bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapy of chemotherapy‐induced peripheral neuropathy
Authors: Kaley Thomas J. , DeAngelis Lisa M. 
Published: January 2009

SummaryChemotherapy‐induced peripheral neuropathy (CIPN) is still a common and disabling side effect of many chemotherapy agents in use today. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful yet. This review will discuss the diagnosis and evaluation of neuropathy in cancer patients, as well as reviewing the various prophylactic and symptomatic treatments that have been proposed or tried. However, sufficient evidence is lacking to recommend any of these treatments to patients suffering with CIPN. Therefore, the best approach is to treat symptomatically, and to start with broad‐spectrum analgesic medications such as non‐steroidal anti‐inflammatory drugs (NSAIDs). If NSAIDs fail, a reasonable second‐line agent in properly selected patients may be an opioid. Unfortunately, even when effective in other types of neuropathic pain, anti‐depressants and anticonvulsants have not yet proven effective for treating the symptoms of CIPN.
Clonal diversity in the myeloproliferative neoplasms: independent origins of genetically distinct clones
Authors: Beer Philip A. , Jones Amy V. , Bench Anthony J. , Goday‐Fernandez Andrea , Boyd Elaine M. , Vaghela Krishna J. , Erber Wendy N. , Odeh Bassam , Wright Christine , McMullin Mary Frances , Cullis Jonathan , Huntly Brian J. P. , Harrison Claire N. , Cross Nicholas C. P. , Green Anthony R. 
Published: January 2009

SummaryThis study looked for clonal diversity in patients with a myeloproliferative neoplasm associated with more than one acquired genetic lesion. A tyrosine kinase mutation and a cytogenetic lesion were present in the same clone in six of seven patients. By contrast, the genetic lesions were present in separate clones in all six patients with two tyrosine kinase pathway mutations. Moreover, in two patients the clones were genetically unrelated by X‐chromosome inactivation studies. These data demonstrated clonal diversity in a subset of patients with early stage haematopoietic malignancy and showed, for the first time, that such clones may arise independently.
Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men
Authors: Meltzer Mirjam E. , Doggen Carine J. M. , De Groot Philip G. , Rosendaal Frits R. , Lisman Ton 
Published: January 2009

SummaryStudies on the relationship between fibrinolysis and arterial thrombosis have been conflicting. Previously, we demonstrated that hypofibrinolysis, as measured by a plasma‐based assay, increased the risk of venous thrombosis. The present study investigated increased clot lysis time (CLT) measured with the same assay as a risk factor for myocardial infarction in a case‐control study including 421 men with a first myocardial infarction and 642 controls below 70 years. CLT was strongly associated with body‐mass index, lipid levels, blood pressure and C‐reactive protein. Overall, risk of myocardial infarction was 1·4‐fold (95% confidence interval (CI) 1·0–1·9) increased for CLT in the fourth quartile (longest CLT) compared with the first quartile. After adjusting for cardiovascular risk factors this risk disappeared (OR 1·0, 95%CI 0·6–1·5). In men aged <50 years the association was pronounced (OR 3·2, 95%CI 1·5–6·7). After adjustment for cardiovascular risk factors the risk was nearly twofold increased (OR 1·8, 95%CI 0·7–4·8). In men aged ≥50 years, no clear association between CLT and risk of myocardial infarction was found. Our study suggests that hypofibrinolysis increases the risk of a first myocardial infarction in young men, although the causality of this association remains to be determined.
The peptide‐semicarbazone S‐2209, a representative of a new class of proteasome inhibitors, induces apoptosis and cell growth arrest in multiple myeloma cells
Authors: Baumann Philipp , Müller Karin , Mandl‐Weber Sonja , Leban Johann , Doblhofer Robert , Ammendola Astrid , Baumgartner Roland , Oduncu Fuat , Schmidmaier Ralf 
Published: January 2009

