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7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Purpose of the study We determined the prevalence of type‐2 diabetes mellitus (DM) in HIV infected (HIV+) and uninfected (HIV‐) subjects. Methods Cross‐sectional analysis on HIV+ patients (pts), aged >18 [...]

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The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.

Type 2 diabetes mellitus is a growing problem in HIV population and a comparison with the general population may help screening and prevention. In this cross-sectional study the authors determined the prevalence of type 2 diabetes mellitus in 4,249 HIV-infected subjects attending the San Raffaele Infectious Diseases Department compared with 9,148 healthy controls recruited in 15 Italian regions, and identified risk factors associated with of type 2 diabetes mellitus. Type 2 diabetes mellitus was defined as reported diabetes, a fasting plasma glucose concentration ≥7.0 mmol/l, or current use of anti-diabetic medication. Prevalence of type 2 diabetes mellitus was higher in HIV-infected than healthy subjects (4.1 vs. 2.5 %; P < 0.0001). At multivariable analysis, HIV-infected subjects (odds ratio 1.70, 95 % CI, 1.12-2.51; P = 0.009), older age (P < 0.0001), higher BMI (P < 0.0001) and hypertension (P = 0.039) were associated with a higher risk of diabetes. Among HIV-infected patients, the risk of type 2 diabetes mellitus increased with older age (P < 0.0001), higher BMI (P = 0.003), higher triglycerides (P = 0.015) lower total cholesterol (P = 0.008), longer duration of HIV infection (P = 0.036) lower nadir CD4 (P = 0.027). Prevalence of type 2 diabetes mellitus in HIV-infected subjects was almost two-fold increased than healthy subjects and it was associated with the typical risk factors of the general population and also to longer duration of HIV infection and lower nadir CD4.

We studied 9145 workers allocated among Italian country employed in the same factory. Most of them were male, mean age 47,6 (20,2

Objective: to determine the immunogenicity of the monovalent vaccine against 2009 pandemic influenza A/H1N1 in HIV-1-infected individuals., Design: a total of 192 participants, including 44 HIV-1-positive individuals and 148 HIV-1-negative healthy controls were enrolled to receive a single dose of MF59-adjuvanted 2009 A/H1N1v vaccine formulated to contain 7.5 microg of haemagglutin antigen., Methods: standard haemagglutination inhibition (HAI) assay was performed to evaluate seroconversion and seroprotecsion rates against the pandemic virus in serum samples collected at baseline (T0) and 3-5-week postvaccination (T28). Seroconversion to vaccination was defined by either prevaccination HAI titer less than 1: 10 with a postvaccination titer higher than 1: 40, or a prevaccination titer higher than 1: 10 and increase of at least four-fold or more after vaccination. Seroprotection was defined by HAI titers higher than 1: 40., Results: the vaccine induced specific antibody titers in HIV-1-positive individuals similar to those of HIV-1-negative controls [215.3, 95% confidence interval (CI) 150.4-308.1 vs. 275.9, 95% CI 232.6-327.3] with postvaccination seroprotection rates higher than 97%. In contrast, the seroconversion rate was lower in the HIV-1-positive individuals as compared with the HIV-1-negative controls (36.4 vs. 79.0%, P < 0.0001), likely as a consequence of their high HAI baseline titers. Multivariable logistic regression analysis showed that seroconversion was less likely in HIV-1-positive individuals [odds ratio (OR) = 0.237, 95% CI 0.104-0.539, P = 0.0006) and with increasing age (OR = 0.805, 95% CI 0.684-0.947, P = 0.009)., Conclusions: a single dose of MF59-adjuvanted 2009 influenza H1N1 vaccine induced an immune response against pandemic H1N1 virus in HIV-1-positive individuals reaching titers similar to those of HIV-1-negative individuals. The seroconversion rate was negatively associated with HIV infection and increasing age., (2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.)

