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Selected AbstractsEFFECT OF FROZEN TEMPERATURE AND STORAGE TIME ON CALPAINS, CATHEPSINS (B, B + L, H AND D) AND THEIR ENDOGENOUS INHIBITORS IN GOAT MUSCLESJOURNAL OF FOOD BIOCHEMISTRY, Issue 2 2006N.S. NAGARAJ ABSTRACT The effects of frozen storage on the biochemical properties of myofibrils, muscle proteinases (cathepsins and calpains) and their endogenous inhibitors were investigated. Longissimus dorsi, biceps femoris, semimembranosus and semitendinosus muscles from goat were frozen (,15C) and studied up to 120 days. The results showed that the percentage change in sarcomere length was 8.4,13.1. The calpain activity was determined after separation on a diethylaminoethyl,Sephacel column (Sigma, St. Louis, MO). Significantly greater percentage of calpain II activity was recovered when compared to calpain I. There was a 15,25% loss in calpastatin inhibitory activity, and the cystatin level fell by 11,16% after 80 days. Cathepsin B, B + L, H and D were very stable when compared to calpains. The calcium concentration may also be the factor for calpain activation. The sodium dodecyl sulfate,polyacrylamide gel electrophoresis result showed the appearance of 55 kDa components. It was concluded that calpains, not cathepsins, play an important role in the proteolysis of myofibrillar proteins at the freezing temperature. [source] Effects of simultaneous kidney-pancreaticoduodenal transplantation on diabetes-induced renal insufficiency in ratsMICROSURGERY, Issue 4 2001Jin Han Yoon M.D., Ph.D. An investigation of the functional and histological changes was done after en-bloc kidney-pancreaticoduodenal transplantation (kpdt) in the diabetes-induced, renal insufficient Lewis rats. For donor preparation, an end-to-side portocaval shunt was performed, and the aortic, vena caval segments, and ureter-bladder patch were obtained. They were anastomosed microsurgically to recipient's aorta, vena cava, and bladder in end-to-side fashion. Of 15 diabetes-induced kpdt rats, 14 survived. Two of the 14 surviving rats showed ischemic necrosis. The remaining 12 transplants showed well-preserved glomeruli and Langerhans islets for 5 months postoperatively. Biochemical data comparing diabetic and sham-operated rats (six rats each), six diabetic controls, and 12 kpdt rats showed no significant statistical difference at said observation period. The diabetes-induced kpdt rats showed improvement of following biochemical data: within 1 week postoperatively, the glucose level fell from 300 to 115 mg/dL; BUN level from >20 to <20 mg/dL; the creatinine level from 1.5 to <1.2 mg/dL. The insulin level returned to normal, 1.1 ng/mL, in 2 weeks. The results demonstrate that the kpdt model is an effective and successful operative technique in diabetic rats and may provide effective therapeutic methods for diabetes-induced renal insufficiency. © 2001 Wiley-Liss, Inc. MICROSURGERY 21:173,178 2001 [source] Allotransplantation of Cryopreserved Parathyroid Tissue for Severe Hypocalcemia in a Renal Transplant RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010S. M. Flechner We report the successful allotransplantation of cryopreserved parathyroid tissue to reverse hypocalcemia in a kidney transplant recipient. A 36-year-old male received a second deceased donor kidney transplant, and 6 weeks later developed severe bilateral leg numbness and weakness, inability to walk, acute pain in the left knee and wrist tetany. His total calcium was 2.6 mg/dL and parathormone level 5 pg/mL (normal 10,60 pg/mL). He underwent allotransplantation of parathyroid tissue cryopreserved for 8 months into his left brachioradialis muscle. Immunosuppression included tacrolimus (target C0 10,12 ng/mL), mycophenolate mofetil and steroids. Within 2 weeks, the left knee pain, leg weakness and numbness resolved, and by 1 month he could walk normally. After a peak at month 2, his parathyroid hormone (PTH) level fell to <10 pg/mL; therefore at month 3 he received a second parathyroid transplant from the same donor. Eight months later (11 months after initial graft) he has a total calcium of 9.3 mg/dL, PTH level 15 pg/mL and is clinically asymptomatic. The amount of parathyroid tissue needed to render a patient normocalcemic is not known. In our case, the need for second transplant suggests that the amount of tissue transferred for an allograft may need to be substantially greater than for an autograft. [source] Sedimentary Response of Different Fan Types to the Paleogene,Neogene Basin Transformation in the Kuqa