bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI‐1) activity in lean women with and without the polycystic ovary syndrome
Authors: Sampson Michael , Kong Chiew , Patel Anita , Unwin Robert , Jacobs Howard S.
Published: November 2003

OBJECTIVE Hyperinsulinaemic women with the polycystic ovary syndrome (PCOS) may be at increased risk of vascular disease later in life, mediated by blood pressure or lipid abnormalities or by elevated plasma levels of plasminogen activator inhibitor‐1 (PAI‐1) activity. PAI‐1 may also be involved in ovarian follicle development and ovarian connective tissue remodelling. We measured plasma PAI‐1 activity and 24‐hour ambulatory blood pressure records in women with and without PCOS.

DESIGN Cross‐sectional study of three groups.

PATIENTS Twenty‐four non‐obese women with a classic ovarian ultrasound appearance of PCO and extreme menstrual disturbance (Group 1), 26 matched controls with a normal menstrual cycle and an ultrasound appearance of PCO (Group 2) and 10 matched controls with a normal menstrual cycle and normal ovarian ultrasound (Group 3).

MEASUREMENTS Twenty‐four hour ambulatory blood pressure recordings (Spacelabs 90207), ovarian ultrasonography, fasting plasma insulin and glucose, plasma PAI‐1 activity, HDL and total cholesterol, triglycerides, gonadotrophins and testosterone. Family history of premature vascular disease.

RESULTS Median fasting plasma insulin was significantly higher in Group 1 (45 .8 pmol/l, range 12.9–161.9) than in Group 2 (28.1 pmol/l; range 13.6–91; P <0.05) or Group 3 (26.0 pmol/l; range 13.5–63.3; P <0.05). There were no differences between groups in 24‐hour, daytime or night‐time ambulatory blood pressure measurements, and no relation between plasma insulin and any blood pressure variable.  Mean plasma PAI‐1 activity was higher in Group 1 (10.0 ±7.1 AU/l) than in Group 2 (6.0 ±4.6 AU/l P < 0.05) or Group 3 (5.1 ± 3.5 AU/l; P =0.06). There was a significant independent direct relation between fasting plasma insulin and PAI‐activity (r = 0.41, R2 = 0.154; F1,59 = 11.38; P = 0.001). Groups did not differ in parental history of premature vascular disease, or in mean HDL or fasting triglyceride levels.

CONCLUSIONS The only measurable vascular risk factor associated with hyperinsulinaemia and menstrual disturbance in non‐obese women with PCOS is an elevated plasma PAI‐1 activity. These women did not differ from controls in ambulatory blood pressure profiles, lipid measurements or in a parental history of premature vascular disease. PAI‐1 and plasminogen are involved in ovarian follicle maturation and the present finding suggests a biologically plausible link between hyperinsulinaemia, anovulation and vascular risk in PCOS.
Plasma cortisol, PRL, ACTH, AVP and corticotrophin releasing hormone responses to direct current cardioversion and electroconvulsive therapy
Authors: Florkowski C. M. , Crozier I. G. , Nightingale S. , Evans M. J. , Ellis M. J. , Joyce P. , Donald R. A.
Published: November 2003

OBJECTIVE We aimed to evaluate and contrast the hypothalamo–pituitary–adrenal (HPA) response to direct current (DC) cardioversion and electroconvulsive therapy (ECT).

SUBJECTS Six male subjects (mean age 61.2 years, range 46–74) with chronic atrial fibrillation were selected for cardioversion. Six subjects with depression (one male, five female; mean age 43.2 years, range 31–59) were selected for ECT. Those taking glucocorticoid drugs, opiates or β‐adrenoceptor antagonists were excluded.

MEASUREMENTS Patients attended for serial blood sampling on the day of cardioversion or ECT, and for an equivalent time period on a control day at least one week before. Intravenous propofol was given to each subject for anaesthesia on the day of cardioversion or ECT. On both study and control days, blood samples were taken at −30, −15, 0 (just prior to cardioversion or ECT), +5, +10, +15, +30, +60, +90 and +120 minutes for assay of cortisol, PRL, ACTH, AVP and CRH.

RESULTS  For cardioversion: plasma cortisol increased from 252.5 ± 39.8 to a maximum of 721.3 ± 50 nmol/l at 30 minutes (P < 0.0001 compared with control day). ACTH increased from 12.8 ± 2.8 to a maximum of 64 ± 14 pmol/l at 5 minutes (P < 0.0001 compared with control day). AVP increased from 6.6 ± 3.3 to a maximum of 42.9 ± 16 pmol/l at 5 minutes post‐cardioversion (P < 0.005 compared with control day). PRL increased from 141 ± 28 mIU/l to a maximum of 873 ± 219 mIU/l at 10 minutes (P < 0.001 compared with control day). There was no significant difference in CRH responses between cardioversion and control days. There was no significant correlation between total electrical energy delivered and maximum ACTH and AVP responses (R = 0.54 and −0.13, respectively).  For ECT: on the day of ECT plasma cortisol increased from 419.5 ± 25.9 to a maximum of 614.7 ± 26.9 nmol/l (P < 0.002 compared with control day). ACTH increased from 22.7 ± 6.2 to a maximum of 77.8 ± 19.1 pmol/l (P < 0.0003 compared with control day). PRL increased from 771 ± 317 to a maximum of 3152 ± 703 mIU/l (P < 0.001 compared with control day, and significantly greater than the peak response to cardioversion, P < 0.03). AVP increased from 13.0 ± 10.8 to a maximum of 35.1 ± 5.6 pmol/l (P < 0.02 compared with control day). There was no significant difference in CRH responses between ECT and control days. Peak cortisol and ACTH responses did not differ significantly between ECT and cardioversion. Baseline cortisol levels, however, were significantly higher in the depressed group compared with the cardioversion group, P < 0.02, but not ACTH or AVP.