SummaryBortezomib is the first approved member of a new class of anti‐myeloma agents, the proteasome inhibitors. Further proteasome inhibitors are needed to optimise this promising treatment option. S‐2209 [1‐[1‐{1‐[(2,4‐Dioxo‐imidazolidin‐1‐ylimino)‐methyl]‐2‐phenyl‐ethylcarbamoyl}‐2‐(1H‐indol‐3‐yl)‐ethylcarbamoyl]‐2‐(1H‐indol)] inhibits the chymotryptic activity of the human 20S proteasome (half maximal effective concentration, IC50∼220 nmol/l) which was determined by a proteasome inhibition assay. A nuclear factor κB inhibition assay revealed a half maximal effective concentration (EC50) of 0·9 μmol/l. The WST‐1 growth assay showed inhibition of cell growth of all tested multiple myeloma (MM) cell lines with an IC50 between 100 nmol/l and 600 nmol/l. Strong induction of apoptosis was seen in MM cells at nanomolar concentrations (IC50∼300 nm) as well as in primary myeloma cells. No induction of apoptosis was detected in peripheral blood mononuclear cells from healthy humans. Upregulation of p53, activation of JNK protein, and downregulation of Mcl‐1 was revealed. Despite the administration of 15 mg S‐2209/kg/d in wistar rats, no toxicity with respect to body weight, hepatic enzymes, creatinine or haemoglobin was seen. Proteasome inhibition in white blood cells isolated from the treated rats was higher in the S‐2209 treated animals in comparison with the control animals treated with 0·1 mg/kg/d bortezomib. S‐2209 is active in myeloma cells and shows a favourable toxicity profile in first in‐vivo studies. S‐2209 is a promising agent for further clinical development.
Novel insights into glucocorticoid‐mediated diabetogenic effects: towards expansion of therapeutic options?
Authors: Van Raalte D. H. , Ouwens D. M. , Diamant M. 
Published: January 2009

AbstractAt pharmacological concentrations, glucocorticoids (GCs) display potent anti‐inflammatory effects, and are therefore frequently prescribed by physicians to treat a wide variety of diseases. Despite excellent efficacy, GC therapy is hampered by their notorious metabolic side effect profile. Chronic exposure to increased levels of circulating GCs is associated with central adiposity, dyslipidaemia, skeletal muscle wasting, insulin resistance, glucose intolerance and overt diabetes. Remarkably, many of these side‐effects of GC treatment resemble the various components of the metabolic syndrome (MetS), in which indeed subtle disturbances in the hypothalamic‐pituitary‐adrenal (HPA) axis and/or increased tissue sensitivity to GCs have been reported. Recent developments have led to renewed interest in the mechanisms of GC's diabetogenic effects. First, ‘selective dissociating glucocorticoid receptor (GR) ligands’, which aim to segregate GC's anti‐inflammatory and metabolic actions, are currently being developed. Second, at present, selective 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) inhibitors, which may reduce local GC concentrations by inhibiting cortisone to cortisol conversion, are evaluated in clinical trials as a novel treatment modality for the MetS.In this review, we provide an update of the current knowledge on the mechanisms that underlie GC‐induced dysmetabolic effects. In particular, recent progress in research into the role of GCs in the pathogenesis of insulin resistance and beta‐cell dysfunction will be discussed.
Iron‐induced platelet aggregation measurement: a novel method to measure platelet function in stenting for ST segment elevation myocardial infarction
Authors: Smit J. J. J. , Van Oeveren W. , Ottervanger J. P. , Slingerland R. J. , Remijn J. A. , Zijlstra F. , Van‘t Hof A. W. J. 
Published: January 2009

AbstractBackground  Iron and (stainless) steel are potent platelet aggregation activators, and may be involved in stent thrombosis, a serious complication after intracoronary stenting. Current platelet function tests are suboptimal, because of inappropriate agonists and/or lack of reproducibility. We tested the feasibility and reproducibility of a novel platelet function test using stainless steel as an agonist and compared it with other platelet function tests.Materials and methods  In 111 patients with acute ST segment elevation myocardial infarction (STEMI), duplo measurements of iron (Fe)‐induced platelet aggregation (FIPA) were performed after clopidogrel, acetylsalicylic acid and/or tirofiban treatment. Within 1 h, citrated blood samples drawn from the femoral sheath before primary percutaneous coronary intervention were added to 100 mg of low carbon steel and after 5 s mixing with vortex, the samples were incubated for 15 min. The ratio between the non‐aggregated platelets in the agonist sample and platelets in a reference sample was calculated as the platelet aggregation inhibition.Results  FIPA measurement was highly reproducible (correlation coefficient (R) = 0·942, P < 0·001 between duplo samples). FIPA correlated well with adenosine diphosphate‐induced platelet aggregation (R = 0·83, P < 0·001) but weakly with platelet function analyser‐100 bleeding time (R = 0·56, P < 0·001). FIPA could be measured in patients in which platelet aggregation could not be measured by platelet function analyser‐100 or after adenosine diphosphate.Conclusion  This study showed good reproducibility of a novel platelet function test using stainless steel as an agonist and showed correlation with validated platelet function tests. We found that the novel platelet function test is a suitable test for measurement of platelet aggregation inhibition in patients undergoing stenting for STEMI, even when they are taking multiple antiplatelet regimens.
Epidemiology of snoring and obstructive sleep apnoea in a Danish population, age 30–60
Authors: JENNUM POUL , SJØL ANETTE 
Published: January 2009

