bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of L‐type amino acid transporter 1 (LAT1) and 4F2 heavy chain (CD98) expression in early stage squamous cell carcinoma of the lung
Authors: Kaira Kyoichi , Oriuchi Noboru , Imai Hisao , Shimizu Kimihiro , Yanagitani Noriko , Sunaga Noriaki , Hisada Takeshi , Ishizuka Tamotsu , Kanai Yoshikatsu , Endou Hitoshi , Nakajima Takashi , Mori Masatomo 
Published: December 2008

The purpose of this study was to evaluate the prognostic value of L‐type amino acid transporter 1 (LAT 1) and 4F2 heavy chain (CD98) in patients with stage I squamous cell carcinoma of the lung. A total of 84 consecutive patients with completely resected pathologic stage I squamous cell carcinoma of the lung were retrospectively reviewed. All patients underwent resection of the tumor and the immunohistochemical analysis was done to determine the expression of LAT 1, CD98, Ki‐67 labeling index, vascular endothelial growth factor, and microvessel density. These pathological parameters were correlated with the prognosis of patients after complete resection of the tumor. A positive rate of LAT 1 expression (87%; 73/84) was significantly higher than that of CD98 expression (65%; 55/84) (P = 0.0018). Cooperative expression of LAT 1 and CD98 was recognized in 62% (52/84). LAT 1 expression was significantly correlated with CD98, Ki‐67 labeling index, vascular endothelial growth factor, and microvessel density. The 5‐year survival rates of the LAT 1‐positive and LAT1‐negative patients were 59% and 88%, respectively (P = 0.2186). Tumor cell proliferation and angiogenesis were not also (a) prognostic factor. However, the 5‐year survival rate of patients with both LAT 1 and CD98‐positivity (57%) was significantly worse than that of other patients (88%; P = 0.0136). Multivariate analysis confirmed that positive cooperative expression of LAT 1 and CD98 was an independent factor for predicting a poor prognosis. A cooperative expression of LAT 1 and CD98 is a significant pathological factor for predicting the poor prognosis in patients with resectable stage I squamous cell carcinoma of the lung. (Cancer Sci 2009; 100: 249–254)
Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT‐C trial
Authors: EVERSON G. T. , SHIFFMAN M. L. , HOEFS J. C. , MORGAN T. R. , STERLING R. K. , WAGNER D. A. , DESANTO J. L. , CURTO T. M. , WRIGHT E. C. ,   THE HALT‐C TRIAL GROUP
Published: December 2008

SummaryBackgroud The impact of virologic response on hepatic function has not been previously defined.Aim To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) ± ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR).Methods Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long‐term Treatment against Cirrhosis (HALT‐C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24‐13C]cholate, galactose and99mTc‐sulfur colloid were administered intravenously; [2,2,4,2‐2H]cholate, [1‐13C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath13CO2, monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured.Results Rates of SVR were 18–26% in patients with good function by QLFTs, but ≤6% in patients with poor function. Hepatic metabolism, measured by caffeinekelim(P = 0.02), antipyrinekelim(P = 0.05) and antipyrineCl(P = 0.02) and the portal circulation, measured by cholateCloral(P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR.Conclusion Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM.
Psychopathology is associated with dyspeptic symptom severity in primary care patients with a new episode of dyspepsia
Authors: MUJAKOVIC S. , DE WIT N. J. , VAN MARREWIJK C. J. , FRANSEN G. A. J. , LAHEIJ R. J. F. , MURIS J. W. , SAMSOM M. , GROBBEE D. E. , JANSEN J. B. M. J. , KNOTTNERUS J. A. , NUMANS M. E. 
Published: December 2008

