Trialogue

Hyperglycaemic patients admitted to hospital have worse clinical outcomes with higher operational costs than normoglycaemic patients. Identifying, defining and treating hyperglycaemia promptly and appropriately is essential during hospitalisation; adequate ‘continuity of care’ must be assured after discharge. This requires a multidisciplinary clinical collaboration between the internist and the diabetes team, which plays a central role in the treatment course and should be involved soon after patient admission to the hospital. This document aims to establish guidelines and recommendations for good clinical practice in managing hyperglycaemic internal medicine patients, with or without previous diagnosis of diabetes. The Associazione Medici Diabetologi (AMD), Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) and Società Italiana di Diabetologia (SID) have decided to publish a document useful for internists in the management of hospitalised patients with hyperglycaemia. The Trialogue project, coordinated by a Board of Scientific Experts from the three scientific societies, was initiated for this purpose. A questionnaire consisting of 16 multiple choice questions on the management of hyperglycaemia in hospital was answered by 660 physicians from over 250 Internal Medicine units distributed throughout Italy. Analysis of responses has yielded an overview of routine clinical practice and provided a wealth of ideas to better identify critical points in the treatment of hospitalised patients with hyperglycaemia. These recommendations were developed with the aim of providing mutually agreed practical guidance (instructions for use) that can be readily applied by healthcare professionals in routine clinical practice.     

Effects of low-dose oral contraceptives on sugar metabolism

The effects on carbohydrate metabolism by four low-dose oral contraceptives were evaluated in four low-dose oral contraceptives were evaluated-66 young women randomly divided in four groups. In the various preparations there were a different dosage of estrogen (ethinylestradiol) together different doses and types of progestogen (desogestrel, gestodene, cyproterone acetate). After six months of treatment, in all groups a slight increase of glycemic and insulinemic responses during OGTT was observed; the significance was achieved with the preparation containing cyproterone acetate alone. Glycated hemoglobin did not change. Our results suggest that these new low-dose oral contraceptives induced negligible metabolic side effects.     

Peptide-antibody conjugates for tumour therapy: A MHC-class-II-restricted tetanus toxin peptide coupled to an anti-IG light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells

Anti-idiotype antibody therapy of B-cell lymphomas, despite numerous promising experimental and clinical studies, has so far met with limited success. Tailor-made monoclonal anti-idiotype antibodies have been injected into a large series of lymphoma patients, with a few impressive complete tumour remissions but a large majority of negative responses. The results presented here suggest that, by coupling to anti-lymphoma idiotype antibodies a few molecules of the tetanus toxin universal epitope peptide P2 (830–843), one could markedly increase the efficiency of this therapy. We show that after 2-hr incubation with conjugates consisting of the tetanus toxin peptide P2 coupled by an S-S bridge to monoclonal antibodies directed to the X light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 T-lymphocyte clone specific for the P2 peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cystein-peptide was also able to induce lysis of the B-lymphoma target by the T-lymphocyte clone, but at a molar concentration 500 to 1000 times higher than that of the coupled peptide. Proliferation assays confirmed that the antibody-peptide conjugate was antigenically active at a much lower concentration than the free peptide. They also showed that antibody-peptide conjugates required an intact processing function of the B cell for peptide presentation, which could be selectively inhibited by leupeptin and chloroquine. It is reasonable to expect that, in vivo, the anti-idiotype antibodies will selectively transport the tetanus toxin peptides to the B-lymphoma cells, which will process the conjugates and present the peptides to the patients' CD4 T-cell repertoire. Our tetanus-toxoid-vaccinated population has T cells specific for the immunogenic peptide and these, in principle, could be further expanded prior to injection of the conjugate.     

Ca(2+) entry blocking and contractility promoting actions of norbormide in single rat caudal artery myocytes

1 Aim of the present study was to investigate the effects of norbormide, a selective vasoconstrictor agent of the rat peripheral vessels, on the whole-cell voltage-dependent L-type Ca(2+) current (I(Ca(L))) of freshly isolated smooth muscle cells from the rat caudal artery, using either the conventional or the amphotericin B-perforated whole-cell patch-clamp method. 2 Norbormide decreased L-type Ca(2+) current in a concentration- and voltage-dependent manner, without modifying the threshold and the maximum of the current-voltage relationship. Norbormide-induced I(Ca(L)) inhibition was reversible upon wash-out. 3 Norbormide both shifted the voltage dependence of the steady-state inactivation curve to more negative potentials by about 16 mV, without affecting the activation curve, and decreased the slope of inactivation. Norbormide, however, did not modify both the activation and the inactivation kinetics of the I(Ca(L)). 4 Norbormide decreased I(Ca(L)) progressively during repetitive step depolarizations, with inhibition depending on the stimulation frequency (use-dependent block) as well as on the holding potential. 5 Addition of 50 micro M norbormide caused the contraction of all freshly isolated cells and also of those impaled with the perforated method, but not of those impaled with the conventional method (i.e. dialysed). 6 In conclusion, these results prove norbormide to be a vascular L-type Ca(2+) channel inhibitor, which preferentially acts on the inactivated and/or open state of the channel. In rat caudal artery smooth muscle, however, this mechanism does not result in a vasodilating effect since it is overwhelmed by the mechanism underlying norbormide-induced vasoconstriction.     

