Vitamin D supplementation in primary hyperparathyroidism: effects on 1,25(OH)2 vitamin D and FGF23 levels.

PURPOSE: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT. METHODS: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)2vitamin D (1,25(OH)2D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)2D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS). RESULTS: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)2D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)2D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups. CONCLUSION: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)2D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.

Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer.

BACKGROUND: Current international guidelines recommend the use of platinum-based chemotherapy with thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage IIIA or IIIB NSCLC were treated with nedaplatin (NP) at 50 mg m(-2) and irinotecan (CPT) at 60 mg m(-2) on days 1 and 8 every 4 weeks for two to four cycles with concurrent TRT (2 Gy per day, total 60 Gy). RESULTS: All 35 patients were able to receive a total of 60 Gy. Adverse effects and events in chemotherapy with TRT were grade 3 or 4 anaemia, neutropenia and thrombocytopenia, which occurred in 3.0%, 32.8% and 6.0% of patients, respectively. There was no grade 3 pneumonitis or oesophagitis. Adverse effects and events in chemotherapy alone were mild. There was no treatment-related death. An overall response rate was 94.3%. The median progression-free and overall survivals were 13.0 and 36.0 months, respectively. The 5-year disease-free and overall survival rates were 25.7% and 40.0%, respectively. CONCLUSION: NP and CPT treatment with concurrent TRT is effective and safe for patients with unresectable, locally advanced NSCLC.

Putative occurrence of lysine decarboxylase isoforms in soybean (Glycine max) seedlings.

The activity of lysine decarboxylase was studied in 3-day-old soybean (Glycine max (L.) Meer cv. Sakai) seedlings also in relation to light conditions. Lysine decarboxylase activity was mainly localized in the roots and to a lesser extent in the hypocotyls and was detectable in both the soluble and particulate fractions. The enzyme activity levels were similar during germination under light and dark conditions. With respect to lysine concentration, the initial decarboxylation rate of the soluble fraction showed a saturating curve. Conversely, the initial decarboxylation rate of the particulate fraction showed a sigmoidal curve. These results could suggest that at least two isoforms of lysine decarboxylase are present in different organs of soybean seedlings. In the root soluble fraction, the suicide inhibitor alpha-difluoromethyl-lysine suppressed the activity of lysine decarboxylase and of ornithine decarboxylase to the same extent, but had no effect on arginine decarboxylase activity.

Analysis of the diagnostic presentation profile, parathyroidectomy indication and bone mineral density follow-up of Brazilian patients with primary hyperparathyroidism.

Primary hyperparathyroidism is an endocrine disorder with variable clinical expression, frequently presenting as asymptomatic hypercalcemia in Western countries but still predominantly as a symptomatic disease in developing countries. The objective of this retrospective study was to describe the diagnostic presentation profile, parathyroidectomy indication and post-surgical bone mineral density follow-up of patients with primary hyperparathyroidism seen at a university hospital. We found 115 patients (92 women, median age 56 years) with primary hyperparathyroidism diagnosed during the last 20 years. We defined symptomatic patients based on the presence of any classical symptom affecting bone, kidney or the neuromuscular system. Surgical criteria followed the guidelines of the National Institutes of Health regarding asymptomatic primary hyperparathyroidism. Symptomatic patients and patients meeting surgical criteria for parathyroidectomy were 66 and 93% of the sample, respectively. Median calcium and parathyroid hormone values were 11.9 mg/dL and 189 pg/mL, respectively. After surgical treatment, 97% of patients were cured, with increases in bone mineral density of 19.4% in the lumbar spine and 15.7% in the femoral neck 3 years after surgery. Greater bone mass increases were detected in pre-menopausal women, men, and in symptomatic and younger patients, both in the lumbar spine and femoral neck. Our results support the previous findings of a predominantly symptomatic disease with a presentation profile that could be mainly related to a delayed diagnosis. Nevertheless, genetic and racial backgrounds, and nutritional factors such as calcium and vitamin D deficiency may play a role in the clinical presentation of primary hyperparathyroidism of Brazilian patients.

Ligand-dependent allosteric transformation of hemoglobins from the blood clam, Anadara broughtonii.