SummaryBackground  Personality and psychiatric disorders are reported to be more common in dyspeptic patients with severe complaints, but it remains unclear whether this association exists for patients with mild and moderate dyspepsia.Aim  To study the association between dyspeptic symptom severity and psychopathology, major life events and coping ability in patients with a new episode of dyspepsia.Methods  Dyspeptic symptom severity was measured using the validated eight symptom Veldhuyzen van Zanten questionnaire. Psychopathology was measured using the Symptom Check List‐90 (SCL 90). Major life events were measured with a modified version of the Social Readjustment Rating Scale (SRRS). Coping styles were measured by a short version of the Utrecht Coping Questionnaire, distinguishing six coping styles. Linear regression was used to assess the relationship between dyspepsia symptom severity and psychological factors.Results  In all, 664 patients with a new episode of uninvestigated dyspepsia, aged >18 years were included. Dyspeptic symptom severity was positively correlated with the presence of depression (P < 0.01), somatization symptoms (P < 0.01), use of an active coping style (P < 0.01) and negatively correlated with age (P < 0.01).Conclusions  Primary care patients consulting with dyspepsia have higher levels of depression and somatization especially at younger age. An active coping style is associated with dyspepsia symptom severity.
Co‐medication of statins and CYP3A4 inhibitors before and after introduction of new reimbursement policy
Authors: Devold Helene M. , Molden Espen , Skurtveit Svetlana , Furu Kari 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • HMG‐CoA reductase inhibitors (statins) are frequently used drugs in the treatment of dyslipidaemia.• Co‐medication with interacting drugs increases the risk of statin‐induced muscular side‐effects.• Simvastatin exhibits particularly high interaction potential due to substantial metabolism via cytochrome P450 3A4 (CYP3A4). WHAT THIS STUDY ADDS • In June 2005, a new reimbursement policy was introduced by the Norwegian Medicines Agency stating that simvastatin should be prescribed as first‐line lipid‐lowering therapy.• Following introduction of the new policy, the number of patients co‐medicated with simvastatin and CYP3A4 inhibitors almost doubled.• A potential consequence is increased incidence of muscular side‐effects in the statin‐treated population.AIMSTo assess the prevalence of co‐medication of statins and CYP3A4 inhibitors before and after introduction of a new Norwegian reimbursement policy, which states that all patients should be prescribed simvastatin as first‐line lipid‐lowering therapy.METHODSData from patients receiving simvastatin, lovastatin, pravastatin, fluvastatin or atorvastatin in 2004 and 2006, including co‐medication of potent CYP3A4 inhibitors, were retrieved from the Norwegian Prescription Database covering the total population of Norway. Key measurements were prevalence of continuous statin use (two or more prescriptions on one statin) and proportions of different statin types among all patients and those co‐medicated with CYP3A4 inhibitors.RESULTSIn 2004, 5.9% (n= 272 342) of the Norwegian population received two or more prescriptions on one statin compared with 7.0% (n= 324 267) in 2006. The relative number of simvastatin users increased from 39.7% (n= 112 122) in 2004 to 63.1% (n= 226 672) in 2006. A parallel increase was observed within the subpopulation co‐medicated with statins and CYP3A4 inhibitors, i.e. from 42.9% (n= 7706) in 2004 to 63.6% (n= 13 367) in 2006. For all other statins the number of overall users decreased to a similar extent to those co‐medicated with CYP3A4 inhibitors.CONCLUSIONSIn both 2004 and 2006, the choice of statin type did not depend on whether the patient used a CYP3A4 inhibitor or not. Considering the pronounced interaction potential of simvastatin with CYP3A4 inhibitors, a negative influence of the new policy on overall statin safety seems likely.
Evaluation of cost of treatment of drug‐related events in a tertiary care public sector hospital in Northern India: a prospective study
Authors: Pattanaik Smita , Dhamija Punit , Malhotra Samir , Sharma Navneet , Pandhi Promila 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drug related events include ADRs, events due to patient or physician noncompliance, drug overdosage and drug interactions.• Economic burden of management of drug related events are substantial and include both direct and indirect costs.• Some data regarding cost of treatment of ADR exist from south and western India. WHAT THIS STUDY ADDS • An approximate cost of management of drug related events presenting to the emergency medical department in a tertiary care hospital over a period of 4 months.• Compares the cost incurred in a public sector hospital to the projected cost of management of same events in a private sector hospital.• Gives a rough estimate of economic burden on the health care system due to adverse drug events.AIMS Drug related events (DREs) contribute significantly to hospital admissions. These are largely preventable events and require optimum use of the therapeutic agents. The study was conducted to analyze the cost of treatment of DREs.PATIENTS & METHODS All visits to medical emergency department of a tertiary care public sector hospital in northern India were recorded in a prospective, non‐interventional manner over a period of 4 months. DREs were recognized and were followed up till their stay in the hospital. Data about the cost generating components of direct and indirect costs of treatment of DREs were collected. The projected cost of treatment of the same DREs in a private sector hospital was estimated and compared.RESULTS Out of 1833 admissions, 92(5.01%) were due to DREs. Maximum cases were due to non compliance (66%) followed by ADR (28%) and drug overdose(6%). The common DREs leading to ED visits were cerebrovascular accident(19.44%), followed by accelerated hypertension(18.36%) and diabetic ketoacidosis(14.04%). Total cost of management of all the 92 DREs in our hospital was calculated to be INR17,37,339(€30,215). The direct cost was INR1,72,961(€3008) and the approximate indirect cost was INR15,64, 378(€27, 206). The projected cost of management of all the 92 DREs was estimated to be INR63,63,872(€1,01, 676) in a private sector hospital.CONCLUSION The study shows that ADEs leading to emergency department visits and hospitalizations constitute a significant economic burden. Training of the patients and the prescribers may lessen the economic burden on the patient as well as the health care system.
The Stanford V regimen is effective in patients with good risk Hodgkin lymphoma but radiotherapy is a necessary component
Authors: Abuzetun Jamil Y. , Loberiza Fausto , Vose Julie , Bierman Philip , Greg Bociek R. , Enke Charles , Bast Martin , Weisenburger Dennis , Armitage James O. ,   for the Nebraska Lymphoma Study Group
Published: December 2008