CONCLUSION  Significant hypothalamic–pituitary–adrenal activation and PRL release occur in response to both cardioversion and ECT. AVP may have an important role in mediating the acute ACTH response to electrical stimulation.
Kallikrein gene expression in human pituitary tissues
Authors: Clements Judith A. , Mukhtar Annie , Verity Karen , Pullar Michael , McNeill Peter , Cummins James , Fuller Peter J.
Published: November 2003

OBJECTIVE The glandular kallikreins are a family of enzymes involved in the post‐translational processing of polypeptides. Three family members have been characterized in the human: glandular kallikrein (KLK1) and two genes expressed in the prostate, KLK2 or hGK1 and KLK3 or prostate specific antigen (PSA). Both kallikrein immunoreactivity and KLK1 mRNA have been detected in the rat anterior pituitary and oestrogen induced prolactinomas. Immunoreactive kallikrein has also been reported in prolactin secreting pituitary tumours in humans. In this study we wished to determine whether KLK1 and/or other KLK genes were expressed in human pituitary tumours.

DESIGN AND PATIENTS Retrospective analysis of KLK gene expression in pituitary tissue obtained at surgery from 11 patients with a range of pituitary syndromes, 10 of which were tumour induced and included four prolactinomas. Three normal pituitaries, obtained at necropsy, were also analysed.

MEASUREMENTS Pituitary total RNA was subjected to both Northern blot analysis, with KLK1 and KLK2 cDNA probes, and KLK‐specific reverse transcriptase—polymerase chain reaction (RT‐PCR).

RESULTS No KLK1 gene expression was detected on Northern blot analysis although expression of PRL, GH and pro‐opiomelanocortin (POMC) was variously detected. KLK RT‐PCR coupled with Southern blot analysis using oligonucleotide probes specific for each of the three KLK genes was positive in many tumours but with varying levels and differential expression. Overall, KLK1 was the most abundant with KLK3 the least. The identity of KLK1 and KLK2 was confirmed by sequencing the PCR products. There was no obvious correlation between KLK1 and hormone gene expression; KLK1 was present in PRL positive and negative tumours and in normal pituitary tissue.

CONCLUSIONS We have demonstrated a low level of expression of KLK1 as well as KLK2 and KLK3 in the human pituitary. The expression of KLK2 and KLK3 in the pituitary is a novel finding. The lack of correlation between PRL and KLK1 gene expression is an unexpected finding suggesting that the interaction between these factors may be more complex in the human pituitary than in the rodent model.
Growth hormone‐binding protein related immunoreactivity is regulated by the degree of insulinopenia in diabetes mellitus
Authors: Kratzsch J. , Kellner K. , Zilkens T. , Schmidt‐Gayk H. , Selisko T. , Scholz G. H.
Published: November 2003

OBJECTIVE Derangements in the GH/IGF axis are common in patients with diabetes mellitus. In insulin‐dependent diabetes mellitus (IDDM), these disturbances seem to be due to a partial defect in GH action on its own receptor or via a post‐receptor defect. In non‐insulin‐dependent diabetes mellitus (NIDDM), data are limited, and the regulation of the GH receptor (GHR) remains unclear. However, animal studies with diabetic rats demonstrated that the GHR density may be influenced by insulin disposal at the hepatocyte. With respect to this hypothesis we studied the relation between peripheral insulin status and the serum GH‐binding protein (GHBP), which reflects indirectly the GHR density in the tissues. Patients with IDDM were compared to a NIDDM group as well as to a group of healthy subjects.

DESIGN AND PATIENTS Basal blood samples for the determination of serum GHBP, GH, and IGF‐I were obtained from patients with IDDM (n = 27), subjects with NIDDM (n = 112) and healthy controls (n = 42). Insulin, proinsulin, C‐peptide and IGF‐binding protein 1 (IGFBP‐1) serum levels were used to estimate the insulin status in diabetic patients.

RESULTS GHBP serum levels were significantly lower in patients with IDDM than in either NIDDM or controls (P < 0.001). Conversely, the IGF‐I levels were reduced in both groups of diabetics. A subgroup of hypoinsulinaemic NIDDM patients showed significantly decreased GHBP concentrations (P < 0.05) compared to the NIDDM subgroup with hyperinsulinaemia. Furthermore, GHBP levels were significantly decreased in insulin‐treated patients with NIDDM compared to either non‐insulin‐requiring subjects or normal controls (P < 0.05). A significant direct relation was found between levels of GHBP and total insulin dose (P < 0.01) in patients with IDDM. In the NIDDM group, GHBP was correlated with proinsulin (P < 0.001), C‐peptide (P < 0.01), insulin (P < 0.05) and inversely with IGFBP‐1 (P < 0.001). Multiple linear regression analysis indicated a significant contribution of proinsulin and IGFBP‐1 to the variation of GHBP.

