Search

Incretin and insulin responses to nutrient loads are suppressed in persons with diabetes, resulting in decreased glycemic control. Agents including sulfonylureas and dipeptidyl peptidase-4 inhibitors (DPP4i) partially reverse these effects and provide therapeutic benefit; however, their modes of action limit efficacy. Because somatostatin (SST) has been shown to suppress insulin and glucagonlike peptide-1 (GLP-1) secretion through the Gi-coupled SST receptor 5 (SSTR5) isoform in vitro, antagonism of SSTR5 may improve glycemic control via intervention in both pathways. Here, we show that a potent and selective SSTR5 antagonist reverses the blunting effects of SST on insulin secretion from isolated human islets, and demonstrate that SSTR5 antagonism affords increased levels of systemic GLP-1 in vivo. Knocking out Sstr5 in mice provided a similar increase in systemic GLP-1 levels, which were not increased further by treatment with the antagonist. Treatment of mice with the SSTR5 antagonist in combination with a DPP4i resulted in increases in systemic GLP-1 levels that were more than additive and resulted in greater glycemic control compared with either agent alone. In isolated human islets, the SSTR5 antagonist completely reversed the inhibitory effect of exogenous SST-14 on insulin secretion. Taken together, these data suggest that SSTR5 antagonism should increase circulating GLP-1 levels and stimulate insulin secretion (directly and via GLP-1) in humans, improving glycemic control in patients with diabetes., (Copyright © 2017 Endocrine Society.)

An array of 4-(aryl or indolyl)pyrrolo[3,4-c]carbazole-1,3-diones (open analogues of indolocarbazole alkaloids), 10-(aryl or indolyl)pyrrolo[3,4-b]carbazole-1,3-diones, and different derivatives have been prepared using a Diels-Alder plus Fischer indolization approach and tested as cytotoxic agents. Some representative compounds display interesting cytotoxic profiles.

The preparation of a range of open analogues of arcyriaflavin A is described. The synthetic approach is based on the use of perhydroisoindole-1,3,5-triones as key intermediates, which were obtained via Diels-Alder methodology using 1-aryl-3-siloxy-1, 3-butadienes as starting materials. Fischer indolization and aromatization processes afforded different methoxy-substituted arylpyrrolocarbazoles. The stereochemistry and conformation of the Diels-Alder products and the regiochemistry of the indolization reactions are supported by NMR and molecular modeling studies.

Introduction: Multiple cranial neuropathy or polineuritis cranealis is rarely seen in everyday clinical practice. It is considered to be a topographically circumscribed form of the Guillain-Barré syndrome. The cases described have a wide range of clinical and biological characteristics. Some of these may be due to infectious agents., Clinical Case: We present the case of a 50 year old man with acute onset of diplopia, dysphagia, anarthria, cervical and right arm flexor-extensor muscle weakness due to involvement of many motor cranial nerves and superior cervical nerve roots. On neurological examination there was mixed involvement, mainly of the axons of the nerve trunks involved. Studies to determine aetiology did not show any demonstrable agent., Discussion and Conclusions: Different topographical varieties of the Guillain-Barré syndrome have been described, including: Fisher's syndrome, pharyngo-cervico-brachial paralysis, arreflexive paraparesia, bilateral facial paralysis with paraesthesias, hyporeflexia and bilateral lumbar polyradiculopathy. We compare the clinical characteristics of our patient with those described in the literature. We found a degree of heterogenicity in the clinical and biological characteristics of the cases described, which may mean that they had different aetiologies. Therefore, we consider that before labelling these conditions as atypical variants of the Guillain-Barré syndrome, a thorough search should be made for a precise aetiology.

Introduction: The mesencephalic alternating syndromes or syndromes of Weber, Benedikt and Claude are uncommon in clinical practice. They are caused by a lesion in the mesencephalus which affects the third cranial nerve bundle, together with the corticospinal pathway, subthalamic nucleus and the dentato-rubric path., Clinical Case: We present the case of a normotensive patient who, as a consequence of a hematoma in the mesencephalic tegmentum, had the association of these three syndromes consecutively. The clinical course was favorable, so that after three months of follow-up only paralysis of the third cranial nerve bundle persisted., Discussion: In the syndromes of Weber, Benedikt and Claude there is the association of ophthalmoplegia with hemiplegia, or a cerebellar hemisyndrome or contralateral abnormal movements compatible with hemiballismus, respectively. Amongst the commonest causes are expansive processes, tumors and arteriovenous malformations. More rarely they are due to cerebrovascular accidents, which are usually ischemic and occasionally hemorrhagic in aetiology., Conclusions: Spontaneous mesencephalic hematomas are infrequent. They make up approximately 1% of all intracranial hematomas. The commonest site is the tegmentum followed by the peduncle and tectum. They have better prognosis than other hematomas of the brainstem.