SummaryOne‐hundred and thirteen patients between the ages of 15 and 88 years with biopsy proven, untreated Hodgkin lymphoma were treated by physicians in the Nebraska Lymphoma Study Group using the Stanford V regimen (bleomycin, doxorubicin, etoposide, mechlorethamine, prednisone, vinblastine and vincristine) between January 1997 and January 2006. With a median follow‐up of all surviving patients of 63 months, the 5‐year overall survival (OS) was 84% and the 5‐year progression‐free survival (PFS) was 74%. Age >60 years, other than nodular sclerosing histological subtype, Ann Arbor Stage III/IV, and the presence of B‐symptoms significantly predicted treatment outcome. Patients with 0–2 of these factors had a 5‐year PFS and OS of 80% and 89% vs. 20% and 40% for patients with 3 or 4 factors. Patients who received radiotherapy had a superior 5‐year PFS (86% vs. 42%) and OS (96% vs. 53%). Patients with 0–2 adverse risk factors who received radiotherapy had an excellent treatment outcome with 5‐year PFS of 88% and a 5‐year OS of 97%. The Stanford V chemotherapy regimen has an excellent treatment outcome for good prognosis patients with Hodgkin lymphoma. The results are compromised when radiotherapy is not utilized.
Pregnancy‐induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw–Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients
Authors: Fujimura Yoshihiro , Matsumoto Masanori , Kokame Koichi , Isonishi Ayami , Soejima Kenji , Akiyama Nobu , Tomiyama Junji , Natori Kazuhiko , Kuranishi Yasunobu , Imamura Yutaka , Inoue Nobumasa , Higasa Satoshi , Seike Masako , Kozuka Teruhiko , Hara Masamichi , Wada Hideo , Murata Mitsuru , Ikeda Yasuo , Miyata Toshiyuki , George James N. 
Published: December 2008

SummaryUpshaw–Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura (TTP) due to mutations in the gene that encodes for ADAMTS13 (ADAMTS13), but its clinical signs may be mild or absent during childhood. We have identified 37 patients with USS (24 females, 13 males) belonging to 32 families. The nine women from six families who were diagnosed during their first pregnancy are the focus of this report. Six of the nine women had episodes of thrombocytopenia during childhood misdiagnosed as idiopathic thrombocytopenic purpura. Thrombocytopenia occurred during the second–third trimesters in each of their 15 pregnancies, with 16 babies (one twin pregnancy), often followed by TTP. Of 15 pregnancies, eight babies were stillborn or died soon after birth, and the remaining seven were all premature except one, who was born naturally following plasma infusions to the mother that had started at 8 weeks’ gestation. All nine USS women had severely deficient ADAMTS13 activity. ADAMTS13 analyses demonstrated that eight women were compound heterozygotes of Y304C/G525D (2 siblings), R125VfsX6/Q1302X (2 siblings), R193W/R349C (2 siblings), I178T/Q929X, and R193W/A606P; one woman was homozygous for R193W. Only the R193W mutation has been previously reported. These observations emphasize the importance of measuring ADAMTS13 activity in the evaluation of thrombocytopenia during childhood and pregnancy.
LONG‐TERM FOLLOW‐UP OF LOW‐DOSE EXTERNAL PITUITARY IRRADIATION FOR CUSHING'S DISEASE
Authors: LITTLEY M. D. , SHALET S. M. , BEARDWELL C. G. , AHMED S. R. , SUTTON M. L. 
Published: December 2008