Depression, Tarim Basin, Xinjiang ProvinceACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 2 2009Zhiyong GAO Abstract: A group of alluvial fans formed in the early Paleogene represent marginal sedimentary facies at the foot of the South Tianshan Mountain, Kuqa Depression, Tarim Basin, Xinjiang province. Two types of fans occurred in the middle,late Paleogene Kumugeliemu and Suweiyi formations: one alluvial, and the other fan delta deposited in a lacustrine setting. Within the early Neogene Jidike Formation, coastal subaqueous fans developed, probably in a deeper water lacustrine setting. The three types of fans are stacked vertically in outcrop with the sequence in ascending order: bottom alluvial, middle fan-delta, and top subaqueous. The subaqueous is a typical coarse-fan deposit occurring in the glutinite member of the Jidike Formation in some wells. Laterally, from the foreland to the lacustrine settings, the distribution pattern of sedimentary facies represents the same three fan types sequentially. The spatial distribution of these fans was controlled by the Paleogene,Neogene Basin transformation, and evolution with different types of fans developed in the Kuqa Depression in response. In the Paleogene, the Kuqa Depression was a rift basin where an alluvial fan was deposited in the foreland setting, which, by early Neogene, became a foreland basin when the lake level changed. With any rise in lake level, fan-deltas migrated from lacustrine to foreland settings, whereas when the lake level fell, fan migration was reversed. In the early Neogene, with increasing slope and rising lake level, fans progressed and covered the previous fan-delta and lacustrine mudstone. Eventually, subaqueous fans developed, forming the present spatial configuration of these three fan types. [source] Short Report: Safe and rapid resolution of severe hypertriglyceridaemia in two patients with intravenous insulinDIABETIC MEDICINE, Issue 9 2010J. M. Triay Diabet. Med. 27, 1080,1083 (2010) Abstract Aim, To rapidly reduce serum triglyceride to a safe serum level. Severe hypertriglyceridaemia is associated with uncontrolled diabetes, obesity and poor physical activity. Even moderate increases in triglyceride levels (> 5mmol/L) confer an increased risk of pancreatitis and coronary artery disease. We present two patients with diabetes and serum triglyceride levels of greater than 85mmol/L despite polypharmacy intervention. Method, 72-hour intravenous insulin infusion was administered. Results, Serum triglyceride levels fell to 9.4 and 4.6 mmol/L respectively, without adverse events and sustained effect over several months. Conclusion, We suggest the use of intravenous insulin infusion where lifestyle and oral drug therapies have failed can impact on severe hypertriglyceridaemia. [source] Mercury accumulation and loss in mallard eggsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2004Gary H. Heinz Abstract Female mallards (Anas platyrhynchos) were fed diets containing 5, 10, or 20 ppm mercury as methylmercury chloride. One egg was collected from each bird before the start of the mercury diets and 15 eggs were collected from each bird while it was being fed mercury. The mercury diets were then replaced by uncontaminated diets, and each female was allowed to lay 29 more eggs. Mercury levels in eggs rose to about 7, 18, and 35 ppm wet-weight in females fed 5, 10, or 20 ppm mercury, respectively. Mercury levels fell to about 0.16, 0.80, and 1.7 ppm in the last egg laid by birds that had earlier been fed 5, 10, or 20 ppm mercury, respectively. Higher concentrations of mercury were found in egg albumen than in yolk, and between 95 and 100% of the mercury in the eggs was in the form of methylmercury. [source] Treatment satisfaction with insulin glargine in patients with diabetes mellitus in a university hospital clinic in SwedenEUROPEAN DIABETES NURSING, Issue 1 2009M Annersten Gershater RN, MNSc Research Nurse Abstract Background: Few studies evaluate patients' perspectives when a new drug is intro-duced to treat chronic diseases such as diabetes mellitus. The clinical role of a new insulin treatment, in terms of the relationship between higher cost and better treat-ment outcomes (as defined from the patient perspective) has been discussed. We sought to explore patient satisfaction with a new insulin treatment (insulin glargine). At its launch in 2002/3 it was purported to provide constant, peakless insulin release following once- or twice-daily administration, thus leading to fewer hypoglycaemic episodes