐7 cell lines exhibited a supra‐additive effect with increasing paclitaxel concentrations. The degree of supra‐additivity was dose‐dependent in the UM‐SCV‐7 cell line with increasing synergy at higher paclitaxel doses. In the current study the combination of paclitaxel and cisplatin had a clear additive or supra‐additive cytotoxic effect on the vulvar SCC cell lines, and it has been successfully used in other gynecologic malignancies; therefore concurrent paclitaxel and cisplatin also deserves further testing in clinical settings in advanced‐stage vulvar carcinoma, which has a poor prognosis. © 2002 Wiley‐Liss, Inc.
Tumor necrosis factor–related, apoptosis‐inducing ligand supports growth of mouse mastocytoma tumors by killing tumor‐infiltrating macrophages
Authors: Strebel Alessandro , Bachmann Felix , Wernli Marion , Erb Peter
Published: October 2002

TRAIL antisense transfected mastocytoma cells (R56VTas) injected into syngeneic DBA/2 mice demonstrate significantly delayed tumor growth compared to mock transfected cells (R56VTMo). TRAIL expression in R56VTas cells was successfully, albeit not completely, downregulated, as shown by Western blots, flow‐cytometric analysis and functionally by loss of cytolytic activity against TRAIL‐R‐bearing target cells. Immunohistochemic and immunoblotting analyses of ex vivo tumors confirmed the lower expression of TRAIL by the antisense transfection compared to the mock transfection. Investigating the mechanism of the delayed tumor growth, it was found that neither T nor NK cells but activated macrophages infiltrated the tumors. The number of infiltrating macrophages was significantly lower in the mock transfected compared to the TRAIL antisense transfected tumor sections, indicating that TRAIL‐expressing tumor cells may lyse macrophages. Indeed, activated macrophages proved to be sensitive to TRAIL‐mediated apoptosis. This indicates that, although macrophages can infiltrate the mastocytoma R56VT, they are in part eliminated by TRAIL‐expressing tumor cells, allowing the tumor to rapidly grow. Hence, downregulation of TRAIL allows more macrophages to survive and to better attack the tumor cells, slowing down tumor growth. In conclusion, TRAIL expressed on R56VT tumor cells can impair an important innate immune defense mechanism against tumors by eliminating effector macrophages. © 2002 Wiley‐Liss, Inc.
Risk factors for lung cancer among nonsmoking women
Authors: Kreuzer Michaela , Heinrich Joachim , Kreienbrock Lothar , Schaffrath Rosario Angelika , Gerken Michael , Wichmann H. Erich
Published: October 2002

To evaluate risk factors for lung cancer in nonsmoking women, we used data of a case‐control study conducted between 1991 and 1996 in Germany. A total of 234 female histologically confirmed lung cancer patients and 535 population controls who had never smoked more than 400 cigarettes in their lifetime were personally interviewed with respect to occupation, exposure to environmental tobacco smoke (ETS), family history of cancer, prior physician‐diagnosed lung diseases or cancer and diet. One‐year radon measurements in the last dwelling were performed. Odds ratios (OR) adjusted for age and region and 95% confidence intervals (CI) were calculated via logistic regression. When cumulative duration of exposure to ETS in hours was considered, the OR for high compared to not or low ETS exposed women was 2.62 (CI:1.35–5.06) for occupational exposure and OR=1.67 (CI:0.86–3.25) for spousal exposure, exhibiting a significant trend for ETS at work. Working more than 10 years in jobs or industries with known or suspected lung carcinogens was associated with OR=2.0 (CI:0.99–4.0). An elevated risk due to prior lung diseases was present for pneumonia (OR=1.6; CI:1.07–2.40) and tuberculosis (OR=1.6; CI:0.77–3.37). No significant increase in risk with increasing residential radon levels or with the presence of a family history of lung cancer was apparent. Protective effects were observed for high vs. low consumption of fresh vegetables (OR=0.5; CI:0.25–0.82) and cheese (OR=0.3, CI:0.21–0.55). ETS at work, occupational hazards and previous pneumonia may be risk factors for lung cancer in nonsmoking women, while a diet rich in fresh vegetables and cheese seems to be protective. © 2002 Wiley‐Liss, Inc.
In vitro and in vivo characterization of graft‐versus‐tumor responses in melanoma patients after allogeneic peripheral blood stem cell transplantation
Authors: Kurokawa Toshiro , Fischer Karin , Bertz Hartmut , Hoegerle Stefan , Finke Jürgen , Mackensen Andreas
Published: October 2002