CONCLUSIONS Decreased GHBP levels in IDDM as well as in NIDDM correlate with insulinopenia. Since the degree of insulinopenia depends on the capability of the β‐cells to secrete proinsulin, C‐peptide and insulin, we hypothesize that these hormones at least partially influence the serum level of GHBP. Low GHBP levels may reflect a reduced GH receptor density and a concomitant GH insensitivity, which leads to an impaired IGF generation in insulin‐deficient patients.
Three years of GH treatment in Turner's syndrome: complex effect of GH dosage on growth parameters
Authors: Bertrand A. M. , Chaussain J. L. , Job B. , Mariani R. , Ponte C. , Rappaport R. , Rochiccioli P. , Chatelain P.
Published: November 2003

OBJECTIVE There have been few studies of GH dose responses in Turner's syndrome. We have therefore compared the growth effect of two doses of subcutaneous rGH: 0.45 (D1) or 0.90 (D2) IU/kg/week.

DESIGN Multicentre study with two parallel randomized groups treated with D1 or D2 dose for one year, then with D2 for the second and third years in both groups.

PATIENTS Ninety‐seven girls with Turner's syndrome aged from 4.8 to 16.5 years.

RESULTS The first mean height velocity (HV) was significantly higher with D2. At one year the girls changed from D1 to D2 showed a further acceleration in HV. During second and third years HV remained above the mean for untreated Turner girls, in both groups. Mean cumulative height gains over the 3 years were 1.06 and 1.17 SDS/CA (Ranke's Turner standard) in groups G1 and G2 respectively. Bone maturation, over 36 months, was 33.7 (G1) and 31.9 (G2) months.

CONCLUSION These results suggest that, if a higher initial GH dose is associated with a greater net initial height gain, the duration of treatment might affect the long‐term results. Intermittent treatment should be considered.
Insulin‐like growth factor‐I raises serum procollagen levels in children and adults with Laron syndrome
Authors: Klinger B. , Jensen L. T. , Silbergeld A. , Laron Z.
Published: November 2003

OBJECTIVE Recombinant IGF‐I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF‐I on soft connective tissue and bone metabolism in a group of patients with this disorder.

PATIENTS AND DESIGN Thirteen patients with Laron syndrome (LS) (8 children and 5 adults) were included in the study. The children with LS were treated with IGF‐I for 3 years with daily doses of 150–200 μg/kg. The adult LS patients were treated for 9 months with daily doses of 50–120 μg/kg. Blood samples for procollagens were collected before, during and at the end of IGF‐I treatment.

MEASUREMENTS Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and of the pyridinoline cross‐linked carboxyterminal telopeptide of type I collagen (ICTP) were determined before and during IGF‐I administration.

RESULTS Untreated patients with LS had lower than normal serum levels of PICP and PIIINP for age. IGF‐I treatment increased significantly the PIIINP levels in children from 7.2 ± 2.8 (SD) to 12.5 ± 2.2 μg/l (P < 0.001), and in adults from 2.7 ± 1.0 to 8.4 ± 3.6 μg/l (P < 0.001); serum PICP increased from 243 ± 123 to 384 ± 190 μg/l (P < 0.087) in children, and in adults from 43.4 ± 8.1 to 135.8 ± 41.9 μg/l (P < 0.001). ICTP levels in children increased from 9.7 ± 3.7 to 14.3 ± 5.9 μg/l (P < 0.001) and in adult patients levels increased from 3.6 ± 0.9 to 5.5 ± 2.2 μg/l (P < 0.001) during treatment and returned to basal values after stopping IGF‐I administration.

CONCLUSIONS Low procollagen levels in untreated Laron syndrome patients and their rise during replacement therapy with IGF‐I provide evidence that IGF‐I plays an important role in bone and soft connective tissue metabolism and that serum procollagen may serve as a marker to reflect some of the biochemical changes induced by IGF‐I in connective tissue in the initial periods of treatment.
Effects of FSH on serum immunoreactive inhibin levels in the luteal phase of the menstrual cycle
Authors: Burger Henry , Hee Jennifer , Bangah Mohan , Prince Mirella , McCloud Philip , Ohara Akira , Iwai Toshiko , Mori Takahide
Published: November 2003

OBJECTIVE FSHcauses a dose‐related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase.

DESIGN Normal volunteers were treated with a single injection of LH‐free FSH (Metrodin, 150 units) or saline as control, during the early, mid‐ or late luteal phase of the cycle, with subsequent hormone measurements.

PATIENTS The 21 volunteers were aged 19–29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1–4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the mid‐luteal phase, 5–9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase.

MEASUREMENTS Oestradiol (E2), progesterone (P), and INH were measured by previously described radioimmunoassays.

RESULTS In both the early and mid‐luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid‐luteal 1553 to 2090 U/l) and E2 (early 371 to 545 pmol/l, mid‐luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2 or P.

CONCLUSIONS It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly distinguish between these possibilities.
A comparison of the overnight and the standard metyrapone test for the differential diagnosis of adrenocorticotrophin‐dependent Cushing’s syndrome
Authors: Avgerinos Peter C. , Nieman Lynette K. , Oldfield Edward H. , Cutler Jr Gordon B.
Published: November 2003

OBJECTIVE We wished to develop optimal criteria for interpreting the single‐dose overnight metyrapone test and to compare the diagnostic efficiency of the overnight and the standard 6‐dose metyrapone tests for the differential diagnosis of ACTH‐dependent Cushing’s syndrome.

DESIGN Retrospective pilot study based on all patients who completed both metyrapone tests and whose diagnoses were subsequently confirmed surgically.

PATIENTS Sixty‐three patients, 57 with pituitary tumours and 6 with ectopic ACTH syndrome, were studied.

MEASUREMENTS The sensitivity and specificity were determined using stimulation of plasma 11‐deoxycortisol and suppression of plasma cortisol as endpoints for the overnight test and stimulation of urine 17‐hydroxysteroid and plasma 11‐deoxycortisol as endpoints for the standard test. The test response that gave the highest sensitivity for the diagnosis of Cushing’s disease, with 100% specificity, was determined for each test endpoint.