Gallbladder volume and contractility were measured, by means of real-time ultrasonography, in 48 insulin treated diabetic patients free from autonomic neuropathy, and in 91 healthy control subjects. All controls and diabetic patients were on a isocaloric and balanced diet. Gallbladder measurements were taken after an overnight fast and again 60-75 minutes after each meal. Gallbladder volume was at all times significantly greater in diabetic patients than in controls, while gallbladder contractility was similar. In diabetic patients, but not in controls, gallbladder volume was greater in the elderly than in adults, with no relationship between gallbladder volume and duration of diabetes. It is concluded that enlargement of the gallbladder might be a risk factor for gallstones in diabetic patients.

Prolactin (Prl) release, both in the experimental animal and in man, is stimulated by serotonin (5HT) and inhibited by dopamine (DA). Data also suggest that LH release in the animal is stimulated by norepinephrine and inhibited by DA. The role of 5HT in the control of LH release is less clear. It would appear to stimulate episodic LH release and to inhibit the LH surge at the pro-oestrus in animals, but the effect of 5HT on LH release has not yet been evaluated in man. In the present paper we have studied the effect of various DA-ergic drugs (DA, iv l-dopa, po l-dopa and bromoergocriptine) and of two anti-5HT drugs, metergoline and methysergide, on Prl and LH release in normal women. DA-ergic drugs lowered plasma Prl and LH levels; anti-5HT drugs, at doses able to lower Prl levels, did not affect basal LH release nor the inhibiting effect of iv l-dopa on LH release. These data indicate that DA inhibits both LH and Prl release in normal women, and that 5HT stimulates Prl release but is not involved in the regulation of LH secretion. The fact that, at variance to all the DA-ergic drugs used, the two anti-5HT drugs did not vary LH release, suggests that metergoline and methysergide are devoid of DA-ergic activity in man, at least at the doses able to inhibit Prl release.

The present experiments were performed to investigate the possible role of histamine and its receptors, H1 and H2, in the control of PRL and LH release in normal adult humans of both sexes. Histamine infusion (200 microgram, iv, in 15 min) induced PRL and LH release in men; in women, histamine inhibited LH release without affecting PRL release. Two H1 antagonists, dexchlorpheniramine (10 mg, iv) and promethazine (50 mg, im), reduced PRL release in both sexes, stimulated LH release in men, and inhibited LH release in women. Cimetidine, an H2 antagonist (400 mg, iv), elicited PRL release in both sexes, more consistently in females than in males, and was without effect on LH release in either sex. These data suggest that in humans, the effect of histamine on PRL release is linked to H1 and H2 receptors, which respectively stimulate and inhibit PRL release independently of sex. The effect of histamine on LH release appears to depend on sex and to be mediated only by H1 receptors. To rule out the possibility that the effects of histamine are merely due to a nonspecific stress reaction, we have evaluated PRL and LH release in otherwise normal men and women undergoing surgery for gallstones. Surgery was accompanied by PRL release in both sexes, more evident in women, and by LH release only in men. These results indicate that the effect of histamine on PRL and LH release in humans is linked to sex and H1 and H2 receptors and is not due to stress; further studies are required to clarify the possible mechanism and site of action of histamine in modifying PRL and LH release in humans.

In order to evaluate the spontaneous variability of prolactin (PRL) release in response to various stimuli applied repeatedly on different occasions, groups of 5 to 12 subjects each underwent consecutive identical tests with one of the following stimuli applied at 3-6 days' intervals: sulpiride (100 mg im), benserazide (50 mg po), insulin hypoglycaemia (0.1 U/kg b. w. iv) and arginine infusion (25 g iv in 30 min). When repeated in the same subjects, arginine and benserazide yielded superimposable results. In contrast to this, insulin hypoglycaemia yielded significantly lower PRL release, while the PRL response to the second sulpiride test was significantly higher than to the first one. When an interval of 10 days was left between two consecutive sulpiride tests, an identical PRL release was observed. These results indicate that arginine and benserazide are reproducible tests for PRL secretion and it is possible that the decreasing effect of insulin hypoglycaemia on PRL release is due to the stressful effect of the stimulus. Finally, sulpiride probably enhances both PRL release and synthesis thus making greater amounts of PRL available to a subsequent stimulus. Since some of the above stimuli are usual tools for the study of the neuroendocrine control of PRL secretion, our findings suggest that caution appears necessary in attributing to any (neuroactive) drug an effect which might be merely due to a lack of reproducibility of the stimulus employed.