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The aim of this study was to demonstrate the macrovascular disease in streptozotocin-induced diabetic rats and assess any possible differences between the histopatholological changes of the coronaries and cerebral arteries. Hearts and brains were obtained after 4 weeks (short-term experimental diabetes, 10 rats) and 12 weeks (long-term experimental diabetes, 10 rats) of streptozotocin injection. Sham injected, control rats were studied in parallel. Muscular-type arteries of 0.10-0.15 mm were examined and semiquantitatively classified either as normal, or slightly, or moderately, or severely thickened by light microscopy: While the arterial wall appeared normal in all sham-injected rats, a varying degree of hyperplasia of the muscular layer and deposition of fibrinoid material resulting in arterial stenosis was prominent in streptozotocin-injected rats. In the group of short-term diabetes there was a slight thickening of the cerebral arteries in the majority of the rats (8/10 rats), while thickening of the coronaries was moderate (9/10 rats). Further progression of arterial wall thickening in both cerebral and coronary arteries was observed in the long-term diabetic group. The mean severity of lesions was significantly higher in the coronaries than in cerebral arteries, both in the short-term (p < 0.0005) and long-term diabetes (p < 0.02). Moreover, by paired statistics within individual animals, we confirmed that wall thickening was significantly more severe in coronaries than cerebral arteries in both groups. These findings suggest an accelerated progress of macrovascular disease in the heart as compared to the brain in the streptozotocin-induced diabetic rat. Although histopathological changes in humans do not always mirror clinical severity, the differences in the macrovascular disease between heart and brain in experimental diabetes may be relevant to the higher relative risk of myocardial infarction compared to stroke for people with diabetes, as compared to people without diabetes.

Background and aim: Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial. state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes. Methods and results: Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meat (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meat consumption and 6 h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P &LT; 0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P = 0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9 &PLUSMN; 1.3 vs. -8.3 &PLUSMN; 3.7 ng/ml h, P = 0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P = 0.001), although the overall response was not significantly different after nateglinide and placebo (P = 0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo. Conclusions: Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes. &COPY; 2005 Published by Elsevier Ltd. Nutrition Metabolism and Cardiovascular Diseases

Macroscopic first- and third-order susceptibilities of ice Ih, ice II, ice IX and ice VIII are calculated using static and frequency-dependent electronic and static vibrational molecular (hyper)polarizabilities at the MP2 level. The molecular properties are in good agreement with experiment and with high-level ab initio calculations. Intermolecular electrostatic and polarization effects due to induced dipoles are taken into account using a rigorous local-field theory. The electric field due to permanent dipoles is used to calculate effective in-crystal (hyper)polarizabilities. The polarizability depends only weakly on the permanent field, but the dipole moment and the hyperpolarizabilities are strongly affected. The calculated linear susceptibility is in good agreement with available experimental data for ice Ih, and the third-order susceptibility for a third harmonic generation experiment is in reasonable agreement with experimental values for liquid water. The molecular vibrational contributions have a small effect on the susceptibilities. The electric properties of a water tetramer are calculated and used to estimate the effect of non-dipolar interactions on the susceptibilities of ice Ih, which are found to be small.

The molecular structure and IR spectra of urea, H2NCONH2, in gas phase and in acetonitrile solution, as well as of the two complexes [MgU4Cl2] and [MgU6]Cl2 have been observed. The influence of environmental changes to geometry and spectra are shown. Various basis sets have been employed to safeguard the validity of the reported findings, using polarization functions for all calculations to get the correct pyramidal amide configuration. The erroneous low energy of the C2v symmetry group, after the addition of the ZPVE correction, is discussed. For the solvated urea molecule a reduction of the energy barrier, compared to the gas phase urea, between the two minimum configurations, C2 and Cs, and the planar geometry, is observed. The lowest energy minimum in acetonitrile is found to be the C2 symmetry group, while for the two complexes, the local symmetry of urea is Cs or C2 depending on the complex, or even on the coordination position of urea in the complex. The wagging motion of the amide group is also discussed in all the studied urea species. The computed geometries and most of the spectroscopic results are in good agreement with the available experimental data.

The electronic structure of the fully lithiated benzene molecule has been calculated at different levels of approximation with particular attention paid to its second hyperpolarizability. It has been estimated that lithiation of the benzene molecule may lead to the enormous increase of the second hyperpolarizability. For hexalithiobenzene the second hyperpolarizability term responsible for the third harmonic generation has been estimated to be of the order of 107e4ao4Eh−3. The reasons for the very large increase of the dipole polarizability, and in particular, of the second hyperpolarizability upon lithiation have been analysed in terms of the electronic structure, orbital energy levels, and the excitation spectrum of the hexalithiobenzene molecule. The main factor responsible for the particularly large values of the studied properties is the electronic valence shell structure of the lithium atom. Although the hexalithiobenzene molecule is used as a model for the study of the lithiation effect, several stable organometallic systems involving alkali metals are known. The present study suggests that among these systems one may find materials of extremly high nonlinear optical efficiency.

The structure-polarization relationship has been investigated in a series of polyenes. Various conjugation patterns have been studied and their effect on the␣polarizabilities and hyperpolarizabilities has been commented upon. Two classes of conjugated oligomers have been shown to have very large second hyperpolarizabilities. It is shown that the known potential of the conjugated chains to lead to large nonlinearities is enhanced by substituting one or more hydrogen atoms with lithium. This interesting and useful point is documented by calculating the hyperpolarizabilities of several selected organolithium derivatives presenting a variety of molecular structures. The largest computed nonlinearity is γ = 4 × 107 a.u., which is an exceptionally large value. The present computations have been performed using the semi-empirical approaches MNDO, PM3 and MNDO/d. This choice of well-tested semi-empirical models, in connection with the available literature values (theoretical and experimental), supports the validity of the reported findings.