It has been shown that after allogeneic peripheral blood stem cell transplantation (PBSCT), donor T cells can induce potent graft‐versus‐tumor (GVT) effects in hematologic malignancies and possibly solid tumors such as renal cell carcinoma. Two patients (27 and 30 years old) with metastatic melanoma received allogeneic PBSCT from an HLA‐identical sibling donor after reduced conditioning with fludarabine, carmustine and melphalan. One patient showed a delayed mixed response with complete regression of lymph node metastases but persistent liver metastasis at day +60 and +120, consistent with a GVT response. In order to generate donor‐derived tumor‐reactive cytotoxic T lymphocytes (CTLs), peripheral blood mononuclear cells were stimulated with donor dendritic cells (DCs) loaded with host tumor lysate. Using these culture conditions, a marked increase in CD8+ CTLs was observed in both donors exhibiting a strong MHC class I‐restricted cytotoxic activity against the host tumor without cross‐reactivity against nonmalignant host cells. CDR3 spectratyping was used to analyze the complexity of T‐cell subpopulations in both CTL lines. Results demonstrate that oligoclonal T cells are expanded in vitro, exhibiting a marked overexpression of TCRVβ3 (donor 1) and TCRVβ4/Vβ11 (donor 2) subfamilies. Functional (ELISPOT assay) and phenotypic (CDR3 spectratyping, sequencing Vβ transcripts) analysis of patients' T cells at different time points after transplantation demonstrated an expansion of alloreactive T cells with a limited TCR Vβ pattern. The Vβ3 cDNA clone, being predominant in the CTL line from donor 1, could not be identified in patient 1 peripheral blood lymphocytes after transplant. Altogether, our results provide the first evidence that GVT effects against melanoma can induce tumor regression and that oligoclonal donor‐derived CTLs specific against host tumor cells can be generated in vitro that may be used for adoptive T‐cell transfer after allogeneic transplantation. © 2002 Wiley‐Liss, Inc.
Extended bioactivity in the proximity of hydroxyapatite ceramic surfaces induced by polarization charges
Authors: Nakamura Satoshi , Kobayashi Takayuki , Yamashita Kimihiro
Published: October 2002

Surface charges of electrically polarized hydroxyapatite (HAp) ceramics were demonstrated to enhance osteoconductivity in the wide gap of the canine bone whereas the bone formation processes varied according to the charge polarity. Cell reactions in the vicinity of the charged surfaces of HAp ceramics were not phagocytic absorption but rather bone formation by stimulated osteoblasts surrounding newly formed bone 7 days after implantation. The bone formation in direct contact with negatively charged ceramic surfaces suggests that the negative charges enhanced the osteobonding ability of the HAp ceramics. In the vicinity of the positively charged HAp surface, the formation of bones derived from osteoid tissues entirely occupied the 0.2–0.3‐mm gaps between the HAp and the bone at 7 days. Surface charges induced by electrical polarization significantly cooperated with the innate bioactivity of HAp and reconstructed the wide bone defects more promptly than did the nonpolarized HAp ceramic surface. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 593–599, 2002
Biodegradation of polycarbonate‐based polyurethanes by the human monocyte‐derived macrophage and U937 cell systems
Authors: Matheson Loren A. , Labow Rosalind S. , Santerre J. Paul
Published: October 2002