SUMMARYTwenty‐four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low‐dose external pituitary irradiation (20 Gy in eight fractions over 10–12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4–36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low‐dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low‐dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505–1150 ng/1). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation‐induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low‐dose pituitary irradiation may be a useful treatment option in selected patients. However, long‐term follow‐up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy.
INHIBITION OF OESTRADIOL PRODUCTION BY EPIDERMAL GROWTH FACTOR IN HUMAN GRANULOSA CELLS OF NORMAL AND POLYCYSTIC OVARIES
Authors: MASON H. D. , MARGARA R. , WINSTON R. M. L. , BEARD R. W. , REED M. J. , FRANKS S. 
Published: December 2008

SUMMARYAnovulation in women with polycystic ovary syndrome results from a disorder of FSH‐mediated follicular maturation which may involve paracrine modulation of FSH action by intra‐ovarian factors. Epidermal growth factor (EGF) is a potent inhibitor of FSH‐stimulated oestradiol production in the rat and has also been shown to inhibit aromatase activity in human granulosa cells obtained after superovulation. The purpose of this study was to investigate the action of EGF on granulosa cell function in human ovaries which had not been previously exposed to treatment with exogenous gonadotrophins and to compare the responses in tissue obtained from normal and from polycystic ovaries. Granulosa cells were obtained from antral follicles <10 mm in diameter after dissection of unstimulated normal or polycystic ovaries (PCO). Cells were pooled, washed, plated and incubated for 48h in the presence of 10‐7 M testosterone and various doses of human FSH. FSH dose responses were obtained with or without the addition of purified EGF (50 pg/ml). Testosterone in the absence of FSH resulted in a fourfold (range 2–7.5) increase in oestradiol accumulation in the medium after incubation of granulosa cells from both normal and polycystic ovaries. This increase was reversed by addition of EGF. FSH treatment stimulated a dose‐related increase in oestradiol regardless of the origin of the granulosa cells. The peak E2 response to FSH, obtained at a dose of 1–2.5 ng/ml was a 20‐fold increase above testosterone alone (range 4–55) in cells from PCO compared to sixfold (2–5.13) in cells from normal ovaries. The concurrent addition of EGF at 50 pg/ml caused an average 57% inhibition of the peak response to FSH. EGF also caused a dose‐dependent inhibition of oestradiol production stimulated by a fixed dose of FSH in cells from both normal and PCO. These data indicate that EGF inhibits FSH‐inducedoestradiol production by granulosa cells of both normal and polycystic ovaries and suggest that EGF, or its analogue, transforming growth factor α, which is known to be synthesized by theca cells, may have a role in human ovarian function.
TRANSSPHENOIDAL SURGERY FOR CUSHING'S DISEASE: DOES WHAT IS REMOVED DETERMINE THE ENDOCRINE OUTCOME?
Authors: BURKE C. W. , ADAMS C. B. T. , ESIRI M. M. , MORRIS C. , BEVAN J. S. 
Published: December 2008