Introduction: The axillary nerve is injured in many clinical situations, mainly in major surgical or traumatic lesions of the shoulder. Equally, it may be found in the context of microtraumatisms or compressive mechanisms. Amyotrophic neuralgia is a clinical entity with pain and later atrophy of the muscle which affects various nerves and nerve groups, as shown by neurophysiological studies., Case Report: We present a lesion with complete axonotmesis of the axillary nerve with a time-relationship to microtraumatism. Initially the patient complained of some pain in the shoulder. During follow-up striking atrophy of the deltoid muscle was seen., Conclusions: We have reviewed the mechanisms described for lesions of the axillary nerve, which do not include the one we found. We discuss the possibility of our case being included in the clinical group described as having amyotrophic neuralgia, although there are some neurophysiological findings which are not typical of this condition. We suggest a review of the many possible trigger factors described in the genesis of amyotrophic neuralgia. Possibly some cases with atypical histories of trauma, and lesions shown by neurophysiological studies to be particularly severe, may be separated from this group.

One hundred and seventy patients were treated with home peritoneal dialysis (PD) in our unit between 1986 and 1994. During this time lapse, several technical improvements were included in our practice. Among others there were: Swan neck permanent catheters, Y-systems, and automated home PD (APD). We reviewed our experience, to assess if these improvements had any impact on patient and technique survival, comparing patients who started PD between 1986 and 1989 (group A), with those who started PD between 1990 and 1994 (group B). Both groups had a comparable basal comorbidity, except for a higher proportion of elderly patients in group B (mean age 48 vs 58 years, p < 0.01). The incidence of peritonitis was lower in group B, while there were no differences in the rates of catheter-related infection or hospital admission. Also, there were no significant differences in patients or technique survival. The increasing presence of elderly patients in our PD unit was, apparently, determinant for the evolution of patient survival. On the other side, technical improvements had a marginal impact on technique survival. A good general PD survival in both groups, with few patients changing to hemodialysis (HD), may explain the lack of significant differences. In addition, peritonitis and inadequate PD/ultrafiltration (UF) were replaced by abdominal surgical events and social reasons as the main causes for PD failure in the second phase of the study.

We have compared the incidence of delayed graft function (DGF) after renal transplantation in our patients undergoing peritoneal dialysis (PD) (group A, n = 92) or hemodialysis (HD) (group B, n = 587), analyzing the prevalence of the main risk factors for DGF in both groups. Both groups were comparable, except for a higher prevalence of diabetes (p < 0.05) and a shorter time on dialysis (p < 0.01) in group A. Immediate graft function occurred in 68.5% of group A and 46.5% of group B, DGF in 22.5% of group A and 39.5% of group B, and there was never any function in 9% of group A and 14% of group B (p < 0.001). When potential risk factors for DGF were compared, no relevant differences could be found. HD was performed more frequently immediately before surgery in group B (p < 0.001), but statistical analysis showed no impact of this measure on the incidence of DGF. In conclusion, in our population, patients on PD present higher rates of immediate graft function after renal transplantation than patients on HD. The explanation for the difference is not clear, but seems to be related to the dialysis modality itself, as the profile of risk factors for DGF is very similar in both populations.

We present the clinical results of a prospective protocol of the treatment of Staphylococcus aureus nasal carriers (SANCs) in our continuous ambulatory peritoneal dialysis unit with mupirocin (Bactroban, SmithKline Beecham Pharmaceuticals, Philadelphia, PA). We monitored the incidence of peritonitis and catheter exit-site infection, the rate of infection-related catheter loss, and the degree of association between SANC state and S aureus infection. The study group included 94 patients with a follow-up of 1,097 patient-months (phase B). The same information was retrospectively collected among 74 continuous ambulatory peritoneal dialysis patients treated during the 24 months preceding the study period (follow-up of 1,043 patient-months) (phase A). S aureus nasal carriage was observed in 47.5% of the patients. Mupirocin was very effective in eradicating S aureus from the nares, but most patients required periodic retreatment. The incidence of S aureus peritonitis decreased from 1 episode/58 patient-months in phase A to 1 episode/548 patient-months in phase B, and the incidence of exit-site infection decreased from one episode/55 patient-months in phase A to 1 episode/137 patient-months in phase B. However, there was a simultaneous increase in the incidence of infections by other gram-positive and -negative bacteria. The rate of catheter loss after peritonitis (P = not significant) or exit-site infection (P < 0.05) tended to decrease from phase A to phase B. Seventy-seven percent of the peritonitis infections and 74% of the exit-site infections by S aureus occurred in SANCs.(ABSTRACT TRUNCATED AT 250 WORDS)

We present the long-term results of a protocol of empirical monotherapy of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis with ciprofloxacin. One hundred and fifteen episodes of peritonitis were studied. The treatment protocol included 5 days of intraperitoneal (IP) administration of the drug, followed by 10 days of oral therapy. A good clinical response was obtained in 83% of the cases, while treatment failure was observed in 4% and relapse in 7%. A decrease in the sensitivity to ciprofloxacin of the peritonitis agents was observed in the study, with Staphylococcus spp. in particular. Three episodes of peritonitis due to bacteria resistant in vitro to ciprofloxacin responded to the treatment protocol. Ciprofloxacin attained good plasma levels both after oral and IP administration. However, dialysate levels were poor after oral administration. The most frequent side effect was gastric intolerance to oral ciprofloxacin. Two patients experienced severe adverse reactions to the drug. Ciprofloxacin may be a good choice for empirical monotherapy of CAPD-related peritonitis. However, the emergence of bacterial resistances must be carefully monitored. The drug should be administered intraperitoneally, at least to induce remission of the infection. Side effects are not frequent, but ciprofloxacin should not be considered an innocuous drug.