RESULTS Both the stimulation of plasma 11‐deoxycortisol and the suppression of plasma cortisol were expressed as the ratio of the post‐metyrapone value to baseline. A plasma 11‐deoxycortisol ratio > than 220 or a plasma cortisol ratio > 0.6 was associated with 100% specificity for diagnosis of Cushing’s disease by the overnight test. When these two criteria were combined, the sensitivity was 65%, which was significantly higher than that obtained using either steroid alone: 42% for both plasma 11‐deoxycortisol and plasma cortisol. The sensitivity of 65% for the overnight test, at 100% specificity, was nearly identical to that of the standard test in the same patients: 67% for the combined criterion of > 70% stimulation of urine 17‐hydroxysteroid or > 480‐fold increase of plasma 11‐deoxycortisol. When the criteria for both the overnight and standard tests were combined, the sensitivity increased to 84%, which was higher than that obtained using the criteria for either test alone (P < 0.02).

CONCLUSION The single‐dose overnight metyrapone test, which can be performed in 24 hours and which avoids the disadvantages associated with timed urine collections, has a nearly identical sensitivity (for a specificity of 100%) as the 6‐dose standard metyrapone test for the diagnosis of Cushing’s disease. Furthermore, the diagnostic performance of a criterion that combines the results of both tests is significantly better than the best criterion for either test alone.
In vivo imaging of pituitary tumours using a radiolabelled dopamine D2 receptor radioligand
Authors: De Herder W. W. , Reijs A. E. M. , Kwekkeboom D. J. , Hofland L. J. , Nobels F. R. E. , Oei H. Y. , Krenning E. P. , Lamberts S. W. J.
Published: November 2003

OBJECTIVE Knowledge of the dopamine D2 receptor status of pituitary tumours may play a predictive role in differential diagnosis and therapeutic decisions. This study was performed to evaluate the value of pituitary dopamine D2 receptor scintigraphy with (S)‐2‐hydroxy‐3‐123I‐iodo‐6‐methoxy‐N‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]benzamide (123I‐IBZM) in the diagnostic evaluation of patients with pituitary tumours.

DESIGN AND PATIENTS Scintigraphy using 123I‐IBZM was performed in 5 patients with PRL‐secreting macroadenomas, 2 patients with PRL‐secreting microadenomas, 17 patients with clinically non‐ functioning pituitary adenomas (NFPAs), 12 patients with GH‐secreting adenomas and 1 patient with a TSH‐secreting macroadenoma.

RESULTS Single‐photon emission tomography (SPECT) showed significant uptake of 123I‐IBZM in the pituitary region in 3/5 macroprolactinoma patients. These results closely correlated with the response of plasma PRL levels to the dopamine D2 receptor agonist quinagolide. In two scan‐positive prolactinoma patients, repeated SPECTs during therapy with quinagolide showed a reduction in the pituitary uptake of 123I‐IBZM. Pituitary SPECT was negative in the 2 microprolactinoma patients, who responded to quinagolide administration. In 4/17 patients with NFPA, significant uptake of the radioligand in the pituitary region was observed. In 2/3 scan‐positive NFPA patients, who were treated with quinagolide, shrinkage of the pituitary tumours was observed. Treatment with quinagolide resulted in stabilization of tumour growth in the other scan‐ positive patients. Four out of 17 patients with NFPA and a negative SPECT were treated with quinagolide. Tumour growth was observed in 1 patient, and tumour size did not change in the other 3 patients. The pituitary region of none of the 12 acromegaly patients showed significant uptake of 123I‐IBZM. Sensitivity of the GH‐secreting adenomas to quinagolide was demonstrated in 8/12 patients in vivo by an acute test, and in 6/9 of the tumours in vitro. Pituitary SPECT was negative in the patient with the TSH‐secreting macroadenoma and this tumour also showed no sensitivity to quinagolide in vivo or in vitro.

CONCLUSIONS We conclude that 123I‐IBZM is a ligand for in vivo imaging of dopamine agonist‐ sensitive macroprolactinomas, but not for microprolactinomas or GH‐secreting adenomas. The technique potentially provides a means of predicting the dopamine agonist‐responses of non‐functioning pituitary adenomas in vivo.
Disruption of transport activity in a D93H mutant thiamine transporter 1, from a Rogers Syndrome family
Authors: Baron Dana , Assaraf Yehuda G. , Drori Stavit , Aronheim Ami
Published: November 2003

Rogers syndrome is an autosomal recessive disorder resulting in megaloblastic anemia, diabetes mellitus, and sensorineural deafness. The gene associated with this disease encodes for thiamine transporter 1 (THTR1), a member of the SLC19 solute carrier family including THTR2 and the reduced folate carrier (RFC). Using transient transfections into NIH3T3 cells of a D93H mutant THTR1derived from a Rogers syndrome family, we determined the expression, post‐translational modification, plasma membrane targeting and thiamine transport activity. We also explored the impact on methotrexate (MTX) transport activity of a homologous missense D88H mutation in the human RFC, a close homologue of THTR1. Western blot analysis revealed that the D93H mutant THTR1 was normally expressed and underwent a complete N‐glycosylation. However, while this mutant THTR1 was targeted to the plasma membrane, it was completely devoid of thiamine transport activity. Consistently, introduction into MTX transport null cells of a homologous D88H mutation in the hRFC did not result in restoration of MTX transport activity, thereby suggesting that D88 is an essential residue for MTX transport activity. These results suggest that the D93H mutation does not interfere with transporter expression, glycosylation and plasma membrane targeting. However, the substitution of this negatively charged amino acid (Asp93) by a positively charged residue (His) in an extremely conserved region (the border of transmembrane domain 2/intracellular loop 2) in the SLC19 family, presumably inflicts deleterious structural alterations that abolish thiamine binding and/or translocation. Hence, this functional characterization of the D93H mutation provides a molecular basis for Rogers syndrome.
Crystal structure of Trypanosoma cruzi glyceraldehyde‐3‐phosphate dehydrogenase complexed with an analogue of 1,3‐bisphospho‐d‐glyceric acid
Authors: Ladame Sylvain , Castilho Marcelo S. , Silva Carlos H. T. P. , Denier Colette , Hannaert Véronique , Périé Jacques , Oliva Glaucius , Willson Michèle
Published: November 2003