Diabetic foot ulceration is currently a serious medical problem and has, therefore, attracted much research attention during the last two decades. Previous foot ulceration, diabetic neuropathy, limited joint mobility, high plantar pressures, microangiopathy, macroangiopathy and diabetic nephropathy have already been identified as risk factors for future foot ulceration. Neuropathy has clearly been shown to be an essential permissive factor in the development of ulceration in the non-ischaemic foot. Moreover, the pathogenetic role of high plantar pressures is crucial in the presence of established clinical neuropathy. Nowadays, our therapeutic efforts clearly aim to prevent than treat foot ulcers. This demands specialist and team work in the setting up of a diabetic foot clinic in an attempt to identify and educate the diabetic patients at risk and, where possible to use suitable plantar pressure-reducing systems (footwear, hosiery etc.). Then only would it be reasonable to postulate that a significant reduction in amputations of diabetic aetiology could be achieved in the near future.

Adrenal incidentalomas (AIs) represent adrenal masses that are incidentally discovered whilst investigating symptoms and signs unrelated to adrenal pathology. The onset and natural course of AIs are unknown, and the possible underlying cardiometabolic abnormalities have not been examined in depth. A growing body of clinical and experimental evidence supports the notion that both functioning and, paradoxically, nonfunctioning AIs are associated with a partially expressed or even full-blown metabolic syndrome (MS) phenotype, through yet unclear mechanisms. Subtle, subclinical or even profound adrenal hormone excess and an increased proinflammatory state might explain to some extent the development of MS disturbances. The emerging association between AIs and MS appears to be important in determining the optimal clinical management of these patients and raises speculation about the exact mechanisms of this interesting cause-effect relationship.

Molecular dynamics (MD) simulation and subsequent analysis of the macroscopic polarization developed in response to “a posteriori” applied electric fields or of spontaneous fluctuations in the instantaneous polarization under zero applied field is used to assess the nonlinear optical properties of a polarizable liquid. Three strategies are proposed for the electrostatic analysis, all using as input static “gas phase” (hyper)polarizabilities, obtained from ab initio calculations. All three strategies are shown to accurately reproduce the experimentally measured refractive index and second nonlinear susceptibility of liquid benzene. The simulation also predicts the distribution of orientations and magnitudes of the local electric fields experienced by the molecules in the liquid, and the nonlinear contributions to the local fields. This approach gives an 8% higher estimate of the second nonlinear susceptibility of liquid benzene than the Lorentz local field factor approach, in better agreement with experimental values.

The polarizabilities and hyperpolarizabilities of C8H6, C8H6Li2 and C8H6Na2 have been computed using MP2 theory. Optimized structures have been employed. The effect of changes in the geometry on the properties is discussed. Distortions induced by lithium and sodium in the anionic moieties are documented. Evidence for the electronic instability of pentalenyl dianion is presented. It has been found that introduction of lithium and sodium into the molecular structure leads to derivatives with very large hyperpolarizabilities. It is thus proposed that organolithium and organosodium compounds are very likely to lead to materials with the required very large nonlinearities, which are necessary in many scientific and industrial applications. Molecular Physics

Static and dynamic polarizabilities and second hyperpolarizabilities are presented for ethylene, including electronic, pure vibrational and zero-point vibrational averaging (ZPVA) contributions. Static pure vibrational hyperpolarizabilities are of commensurate size with their electronic counterparts but show less dependence on basis set and (MP2) electron correlation. A Hartree–Fock estimate for the static ZPVA correction to γ is found to be 10% of the corresponding electronic contribution. The dynamic pure vibrational hyperpolarizability, despite being significant for the optical Kerr effect and intensity-dependent refractive index, reduces in magnitude for second and third harmonic generation, leaving ZPVA as the dominant vibrational effect.

The polarizability (α) and the second hyperpolarizability (γ) of tetrakis(phenylethynyl)ethene (TPEE) are compared and analyzed in connection with the properties (α, γ) of a series of selected/designed molecules having different conjugation patterns. Several lithiated derivatives of TPEE are designed and shown to have very enhanced second hyperpolarizabilities; for example, one of the lithiated TPEE has a 1.6×103 times larger second hyperpolarizability than that of benzene. The potential of the proposed derivatives for applications in photonics is noted. The polarizabilities and the hyperpolarizabilities of the considered molecules have been computed employing the PM3 method which has been proven to be adequate for the present comparative study. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 72: 177–187, 1999

Dipole moments, linear and non-linear polarizabilities of [Mo(NO){HB(dmpz)3}Cl{OC6H4[CHCHC6H4N(CH3)2-4]-4} (dmpz = 3,5-dimethylpyrazolyl) (DMAMoS) and p,p′-dimethylaminonitrostilbene (DMANS) calculated at the SCF and second-order Moller–Plesset correlation (MP2) level with an effective core potential (ECP) basis set are reported. It is shown for DMANS that the ECPs are as accurate as calculations using all-electron basis sets of comparable quality. The effect of diffuse functions on the dominant components of the hyperpolarizabilities of DMANS is small. The dipole moment and linear polarisabilities of DMANS are in very good agreement with experimental values. The calculated hyperpolarisabilities are much smaller than the reported experimental values, but there are large uncertainties among the latter concerning calibration factors, concentration dependence and permanent local field effects, which render direct comparison difficult. Electronic correlation effects on the hyperpolarisabilities are large, especially for DMAMoS, for which the dominant component of the first hyperpolarisability increases by a factor of 5. Generally, the hyperpolarisabilities of DMANS are found to be larger than those of DMAMoS, in spite of the highly polarisable electronic charge-transfer character of the latter.