SUMMARYFifty‐seven patients with pituitary‐dependent Cushing's syndrome and eight with Nelson's syndrome underwent transsphenoidal pituitary exploration, with removal of macroscopically abnormal tissue in 64 patients and detailed histology of this in 63. The cure rate by stringent criteria 1 month later was 48 (83%) of the 58 with assessable data, who were followed for 225 patient‐years. Two patients relapsed later, a rate of one per 112 patient‐years of follow‐up. In 27% of patients, the macroscopically abnormal tissue removed was histologically indistinguishable from normal pituitary gland but the cure rate was 82%, and a quarter of the patients in this group assessable for recovery of normal ACTH function gained it. Another 53% of biopsies showed corticotropin adenomas, and the cure rate in these was 89% though rather more (69%) recovered normal ACTH function. The remaining 20% of biopsies were consistent with corticotroph hyperplasia. The cure rate varied little whether the lesion was diffuse or localized, whether or not it was in the invasion zone/interlobar cleft, whether or not there was pituitary enlargement, or whether the surgery was radical or selective. Six patients, of whom three are cured, showed surgical or radiological evidence of invasion outside the pituitary fossa. The data are consistent with the idea that pituitary adenoma is merely the end stage of some other process in the corticotrophs, and cure often follows removal of a lesion other than adenoma. Of patients who were permanently cured, 47% regained normal ACTH function within 3 years of operation (none later), 53% remaining ACTH‐deficient at 3 years or more. Of all patients 48% acquired gonadotrophin deficiency, 28% have TSH deficiency and 25% permanent diabetes insipidus. All these pituitary function deficits were more common after radical surgery and in patients with normal histology. The literature contains so little objective data on these functions that we cannot say whethere the endocrine damage in our patients is exceptional or not.
THE EFFECT OF DANAZOL AND THE LHRH AGONIST ANALOGUE GOSERELIN (ZOLADEX) ON THE BIOLOGICAL ACTIVITY OF LUTEINIZING HORMONE IN WOMEN WITH ENDOMETRIOSIS
Authors: MAOURIS P. , DOWSETT M. , ROSE GILLIAN , EDMONDS D. K. , ROTHWELL CLAIRE , ROBERTSON W. R. 
Published: December 2008

SUMMARYIn an attempt to determine whether the suppression in oestradiol levels caused by danazol is due to an effect on the hypothalamic‐pituitary axis, we compared the endocrine effects of danazol with those of the LHRH (GnRH) agonist analogue goserelin. Serum levels of immunoreactive LH (I‐LH), FSH, 17β‐oestradiol (E2) and bioactive LH (B‐LH) (using a mouse Leydig cell bioassay), were measured in ten and 20 women with endometriosis treated with danazol and goserelin, respectively. I‐LH was measured both by radioimmunoassay (RIA) and immunoradiometric assay (IRMA). During 6 months of treatment with 600 mg of danazol daily, mean serum E2 decreased (P <0.05) to levels near the upper limit of the post‐menopausal range (to a mean (and 95% confidence interval of the mean) of 117 (65–169) pmol/1) whereas FSH, I‐LH (both by RIA and IRMA) and B‐LH levels were not significantly altered. During 6 months of treatment with monthly depot injections of 3–6 mg goserelin, mean serum E2 decreased (P<0.001) to well within the post‐menopausal range (to 23 (18–28) pmol/1). The mean FSH, I‐LH and B‐LH levels also decreased (P <0.05) during therapy with goserelin (from 3.9 (3–1–4.7) to 2.0 (1.6‐2.4) IU/1 for FSH, from 5.3 (4.5–6.1) to 1.9 (1.7–2.1) IU/1 for RIA‐LH, from 2.9 (2.5–3.3) to <0.5 (<0.5) IU/1 for IRMA‐LH and from 9.1 (7.1–11.1) to 2.9 (2.6–3.2) IU/1 for B‐LH). The bioactive to immunoreactive (B:I) RIA LH ratio was altered during the first month of treatment with both drugs, increasing with danazol from 1.6(1.3.1.9) to 2.0(1.7‐2.3) (P<0.05) and decreasing with goserelin from 1.7 (1.5‐1–9) to 1.4 (1.2–1.6) (P<0.05). The data indicate that danazol causes a relatively hypo‐oestrogenic state which cannot be attributed to a decrease in the immunoreactive gonadotrophin levels or to a decrease in the biological activity of LH and is associated with an increase in B: ILH ratio. In contrast, goserelin acts on the pituitary to produce suppression of gonadotrophin levels and effective down‐regulation of the pituitary.
Bone protective therapy in the young patient with fractures and chronic disease: what drug(s) should be given and for how long?
Authors: Cooper Mark 
Published: December 2008

SummaryFractures are fortunately rare in younger people even with severe chronic disease but when they occur they need to be carefully evaluated. When considering such a patient there needs to be an assessment of the risk of future fractures and their type, a search for potentially modifiable risk factors and an evaluation of the risks vs. benefits of bone protective therapy. These factors will have to be considered in the context of the underlying chronic disease and the way that this impacts on the patient. In those individuals where bone protective therapy is given a clear plan is needed relating to how long the treatment is used and what type of monitoring is warranted.