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S M Webb

Publications and source records attributed to S M Webb.

At least 19 recordsLinked to original sources
PubMed2006

Determination of uranyl incorporation into biogenic manganese oxides using x-ray absorption spectroscopy and scattering.

Biogenic manganese oxides are common and an important source of reactive mineral surfaces in the environment that may be potentially enhanced in bioremediation cases to improve natural attenuation. Experiments were performed in which the uranyl ion, UO2(2+) (U(VI)), at various concentrations was present during manganese oxide biogenesis. At all concentrations, there was strong uptake of U onto the oxides. Synchrotron-based extended X-ray absorption fine structure (EXAFS) spectroscopy and X-ray diffraction (XRD) studies were carried out to determine the molecular-scale mechanism by which uranyl is incorporated into the oxide and how this incorporation affects the resulting manganese oxide structure and mineralogy. The EXAFS experiments show that at low concentrations (<0.3 mol % U, <1 microM U(VI) in solution), U(VI) is present as a strong bidentate surface complex. At high concentrations (>2 mol % U, >4 microM U(VI) in solution), the presence of U(VI) affects the stability and structure of the Mn oxide to form poorly ordered Mn oxide tunnel structures, similar to todorokite. EXAFS modeling shows that uranyl is present in these oxides predominantly in the tunnels of the Mn oxide structure in a tridentate complex. Observations by XRD corroborate these results. Structural incorporation may lead to more stable U(VI) sequestration that may be suitable for remediation uses. These observations, combined with the very high uptake capacity of the Mn oxides, imply that Mn-oxidizing bacteria may significantly influence dissolved U(VI) concentrations in impacted waters via sorption and incorporation into Mn oxide biominerals.

Bacteria↗
PubMed2005

VUV photoabsorption spectroscopy of sulfur dioxide ice.

In this paper we present the first study of the VUV photoabsorption spectrum of condensed phase SO(2) recorded over the VUV region 120 to 320 nm (10.33 to 3.64 eV). Distinct spectral features were observed that can be used to distinguish between the formation of amorphous and crystalline ice structures. These signatures may then be used to probe the formation of different ice structures as a function of both deposition rate and substrate temperature.

Absorption↗
PubMed2005

Determinants of neurosurgical outcome in pituitary tumors.

OBJECTIVE: Neurosurgery is one of the main therapies for pituitary tumors; optimising outcome is highly desirable for the patient and the health system. We have analysed predictors of outcome in surgically treated pituitary adenomas operated in this centre. DESIGN AND PATIENTS: A total of 289 patients underwent neurosurgery for a pituitary tumor, by the same two neurosurgeons, between 1982 and 2001. Their records were examined to find predictors of post-surgical outcome. Thirty-eight percent were males, with a median age of 40.8 (8-82.7) yr; 51.9% had been operated since 1992, 92.2% by the transsphenoidal route. Most tumors (70.2%) were macroadenomas; 28.4% were non-functioning, 27.3% secreted PRL, 26.3% GH of which 14 (4.8%) also secreted PRL, 17.3% ACTH, 0.3% FSH and 0.3% TSH. RESULTS: A stepwise, forward logistic regression analysis revealed tumor size as the only significant predictor of radiological cure [odds ratio (OR) for macroadenoma 0.16 vs microadenoma, p=0.0005]. Hormonally, PRL-secretion by the tumor was a predictor of poor prognosis (OR 3.29 for cure of non-PRL-secreting tumors, p=0.005), as was tumor size (OR 0.45 for cure of macroadenomas, p=0.005). Considering simultaneous radiological and hormonal remission, tumor size (OR 0.35 for macroadenoma, p=0.0002), and operation date (OR 0.40 for up to 1991, p=0.0002) were the only significant predictors. CONCLUSIONS: PRL secretion, tumor size and operation date are the main predictors of neurosurgical outcome in pituitary tumors, the latter suggesting that neurosurgical experience plays an important role.

Adenoma↗
PubMed2005

Biochemical evidence in favor of revising Cortina criteria.