Multiple myeloma (MM) is charecterized by great clinical heterogeneity. Among known prognostic factors the cytogenetic abnormalities are thought to be of major importance. The aim of this study was to correlate certain chromosomal abnormalities with immunoglobulin isotype and survival in MM patients.Forty-nine Greek MM patients, homogeneously treated with conventional-dose chemotherapy, were cytogenetically studied by direct culture of bone marrow cells and G-banding technique.Twenty-four patients had a normal karyotype while the remaining 25 patients presented numerical and structural abnormalities. Recurrent structural abnormalities were observed. Translocations involving the 14q32 region were observed in 8 cases, while 6 cases exhibited a del(1)(p12). We confirmed the negative impact of chromosomal abnormalities on the overall survival of MM patients and we also showed that t(11;14) had a worse impact on disease outcome as compared to t(14q32) with an unidentified partner chromosome. The presence of del(1) (p12) significantly worsened the prognosis in MM patients. No correlations existed between the association of immunoglobulin isotype with survival or certain chromosomal changes.Further studies are indicated at the molecular level to clarify the exact role and the prognostic value of 1p12 involvement in MM patients.

Background and Study Aims: Many factors, such as oxygen and vasculature, are involved in the cytotoxic effect of photodynamic therapy (PDT). It is known that somatostatin and its analog octreotide decrease the splanchnic blood flow and have multiple inhibitory effects in different functions of the peptic system. The aim of this experimental study was to assess the effect of octreotide administration on PDT outcome in normal pig stomach. Methods: 28 healthy pigs, randomly assigned to two groups, A and B, were studied. Pigs in both groups were sensitized with 0.3 mg/kg intravenous meta-tetra (hydroxyphenyl) chlorin (mTHPC), and 48 hours later light of wavelength 650 nm was delivered from a 50-mW diode laser for 300 s (energy fluence 15 J/ cm(2)) through a gastroscope to the gastric mucosa. Group A underwent PDT without octreotide and group B had PDT with administration of octreotide. At 72 h after light delivery, all the animals were sacrificed for macroscopic and histological evaluation of the irradiated site. Results: The macroscopic images and the histology of the stomach PDT lesions (inflammation, ulceration, necrosis) showed significantly less severity in the group of animals with octreotide injection (group B). In this group, full-thickness necrosis was observed in 28.5 %, compared with over 71.4 % in group A; this was statistically significant (P< 0.05). Conclusion: Octreotide may have a modulating effect on mTPHC PDT in normal gastric tissue in pigs, probably due to alterations of hemodynamics in the stomach and to suppression of the inflammatory process.

Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method.Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72).In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.

There are no guidelines on second-line therapies for Helicobacter pylori eradication failures of omeprazole-clarithromycin-amoxicillin triple therapy.To compare the efficacy of two second-line therapies for persistent H. pylori infection.Over a 6-year period, patients with persistent H. pylori infection following omeprazole-clarithromycin-amoxicillin eradication therapy were randomized to receive omeprazole, 20 mg twice daily, bismuth, 120 mg four times daily, metronidazole, 500 mg twice daily, and either tetracycline, 500 mg four times daily, or clarithromycin, 500 mg twice daily, given for 7 days. Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori infection was confirmed by histology.Of the 95 randomized patients, 88 (93%) completed the study. Age, sex, smoking, ulcer/non-ulcer dyspepsia ratio and antibiotic resistance were not significantly different between the treatment groups. On intention-to-treat analysis, eradication was achieved in 41 of the 49 patients (84%; 95% confidence interval, 70.4-92.7%) and 27 of the 46 patients (59%; 95% confidence interval, 43.3-73.0%) of the tetracycline- and clarithromycin-containing groups, respectively (P=0.007). On multivariate regression analysis, the sensitivity of H. pylori to metronidazole had a likelihood ratio of 5.2 (P=0.022), followed by the type of quadruple therapy (likelihood ratio, 4.4; P=0.036).Tetracycline-containing quadruple rescue therapy is highly effective in treating H. pylori eradication failures of the omeprazole-amoxicillin-clarithromycin regimen.

Changes in blood rheology have been described in diabetes mellitus. Buflomedil, a vasoactive substance with hemorheological properties, has been widely used in the treatment of intermittent claudication. The aim of this study was to evaluate the effect of buflomedil on clinical and hemorheological parameters in subjects with type 2 diabetes and intermittent claudication.Forty patients were randomly assigned to oral buflomedil or matching placebo for six months in a double-blind manner. Initial and absolute walking distances were assessed by a standard treadmill testing protocol. Erythrocyte deformability was estimated with a whole blood filtration technique. ADP- and collagen-induced platelet aggregation was assessed with an aggregation profiler. beta-thromboglobulin and platelet factor-4 were measured with radioimmunoassays. All tests were performed at baseline and after three and six months of treatment.A significant increase in the mean initial (71%) and absolute (68%) walking distance was achieved only in the buflomedil group. ADP- and collagen-induced platelet aggregation was significantly reduced in the buflomedil group, while no significant changes in erythrocyte deformability, beta-thromboglobulin and platelet factor-4 levels were noticed. However, beta-thromboglobulin levels increased significantly in the placebo group.These findings suggest the therapeutic efficacy of buflomedil in diabetic subjects with intermittent claudication. The inhibition of platelet aggregation and the influence on platelet activity exerted by the drug could play an important role in its clinical effect and may be of value in the treatment of such patients.