1. Oligomeric Hb I and II of Anadara broughtonii, which are unusual with respect to having no Bohr effect, were shown to have a R-T transformation on ligand-binding on the basis of the following experimental results. (a) Iodoacetamide reacted preferentially with the oxyiforms of the hemoglobins. (b) CD spectra at the far-ultraviolet regions significantly changed on ligand-binding. (c) 1-Anilinonaphthalene-8-sulfonate bound to the hemoglobins with a preference for deoxyforms. From these results and previous findings [1], it is concluded that the absence of the Bohr effect in these hemoglobins is due to the lack of the Bohr proton ionizing groups in the molecules. 2. Hb I and II treated with p-chloromercuribenzoate, designated as PMB-I and PMB-II, showed greatly increased oxygen affinity and decreased cooperativity. CD spectra at the far-ultraviolet of the PMB-Hb in the oxygen liganded state gave similar patterns to those of native oxygenated Hb. However no changes in the spectra were observed on deoxygenation. These findings suggest that the PMB-I and PMB-II retain their native oxy conformation even in the deoxy states. The PMB-modification might prevent the initial ligand-induced conformational change within the protomers.

Ligand-dependent polymerization of tetrameric hemoglobin from the blood clam Anadara broughtonii.

Hemoglobin (Hb II) of the blood clam Anadara broughtonii has a alpha 2 beta 2 sub-unit structure in athe oxy form with a sedimentation constant of 4.8 S. When deoxygenated, Hb II polymerizes with a major component, S20,w = 11.5 (above 150 microM in heme). Deoxy polymerization was not observed in a highly diluted protein below 20 microM (in heme). Gel filtration of Hb II in the deoxygenated state indicated that the major component has an apparent molecular weight of 195 000, which corresponds to a dodecamer. However, the sedimentation pattern and the elution profile of gel filtration showed the polymerization to be somewhat asymmetric. These results suggest that deoxy Hb II may polymerize with different polymerization states. We examined oxygen equilibria of Hb II in a range of 3--180 microM (in heme). Influences of the polymerization on its oxygen affinity and cooperativity were found to be very small. We have also found that the deoxy polymerization was completely prevented when all the sulfhydryl groups of the hemoglobin molecule were modified with p-chloromercuribenzoate.

Induction of interleukin-8 in human neutrophils after MHC class II cross-linking with superantigens.

Neutrophils have been shown to express major histocompatibility complex class II (MHC II) after stimulation. However, reports concerning the functional effect of MCH II expression are still lacking. In our hands, granulocyte-monocyte colony-stimulating factor (GM-CSF) alone and in combination with interferon (IFN)-gamma, but not IFN-gamma or interleukin (IL)-3, induced a significant level of expression of human leukocyte antigen DR on neutrophils. The addition of staphylococcal enterotoxin E to neutrophils resulted in a significant increase in IL-8 production only after prestimulation with GM-CSF alone or in combination with IFN-gamma but had no effect on neutrophils preincubated with IFN-gamma alone or IL-3. Staphylococcal enterotoxin A, another bivalent superantigen, also stimulated production of IL-8 by preincubated polymorphonuclear neutrophils, whereas staphylococcal enterotoxin A mutants that are not able to cross-link MHC II molecules failed to induce IL-8 production. Taken together, our results clearly demonstrate that after induction of MHC II, neutrophils are able to respond to MHC II-specific stimulation. These findings support the ideas that the induced MHC II complex is completely functional and that neutrophils may be able to present antigens.

Changes in clinical and laboratory findings at the time of diagnosis of primary hyperparathyroidism in a University Hospital in São Paulo from 1985 to 2002.