We report here the first crystal structure of a stable isosteric analogue of 1,3‐bisphospho‐d‐glyceric acid (1,3‐BPGA) bound to the catalytic domain of Trypanosoma cruzi glycosomal glyceraldehyde‐3‐phosphate dehydrogenase (gGAPDH) in which the two phosphoryl moieties interact with Arg249. This complex possibly illustrates a step of the catalytic process by which Arg249 may induce compression of the product formed, allowing its expulsion from the active site. Structural modifications were introduced into this isosteric analogue and the respective inhibitory effects of the resulting diphosphorylated compounds on T. cruzi and Trypanosoma brucei gGAPDHs were investigated by enzymatic inhibition studies, fluorescence spectroscopy, site‐directed mutagenesis, and molecular modelling. Despite the high homology between the two trypanomastid gGAPDHs (> 95%), we have identified specific interactions that could be used to design selective irreversible inhibitors against T. cruzi gGAPDH.
Effect of magnetostriction on fracture of a soft ferromagnetic medium with a crack‐like flaw
Authors: WAN Y. P. , FANG D. N. , SOH A. K. , HWANG K. C.
Published: November 2003

The magnetic‐induction field in the vicinity of an elliptical inclusion embedded in an infinite soft ferromagnetic medium is determined based on complex potential theory. By using a constitutive relation of magnetostriction for isotropic materials, the stress field in the vicinity of an elliptical flaw is obtained. Furthermore, the stress field at the tip of a slender elliptical crack is determined for the case in which only an external magnetic field perpendicular to the major axis of the ellipse is applied at infinity. The results indicate that the stress field in the neighbourhood of the tip is governed by the magnetostriction and permeability of the soft ferromagnetic material. The induction magnetostrictive modulus is a key parameter in determining which of the two mechanisms, i.e., magnetostriction and magnetic‐force‐induced deformation, is dominant in determining the stress field in the neighbourhood of the tip of a crack‐like flaw. With regard to the influence of the magnetic field on the apparent toughness of a soft ferromagnetic body with a crack‐like flaw, soft ferromagnetic materials can be roughly divided into two categories: one possesses a large induction magnetostrictive modulus and the other has a small modulus. An approximate criterion for categorizing the materials is presented. For the benefit of engineering design, the expressions of the stress‐intensity factor for these two categories of soft ferromagnetic materials are presented. The results show that the stress‐intensity factor is affected not only by the flaw geometry, but also by the permeability of the medium inside the flaw.
Improvement in quality of colorectal cancer pathology reporting with a standardized proforma – a comparative study
Authors: Beattie G. C. , McAdam T. K. , Elliott S. , Sloan J. M. , Irwin S. T.
Published: November 2003

Background  Histopathological evaluation is a critical component in the management of patients with colorectal cancer (CRC). It is the single most powerful prognostic indicator in CRC and determines if adjuvant chemotherapy is indicated. The aim of this study was to assess if the introduction of a comprehensive standardized pathology proforma improved the quality of histopathology reporting.

Methods  A standardized pathology proforma, based on the 1996 minimum dataset for colorectal histopathology reporting, was introduced in our pathology department in 1998. Pathology reports for all colonic resection specimens for 1996 (n = 85) and 2000 (n = 86) were identified, retrieved and entered on to database. Comparison was made with the minimum dataset published in the 1996 guidelines for the management of colorectal cancer.

Results  Demographic details were complete in all cases. Clinical data was incomplete in 57 (67%) patients in 1996 and 63 (73%) in 2000 (ns; χ2). There were 24 (28%) (7 Abdomino‐perineal resections (APER)) and 40 (47%) (17 APER's) rectal specimens for 1996 and 2000, respectively. The presence or absence of pathological background abnormalities were commented on in 18 (21%) reports in 1996 and 80 (93%) reports in 2000 (P < 0.01; Fishers exact test (Fisher)). Histological differentiation was commented on in 73 (86%) and 86 (100%) in 1996 and 2000, respectively (P < 0.01; Fisher). Dukes' stage was stated in 33 (39%) reports in 1996 and 86 (100%) in 2000 (P < 0.01; Fisher) but Dukes' stage was calculable in 84 (99%) in 1996 and 86 reports (100%) for 2000 (ns; Fisher). The apical node was commented on in 34 (40%) reports in 1996 and 85 (99%) reports in 2000 (P < 0.01; Fisher). The median (IQR) number of nodes assessed in 1996 was 8 (5–12) compared to 12 (8–17) in 2000 (P < 0.001; Mann–Whitney (MW)). Complete resection was mentioned in 74 (87%) reports in 1996 and 86 (100%) in 2000 (P < 0.01; Fisher). Regarding rectal specimens, the circumferential resection margin (CRM) was commented on in 19 of 24 specimens in 1996 and 38 of 40 specimens in 2000 (ns; Fisher). Relationship to the peritoneal reflection was commented on in 1 (1%) rectal specimen in 1996 and 30 (35%) in 2000 (P < 0.001; Fisher).