Thrombotic thrombocytopaenic purpura (TTP) is characterised by platelet aggregation in the capillaries, thrombocytopaenia and microangiopathic haemolytic anaemia that result in organ ischaemia, mainly of the CNS and kidneys. Since the institution of plasma exchange therapy no further treatments have been proved to improve the survival and the relapse rate of TTP patients. In this retrospective study, we evaluated the efficacy of normal human immunoglobulin treatment in 44 patients suffering from TTP. Patients were divided into two groups that either did not receive (group A: 15 patients) or received (group B: 29 patients) 400 mg/kg of human normal immunoglobulin intravenously (ivIgG) for 5 days. All patients received treatment with corticosteroids, anti-platelet agents and plasma exchange. The results clearly showed that there was no statistically significant difference between the two groups in either remission rate or time to relapse following remission. In conclusion, this study did not prove any beneficial effect of ivIgG in the treatment of TTP patients.

There is evidence that Helicobacter pylori eradication might predispose to gastroesophageal reflux disease (GERD). The aim of this prospective study was to examine the effectiveness of antisecretory treatment, after successful H. pylori eradication, in preventing GERD, since no data exist so far. Eighty initially H. pylori(+) patients, without GERD at the time of H. pylori eradication [50 peptic ulcer (PU) and 30 nonulcer (NU), 55 men, 25 women, median age 38 years, range 19-57], after successful H. pylori eradication were randomized to recieve either omeprazole 20 mg daily (group A) or no treatment (group B) for one year. All patients underwent upper gastrointestinal endoscopy at 0, 6, and 12 months or when GERD symptoms occurred. There were 40 patients in each group, and there were no statistically significant differences between the two groups in terms of sex, age, body weight, ulcer/no ulcer ratio, and other demographic data. Seven patients from group A and five patients from group B were lost to follow-up, and therefore there were 33 and 35 patients in groups A and B, respectively, who completed the study. One of 33 patients in group A (3%) and 10/35 (28.5%) in group B developed GERD symptoms during follow-up (P = 0.0022). The respective values for esophagitis were 0/33 (0%) and 6/35 (17.1%) (P = 0.0083). In conclusion, antisecretory treatment in H. pylori(+) patients, after successful eradication, is effective in preventing GERD.

Normal subjects may incompletely absorb either lactose, fructose, or sorbitol and may therefore have abdominal symptoms. The frequency of coincidental malabsorption of these sugars is not known. This is clinically important, since we often ingest them during the same day and malabsorption may cause abdominal symptoms. To shed light on this issue we studied 32 normal subjects. Volunteers drank in random order the following solutions: 20 g lactulose, 50 g sucrose, 50 and 25 g lactose, 50 and 25 g fructose, 20 and 10 g sorbitol. Semiquantitative carbohydrate malabsorption was estimated with lactulose standards. Frequency of 50-g lactose (69%), 50-g fructose (81%), and 20-g sorbitol (84%) malabsorption was not significantly different (P = 0.3). The estimated median fraction of the ingested high dose malabsorbed was 42, 19, and 68% for lactose, fructose, and sorbitol, respectively. At low challenging doses, 63% of the volunteers absorbed two of three or all three sugars, and 88% were asymptomatic to two or all three sugars. In conclusion, the frequency of coincidental malabsorption of lactose, fructose, and sorbitol and intolerance to these sugars is not common, when normal adults ingest them at low doses.

Splenectomy in patients with non-Hodgkin's lymphoma (NHL) is performed for either diagnostic or therapeutic reasons. We report on a series of 29 patients with NHL and splenomegaly who underwent splenectomy during the years 1979-1998 in our hospital. According to the indication for splenectomy our patients were categorized in three groups. Group A: In 20 patients splenectomy was performed for diagnostic reasons. Group B: Three patients were splenectomized for autoimmune haemolytic anaemia (AIHA). Group C: Six patients underwent splenectomy because of hypersplenism. A definitive histopathological diagnosis of NHL was obtained in all patients of group A. Hypersplenism and AIHA were resolved in all patients after splenectomy. One (3.5%) patient died postoperatively because of septicemia complicated by disseminated intravascular coagulation. Six postoperative complications were observed in 4 (14%) patients. Splenectomy, with an acceptable surgical risk, has the potential to establish the diagnosis of NHL in patients with splenomegaly without lymphadenopathy and negative bone marrow findings. Moreover, splenectomy has the capacity to modify the disease course in patients with NHL complicated by AIHA or hypersplenism.