SUMMARY  Several epidemiological studies have estimated the prevalence of obstructive sleep apnoea syndrome (OSAS). As many of those suffering from sleep apnoea may be asymptomatic, the occurrence of sleep apnoea may be underestimated. The epidemiology of self‐reported snoring, sleep apnoea and OSAS, and their relationships with various symptoms, were evaluated in 1504 randomly selected males and females, aged 30, 40, 50 and 60 years. Nocturnal respiration was determined in 748 participants using inductive plethysmography.Habitual snoring was reported by 19.1% (9.2–24.2%, age 30–60 years) of the males and 7.9% (3.8–11.7%, age 30–60 years) of the females. Respiratory Distress Index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour lasting longer than 10s. RDI≥5 per hour was found in 10.9% (7.1–18.3%, age 30–60 years) of the males and in 6.3% (5.3–7.6%, age 30–60 years) of the females. Hypersomnia increased with the severity of sleep apnoea (P< 0.005) and was reported by 15.9% of those with RDI≥5.The prevalence of OSAS (hypersomnia and RDI ≥5) was 0.9% in the females, 1.9% in the males, and in total 1.4% of all aged 30–60 years. The sensitivity was 70.8% and the specificity was 47.7% for self‐reported snoring predicting RDI ≥5.The following factors were associated with RDI ≥5: age (P<0.05), gender (P< 0.0001), BMI (P< 0.0001), tobacco (P<0.02) and alcohol (P<0.05) consumption. Snoring correlated with age (P<0.02), gender (P<0.001), BMI (P<0.0001) and alcohol consumption (P<0.05).We conclude that sleep apnoea is common and many of those with sleep apnoea are asymptomatic. Self‐reported hypersomnia and snoring are not sensitive enough alone to identify those with sleep apnoea. Sufficient control of the questionnaire is thus essential in studies on snoring and the risk of cardiovascular diseases.
The severity of obstructive sleep apnoea is associated with insulin resistance
Authors: TIIHONEN MIKKO , PARTINEN MARKKU , NÄRVÄNEN SAKARI 
Published: January 2009

SUMMARY  Oral glucose tolerance tests (OGTT) were performed on eighteen patients with suspected obstructive sleep apnoea who also completed a whole‐night polygraphic recording with oximetry. Insulin resistance indices (IRI) were calculated as the product of areas under glucose and insulin curves. In the resulting multiple regression analysis the dependent variable was IRI and the independent variables were age, body mass index (BMI) and the number of nocturnal hypoxic episodes with over 4% desaturation per hour (ODI4).ODI4 was between 4.6 and 70 (median 22.3); IRI ranged from 2.20 to 33.55 (median 7.50). In the regression model the coefficient of determination (R2) for IRI was 0.441 (F‐ratio = 3.681, P= 0.038). The strongest determinant of IRI was ODI4 and the regression coefficient of BMI was not significantly different from zero even when possible outliers were excluded.It was found that insulin resistance is related to the severity of sleep anoea. This may be due to a hypoxia‐induced hormonal stress reaction which decreases tissue insulin sensitivity. Since upper body obesity is associated with both insulin resistance and sleep apnoea, the distribution of fat should be taken into account in future studies.
Changes of sleep EEG slow‐wave activity in response to sleep manipulations: to what extent are they related to changes in REM sleep latency?
Authors: BEERSMA D. G. M. , ACHERMANN P. 
Published: January 2009

SUMMARY  Sleep interventions may have direct effects on slow‐wave activity (SWA, i.e. power of the sleep EEG signal in the 0.75‐4.5 Hz range) as well as indirect ones caused by changes in REM sleep (REMS) latency. The effects of changes in REMS latency on SWA were investigated by analysing simulations with a mathematical model. Mean SWA in the first non‐REMS episode shows an initial increase and a later decline as a function of REMS latency. In the second non‐REMS episode, mean SWA decreases with increasing REMS latency. These results of the simulations were validated with experimental data.In the evaluation of the effects of sleep interventions on SWA the effects of the timing of REMS have to be accounted for. The analysis of SWA over a sufficiently long constant amount of time spent in non‐REMS proves to be relatively independent of REMS latency, which allows conclusions about the effects of sleep interventions on SWA per se.
Diurnal sleep/wake‐related immune functions during the menstrual cycle of healthy young women
Authors: MOLDOFSKY HARVEY , LUE FRANKLIN A. , SHAHAL BARUCH , JIANG CHENG‐GAN , GORCZYNSKI REGINALD M. 
Published: January 2009