In contrast to most developed countries, most patients with primary hyperparathyroidism in Brazil are still symptomatic at diagnosis. However, we have been observing a change in this pattern, especially in the last few years. We evaluated 104 patients, 77 females and 27 males aged 11-79 years (mean: 54.4 years), diagnosed between 1985 and 2002 at a University Hospital. Diagnosis was made on the basis of clinical findings and of high total and/or ionized calcium levels, high or inappropriate levels of intact parathyroid hormone and of surgical findings in 80 patients. Patients were divided into three groups, i.e., patients diagnosed from 1985 to 1989, patients diagnosed from 1990 to 1994, and patients diagnosed from 1995 to 2002. The number of new cases diagnosed/year increased from 1.8/year in the first group to 6.0/year in the second group and 8.1/year in the third group. The first group comprised 9 patients (mean serum calcium +/- SD, 13.6 +/- 1.6 mg/dl), 8 of them (88.8%) defined as symptomatic. The second group comprised 30 patients (mean calcium +/- SD, 12.2 +/- 1.63 mg/dl), 22 of them defined as symptomatic (73.3%). The third group contained 65 patients (mean calcium 11.7 +/- 1.1 mg/dl), 34 of them symptomatic (52.3%). Patients from the first group tended to be younger (mean +/- SD, 43.0 +/- 15 vs 55.1 +/- 14.4 and 55.7 +/- 17.3 years, respectively) and their mean serum calcium was significantly higher (P < 0.05). All of symptomatic patients independent of group had higher serum calcium levels (12.4 +/- 1.53 mg/dl, N = 64) than asymptomatic patients (11.4 +/- 1.0 mg/dl, N = 40). Our data showed an increase in the percentage of asymptomatic patients over the years in the number of primary hyperparathyroidism cases diagnosed. This finding may be due to an increased availability of diagnostic methods and/or to an increased awareness about the disease.

Human neutrophils produce macrophage inhibitory protein-1beta but not type i interferons in response to viral stimulation.

Several cell types have been shown to produce type I interferons (IFN). Of human leukocytes, monocytes and especially type 2 dendritic cell precursors (pDC2) seem to be the main producers and also have a wide spectrum of cytokine production. However, neutrophils seem to have a limited capacity for cytokine production but possess efficient defense mechanisms vs. bacterial infection by phagocytosis and degranulation. To determine whether they also have antiviral functions, IFN-alpha and IFN-beta were measured in preparations of pure neutrophils. The capacity of neutrophils to produce type I IFN is controversial. Additionally, macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta were measured, as they are described to have indirect or direct antiviral activity. As stimulants, active and inactivated Newcastle disease virus (NDV), Sendai virus, and granulocyte colony-stimulating factor (G-CSF) were used. Peripheral blood mononuclear cells (PBMC) from the same donors were highly reactive to viral stimulation, whereas neutrophils failed to produce IFN but produced MIP-1beta in response to NDV. We conclude that neutrophils fail to prevent viral infection by IFN production but probably possess alternative mechanisms, such as secreting MIP-1beta in response to viruses.

Differentiation of prolonged colonic transit using scintigraphy with indium-111-labeled polystyrene pellets.

UNLABELLED: Prolonged colonic transit can be caused either by slow transit constipation or by pelvic outlet obstruction needing different therapeutic regimes. The aim of this study was to prove the value of scintigraphic assessment. METHODS: Colon scintigraphy was performed in 32 patients (28 women, 4 men; age range 8-68 yr) with idiopathic constipation at 8, 24 and 48 hr in ventral and dorsal projection after oral administration of a pH-sensitive, methacrylate-coated capsule of nonresorbable 111In-labeled polystyrene (cathion exchanger) micropellets (3.5 MBq/capsule). The geometric center (GC) as the sum of products of colon segment activity and colon segment number (1 = colon ascendens; 2 = transverse colon; 3 = colon descendens; 4 = rectosigmoid colon; and 5 = stool) dividing by the total counts was used to determine the velocity of colonic transit at least at 24 hr as the proximal colonic emptying (PCE) rates. Stool activity was evaluated indirectly as decay-corrected colon activity loss between two examinations. Results were compared with data obtained from 22 healthy subjects. RESULTS: Twenty-six patients had a significant prolongation of colonic transit after 24 and 48 hr (the 95% confidence interval of the patient's GC showed no overlap to the 95% confidence interval of GC calculated from 22 healthy controls as normal range) revealing slow transit constipation. Six patients had normal or accelerated transit (GCs and PCE rates) up to the rectum but delayed rectal emptying indicating pelvic outlet obstruction. CONCLUSION: By the help of this method it was possible to differentiate the two subtypes of colon transit prolongation by use of the reported scintigraphic technique, which leads to different therapeutic management of the patients. Compared with x-ray methods (Hinton test), this method has the capability of a continuous observation of colonic transit without increasing radiation exposure.