while providing metabolic control equivalent to that achieved with NPH human basal insulin. Aims: To investigate the indications used for prescription of a new drug and its clinical effects on glycosylated haemoglobin (HbA1c) levels, perceived hypoglycaemic events and patient satisfaction. Methods: The Diabetes Treatment Satisfaction Questionnaire (Status Version, DTSQ-s), which measures satisfaction with treatment regimen, and perceived frequency of hyperglycaemia and hypoglycemia, was circulated to all living patients who had ever started treatment with insulin glargine at the Department of Endocrinology at Malmö University Hospital. Medical records of 913 patients were assessed for HbA1c levels at 0 and 12 months after starting insulin glargine therapy. Results: Completed questionnaires were returned by 615 of 960 patients (64%) who had ever started insulin glargine. The main indications for starting treatment were physicians' or nurses' initiatives, desire for fewer fluctuations and improved metabolic control. HbA1c levels fell by 0.41% for patients with type 1 diabetes and by 0.68% for those with type 2 diabetes. The mean DTSQ-s score was 28.45 for satisfaction, whereas the mean perceived hypoglycaemic/hyperglycaemic events score was 3. Conclusion: Treatment satisfaction was very high and perceived frequency of hypoglycaemia/hyperglycaemia was very low. The indications for treatment of insulin glargine are being followed in accordance with national recommendations. Copyright © 2009 FEND [source] Management of acquired von Willebrand's sryndrome in a patient requiring major surgeryHAEMOPHILIA, Issue 6 2005J. M. Maddox Summary., We present the case of a patient with acquired von Willebrand's syndrome and a monoclonal gammopathy of undetermined significance who required cystectomy for relapsed transitional cell carcinoma (TCC) of the bladder. We demonstrated that infused von Willebrand factor (VWF) containing factor VIII concentrates had an unacceptably short half-life, but that this was significantly prolonged following combined therapy with plasma exchange and intravenous immunoglobulin (IVIgG). This approach was successfully utilized peri-operatively, with the total surgical blood loss less than would be expected even for a haemostatically normal patient. Trough VWF antigen and Ristocetin co-factor activity levels fell on the second postoperative day and we therefore administered further IVIgG. Levels again fell on the fifth postoperative day with the development of a Staphylococcus aureus septicaemia. At this point bleeding occurred from a surgical drain site requiring ,factor VIII inhibitor bypass activity' to secure haemostasis while further plasma exchange and IVIgG were administered. Now 5 years later, there is no evidence of recurrence of the TCC or progression of the monoclonal gammopathy. [source] Induction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid inhibits expression of glutathione synthetic enzymes and contributes to cholestatic liver injury in mice,HEPATOLOGY, Issue 4 2010Heping Yang We previously showed that hepatic expression of glutathione (GSH) synthetic enzymes and GSH levels fell 2 weeks after bile duct ligation (BDL) in mice. This correlated with a switch in nuclear anti-oxidant response element (ARE) binding activity from nuclear factor erythroid 2,related factor 2 (Nrf2) to c,avian musculoaponeurotic fibrosarcoma (c-Maf)/V-maf musculoaponeurotic fibrosarcoma oncogene homolog G (MafG). Our current aims were to examine whether the switch in ARE binding activity from Nrf2 to Mafs is responsible for decreased expression of GSH synthetic enzymes and the outcome of blocking this switch. Huh7 cells treated with lithocholic acid (LCA) exhibited a similar pattern of change in GSH synthetic enzyme expression as BDL mice. Nuclear protein levels of Nrf2 fell at 20 hours after LCA treatment, whereas c-Maf and MafG remained persistently induced. These changes translated to ARE nuclear binding activity. Knockdown of c-Maf or MafG individually blunted the LCA-induced decrease in Nrf2 ARE binding and increased ARE-dependent promoter activity, whereas combined knockdown was more effective. Knockdown of c-Maf or MafG individually increased the expression of GSH synthetic enzymes and raised GSH levels, and combined knockdown exerted an additive effect. Ursodeoxycholic acid (UDCA) or S-adenosylmethionine (SAMe) prevented the LCA-induced decrease in expression of GSH synthetic enzymes and promoter activity and prevented the increase in MafG and c-Maf levels. In vivo knockdown