Conclusion  The introduction of a standardized proforma for reporting CRC resection specimens improves the quality of histopathological reporting. This aids decision‐making regarding adjuvant chemotherapy or radiotherapy and further surveillance.
The proportional decrease in prostate specific antigen level best predicts the duration of survival after hormonal therapy in patients with metastatic carcinoma of the prostate
Authors: Evans C.P. , Gajendran V. , Tewari A. , Aslam K. , Juster R. , Gange S. , Eason A. , Narayan P.
Published: November 2003

Objective To examine the usefulness of a test for prostate specific antigen (PSA) to predict survival in hormonally treated patients with metastatic prostate cancer.

Patients and methods The study comprised 49 patients (mean age 72 years, sd 6) who underwent orchidectomy for metastatic prostate cancer. PSA was measured before orchidectomy and after 6 months, and the absolute, differential and proportional decreases calculated. A Cox proportional hazards regression model, which controlled for patient age, tumour (Gleason) grade and the number of skeletal metastases, was then used to evaluate these estimates of PSA as predictors of survival.

Results The 6‐month proportional decrease in PSA from the pre‐operative level was the most accurate predictor of patient survival (P=0.006) after hormonal therapy for metastatic prostate cancer.

Conclusion This information may help to direct appropriate patients to new and experimental therapies for metastatic disease.
Wegener's granulomatosis involving the urogenital tract
Authors: Davenport A. , Downey S.E. , Goel S. , Maciver A.G.
Published: November 2003

Objective To report eight cases of limited Wegener's granulomatosis (WG) affecting the urogenital tract (testis, ureter, bladder, urethra and penis) and to emphasize the importance of the anti‐neutrophil cytoplasm antibody (ANCA) test in establishing the diagnosis.

Patients and methods Eight patients (six men and two women, aged 41–77 years) were diagnosed with WG, based on their previous medical history, the ANCA test and by biopsy.

Results In each case, there were difficulties and delay in establishing the diagnosis of WG and starting appropriate treatment. The ANCA test was positive in seven cases and helped in establishing the diagnosis, in conjunction with the confirmation of vasculitis and granulomata by biopsy.

Conclusion We advocate ANCA testing in patients presenting with limited urogenital disease in association with a past or present relevant history of arthritis, skin vasculitis and/or biopsies showing necrosis or non‐specific inflammation.
The role of the Sertoli cell in active immunosuppression in the human testis
Authors: Turek P.J. , Malkowicz S.B. , Tomaszewski J.E. , Wein A.J. , Peehl D.
Published: November 2003

Objective To define the involvement of Sertoli cells in immune suppression within the testis by identifying surface receptor molecules that describe or communicate with cells of the immune system.

Materials and methods Ten pairs of human testes obtained from orchidectomy were stained immunohistochemically with established monoclonal antibodies that identify common cells of the immune system.

Results Patterns of staining were similar in all testes. Class I major histocompatibility complex (MHC) antigen, important for self/non‐self recognition, was found on Sertoli cells. Class II MHC antigen, important for immune cell interaction and limited to immune cells, was absent. Leu M3, characteristically found on macrophages, was also seen on Sertoli cells but no receptor antigens defining basic T cell types (CD4, CD8), B cells (Leu 12) or natural killer cells (Leu 11) were seen on Sertoli cells.

Conclusions The Sertoli cell membrane lacks lymphocyte‐cell surface markers but harbours somatic cell and macrophage markers. This suggests that immunosuppression within the testis is not maintained through classic lymphocyte receptors. The presence of a macrophage marker is consistent with the known phagocytic activity of the Sertoli cell.
Six chromophobe cell carcinomas and one mixed renal
Authors: Usubütün A. , Uygur M.C. , Ayhan A. , Özen H. , Remzi D.
Published: November 2003

Objective

 To determine the incidence and clinical and pathological features of chromophobe cell carcinoma (CCC) among renal cell carcinomas (RCCs).

Materials and methods

 The records and nephrectomy samples from 166 patients who were operated on and followed up thereafter with a diagnosis of RCC were re‐evaluated. New sections were cut and specific staining performed when deemed necessary.

Results

 Of 166 patients with RCC, six were diagnosed as having CCC and, unusually, one patient had a mixed RCC with areas of CCC. Neither the symptoms nor radiological features of these seven patients differed from those of the patients with RCC; the serum ferritin levels of these seven patients were also within the normal range. These patients appeared to have a favourable clinical course.

Conclusion

 Chromophobe cell carcinoma is a distinct entity and must be distinguished particularly from oncocytoma and other variants of RCC. Although it seems to have a low malignant potential, metastatic CCC may have a worse prognosis.
Impact of the prostatic apex on continence and urinary flow in patients with intestinal neobladders
Authors: Koraitim M.M. , Atta M.A. , Foda M.K.
Published: November 2003

Objective To determine the impact of preserving the prostatic apex on continence and urinary flow in patients with post‐cystectomy intestinal bladder substitutes.