Measurement of small bowel and colonic transit: indications and methods.

In this article, we review the currently available techniques for measuring small intestinal and colonic transit. In addition, we describe the characteristics of an ideal test that provided the rationale for the development and validation of a gastrointestinal and colonic transit test at the Mayo Clinic. This new technique assesses regional transit of solid radiolabeled particles of the same size through the entire digestive tract and provides further insights into motor physiologic processes of the gut. By means of a delayed-release methacrylate-coated capsule, isotopically labeled pellets are delivered to the colon as a single bolus; thereby, dispersion of isotope throughout the small bowel is avoided because of the gradual emptying of chyme from the stomach. Similar pellets labeled with a different isotope can be used to assess gastric and small bowel transit. These new methods for measuring transit have also led to insights into the pathogenesis of unexplained gastrointestinal symptoms and disease states. Thus, we demonstrated that in healthy subjects, ileocolonic transfer of chyme occurs in boluses; this transfer is impaired in patients with myopathic pseudo-obstruction. The emptying rate of the proximal colon is an important determinant of the pathophysiologic features of colonic disease; thus, colonic transit is delayed in cases of severe idiopathic constipation. In contrast, rapid emptying of the proximal colon influences stool weight in diarrhea-predominant irritable bowel syndrome. An integrated approach for studying gastric, small bowel, and colonic transit by using the same radiolabeled particle provides a useful, clinically applicable method for evaluating gastrointestinal symptoms and for measuring motor function of the entire digestive tract without need for intubation; cost and radiation exposure are acceptable.

P wave height during incremental exercise in patients with chronic airway obstruction.

We examined changes in P wave height in lead 2 of an ECG obtained during progressive exercise in 23 patients with COPD, and measured both P wave changes and pulmonary hemodynamics during exercise at a constant workload corresponding to approximately 50 to 60 percent of VO2 max in nine patients. The P wave response to exercise (delta P/delta VO2, %/ml/min), estimated by the relationship between percentage of change in P wave height and VO2, was significantly greater (p less than 0.01) in 15 patients who had a decrease in PaO2 with exercise (group A) than eight patients who did not have a fall in PaO2 with exercise (group B). There was a significant negative correlation between change in PaO2 and change in P wave height from rest to maximal exercise (r = -0.68, p less than 0.001). Oxygen therapy in nine patients in group A reduced the increase in P wave height during exercise. Furthermore, change in P wave height from rest to exercise correlated significantly with that of mean pulmonary artery pressure (r = 0.75, p less than 0.01). These results suggest that increase in P wave height during exercise in COPD patients is related partly to oxygen desaturation during exercise, and continuous measurement of P wave change may be useful for noninvasively predicting the pulmonary vascular pressure response to exercise.

Studies on the heterotropic interaction of hemoglobin. I. Mass spectrometric method for determination of the pKa of the beta-146 histidine residue in human hemoglobin.

A mass spectrometric method was developed to determine pH-dependent hydrogen-deuterium exchange at the C-2 position of the imidazole ring of histidine, after converting the amino acid to the methylthiohydantoin derivative. The amount of deuterium exchange in N-acetyl-histidine estimated by the present method was confirmed to be in good agreement with that determined by NMR spectrometry. N-Acetylhistidine was deuterated at various pH's. From the amount of deuterium exchange, a pseudo-first order rate constant (kpsi) was calculated. A pKa value of 7.2 for the amino acid was obtained from the relation between kpsi and pH. This method was applied to estimate the pKa value of beta-146 histidine in human hemoglobin. Human hemoglobin deuterated at various pH's was digested with carboxypeptidase A [EC 3.4.12.2] to release the beta-146 histidine. The amount of deuterium exchange in the isolated histidine was determined to obtain kpsi. From these measurements pKa values of 7.0 for the histidine in oxyhemoglobin and of 8.2 for that in deoxyhemoglobin were found at 36.5 degrees, respectively.

Subunit structure of hemoglobins from erythrocytes of the blood clam, Anadara broughtonii.