Factors affecting Helicobacter pylori eradication rate with omeprazole (OME), clarithromycin (CL), and amoxicillin (AMO) have not been extensively studied. We have investigated the effect of age, sex, smoking, ulcer disease, compliance with therapy, H. pylori colonization density, degree and activity of antral gastritis, the coexistence of corpus gastritis, and the presence of lymphoid follicles on H. pylori eradication rate. We studied 80 consecutive H. pylori-positive patients, with duodenal ulcer (N = 35) or nonulcer dyspepsia (N = 45) treated with OME 20 mg, CL 500 mg, and AMO 1 g, each given twice daily for 10 days. H. pylori was eradicated in 71/80 (88.8%, 95% CI 82-96%) patients. The regimen failed to eradicate the only strain (1.8%, 95% CI 0-5.2%) that was clarithromycin resistant. Multivariate discriminant analysis showed that two histological variables (Wilks lambda = 0.74, chi2 = 23.41, df = 2, P0.001), absence of lymphoid follicles in routine gastric biopsies (F = 13.63, P0.001) and coexistence of antral and body gastritis (F = 13.68, P0.001), significantly increased H. pylori eradication rate. No other factor examined predicted H. pylori eradication with this regimen. Our data suggest that body gastritis is a positive and presence of lymphoid follicles in routine gastric biopsies is a negative predictive factor of treatment outcome with the omeprazole, clarithromycin, and amoxicillin regime.

Treating patients with erosive esophagitis and maintaining remission in a cost-effective fashion is a desirable goal in clinical practice. There are no established criteria to identify patients with healed esophagitis who will subsequently remain in remission with low-dose omeprazole therapy. We investigated whether 24-h esophageal-gastric pH monitoring could provide criteria to select patients for low-dose omeprazole maintenance therapy.Seventy consecutive symptomatic outpatients with grade 2-3 reflux esophagitis were prospectively investigated. They were treated with 20 mg/day omeprazole for 2 months. Those with healed esophagitis were given alternate-evening 20-mg omeprazole maintenance therapy for 6 months. Clinical evaluation, endoscopy, and 24-h esophageal-gastric pH were done at the end of each treatment period. Results of pH studies of patients in remission were compared with those with endoscopically documented relapse of esophagitis.In 63/70 patient (intention-to-treat, 90%; 95% confidence interval [CI], 83-97%) esophagitis was healed at 2 months. During the 6-month maintenance period esophagitis remain healed in 28 (G1) (40%; 95% CI, 29-52%), but recurred in 32 patients (G2). During healing with omeprazole 20 mg/day the 24-h gastric pH was below 4 for10% of the time in 96% of the patients, who subsequently remained in long-term remission with low-dose maintenance therapy (G1), but not in any patient with recurrence of esophagitis (G2). The 10% threshold value has a specificity of 1.00 and sensitivity of 0.96.The 24-h intragastric pH monitoring during 20 mg/day omeprazole therapy provides criteria by which to preselect patients with reflux esophagitis who will remain in remission with low-dose omeprazole therapy.

Early menopause, whether it be natural or surgical, is one of the established risk factors for osteoporosis. Surgical menopause, however, differs from natural menopause owing to the abrupt cessation of estrogen secretion. This study attempts to investigate the influence of menopause type on bone mineral density (BMD) changes.Four groups, each consisting of 30 women, were compared: early menopause (EMP), surgical menopause (SUMP) and two groups of natural menopause. The two groups share a similar number of years since menopause (YSM) but have a different chronological age (NMPO), or share a similar age but different YSM (NMPY) to the EMP and SUMP. BMD was measured by the DXA method at L2-L4 vertebrae and proximal femur.Mean vertebral BMD of EMP was lower than that of SUMP (P0.05) and of NMPY (P0.001) women. Femoral neck BMD did not differ between SUMP and EMP women but both exhibited significantly lower BMD than either natural menopause groups. BMD of SUMP and vertebral BMD of NMPY women was inversely correlated to chronological age and to number of YSM. Pertaining to T-score values according to the osteoporotic range, NMPO, EMP and SUMP women being homogeneous exhibited significantly lower values than NMPY in the vertebrae (F-ratio = 7.84, P0.001). Whereas, in the femoral neck and the trochanter major, EMP and SUMP categories presented significantly lower T-score values than the NMPO and NMPY (F = 3.61, P0.01 and 2.8, P0.05 respectively).Women with early menopause exhibit lower vertebral BMD than women of similar age after either surgical or natural menopause. In women of similar age, surgical menopause results in lower vertebral and femoral neck densities compared to natural menopause. Chronological age and the interval after menopause negatively affects bone density in women with similar age whether in surgical or natural menopause.

Follicular gastritis is an important histological entity, because it may progress to overt gastric MALT lymphoma. However, there is no universal agreement on whether there is any correlation of follicular gastritis with histological features of the antral mucosa or on the prevalence of follicular gastritis. To shed further light on these issues, we studied antral biopsies obtained from 735 adult patients, who had participated in six consecutive clinical trials. They included 348 patients with duodenal ulcer, 82 with gastric ulcer, and 305 with nonulcer dyspepsia. The Sydney classification system of gastritis was used, using a score of 0-3 to grade degree and activity of inflammation, gland atrophy, intestinal metaplasia, and H. pylori colonization density. Follicular gastritis was defined as prominent lymphoid follicles with no lymphoepithelial lesion. None of the H. pylori-negative patients (N = 159) had follicular gastritis. Among H. pylori-positive patients, 80/340 (23.5%) with duodenal ulcer, 5/77 (6.5%) with gastric ulcer, and 20/159 (12.6%) with nonulcer dyspepsia had follicular gastritis (P0.001). Multivariate discriminant analysis selected the following four significant predictor variables for follicular gastritis (Wilks lambda = 0.91, chi2 = 70.6, df = 4, P0.001): gastritis sum score, atrophic gastritis, age of the patient, and disease. The prevalence of follicular gastritis was linearly correlated (gamma = 24.55 - 0.98chi, r = -0.62, F1,11 = 6.12, P = 0.03) with the age groups of the 576 H. pylori-positive patients studied. In conclusion, follicular gastritis is highly correlated with H. pylori-caused severe, active gastritis. It is mostly prevalent in the young H. pylori-infected patients with duodenal ulcer.