SUMMARY  Animal and human studies have related the sleeping/waking brain to the immune system. Because women are more susceptible to certain immunological illnesses, and sex steroids regulate immune functions, it was investigated whether the diurnal sleep/wake pattern of aspects of cellular immune functions and interleukin‐1 (IL‐1) and IL‐2‐like activities differed during low and high progesterone phases of the menstrual cycle.Eleven healthy women, mean age 24y, were assessed over 24h with serial venous blood samples. Peripheral blood monocytes were assayed for mitogen responses, i.e. phytohemagglutin (PHA) and pokeweed (PWM) and natural killer (NK) cell activities. Plasma was assayed for IL‐1 and IL‐2‐like activities, cortisol and progesterone. Data were standardized by Z transformation and analysed by repeated‐measures analysis of variance by comparing high (N= 5) vs. low (N= 6) progesterone phases.During the high progesterone phase, delayed slow‐wave sleep (SWS) onset time and reduced amount of SWS was accompanied by a delay in the decline of NK cell activity, but rise in PHA activity following sleep onset. With the low progesterone phase, the pattern was similar to men with an early sleep decline in NK cell and late sleep rise in PHA activities. PWM rose during the night and plasma IL‐1‐like activity peaked during midday and during nocturnal sleep irrespective of the amount of progesterone.Slow‐wave sleep and sleep‐related NK cell and PHA activities differed over the menstrual cycle, but not PWM response. Increases in plasma IL‐1 functions during midday and night are consistent with predisposition to sleepiness during these times.
Haemodynamics during sleep: old results and new perspectives
Authors: COCCAGNA GIORGIO , LUGARESI ELIO 
Published: January 2009

SUMMARY  After the advent of polygraphic recordings in the 1960s a great deal of interest focused on cardiocirculatory and respiratory activity during sleep.The Bologna sleep laboratory was the first to make direct recordings of systemic arterial pressure, pulmonary arterial pressure and alveolar ventilation in normal subjects, measuring gas‐blood values during different sleep stages. In the 1960s, neurophysiologists rediscovered a syndrome known to pneumologists for a decade as Pickwickian Syndrome. Polygraphic studies performed in sleep laboratoires all over Europe (Germany, France and Italy) led to a major discovery: the syndrome was not caused by respiratory overload due to obesity, but usually by the presence of obstructive apnoeas arising during sleep. By means of continuous sleep recordings, our laboratory documented the severe repercussions of apnoeas on ventilatory and cardiocirculatory functions. Hypnologists pointed to tracheostomy as the logical effective treatment for the syndrome. Surgery was first performed in Germany by Kuhlo and coworkers and then in Bologna.In the early 1970s, following the Bologna group's research, there emerged the now accepted concept that obstruction of the upper airways is a continuum stretching from snoring to full‐blown sleep apnoea syndrome. The Bologna team was also the first to conduct epidemiological surveys that indicated that snoring is a relevant risk factor for the cardiocirculatory system.Here the trends of haemodynamic and ventilatory parameters during sleep are investigated in syndromes of obstructive respiratory failure. The conclusion is that sleep, particularly REM‐sleep, exacerbates all these disorders, and the topic provides a basis for a wider look at how cardiocirculatory activity varies during sleep under normal and pathological conditions.
The effect of decreased intrathoracic pressure on ventricular function
Authors: SCHARF STEVEN M. 
Published: January 2009

SUMMARY  Large decreases in inspiratory intrathoracic pressure (ITP) occur during obstructive apnoeas. The cardiac effects of apnoea‐associated decreased ITP come from the interaction of increased preload (venous return) on the right ventricle (RV) and increased afterload on the left ventricle (LV), and are modulated by the autonomic effects of shifts in blood volume and hypoxaemia. During obstructed breathing, venous return increases by as much as three‐fold during inspiration even though mean flow may change little. This leads to a substantial inspiratory increase in RV end‐diastolic and stroke volume. Because of ventricular interdependence, there is a decrease in LV diastolic compliance and corresponding decrease LV preload.Sustained decreases in ITP (Müller manoeuvre) inhibit LV ejection, and hence increase LV afterload. However, breathing against an obstructed airway (repetitive short Müller manoeuvre) is not necessarily modelled by the sustained manoeuvre. Animal studies indicate that with airway obstruction, for the first beat or two of inspiration the primary effect on the LV is a reduction in stroke volume related to a decrease in preload, and afterload, if anything, decreases. In fact, afterload only increases during early expiration when stroke volume increases. When obstructive and central apnoeas are paired for duration and blood‐gas alterations, there are increases in pulmonary blood volume with central apnoeas and in RV volume with obstructive apnoeas, consistent with the postulation that the primary effect of obstructive apnoeas is on venous return.In conclusion, the putative role of decreased ITP in increasing LV afterload under conditions appropriate to OSA is not well supported by experimental studies. However, effects with very large swings in ITP as might be seen under the most extreme forms of OSA, and differences in timing of the swings between diastole and systole have yet to be investigated.
Influence of obstructive sleep apnoea on circadian blood pressure profile
Authors: PANKOW W. , NABE B. , LIES A. , KOHL F. V. , LOHMANN F. W. 
Published: January 2009