Intracellular hemoglobins of the sea blood clam Anadara broughtonii consist of HbI dimer (33%) and HbII tetramer (60%). The molecular weights of globins of HbI and HbII were determined by sodium dodecyl sulfate (SDS)-gel electrophoresis to be 15,500 and 16,500, respectively. The existence of two dissimilar chains, alpha and beta, in globin from HbII tetramer was confirmed electrophoretically and the chains were separated by CM-cellulose chromatography in 8 M urea. In contrast, globin from HbI dimer showed a single band on two types of electrophoresis. The NH2-terminus and the COOH-terminus of HbI were determined to be proline and leucine, respectively. From the results of finger-printing, the alpha and beta chains from HbII were considered to have a rather similar profile, whereas globin from HbI was very different. The results obtained by amino acid analysis of each chain also supported the above findings. It was thus shown that HbII has an alpha2beta2 subunit structure, which is rare among invertebrate hemoglobins. On the other hand, HbI seems to have two identical subunits, designated as "gamma", and to exist as a "gamma2" dimer structure. Both Anadara Hb's appear to have no functional groups relating to the Bohr effect and to be unable to form a binding site for organic phosphates.

Determination of the primary structure of intermolecular cross-linking sites on the Ca2(+)-ATPase of sarcoplasmic reticulum using 14C-labeled N,N'-(1,4-phenylene)bismaleimide or N-ethylmaleimide.

To determine the intermolecular cross-linking site on the primary structure sarcoplasmic reticulum (SR) Ca-ATPase, the conditions for the specific binding of 14C-labeled 1,4-phenylene bis maleimide (PBM) or 14C-labeled N-ethylmaleimide (NEM) to the ATPase were explored. SR vesicles were preincubated with nonradioactive PBM in the presence of 1 mM vanadate for 1 h, then washed by centrifugation to remove free PBM and vanadate. When the pretreated SR vesicles were allowed to react with 1 mM [14C]PBM in the presence of 1 mM AMPPNP, the amount of [14C]PBM incorporated into the ATPase increased with time in parallel with the formation of dimeric ATPase and reached the maximum labeling density of 1 mol of [14C]PBM per mol of dimeric ATPase at 40 min after the start of the reaction. When the pretreated SR vesicles were allowed to react with 2 mM [14C]NEM in the absence of AMPPNP, a maximum of about 2 mol of NEM was bound per mol of the ATPase monomer. The labeling density of [14C]NEM decreased from 2 to 1 mol per mol of the ATPase when the SR vesicles were allowed to react with [14C]NEM in the presence of AMPPNP. From the analysis of the amino acid composition of the two major [14C]NEM-labeled peptides isolated from the thermolytic digest of the enzyme after the reaction of SR with [14C]NEM in the absence of AMPPNP, we deduced that [14C]NEM was incorporated into Cys377 and Cys614. On the other hand, the labeling of SR in the presence of AMPPNP resulted in inhibition of the [14C]NEM binding to Cys614, leaving Cys377 unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen exchange during the acto-subfragment-1 ATPase reaction: evidence for the two-route mechanism of the actomyosin ATPase reaction.

The oxygen exchange occurring during the acto-S-1 ATPase reaction was analyzed based on the distribution of 18O-labeled species of P1 using [gamma-18O]ATP as a substrate. Evidence was found for the two-route mechanism in which ATP is hydrolyzed via the dissociation of acto-S-1 into F-actin and the S-1-phosphate-ADP complex, S-1PADP, and their recombination, and also hydrolyzed without the dissociation of acto-S-1 (Inoue, A., Shigekawa, M., & Tonomura, Y. (1973) J. Biochem. 74, 923-934; Inoue, A., Ikebe, M., & Tonomura, Y. (1980) J. Biochem. 88, 1663-1677). When ATP was mainly hydrolyzed without the dissociation of acto-S-1, the extent of oxygen exchange was low. When ATP was hydrolyzed by both routes, the distribution of product P1 with 3, 2, 1, and 0 18O atoms showed a mixture resulting from low and high oxygen exchange. The rate of ATPase without the dissociation of acto-S-1 can be estimated from the rate of the overall reaction (v), the rate of recombination of S-1PADP with F-actin (vr), and the extent of dissociation of acto-S-1 (a). The distribution of the P1 species measured was almost equal to that calculated from the ratio of ATP hydrolysis via the two pathways as avr and v-avr, respectively. This result indicates that the rates of the dissociation of acto-S-1PADP into S-1PADP and F-actin and their recombination are much lower than the rate of decomposition of the acto-S-1PADP complex into acto-S-1 + ADP + Pi.