The polarizability and first and second hyperpolarizabilities of several 4,4'-disubstituted trans- stilbene (tSB) derivatives, which include the NO2 group as an acceptor (A) and several lithium containing donors (D) have been computed. Ab initio theory using a 6-31G basis set at the SCF and MP2 levels has been sued to optimize the structure of tSB and the disubstituted derivative which includes the NO2 (A) and the NLi2 (D). Their polarizabilities and hyperpolarizabilities have also been computed at the SCF level. MP2 theory has been used to assess the effect of correlation on the largest polarizability and second hyperpolarizability components of the above compounds. The preset results, together with our recent work show that the second hyperpolarizabilities of some lithiated derivatives depend quite a lot on the molecular geometries and lithiation leads to a big increase of the hyperpolarizabilities of the resulting derivatives. This finding suggests that at lest some of the lithiated derivatives are very likely to be useful for non-linear optical applications.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

To date it is not known whether gastric juice vitamin C levels are influenced by Helicobacter pylori CagA(+) strains. The aim of the present study, therefore, was to study the impact of H. pylori CagA status on gastric juice vitamin C levels.We studied 30 H. pylori(+) patients, and the results were compared with 10 endoscopically and histologically normal H. pylori(-) subjects (control group) who were similar to the H. pylori(+) group in terms of age and sex. In all patients, gastric juice vitamin C levels were determined and the severity of gastritis was graded on a scale of 0 (absent) to 3 (severe). CagA was determined by immunoblotting the sera from patients against H. pylori antigens.Among 30 H. pylori(+) patients, 20 were CagA(+) and 10 CagA(-). In the entire group of H. pylori(+) patients, the median gastric juice vitamin C levels (mg L-1) were 16.35 (range 3.5-33.6) and were significantly lower (P0.001) than in the control group of H. pylori(-) patients [35.5 (23.1-50.2)]. In addition, in the entire group of H. pylori(+) patients there was a highly significant (P0.0001) inverse correlation between the gastritis activity score and the gastric juice vitamin C levels. In the group of H. pylori CagA(+) patients, the median levels of gastric juice vitamin C were 13.8 (3.5-31.2) and were significantly lower than the corresponding levels in both the H. pylori CagA(-) group [24.8 (22-33.6), P0.01] and the H. pylori(-) control group [35.5 (23.1-50.2), P0.001], the last groups being similar. Furthermore, the gastritis activity median score in the H. pylori CagA(+) group [2 (1-3)] was significantly higher (P0.05) than in the H. pylori CagA(-) group [1 (1-2)].These data indicate that infection with CagA(+) H. pylori strains significantly lowers the gastric juice vitamin C levels in comparison with CagA(-) H. pylori strains, which might have a significant impact on gastric carcinogenesis.

In a double-blind, randomized study, miglitol (BAY m 1099), an alpha-glucosidase inhibitor, 100 mg tds or placebo was given orally with meals for a period of 24 weeks in 117 patients with Type 2 (non-insulin-dependent) diabetes mellitus (DM) treated with insulin. Fasting and 1 h postprandial plasma glucose and C-peptide were measured at the beginning and at the end of each 4-week interval and glycosylated haemoglobin was determined at day 0 and at the end of the 12th and 24th week. One hour postprandial plasma glucose was significantly lower in the miglitol group at the end of the 24th week (placebo: 11.6 +/- 1.5 vs miglitol: 8.2 +/- 1.5 mmol l-1, mean +/- SD, p = 0.001). Diabetes control improved in the same group as the HbA1 was lowered by 16% (p =0.0001) at the end of the treatment. Mild reversible adverse effects were observed in 37 patients of the miglitol group (mainly flatulence and mild hypoglycaemia) and 2 of the placebo group. Urinary glucose was rendered negative in 41 patients in the miglitol group only. Thus miglitol appears to be a safe and effective adjunct in the management of Type 2 DM, in association with insulin.

Octreotide is used to arrest peptic ulcer hemorrhage. Since it has anti-secretory properties, it could also be used in Helicobacter pylori eradication therapy, to cure peptic ulcer before discharging patients from hospital. The aim of this pilot study was to determine safety and efficacy of an ultra short quadruple octreotide containing H. pylori eradication therapy in patients with peptic ulcer.Twenty-six consecutive symptomatic H. pylori-positive patients with duodenal (n = 20) or gastric ulcer (n = 6), were treated with a three-day course of octreotide 0.3 mg/day subcutaneously, amoxicillin plus metronidazole 2 g/day orally and colloid bismuth subcitrate 480 mg/day. CLO-test, culture and crush tissue smears were performed on admission to the study, at 4 and 8 weeks post treatment. The effect of octreotide on intragastric pH (n = 10) was also investigated.Octreotide significantly increased the mean 24-hour intragastric pH3 over 68.9% of the time (37.1%-99.5%). There were no treatment side effects. Ulcer pain was abolished at between 2-12 days. By intention-to-treat 24/26(92.3%, 95% CI 82%-100%) ulcers had healed at 4 weeks. H. pylori eradication rate at 8 weeks was 88.5% (23/26) (95% CI 76%-100%).Our ultra-short octreotide containing quadruple therapy is a safe and effective regime in eradicating H. pylori and healing peptic ulcers. It may be a suitable therapy for hospitalized patients with peptic ulcer hemorrhage.