Carotid endarterectomy: a new technique replacing internal shunts

Summary  Background. Carotid endarterectomy has been reported to increase the time free from cerebral ischemic events in both symptomatic and asymptomatic patients with a high grade of stenosis of the internal carotid artery. In cases in whom the compensatory circulation during the carotid clamp time is not sufficient, the use of intraluminal shunts has been proposed. However, the use of intraluminal shunts present several problems, such as the tecnical difficulties in positioning the shunt, the variability of time requested for the placement, the inconstancy of the blood flow during surgery, and the need to clamp off the carotid to introduce and remove the shunt.  For these reasons, most operators prefer not to employ intraluminal shunts, while others do use them only in selected cases. The purpose of this work is to present, for the first time, a new type of temporary extraluminal shunt, connecting the femoral to the internal carotid artery with the interposition of a roller pump to regulate the blood flow. This method allows one to perform carotid endarterectomy without interrupting the blood flow to the brain.  Methods. 407 consecutive patients, who underwent carotid endarterectomy between August 1992 and April 2000, were considered. 35 patients presented an absolutely insufficient collateral circulation, demonstrated by important modifications of the electroencephalographic monitoring during the carotid clamp time. In these patients the endorterectomy was performed using a new femoral-carotid extraluminal shunt.  Findings. In all the cases in whom the femoral-carotid extraluminal shunt was positioned, the normalisation of electroencephalographic monitoring was achieved by regulating the blood flow with the interposed roller pump. The use and the placement of the shunt was simple and easy. None of the patients showed postoperative complications, except for one who had a stroke two days after surgery.  Interpretation. The results obtained, although to be confirmed by further studies, seem to demonstrate the effectiveness of our femoral-carotid extraluminal shunt, which was simple to use and safe.     

Prevalence of Infections After In-Office Hysteroscopy in Premenopausal and Postmenopausal Women

Study Objective

To estimate the incidence of infection after diagnostic and operative hysteroscopic procedures performed in an in-office setting with different distension media (saline solution or CO₂).

Normoprolactinemic galactorrhea in a fertile woman with a copper intra-uterine device (copper IUD)

We report a case of galactorrhea in a normoprolactinemic fertile woman (30 years old) wearing a copper intra-uterine device (Gravigard). The Gravigard was first inserted in July 1977. In February 1979 our patient noted spontaneous galactorrhea, mainly on the left, but it was also present on the right, after breast pressure. X-ray film of the sella turcica, visual-field examination, thyroid function and basal prolactin levels were all within normal limits. In May 1979 the Gravigard was withdrawn and milk loss stopped finally in December 1979. In March 1980 the IUD was replaced; after only 3 days, mild spontaneous lactation again ensued, on the right side. The patient never took drugs which might have occasioned a prolactin rise. Possible explanations for this unusual phenomenon are discussed.     

A strong CD8+ T cell response is elicited using the synthetic polypeptide from the C-terminus of the circumsporozoite protein of Plasmodium berghei together with the adjuvant QS-21: quantitative and phenotypic comparison with the vaccine model of irradiated sporozoites

Stable protective immunity can be achieved against malaria by the injection of radiation-attenuated sporozoites (gamma-spz) and is mediated by IFN-gamma producing CD8+ T cells targeting the pre-erythrocytic stages. An efficient malaria vaccine should mimic this immunity. We compared the immune response specific for the circumsporozoite protein (CSP) of Plasmodium berghei (P. berghei), an important target of this protective response, elicited in mice immunized with the long synthetic polypeptide (LSP) PbCS 242-310, representing the C-terminus of the CSP of P. berghei, with the adjuvant QS-21 or injected with gamma-spz. The ex vivo evaluation of the CD8+ T cell response by IFN-gamma ELISPOT assay revealed that the injection of LSP with QS-21 induced, compared to gamma-spz, a similar frequency of peptide-specific lymphocytes in the spleen but a eight-fold increase in the draining lymph-nodes. A very high frequency of CD8+ T cells, specific for the sequence PbCS 245-253, a H-2Kd-restricted CTL epitope, was obtained in the liver and spleen of mice immunized with the two regimens. Even though the frequency of H-2Kd PbCS 245-253 multimer+, CD8+ T cells was higher in gamma-spz immunized mice, the frequency of IFN-gamma producing CD8+ T cells was comparable. The phenotype of the CD8+ T cell responses was characterized with the help H-2Kd PbCS 245-253 multimer and most of the CSP-specific CD8+ T cells represented an intermediate subset between effector and central memory with CD44(high), CD45RB(high), CD62L(low) and CD122(high). The number of memory CD8+ T cells decreased after the last LSP immunization but could be boosted to higher level with live spz. The unique combination of LSP PbCS 242-310 and the adjuvant QS-21 induced an immune response that was comparable in terms of quality to the one generated with gamma-spz. This confirmed the potential of LSP as malaria vaccine candidates as well as for the study of the repertoire of targets of protective immunity in the gamma-spz vaccine model.