The prominent cell type found on implanted medical devices during the chronic inflammatory response is the monocyte‐derived macrophage (MDM). Using an activated in vitro cell system, it was possible to show that MDMs possess esterolytic activities that may contribute to the degradation of polyurethanes. In the present study, the U937 cell line was paralleled to the MDM cell system in order to validate the use of a cell line that could expedite studies on biomaterial biocompatibility and biostability. Using 12‐o‐tetradecanoylphorbol 13‐acetate (PMA), the optimum differentiation time for the U937 cells was 72 h based on biodegradation, degradative potential, and 35S‐methionine uptake. After activation of the cells by resuspending from tissue culture polystyrene plates and reseeding onto a 14C‐labeled polycarbonate‐based polyurethane (PCNU), both U937 cells and the MDMs elicited comparable radiolabel release (measure of polymer breakdown) and esterase activity (measure of degradative potential) at 48 h. There was no difference in the effect on radiolabel release and esterase activity elicited by both cell types with inhibitors of protein synthesis, esterase activity, and phospholipase A2. This established that both cell types likely used similar hydrolytic activities and signaling pathways to cause degradation of the PCNU. Immunoblotting demonstrated that both cell systems secreted monocyte‐specific esterase and cholesterol esterase enzymes previously shown to degrade PCNUs. The U937 cell system is more convenient and reproducible than MDMs for pursuing possible biological pathways elucidating the mechanism of polyurethane biodegradation. Once established with U937s, the pathways can then be validated with the more physiologically relevant human MDM cell system. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 505–513, 2002
Formation of nitrosothiols from gaseous nitric oxide at pH 7.4
Authors: Palmerini Carlo Alberto , Saccardi Carla , Arienti Giuseppe , Palombari Roberto
Published: October 2002

Nitric oxide (NO) is generated in biological systems and plays important roles as a regulatory molecule. Its ability to bind to haem iron is well known. Moreover, it may lose an electron, forming the nitrosonium ion, involved in the synthesis of S‐nitrosothiols (SNOs). It has been suggested that S‐nitrosohaemoglobin (−SNO Hb) and low molecular weight SNOs may act as reservoirs of NO. SNOs are formed in vitro, at strongly acidic pH values; however, the mechanism of their formation at neutral pH values is still debated. In this paper we report the anaerobic formation of SNOs (both high‐ and low‐molecular weight) from low concentrations of NO at pH 7.4, provided Hb is also present. We propose a reaction mechanism entailing the participation of Fehaem in the formation of NO+ and the transfer of NO+ either to Cysβ93 of Hb or to glutathione; we show that this reaction also occurs in human RBCs. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:135–139, 2002. DOI 10.1002/jbt.10028
Transfusion‐related acute lung injury during plasma exchange: Suspecting the unsuspected
Authors: Askari Sabeen , Nollet Kenneth , Debol Steven M. , Brunstein Claudio G. , Eastlund Ted
Published: October 2002

Transfusion‐related acute lung injury (TRALI) has been implicated with use of almost all types of blood products that contain variable amounts of plasma. Even though the reported incidence of TRALI is rare, its overall occurrence is thought to be more common, as less severe cases remain unreported. More TRALI cases are unrecognized and misdiagnosed due to lack of suspicion and absence of appropriate investigation. There are exceedingly rare reports of TRALI during plasma exchange despite the fact that liters of plasma may be used for replacement during a single procedure. We describe a mild case of TRALI during plasma exchange for thrombotic thrombocytopenic purpura in a 56‐year‐old woman, status post autologous hematopoietic stem cell transplant for non‐Hodgkin's lymphoma. She developed severe rigors, peripheral cyanosis, hypoxia, and a transient diffuse pulmonary infiltrate. Of the 10 U of plasma used, one was from a multiparous female donor with HLA antibodies reactive with patient's granulocytes in immunofluorescence and agglutination assays. This case emphasizes the fact that the physicians and apheresis staff should consider TRALI in the differential diagnosis for patients developing respiratory distress during or soon after the procedure. Diagnosing TRALI has implications not only for the plasma exchange recipient, but also for the management of donors found to have leukocyte antibodies. J. Clin. Apheresis 17:93–96, 2002. © 2002 Wiley‐Liss, Inc.
IT Performance: How Do You Measure a Moving Target?
Authors: Stanwick Peter , Stanwick Sarah
Published: October 2002

Measuring the payoff of investments in IT is a huge challenge. The authors explain how to do it—and how

to ensure that your company effectively evaluates IT investments. © 2002 Wiley Periodicals,

Inc.
Protecting Your Web Site from Criminal Hackers
Authors: Schroeder Chris , Smith Gordon
Published: October 2002

Do you think you're protected from hackers because you have nothing valuable on your Web site? Or

do you think company data are safely hidden behind a “firewall”? Better take another look,

warn the authors, whose security audits routinely uncover problems. © 2002 Wiley Periodicals,