Laser Doppler (LD) flux and transcutaneous oxygen tension (TcPO2) were measured in supine and sitting position at the dorsum of the foot with local skin temperature of 37 degrees C and 44 degrees C in 50 patients with stage IIb of chronic peripheral arterial occlusive disease (CPAOD) and in 30 healthy controls. The statistical analysis showed no significant differences between patients and controls in the supine and sitting position at 37 degrees C. A lower increase of LD- flux and TcPO2 could be noticed during hyperthermia and reactive hyperaemia in the patients group as well as a significant prolongation of oxygen (ORT) and flux reappearance time, of postocclusion time to peak flux and oxygen peak, of postocclusion time to half of peak flux and oxygen peak and of time to flux restoration at preocclusion levels (FTMAX) during reactive hyperaemia test. FTMAX and ORT allowed a clear separation between patients and controls and exhibited a high reproducibility. A regression analysis equation was derived with the most significant parameters indicating the presence and the severity of the disease. Moreover, the estimated time parameters of LD - flux and TcPO2 were correlated with the US - Doppler ankle systolic blood pressure indices and therefore with the impairment of the macrocirculation. In summary, we find that skin perfusion in patients with intermittent claudication is not different from normal subjects under basal conditions. However, maximal perfusion is reduced and the time to peak perfusion after a provocative stimulus is delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary OBJECTIVE The few published prospective studies suggest a strong association of colonic tumours with acromegaly, but include small numbers of patients. In addition, the upper gastrointestinal tract of these patients has never been prospectively studied. The aim of the present study was to investigate the incidence of gastric and colonic tumours in a large cohort of acromegalic patients. DESIGN Acromegalic patients consecutively admitted to an Endocrinology Department for diagnosls and follow-up, were submitted to gastroscopy and colonoscopy, to identify those harbouring gastrointestinal tumours. PATIENTS Over a 5-year period, 54 out of 61 patients (78% with active disease) received colonoscopy and 42 out of 61 gastroscopy. No patient had a past history of gastrointestinal malignancy. MEASUREMENTS All polypoid lesion8 found at colonoscopy and gastroscopy were separately recorded and biopsled. RESULTS No case of gastrointestinal cancer or gastric polyp was discovered. Nineteen patients (35%) had 1-8 colonic polyps, including 5 (9·3%) with adenomas. When compared to patients with a normal colon, those with polyps were significantly older (44·±14· vs 52· f 10·9 years, P= 0·47), but the duration of acromegaly (10·±8· vs 10·±7· years, P= 0·9) and the number of patients with active disease were similar in both groups. CONCLUSIONS Acromegalic patients do not have an increased incidence of gastric tumours. The observed significant variation in the prevalence of colonic adenomas (9-35%, P= 0·03) and cancer (0-15%, P= 0·017), between our patients and those of the published prospective studies with similar demographic characteristics, suggest that environmental and hereditary factors may be more important than the presence of acromegaly.

The magnitude of complex carbohydrate malabsorption in exocrine pancreatic insufficiency has not been well quantified in the past. The quantity of carbohydrate malabsorbed after a rice starch (100 g) meal in 20 patients with chronic pancreatitis (n = 10) or pancreatic cancer (n = 10) was therefore estimated. Patients had a three day stool fat collection (80 g/24 hour fat intake), a lactulose (20 g), and a rice flour (100 g) breath hydrogen test. Normal controls (n = 29) had a postprandial H2 increase < or = 14 ppm and malabsorbed (mean (SEM)) 1.12 (0.44) (range 0-11.10) g of the 100 g of carbohydrate ingested. Patients malabsorbed significantly more carbohydrate (11.36 (2.23) (range 8.90-32.60) g, F1.47 = 29.92, p < 0.001). The number of patients with fat (> 7 g, n = 8) or carbohydrate (increase in H2 > or = 20 ppm, n = 10) malabsorption was not different (chi 2 = 0.10, p = 0.75). There was a significant correlation between faecal fat and amount of malabsorbed carbohydrate (r = 0.60, F1.17 = 9.70, p = 0.006) and faecal fat and stool wet weight (r = 0.57, F1.18 = 8.67, p < 0.009), but not between stool wet weight and amount of malabsorbed carbohydrate (r = 0.28, F1.17 = 1.45, p = 0.25). Although patients with exocrine pancreatic insufficiency malabsorb 10%-30% of the ingested complex carbohydrate, the main determinant of stool wet weight could be faecal fat.