Oxygen exchange reaction during ATP hydrolysis by glycerinated muscle fibers, myofibrils, and synthetic actomyosin filaments.

The oxygen exchange during ATP hydrolysis by glycerinated muscle fibers, myofibrils, and synthetic actomyosin filaments was studied from the distribution of the [18O]Pi species produced by the hydrolysis of [gamma-18O]ATP. The products were mixtures of two species, one with a low extent of oxygen exchange and the other with a high extent. The low and high extents of oxygen exchange in these two Pi species were the same as those of the acto-S-1 ATPase reaction through the routes with and without the dissociation of actomyosin, respectively (Yasui, M., Ohe, M., Kajita, A., Arata, T., & Inoue, A. [1988] J. Biochem. 104, 550-559). During isometric contraction of glycerinated muscle fibers at 20 degrees C, the fraction of ATP hydrolysis with low extent of oxygen exchange was 0.83 and 0.70, respectively, in 0 and 120 mM KCl. In myofibrils, the fraction of ATP hydrolysis with a low extent of oxygen exchange was 0.72-0.88 in 0-120 mM KCl at 20 degrees C. Therefore, in glycerinated muscle fibers and myofibrils ATP seems to be mainly hydrolyzed through a route without the dissociation of actomyosin, especially at low ionic strength and at room temperature when the tension development is high. ATP hydrolysis through this route may be coupled with muscle contraction.

A technique of scatter-glare correction using a digital filtration.

A scatter-glare correction technique for x-ray images acquired with an antiscatter grid was developed. In the technique, the scatter-glare image was estimated from exposure conditions and subtracted from the acquired image. The basic procedure in the estimation of the scatter-glare image is convolution filtering; however, the novel aspects of the technique are as follows: (1) To estimate the scatter-glare intensity, a formula that does not include the term of object thickness was used. With this formula, the correction can be performed, even for nonuniform phantoms; (2) To estimate the scatter-glare distribution, the experimental scatter-glare point spread function (PSF) was directly used as a convolution kernel. Although the shape of the PSF changed slightly for water thicknesses of 5-25 cm, we applied the PSF measured at a water thickness of 15 cm to the correction experiments. For the stepped water phantom (10-20 cm), scatter-glare estimation produced an average error of 10%, with respect to the lead bar data. Furthermore, the improvement of image quality and quantitative accuracy resulting from the correction was examined.

Diarrhoea in patients with diabetes mellitus.

Diarrhoea in patients with diabetes mellitus may be due to anorectal or rectal dysfunction that results in incontinence, intestinal secretion or rapid intestinal transit, or may be associated with disorders that typically cause malabsorption. The latter include small bowel bacterial overgrowth, coeliac sprue and pancreatic insufficiency. A practical algorithm for diagnosis and advances in therapy is discussed.

Influence of the LH-RH analogue buserelin on cyclic ovarian function and on endometrium. A new approach to fertility control?

The long-acting stimulatory luteinizing hormone - releasing hormone analogue D-Ser(TBU)6-EA10-LH-RH (buserelin) was administered intranasally once daily in a dose of 400 mcg to 24 normally ovulating women and to 4 women with pre-existing endocrine dysregulation. Ovulation was inhibited in 136 out of 156 treatment months. In 20 treatment months, progesterone values temporarily increased indicating luteinization of follicles or ovulation with defective corpus luteum function. Estradiol secretion showed a tendency to lower values as treatment progressed but individually indicated follicle maturation until the end of the observed medication period. Bleeding pattern ranged from menses-like bleeding in regular as well as irregular intervals to amenorrhea. The morphological findings of 31 endometrial biopsies of 20 volunteers ranged from atrophy (n = 4) to proliferation (n = 25) with early signs of hyperplasia as well as early secretory transformation (n = 2). The morphological alterations indicate that unopposed estrogen stimulation of the endometrium is the main problem of long-term contraception with the dose schedule of buserelin used.