Inc.
Does PTH have a direct effect on intestine?
Authors: Nemere I. , Larsson D.
Published: October 2002

Dogma for the past three decades has dictated that parathyroid hormone (PTH) has no direct effect on intestine with regard to calcium or phosphate absorption, but rather that PTH acts to promote the synthesis of a hormonally active form of vitamin D, namely 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3]. However, diverse laboratories have each provided some evidence to suggest PTH does indeed have a direct effect on intestine. We will briefly review the evidence for biological effects, biochemical effects, and the presence of intestinal receptors for PTH, and conclude with the implications for biomedical research. J. Cell. Biochem. 86: 29–34, 2002. © 2002 Wiley‐Liss, Inc.
Molecular characterization of protein kinase C‐α binding to lamin A
Authors: Martelli Alberto M. , Bortul Roberta , Tabellini Giovanna , Faenza Irene , Cappellini Alessandra , Bareggi Renato , Manzoli Lucia , Cocco Lucio
Published: October 2002

Previous results from our laboratory have identified lamin A as a protein kinase C (PKC)‐binding protein. Here, we have identified the regions of PKC‐α that are crucial for this binding. By means of overlay assays and fusion proteins made of glutathione‐S‐transferase (GST) fused to elements of rat PKC‐α, we have established that binding occurs through both the V5 region and a portion of the C2 region (i.e., the calcium‐dependent lipid binding (CaLB) domain) of the kinase. In particular, we have found that amino acid 200–217 of the CaLB domain are essential for binding lamin A, as a synthetic peptide corresponding to this stretch of amino acids prevented the interaction between the CaLB domain and lamin A. We also show that the presence of four lysine residues of the CaLB domain (K205, K209, K211, and K213) was essential for the binding. We have determined that binding of elements of PKC‐α to lamin A does not require the presence of cofactors such as phosphatidylserine (PS) and Ca2+. We have also found that the binding site of lamin A for the CaLB domain of PKC‐α is localized in the carboxyl‐terminus of the lamin, downstream of amino acid 499. Our findings may prove to be important to clarify the mechanisms regulating PKC function within the nucleus and may also lead to the synthesis of isozyme‐specific drugs to attenuate or reverse PKC‐dependent nuclear signaling pathways important for the pathogenesis of cancer. © 2002 Wiley‐Liss, Inc.
Human endothelial cells selectively express large amounts of pancreatic‐type ribonuclease (RNase 1)
Authors: Landré Julien B.P. , Hewett Peter W. , Olivot Jean‐Marc , Friedl Peter , Ko Yon , Sachinidis Agapios , Moenner Michel
Published: October 2002

Pyrimidine‐specific ribonucleases are a superfamily of structurally related enzymes with distinct catalytic and biological properties. We used a combination of enzymatic and non‐enzymatic assays to investigate the release of such enzymes by isolated cells in serum‐free and serum‐containing media. We found that human endothelial cells typically expressed large amounts of a pancreatic‐type RNase that is related to, if not identical to, human pancreatic RNase. This enzyme exhibits pyrimidine‐specific catalytic activity, with a marked preference for poly(C) substrate over poly(U) substrate. It was potently inhibited by placental RNase inhibitor, the selective pancreatic‐type RNase inhibitor Inhibit‐Ace, and a polyclonal antibody against human pancreatic RNase. The enzyme isolated from medium conditioned by immortalized umbilical vein endothelial cells (EA.hy926) possesses an amino‐terminal sequence identical to that of pancreatic RNase, and shows molecular heterogeneity (molecular weights 18,000–26,000) due to different degrees of N‐glycosylation. Endothelial cells from arteries, veins, and capillaries secreted up to 100 ng of this RNase daily per million cells, whereas levels were low or undetectable in media conditioned by other cell types examined. The corresponding messenger RNA was detected by RT‐PCR in most cell types tested so far, and level of its expression was in keeping with the amounts of protein. The selective strong release of pancreatic‐type RNase by endothelial cells suggests that it is endowed with non‐digestive functions and involved in vascular homeostasis. J. Cell. Biochem. 86: 540–552, 2002. © 2002 Wiley‐Liss, Inc.