of the Maf genes protected against the decrease in GSH enzyme expression, GSH level, and liver injury after BDL. Conclusion: Toxic bile acid induces a switch from Nrf2 to c-Maf/MafG ARE nuclear binding, which leads to decreased expression of GSH synthetic enzymes and GSH levels and contributes to liver injury during BDL. UDCA and SAMe treatment targets this switch. (HEPATOLOGY 2010.) [source] Gene position in a long operon governs motility development in Bacillus subtilisMOLECULAR MICROBIOLOGY, Issue 2 2010Loralyn M. Cozy Summary Growing cultures of Bacillus subtilis bifurcate into subpopulations of motile individuals and non-motile chains of cells that are differentiated at the level of gene expression. The motile cells are ON and the chaining cells are OFF for transcription that depends on RNA polymerase and the alternative sigma factor ,D. Here we show that chaining cells were OFF for ,D -dependent gene expression because ,D levels fell below a threshold and ,D activity was inhibited by the anti-sigma factor FlgM. The probability that ,D exceeded the threshold was governed by the position of the sigD gene. The proportion of ON cells increased when sigD was artificially moved forward in the 27 kb fla/che operon. In addition, we identified a new ,D -dependent promoter that increases sigD expression and may provide positive feedback to stabilize the ON state. Finally, we demonstrate that ON/OFF motility states in B. subtilis are a form of development because mosaics of stable and differentiated epigenotypes were evident when the normally dispersed bacteria were forced to grow in one dimension. [source] Hydroxyurea therapy lowers circulating DNA levels in sickle cell anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008Pinar Ulug Hydroxyurea reduces the frequency of acute pain in sickle cell disease (SCD). We sought to determine if hydroxyurea therapy affects cell free DNA (cfDNA) levels in SCD. cfDNA levels fell in all 10 patients studied; before hydroxyurea, mean was 1,879 (95% CI 1,104,3,199) GE/mL; after hydroxyurea, mean was 780 (95% CI, 634,959) GE/mL (P = 0.002). Mean cfDNA level in the 10 HbSS adults prior to starting hydroxyurea was also significantly higher than that in 115 HbSS case controls who had never taken hydroxyurea (1,879 vs 975 GE/mL, P = 0.02). cfDNA levels may be useful in monitoring response to hydroxyurea therapy in SCD. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Variation in fecal testosterone levels, inter-male aggression, dominance rank and age during mating and post-mating periods in wild adult male ring-tailed lemurs (Lemur catta)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 12 2007L. Gould Abstract In primate species exhibiting seasonal reproduction, patterns of testosterone excretion in adult males are variable: in some species, peaks correlate with female receptivity periods and heightened male,male aggression over access to estrous females, in others, neither heightened aggression nor marked elevations in testosterone have been noted. In this study, we examined mean fecal testosterone ( f,T) levels and intermale aggression in wild adult male ring-tailed lemurs residing in three groups at Beza Mahafaly Reserve, Madagascar. Results obtained from mating and post-mating season 2003 were compared to test Wingfield et al. [1990. Am Nat 136:829,846] "challenge hypothesis", which predicts a strong positive relationship between male testosterone levels and male,male competition for access to receptive females during breeding season. f,T levels and rates of intermale aggression were significantly higher during mating season compared to the post-mating period. Mean f,T levels and aggression rates were also higher in the first half of the mating season compared with the second half. Number of males in a group affected rates of intermale agonism, but not mean f,T levels. The highest-ranking males in two of the groups exhibited higher mean f,T levels than did lower-ranking males, and young males exhibited lower f,T levels compared to prime-aged and old males. In the post-mating period, mean male f,T levels did not differ between groups, nor were there rank or age effects. Thus, although male testosterone levels rose in relation to mating and heightened male,male aggression, f,T levels fell to baseline breeding levels shortly after the early mating period, and to baseline non-breeding levels immediately after mating season had ended, offsetting the high cost of maintaining both high testosterone and high levels of male,male aggression in the early breeding period. Am. J. Primatol. 