SUMMARY  A high prevalence of systemic hypertension in obstructive sleep apnoea (OSA) has been described but data on circadian blood pressure (BP) profile are limited and give inconsistent results. The present study examines 24‐h BP in 106 patients referred because of loud snoring or excessive daytime sleepiness in combination with snoring. Patients were classified as OSA (n = 62) or habitual snorers (HS) (n = 44). Respiratory disturbance index (RDI) in OSA was 47 ± 24 vs. 2 ± 2 in HS. Mean age and body mass index in OSA was significantly higher.BP was measured non‐invasively at 15‐min intervals during a 24‐h period. Daytime and night‐time BP was higher in OSA compared to HS. BP night/day ratio in OSA was 0.92 ± 0.07 vs. 0.86 ± 0.06 in HS (P < 0.05). To investigate the influence of variables other than breathing abnormalities during sleep on our results we compared BP profiles of 25 OSA and 25 HS matched for sex, age and body weight. Again differences in daytime and night‐time BP and BP night/day ratio were significant. Using a value of at least 10% fall in nocturnal BP to describe a regular BP profile (dipper) 68% of OSA were classified as non‐dippers vs. 24% of HS.Influence of short‐term (2–4 days) nCPAP therapy on circadian BP profile was investigated in 34 patients with OSA. Systolic and diastolic nocturnal (but not daytime) BP was significantly reduced. The percentage of non‐dippers was 79% before and 50% after treatment. In conclusion results of this study indicate a causal link between OSA and abnormal circadian BP profile.
Cerebral perfusion during sleep‐disordered breathing
Authors: HAJAK GÖRAN , ELHÖFER JÜRGEN KLING , SCHULZ‐VARSZEGI MARIA , SANDER DIRK , STAEDT JÜRGEN , CONRAD BASTIAN , RÜTHER ECKART 
Published: January 2009

SUMMARY  Snoring, a leading symptom of the sleep apnoea syndrome (SAS), has been reported to be one of the risk factors for sleep‐related cerebral strokes. Episodes of apnoea are accompanied by hypoxaemia as well as hypercapnia. As CO2 constitute a major regulatory factor controlling cerebral blood flow, it is likely that changes in cerebral perfusion are to be found in patients with SAS, which may be related to nocturnal stroke. A computer‐assisted pulsed (2 mHz) Doppler ultrasonography system has been modified for continuous long‐term and on‐line recording of cerebral haemodynamics together with simultaneous polysomnography, continuous blood pressure recordings, and measurement of the end‐expiratory CO2. The dynamics of cerebral blood flow velocity (CBFV) during sleep were measured in the right middle cerebral artery in 10 SAS patients.CBFV showed a characteristic nocturnal pattern with decreases during non‐rapid eye movement (NREM) sleep and increases during REM sleep. Changes in sleep stage patterns as well as awakenings from NREM sleep were not regularly accompanied by corresponding changes in CBFV. Dramatic increases in CBFV could be observed during apnoeic episodes, with maximum increases during REM sleep. CO2 reactivity and changes in CBFV related to apnoea duration were markedly increased during sleep compared with the waking state in SAS patients.The dynamic feature of CBFV in relation to sleep patterns reflects quantitative uncoupling between cerebral electrical activity and cerebral perfusion during sleep in SAS patients as has been previously reported for normal subjects (Hajak et al. 1994). It supports a dissociation in the activity of central regulatory mechanisms during human sleep which might cause abnormal cerebral perfusion under certain circumstances. The increased CO2 reactivity during sleep in SAS suggests a ‘hypersensitivity’ of intracranial vasoactive receptors and/or disturbances in the central autonomic control of cerebrovascular functions. It may be concluded that, under certain conditions, the interaction of decreased cerebral perfusion in SAS patients with sleep‐related cerebral perfusion patterns and haemodynamic changes during apnoeic episodes might lead to a critical reduction in cerebral perfusion.