There is evidence that the Cortina criteria for the cure of acromegaly are not strict enough if the aim is to predict patients where cure will be successful as opposed to patients who will suffer disease recurrence or will have mortality and morbidity return to disease-like levels. These criteria depend on biochemical measurements of GH and IGF-I that are not universally standardised or comparable, even when excluding the older, less sensitive polyclonal radio immuno assay (RIA). The biochemical evidence suggesting a revision of the criteria for curing acromegaly and derived proposals can be summarised as follows: A) Using immunoradiometric assay (IRMA) for GH measurement, no acromegalic patient with elevated IGF-I suppressed GH after 100 g oral glucose tolerance test (OGTT) to < or = 0.14 microg/l, but 50% suppressed to <1microg/l. B) With hourly GH measurements using IRMA, cured acromegalic patients exhibit basal GH values < or = 0.33 microg/l (x +/- 2 SD). C) In patients with normal IGF-I having GH after OGTT suppressed to < or = 0.14microg/l no recurrences were observed, while in 19% with GH >0.14 microg/ showed recurrences (4, 5); however, this was not the experience of others. D) Polyclonal assays for GH exhibit overlap of GH suppression after OGTT between normal subjects and active patients and should therefore be avoided. E) A recent agreement for implementing universal rhGH reference standards by September 2006 will hopefully facilitate the comparison of different assays in the future. F) Reliable IGF-I assays require age- and sex-matched reference ranges. G) For evaluation of long-term biochemical assessment after treatment, both GH and IGF-I should be undertaken. H) In order to monitor treatment with GH-receptor antagonists, a reliable IGF-I assay is of critical importance, since GH measurements cannot be used to evaluate treatment efficacy.

Acromegaly↗
PubMed2004

Testosterone replacement therapy: current trends and future directions.

Male hypogonadism is characterized by abnormally low serum testosterone levels associated with typical symptoms, including mood disturbance, sexual dysfunction, decreased muscle mass and strength, and decreased bone mineral density. By restoring serum testosterone levels to the normal range using testosterone replacement therapy, many of these symptoms can be relieved. For many years, injectable testosterone esters or surgically implanted testosterone pellets have been the preferred treatment for male hypogonadism. Recently, newer treatment modalities have been introduced, including transdermal patches and gels. The development of a mucoadhesive sustained-release buccal tablet is the latest innovation, which will provide patients with an additional option. The availability of new treatment modalities has helped to renew interest in the management of male hypogonadism, highlighting the need to address a number of important but previously neglected questions in testosterone replacement therapy. These include the risks and benefits of treatment in different patient populations (e.g. the elderly) and the need for evidence-based diagnosis and treatment monitoring guidelines. While some recommendations have been developed in individual countries, up-to-date, internationally accepted evidence-based guidelines that take into account national differences in clinical practice and healthcare delivery would optimize patient care universally.

Androgens↗
PubMed2004

Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction.

Congenital GH insensitivity syndrome (GHIS) is usually the result of a mutation in the extracellular domain of the GH receptor (GHR). We report one of only a small number of mutations so far identified within the intracellular domain of the GHR. The probands are a 53-yr-old woman, height 114 cm (SD score, -8.7), peak GH 45 microg/liter during hypoglycemia, IGF-I 8.0 microg/liter [normal range (N) N 54-389], IGF binding protein-3 16 nmol/liter (N 61-254), GHBP 6.8% (N > 10); and her 57-yr-old brother, height 140 cm (SD score, -6), IGF-I 38.8 micro g/liter (N 54-290), IGF binding protein-3 30 nmol/liter (N 61-196). Both patients were homozygous for a 22-bp deletion in the DNA encoding the cytoplasmic domain of the GHR, resulting in a frameshift and premature stop codon. The resultant GHR is truncated at amino acid 449 (GHR1-449) after Box1, the Janus kinase 2 binding domain of the receptor. Functional studies in HEK293 and Chinese hamster ovary cells show GHR1-449 to have a cellular distribution similar to that of the wild-type GHR, judged by binding of iodinated GH, FACS analysis, and immunocytochemistry. Western blot analysis showed GH-induced phosphorylation of Janus kinase 2, signal transducer and activator of transcription (Stat)3, and Erk2 for both GHR1-449 and wild-type GHR. However, no Stat5 activity was detected in cells expressing GHR1-449, consistent with the fact that GHR1-449 contains no Stat5 binding site. In conclusion, we report two adult siblings with GHIS due to a mutation in the intracellular domain of GHR resulting in a selective loss of Stat5 signaling. Results are consistent with the hypothesis that the loss of signaling through the Stat5 pathway results in GHIS.