Patients and methods A total of 38 male patients underwent radical cystectomy for bladder carcinoma and construction of a neobladder from ileum [9], sigmoid [9] or an ileocaecal segment [20]. The intestinal reservoir was anastomosed to the membranous urethra in 25 patients and to the apical prostatic capsule in 13. A subjective evaluation of urinary continence, uroflowmetry and urethral pressure profilometry were performed 1–3 years after surgery.

Results The only variable which showed a significant difference between patients with and without preservation of the prostatic apex was the functional profile length (P<0.05). Conversely, there was no statistically significant difference in the continence result, peak flow rate and maximum urethral pressure between these two groups. However, there was a significant difference (P<0.05) in peak flow rate among the three versions of neobladder in patients with a preserved prostatic apex (9.4 mL/s in ileal vs 15.8 mL/s in sigmoid and ileocaecal segments).

Conclusion Preservation of the prostatic apex does not improve urinary continence in patients with intestinal neobladders and may present an element obstructing the evacuation of ileal bladders.
Local staging of prostate cancer by endorectal MRI using fast spin‐echo sequences: prospective correlation with pathological findings after radical prostatectomy
Authors: Cornud F. , Belin X. , Flam T. , Chrétien Y. , Deslignieres S. , Paraf F. , Casanova J.M. , Thiounn N. , Hélénon O. , Debré B. , Dufour B. , Moreau J.F.
Published: November 2003

Objective To evaluate the accuracy of endorectal magnetic resonance imaging (MRI) with fast spin‐echo sequences in the local staging of clinically localized prostate cancer.

Patients and methods Seventy‐one patients with a clinical T1 (18 patients) or T2 tumour (53 patients) underwent endorectal MRI 2–12 weeks before radical prostatectomy. Extraprostatic tumour was diagnosed if MRI showed signs of capsular penetration and/or invasion of the seminal vesicle and/or distal urethra or bladder neck. If the pathological examination showed a single positive margin with no periprostatic tissue, the tumour was classified as indeterminate and not as a T3 tumour.

Results Of the 25 cases of capsular penetration, MRI correctly identified 10 (sensitivity 42%, specificity 100%). Of the 14 cases with seminal vesicle invasion, MRI correctly identified six (sensitivity 43%, specificity 100%), but showed other signs of extraprostatic tumour spread in seven of the eight unidentified cases. Overall, MRI identified 16 of the 30 patients (53%) with occult extraprostatic spread of tumour; there was only one false‐positive result. The sensitivity, specificity and accuracy of MRI were 53, 96 and 74%, respectively.

Conclusion Endorectal MRI can reduce the rate of pre‐operative understaging from 42% to 22% and it can be used for a given individual because it can detect extraprostatic invasion with 96% specificity, ensuring that very few, if any, patients will be deprived of curative surgery.
Influence of transurethral resection on sexual dysfunction in patients with prostate cancer
Authors: Bieri S. , Miralbell R. , Rohner S. , Kurtz J.
Published: November 2003

Objective To evaluate retrospectively the potential influence of disease‐related factors and transurethral resection of the prostate (TURP) on the sexual function of patients who had undergone curative radiotherapy for prostate cancer.

Patients and methods The study comprised 104 patients (median age 69.5 years, range 49–81) who had been treated with curative radiotherapy and no first‐line hormones: 16, 52, 33 and three patients had T1, T2, T3 and T4 tumours, respectively. TURP was performed in 73 patients before RT, and needle biopsy alone in 31 patients. They were interviewed about their past and present sexual lives using a questionnaire designed to evaluate the potency of the patients at age 45 years, at 1 year before the diagnosis of the disease, before radiotherapy (after TURP or needle biopsy) and at the last follow‐up. Information concerning associated diseases, routine medication and the weight of the resected material was also collected.

Results Before diagnosis, 20 patients had no erections while 84 were potent. Of the 60 potent patients undergoing a TURP, 31 (51%) indicated complete impotence immediately thereafter. There was no statistical difference between impotent and potent patients after TURP in age, associated diseases, medical treatment and the weight of the resected material.

Conclusion TURP may lead to impotence in a significant proportion of patients. As TURP is an important component of ‘conservative’ treatment approaches, its potential sexual morbidity should be taken into consideration in the comparative risk‐benefit analysis of different therapeutic strategies.
Reduction of length of stay and cost of transurethral resection of the prostate by early catheter removal
Authors: Mueller E.J. , Zeidman E.J. , Desmond P.M. , Thompson I.M. , Optenberg S.A. , Wasson J.
Published: November 2003

Objective To determine whether early removal of the indwelling Foley catheter after transurethral resection of the prostate (TURP) significantly shortens the hospital stay without causing additional morbidity and thus saves costs.

Patients and methods For the year commencing 1 July 1991, 119 patients who had undergone TURP had their indwelling catheter removed on the first day after surgery. The results and morbidity of this group of patients were compared with those in 152 patients undergoing TURP during the previous year. The economic consequences of this protocol were calculated using both Medicare and CHAMPUS data.

Results The demographics of the patients in both groups were similar. Post‐operative complications occurred in 5% of the study patients and in 6.6% of controls; a transfusion was required in 2.5% and 1.3%, clot retention developed in 1.7% and 3.3% and the hospital stay was reduced from 3.1 to 1.28 days in the study and control patients, respectively. Using Medicare data, the mean cost saving of early catheter removal would be $829 and $1406 for patients aged <70 and >70 years, respectively. For CHAMPUS patients, the cost saving would be $1983.