69:1325,1339, 2007. © 2007 Wiley-Liss, Inc. [source] Maternal renal dysfunction in sheep is associated with salt insensitivity in female offspringTHE JOURNAL OF PHYSIOLOGY, Issue 1 2009A. E. Brandon To examine the programming effects of maternal renal dysfunction (created by subtotal nephrectomy in ewes prior to mating; STNx), renal and cardiovascular function were studied in 6-month-old male and female offspring of STNx and control pregnancies. After studies were conducted on a low salt diet (LSD) some female offspring underwent salt loading (0.17 m NaCl in the drinking water for 5,7 days; HSD). On LSD both male and female offspring of STNx had similar mean arterial pressures (MAP), heart rates, cardiac outputs and renal function to those measured in offspring of control ewes. In female STNx offspring on a HSD, plasma sodium levels increased and haematocrits fell, indicating volume expansion (P < 0.05). Plasma renin levels were not suppressed despite the increases in plasma sodium concentrations, but aldosterone levels were reduced. In control animals plasma renin levels fell (P < 0.05) but there was no change in plasma aldosterone concentrations. There was a positive relationship between GFR and MAP which was present only in female STNx offspring. In conclusion, in STNx offspring there was an impaired ability to regulate glomerular filtration independent of arterial pressure, renin release was insensitive to a high salt intake and control of aldosterone secretion was abnormal. This study provides evidence of abnormal programming of the renin,angiotensin system and glomerular function in offspring of pregnancies in which there is impaired maternal renal function. [source] A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody,associated vasculitisARTHRITIS & RHEUMATISM, Issue 7 2009Rachel B. Jones Objective B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA),associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA-associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as re-treatment biomarkers. Methods Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA-associated vasculitis at 4 centers in the UK was used. Results All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P = 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty-eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty-eight patients received ,2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty-six serious adverse events occurred, including 2 episodes of late-onset neutropenia, which were attributed to rituximab. Conclusion Rituximab was effective remission induction therapy for refractory ANCA-associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re-treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re-treatment. [source] LDL Apheresis: A Novel Technique (LIPOCOLLECT 200)ARTIFICIAL ORGANS, Issue 12 2009Claudia Stefanutti Abstract Therapeutic means to lower Lp(a) are limited. The most effective method to reduce plasma Lp(a) concentration significantly is therapeutic apheresis, namely, low-density lipoprotein (LDL) lipoprotein(a) (Lp(a)) apheresis. A novel technique based on reusable LDL adsorber called Lipocollect 200 (Medicollect, Rimbach, Germany) allows the removal of both LDL and Lp(a) from plasma. Two male patients with hyperLp(a)lipoproteinemia and angiographically established progressive coronary heart disease, without rough elevation of LDL-cholesterol, who did not respond to diet and medication were submitted to 50 LDL Lp(a) aphereses with Lipocollect 200 LDL Lp(a)-adsorber at weekly and biweekly intervals. Total cholesterol and LDL cholesterol plasma levels fell significantly by 48.3% (±6.7) to 61.6% (±12.7) (first patient), and 42.5% (±6.3) to 60.6% (±14.3) (second patient), respectively (all differences: P , 0.001). High-density lipoprotein (HDL)-cholesterol concentration in plasma did not show statistically significant change. Plasma triglycerides were also significantly reduced by 43.6% (±24.4) (first patient) and 42.3% (±13) (second patient) (both differences: P , 0.001). Plasma Lp(a) showed a statistically significant percent reduction in plasma as expected: 64.7 ± 9.5 (first patient), and 59.1 ± 6.7 (second patient) (both differences: P , 0.001). Plasma fibrinogen concentration was decreased by 35.9% (±18.7) (P , 0.05) (first patient) and 41.8% (±11.5) (second patient) (P , 0.005). Considering the reduction rate between the first and the last procedures, we have compared the mean percent reduction of the first five treatments (from session #1 to #5) with the last five treatments (from session #21 to #25). We have observed an increasing reduction of all activity parameters on both patients apart from HDL-cholesterol (first patient) and triglyceride (second patient) that showed a decreasing reduction rate. Both patients followed the prescribed schedule and completed the study. Clinically, all sessions were well tolerated and undesired reactions were not reported. The Lipocollect 200 adsorber proved to have a good biocompatibility. In this study, the adsorber reusability for several sessions was confirmed. [source] Cryotherapeutic ablation of liver tumoursBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2002A. J. Sheen Background: This paper reports a 7-year experience of cryoablation for colorectal and non-colorectal liver metastases. Methods: A retrospective review was undertaken of patients treated in two adjacent UK centres in the north-west of England. Results: Over a 7-year period (1993,2000), 57 patients underwent cryotherapy for malignant hepatic tumours (41 colorectal, 16 non-colorectal). In the patients with colorectal metastases, preoperative carcinoembryonic antigen (CEA) levels fell significantly, from a mean of 444·1 to 6·22 µg/l (P = 0·002). One patient died, two developed cryoshock and six had cardiorespiratory complications. All patients with colorectal metastases subsequently received 5-fluorouracil-based chemotherapy. The remaining 16 patients with non-colorectal tumours (seven neuroendocrine metastases, five hepatocellular carcinomas, three sarcomas, one cholangiocarcinoma) all received cryotherapy alone, with no major complications. The median survival for patients with non-colorectal metastases was 37 months, compared with 22 months for those with colorectal metastases (P = 0·005). Conclusion: Hepatic cryotherapy is effective and safe, as demonstrated by the significant reduction in postoperative CEA concentration and the low risk of complications. However, this initial short-term success was not reflected in 5-year survival rates. Cryotherapy for non-colorectal metastases had a greater long-term survival benefit and is a useful means of controlling symptoms. © 2002 British Journal of Surgery Society Ltd [source] Surgical debulking of pituitary macroadenomas causing acromegaly improves control by lanreotideCLINICAL ENDOCRINOLOGY, Issue 6 2008N. Karavitaki Summary Background, Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case. Objective, We carried out a prospective study to assess whether surgical debulking of pituitary macroadenomas causing acromegaly improved the subsequent control of acromegaly by the somatostatin analogue lanreotide. Patients and methods, We treated 26 consecutive patients [10 males and 16 females , median age 53·5 years (range 22,70)] with macroadenoma causing acromegaly unselected for somatostatin response for 16 weeks with lanreotide, maximizing GH and IGF-I suppression, if necessary, by incremental dosing. Surgical resection was carried out and the patients were re-assessed off medical treatment at 16 weeks following surgery. Those with nadir GH > 2 mU/l in the oral glucose tolerance test (OGTT) and a mean GH in the GH day curve (GHDC) > 5 mU/l were subsequently restarted on lanreotide and the responses were assessed at the same time points as during the preoperative lanreotide treatment. Results, GH values fell on lanreotide treatment and prior to surgery they were considered ,safe' (mean GH in GHDC < 5 mU/l) in eight patients (30·7%). After surgery, they were ,safe' in 18 patients (69·2%). The figures for normal IGF-I were 11 (42·3%) before surgery and 23 (88·5%) after surgery. After surgery, six patients had nadir GH > 2 mU/l in the OGTT and ,unsafe' GH levels (mean GH in GHDC > 5 mU/l); on re-exposure to lanreotide, GH levels fell in all patients and at the end of 16 weeks postsurgery, they were ,safe' in three of them (50%) (P < 0·05). Pituitary tumour volume was also assessed prospectively, preoperatively on lanreotide and showed a mean fall of 33·1%. Eighty-three percent of patients had > 20% shrinkage. Conclusions, In this first prospective study using lanreotide, surgical debulking of pituitary tumours causing acromegaly improved subsequent postoperative control by the somatostatin analogue lanreotide. Surgery should, therefore, be considered in patients with macroadenoma causing acromegaly, even if there is little prospect of surgical cure. Lanreotide causes significant pituitary tumour shrinkage in the majority of patients. [source] | ||||||||||||||||||||||