Amino Acid Sequence↗
PubMed2002

Acromegaly Quality of Life Questionnaire (ACROQOL) a new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties.

OBJECTIVE: To develop a disease-specific questionnaire suitable to measure health-related quality of life (HRQOL) in acromegaly (ACROQOL). DESIGN, PATIENTS AND MEASUREMENTS: For the development of the ACROQOL questionnaire different sources of information were used: First, a literature search was performed to identify relevant papers describing the impact of acromegaly in HRQOL. Second, 10 endocrinologists identified the main domains of impact on HRQOL in patients with acromegaly. Third, 10 in-depth, semistructured interviews were conducted in acromegalic patients to identify domains and items related to the self-perceived impact of acromegaly in patients' life. Qualitative analyses of the information were performed identifying domains and items to be included in the questionnaire. Those items considered ambiguous, complicated to read, double-barrelled, with jargon terms, too long, or negatively worded were excluded. Each remaining item was subsequently rated by the same panel of endocrinologists and experts in HRQOL evaluation, and assessed according to clarity of wording, frequency of occurrence and importance among patients with acromegaly. Analysis of internal consistency of the questionnaire was evaluated with a Cronbach's Alpha. A preliminary questionnaire was administered to 72 patients with acromegaly. Rasch analysis (dichotomous logistic response model) of the answers given by these patients allowed parameter estimates and model data fit indices to be computed and misfitting items deleted. Frequency of occurrence and degree of agreement with the statements were selected as response choices in a 5-point Likert type scale. RESULTS: The following domains related to HRQOL in acromegaly were identified: physical and psychological functions, social, daily activities, symptoms, cognition, general health perception, sleep, sexual function, pain, energy and body image. An initial set of 204 expressions were identified from the initial transcripts of the patient interviews. After elimination of ambiguous or unclear expressions, 142 items remained drafted in question form. From the quantitative analysis of the item rank position within each of the three areas of clarity, frequency and importance, the 38-item questionnaire was produced, with satisfactory internal consistency (Cronbach's Alpha 0.94). Rasch analysis produced a further reduction to the final 22-item questionnaire (Cronbach's Alpha 0.91) containing two scales that evaluate physical (eight questions) and psychological aspects related to appearance and personal relations (seven items each). The evaluation of the item parameters confirmed the construct validity of the new instrument. The substantial reliability of the questionnaire suggested the sample was well targeted by the questionnaire. The initial Spanish version was translated into English and presented to five English-speaking Australian patients with acromegaly to assess and correct for comprehension, clarity, cultural relevance and suitable wording. CONCLUSIONS: We present the ACROQOL questionnaire, developed and preliminarily validated to specifically assess HRQOL in patients with acromegaly.

Acromegaly↗
PubMed2001

Quick X-ray absorption spectroscopy for determining metal speciation in environmental samples.

We present a method for determining the chemical speciation of metals in environmental particles based on Quick-X-ray Absorption Spectroscopy. The approach can be applied to either the extended or the near edge fine structure, and consists in the decomposition of the XAS spectrum of an unknown sample on a reference set of standards' spectra using quadratic linear programming. The analysis accounts for the statistical experimental errors generated during the acquisition of X-ray absorption data, and leads to error estimates on the various fractions determined via a Monte Carlo procedure. An application example is presented for the speciation of inorganic Zn in a contaminated sediment sample.

Geologic Sediments↗
PubMed2001

An EXAFS study of zinc coordination in microbial cells.

Five microbes were isolated from metal amended enrichment cultures derived from the sediments of a lake contaminated by a zinc smelter. Each of these organisms was grown in pure culture in the presence of zinc. Quick Extended X-ray Absorption Fine Structure (QEXAFS) spectroscopy was used to investigate the average coordination environment of the zinc associated with the microbial biomass. Fitting of the first coordination shell of zinc shows that significant differences exist for each microbial species examined. The coordination environment of zinc varies between sulfurs to six-fold nitrogen/oxygen. with two microbial strains showing mixed coordination shells. Further study is required in order to characterize these sites and their locations within the cell.

Bacteria↗
PubMed2001

Decreased insulin requirements after LAR-octreotide but not after lanreotide in an acromegalic patient.