Conclusion Early removal of the catheter after TURP did not increase morbidity and maintained the efficacy of the procedure. If this practice was adopted nationally, the savings resulting from the reduction in hospital stay would be considerable.
A retrospective analysis of 82 cases of cancer of the penis
Authors: Lindegaard J.C. , Nielsen O.S. , Lundbeck F.A. , Mamsen A. , Studstrup H.N. , Von Der Maase H.
Published: November 2003

Objective To identify prognostic factors for penile cancer and to evaluate the treatment strategy for early‐stage disease, proposed recently by the European Board of Urology (EBU).

Patient and methods The records of 82 patients consecutively referred to the uro‐oncological centre at Aarhus University Hospital between 1965 and 1993 were reviewed. The importance of tumour stage, differentiation, patient age, local control and regional lymph node control were assessed using univariate and multivariate analyses.

Results Cox multivariate analysis identified differentiation (odds ratio [OR]=6.04), UICC‐1978 T‐stage (OR=1.88) and age (OR=1.04) as independent prognostic variables for survival. Penile amputation in tumours <4 cm in diameter improved local control but not survival. Regional control and survival were not significantly improved by prophylactic adenectomy.

Conclusion Differentiation, T‐stage and age were prognostic factors for survival. The results support the EBU treatment strategy involving penis‐conserving therapy and watchful waiting for early‐stage disease.
Detrusor myopathy: an accurate predictor of bladder hypocompliance and contracture in interstitial cystitis
Authors: Christmas T.J. , Smith G.L. , Rode J.
Published: November 2003

Objective To determine whether any histological characteristics within the detrusor in cases of early interstitial cystitis (IC) predict the subsequent development of severe symptoms due to bladder contracture.

Patients and methods The detrusor muscle component of bladder biopsies from 21 patients with IC was examined in sections stained with haematoxylin and eosin. Videocystometrography was performed at least 2 months after the biopsy and the patients were then followed up clinically for at least 3 years.

Results The detrusor appeared normal in 13 patients; in eight there was evidence of detrusor myopathy. Patients with biopsies confirming detrusor myopathy were significantly more likely to have hypocompliant bladders than those with normal detrusor muscle histology (P<0.02). Over the following 3 years, six of the eight patients with detrusor myopathy developed progressively severe symptoms and required subtotal cystectomy and enterocystoplasty. None of the 13 patients without detrusor myopathy required bladder substitution.

Conclusion In IC, detrusor myopathy is associated with bladder hypocompliance. Patients with detrusor myopathy appear to have more severe disease and are more likely to progress to bladder contracture requiring substitution enterocystoplasty.
The effects of intranasal midazolam on urodynamic
Authors: Bozkurt P. , Kiliç N. , Kaya G. , Yeker Y. , Eliçevik M. , Söylet Y.
Published: November 2003

Objective

 To determine the influence of midazolam on the function of the lower urinary tract when used to sedate the patient.

Patients and methods

Urodynamic studies were performed on 20 patients (seven boys and 13 girls, mean age 4.04 years, range 1 day to 10 years) before and after the intranasal administration of 0.5 mg/kg of midazolam. The patients' heart rate, respiratory rate and oxygen saturation were monitored and the level of sedation recorded by an anaesthesiologist and a surgeon during the study.

Results

Heart rate and respiratory rate did not change and the percentage oxygen saturation remained stable throughout the study period. The childrens' behaviour began to change 3–5 min after the intranasal administration of midazolam. The sedation lasted 2 h and the full co‐operation of the patient was assured. The difference between the initial and post‐midazolam evaluation of maximal cystometric capacity, contractility, compliance, intravesical pressure, maximum flow rate, intravesical pressure at maximum flow and the amount of residual urine were statistically insignificant (P>0.05). Electromyographic characteristics showed no significant change with the use of midazolam (P>0.05).

Conclusion

Despite the suggestion that benzodiazepines, especially diazepam, are useful for the relaxation of pelvic floor striated musculature in voiding dysfunctions, there was no effect on urodynamic variables when midazolam was used in a single dose intranasally. The anxiolytic and sedative effects allowed children to undergo urodynamic studies in comfort.
Isothermic irrigation during transurethral resection of the prostate: effects on peri‐operative hypothermia, blood loss, resection time and patient satisfaction
Authors: Pit M.J. , Tegelaar R.J. , Venema P.L.
Published: November 2003

Objectives To investigate the effect using irrigation fluid at body temperature (isothermic) on patients' (core) temperature during a transurethral resection of the prostate (TURP) and on the amount of peri‐operative blood loss, the resection time and the subjective assessment of comfort by the patients.

Patient and methods In a randomized study, patients undergoing TURP under spinal anaesthesia were divided into those receiving either isothermic irrigation fluid (Group 1, 28 patients) or fluid at room temperature (Group 2, 31 patients). In Group 1, a fluid heater maintained the irrigation fluid at body temperature until it reached the bladder. The body temperature of the patients was recorded rectally and orally during and after TURP and the peri‐operative blood loss was also measured. The patients were interviewed on the first day after TURP to determine their assessment of comfort during the procedure.

Results The decrease in body temperature was 0.74°C in Group 1 and 1.71°C in Group 2, which was significantly different (P<0.001). There was no significant difference in blood loss or resection‐time. In Group 1, only four (14%) of the patients were aware that their body was cooler, compared to 15 (50%) in Group 2 (P=0.038).

Conclusion Isothermic irrigation during TURP prevents excessive cooling and reduces the level of hypothermia. The reported increased mortality after TURP is probably related to peri‐operative cardiac stress, an important factor which could be caused by the rapid decrease in body temperature which accompanies normal irrigation. Because the heating equipment presently available does not interfere with TURP, there are strong arguments for performing every TURP with irrigation fluid at body temperature.