The significance of main pancreatic duct width in the diagnosis of pancreatic disease, was studied in 338 endoscopic retrograde pancreatographies. Two hundred and forty patients referred for suspected biliary disease had normal pancreatograms (Group 1), 60 had pancreatic carcinoma (Group 2) and 38 had a history and pancreatogram compatible with chronic pancreatitis (Group 3). After categorizing patients by decade, in group 1 the effect of aging on the pancreatic duct width in the head, body and tail (F5,2343.71, p0.003) was pronounced, especially after the fifth decade. There was a significant difference between groups 1, 2 and 3 in terms of the width of the main pancreatic duct in all three parts of the pancreas (F2,32542.24, p0.001). The upper range of normal pancreatic duct width was 8.0 mm, 4.0 mm and 2.4 mm in the head, body and tail, respectively. Abnormal ductograms were wider than the normal ranges in the head, body and tail of the pancreas in 14%, 49% and 59% (p0.001) of the patients, respectively. Establishing normal ranges of the pancreatic duct width may help in the diagnosis of pancreatic disease. Measurements in the body and tail, as compared with the head, are a more sensitive indicator of pancreatic duct dilation.

The aim of the medical treatment of acute pancreatitis is to rest the gland and to reduce complication and mortality rates. The effect of various treatment modalities on the course and outcome of acute pancreatitis have been disappointing. This review critically considers the results of reported therapeutic trials and our own unpublished data of somatostatin and its long-acting synthetic analogue, octreotide, in acute pancreatitis. It is concluded that somatostatin is a promising drug. It reduces pancreatic enzyme secretion, the clinical need for analgesic drug administration, and the local complication rate, and shortens hospitalization. However, its effect on mortality rates is questionable. It is suggested that large-scale, carefully designed studies of somatostatin are needed to evaluate the beneficial effect of this drug on the course and outcome of acute pancreatitis. Since most of the trials included pancreatitis of various etiologies, it is also suggested that cases of acute biliary pancreatitis should be excluded or evaluated separately, as these patients are best treated by endoscopic sphincterotomy.

The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha-glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption.

Gene technology has made significant amounts of biosynthetic human proinsulin (BHP) for biological and clinical studies available. It has been shown both in vitro and in vivo that BHP is about 10% as active as biosynthetic human insulin. More specifically it is 8% as potent regarding its action in stimulating peripheral glucose disposal and 12% as potent in suppressing hepatic glucose output. Its hypoglycemic effect is rather produced by the intact molecule or its intermediates and not by conversion to insulin or C-peptide. BHP appears to exert a more prolonged action when administered subcutaneously compared to NPH insulin. Furthermore because of its weaker effect on peripheral glucose utilization it is expected to create less profound hypoglycemia. Under conditions of equipotency BHP may stimulate triglyceride synthesis in a lower degree and in that way be less lipogenic. On longterm basis BHP proved to have a low immunogenic potential. We investigated the efficacy of BHP in split doses in type II diabetics with relative insulin resistance. Glucose levels at 1600 and 2000 and 0400 hrs as well as integrated glycemia over the 24 h period were lower under BHP. The potency of BHP in this and other studies has been demonstrated after application of greater quantities from it in terms of equimolarity. Nevertheless there are certain features such as the protracted action, the stronger effect on hepatic glucose production and the lower suppression of endogenous insulin secretion which make proinsulin a promising agent in the future management of type II diabetes.

In order to investigate the relationship between the in vivo platelet activity and diabetic macroangiopathy we have measured plasma beta-thromboglobulin (beta-TG) concentrations by means of a very sensitive radioimmunoassay in 55 diabetics, aged 47-80 years, and in 27 non-diabetic healthy controls (group A) of respective age and sex. Among diabetics 17 were free of vascular complications (group B) in terms of diabetic micro- or macroangiopathy, while the remaining 38 (group C) suffered from peripheral occlusive arterial disease (POAD) of the lower limbs. All subjects underwent a thorough clinical and laboratory investigation. The diagnosis of POAD was based upon the findings of Doppler ultrasound examination and was confirmed by selective arteriography. The mean plasma beta-TG concentrations were significantly higher in the two groups of diabetics compared to the non-diabetic controls (p0.001), whereas the highest beta-TG levels were found in diabetics with POAD (py 0.001), (beta-TG: mean +/- 1 SD ng/ml; group A: 26.50 +/- 13.14; group B: 55.88 +/- 26.56; group C: 106.50 +/- 52.65). These findings reveal an increased release reaction of platelets in diabetics and an enhanced in vivo platelet activity especially in POAD subjects. However, this may occur not only in cases with prominent macroangiopathy but also in the early stages of diabetic angiopathy when the vascular lesions cannot be traced clinically.

Liver uroporphyrinogen synthetase activity was measured in 45 mice, divided in three groups. The mice of the 1st group served as controls, those of the 2nd starved for 24 hours, while those of the 3rd were injected intraperitoneally with phenobarbital. The enzymic activity was found significantly (p less than 0.001) lower in the animals of the 2nd group (17.49 +/- 2.25 nmol/g/h) and higher in those of the 3rd (25.82 +/- 3.73 nmol/g/h) as compared to the controls (20.89 +/- 2.11 nmol/g/h). If these effects also exist in the human it could be suggested that starvation may be doubly harmful for the patients with acute intermittent porphyria by aggravating both their enzymic disorders. On the contrary, in the case of phenobarbital its undesired effect on porphyria may be moderated by a simultaneous induction of the uroporphyrinogen synthetase.

Organ transplantation depends on a display of public confidence. Health authorities have the duty to protect public confidence against any action that would put in doubt the quality of the health services offered and/or the ethical issues connected with the health services. On the other hand, there has been a period of access to the practice of “transplantation on the free market”, something which creeping its way in to several countries and which will hopefully come to an end shortly. Our aim is to present another aspect of commercialism, more complicated than usual, and in which conflicting evidence has been presented at different periods; this aspect will also be ending soon.