A diabetic acromegalic man, not cured after surgery and radiosurgery, received lanreotide i.m. with great clinical and biochemical improvement. He required NPH insulin (76 to 84 units/day) to control his diabetes mellitus. Thirty-six hours after changing to LAR-octreotide (20 mg i.m/month) he presented symptomatic hypoglycemia, repeated at 48 and 72 h (50 mg/dL), despite reducing insulin to 26 Units/day. Thereafter, he reduced insulin by 30 to 50% for the first week after each LAR-octreotide injection, and gradually increased it again over the next 3 weeks. This situation persists after every injection 3 years later; this consistent behavior supports a specific effect of LAR-octreotide, and not a by chance phenomenon. No marked changes in circulating GH, IGF-1, immunoreative insulin, C-peptide, testosterone and glucose were observed prior to, and 3, 7, 14, 21, and 28 days after LAR-octreotide; however, there was 28% fall in plasma glucagon after 7 days, which rose thereafter. C-peptide (< 1.8 ng/mL) was indicative of decreased beta-cell function. To our knowledge, this is the first report of such a distinct differential behaviour of blood glucose and insulin requirements with different somatostatin analogs, and is worth recalling when starting an insulin-treated diabetic patient on this treatment. It may be related to a preferential binding of LAR-octreotide to subtype 2 somatostatin receptors in the pancreas, while lanreotide preferentially binds to subtype 5, not expressed in this tissue; this would explain the fall in glucagon, in parallel to the decrease in insulin requirements after LAR-octreotide; however, a contribution of differences in the effect of both somatostatin analogues on postreceptor signalling systems and/or intestinal carbohydrate absorption cannot be entirely ruled out.

Acromegaly↗
PubMed2001

Effects of dietary rice bran, lasalocid, and sex of calf on postpartum reproduction in Brahman cows.

To determine the effects of dietary lasalocid and increased dietary fat on reproduction, multiparous Brahman cows (n = 68), body condition score (BCS) of 6.2 +/- 0.7 and BW of 500.9 +/- 42.6 kg, were randomly assigned within sex of calf to receive one of four rations. All treatment groups grazed Coastal bermudagrass overseeded with rye-ryegrass and were given ad libitum access to hay and water. The control (n = 17) group received 4.17 kg x d(-1) x cow(-1) of 4:1 corn:soybean meal. The rice bran (n = 17) group received 4.35 kg x d(-1) x cow(-1) of 3:1:1 corn:soybean meal:rice bran (5.2% dietary fat). The lasalocid (n = 17) group received the Control diet with the addition of 200 mg of lasalocid x d(-1) x cow(-1). The rice bran-lasalocid (n = 17) group received the rice bran diet with the addition of 200 mg of lasalocid x d(-1) x cow(-1). Diets were fed once daily from d 1 after parturition through the detection of first estrus. Weight and BCS of cows and BW of calves were recorded at 14-d intervals from d 1 after parturition through detection of first estrus and at weaning. Cows were bled on d 1, 3, 5, 7, and 14 and at weekly intervals until estrus and on d 7 and d 10 after estrus. Ovarian follicular populations were monitored by transrectal ultrasonography weekly from d 14 after parturition through detection of first estrus. Plasma 13-14-dihydro-15-ketoprostaglandin-F2alpha (PGFM) and progesterone (P4) concentrations were quantified using RIA. Concentrations of PGFM from d 1 to 7 and P4 concentrations on d 7 and 10 after estrus were not influenced (P > 0.10) by diet or sex of calf. Changes in BW and BCS were not affected (P > 0.10) by diet. The number of medium-sized follicles tended to be greater (P < 0.06) in Controls than in cows on lasalocid or rice bran + lasalocid treatments on d 21. Cumulative return to estrus with a functional corpus luteum by d 60 postpartum was greater (P < 0.02) in the rice bran (70.6%) and lasalocid groups (76.5%) than in Controls (52.9%) or the group given rice bran + lasalocid (25.0%). Normal first estrous cycles were less likely (P < 0.07) to be exhibited in cows given rice bran + lasalocid than in other groups. Intervals from calving to corpus luteum formation, functional corpus luteum, and first P4 > or = 1 ng/mL were longer (P < 0.02) in cows given rice bran + lasalocid than in other cows. Combining increased dietary fat (5.2%) with lasalocid lengthened the time to reproductively important events.

Animal Feed↗
PubMed2000

Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly.

BACKGROUND AND OBJECTIVE: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.

Acromegaly↗
PubMed2000

Antiproliferative effect and cell cycle modulation by melatonin on GH(3) cells.

We have investigated the effect of melatonin on cell proliferation and modulation, in the GH(3) experimental rat pituitary cell line; the expression of oncogenes c-myc, c-jun and the tumor suppressor gene p53 were also analyzed basally and after exposure to melatonin (10(-6), 10(-8) and 10(-10) M). Melatonin exhibited an antiproliferative effect at all the doses tested, decreasing the proliferating index by 50%. After exposure to melatonin, a decrease in Ki67 and Proliferation cell nuclear antigen occurred acute- and transiently (at 2 h) after a single dose which recovered at 4 h, as well as chronically after repeated 12-hour doses which persisted at 48 h; a similar behavior was observed both acute- and chronically for c-myc and c-jun, while it was opposite for p53, rising acute- and transiently as well as after repeated exposure. These results demonstrate that melatonin modulates the proliferation mechanisms of the GH(3) cells.

Animals↗
PubMed2000

Transient pituitary hypothyroidism in a patient with ectopic adrenocorticotrophic hormone secretion.

We report the case of a 55-year-old woman who presented with hypercortisolism secondary to ectopic adrenocorticotrophic hormone secretion and severe non-thyroidal illness syndrome (NTIS) due to metastatic small cell lung carcinoma associated with severe infections. The patient initially showed hormonal profiles of pituitary hypothyroidism and gonadal hypofunction. After decrease in cortisol production following treatment with chemotherapy and metyrapone, serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations normalized. Study of the relative contributions of cortisol and pro-inflammatory cytokines (interleukin-6 and tumour necrosis factor alpha) to the overall variability in thyroid function tests disclosed a significant and independent effect of serum cortisol on serum TSH concentrations; the variability in free thyroid hormone concentration was explained only by changes in TSH concentration. These observations indicate that cortisol could be the major determinant of changes in serum TSH concentrations in clinical conditions accompanied by hypercortisolism, as occurs in NTIS.

Adrenocorticotropic Hormone↗
PubMed1999

Cost-effectiveness and accuracy of the tests used in the differential diagnosis of Cushing's syndrome.

AIM: Establish the minimal biochemical and radiological examinations necessary and their cost-effectiveness to accurately diagnose the etiology of Cushing's syndrome (CS). MATERIAL AND METHODS: In 71 patients with CS followed between 1982 and 1997 biochemical studies (basal ACTH, 8 mg dexamethasone suppression test-HDST-, metyrapone stimulation test-MST-, or inferior petrosal sinus catheterization-IPSC-) and radiological investigations (abdominal CT scan, pituitary CT scan or MRI) were performed. Once pathology confirmed the diagnosis (48 pituitary Cushing's disease-CD, 17 adrenal neoplasms, 2 bilateral macronodular hyperplasia-BMH-, and 4 ectopic ACTH syndrome-ES-), the sensitivity, specificity, positive and negative predictive value of the different studies was calculated to establish the most accurate and cost-effective diagnostic protocol. RESULTS: In ACTH-independent CS (ACTH < or = 9 pg/ml; normal 9 to 54) a unilateral tumor was identified on abdominal CT scanning in 17, and BMH in 1; the other BMH had detectable ACTH (43.2 pg/ml). In ACTH-dependent CS, ACTH was > 9 pg/ml and IPSC (performed in 22) correctly identified 20 patients with CD and differentiated them from 2 with an ES (100% specificity and sensitivity). Pituitary MRI or CT did not disclose an adenoma in 41.7% of patients with CD, and was reported to exhibit a microadenoma in 2 of the 4 patients with ES. HDST and MST were of no additional use in the differentiation between CD and ES. CONCLUSIONS: Once CS is diagnosed low ACTH and an abdominal CT scan correctly identified all patients of adrenal origin. In ACTH-dependent CS IPSC was the best predictive test to differentiate CD from ES. BMH may behave as ACTH-dependent or independent. The other biochemical and radiological studies performed are not cost-effective and may even be misleading, and should not be routinely performed.

ACTH Syndrome, Ectopic↗