Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases.

BACKGROUND: Macrolides have long been recognised to exert immunomodulary and anti-inflammatory actions. They are able to suppress the "cytokine storm" of inflammation and to confer an additional clinical benefit through their immunomodulatory properties. METHODS: A search of electronic journal articles was performed using combinations of the following keywords: macrolides, COPD, asthma, bronchitis, bronchiolitis obliterans, cystic fibrosis, immunomodulation, anti-inflammatory effect, diabetes, side effects and systemic diseases. RESULTS: Macrolide effects are time- and dose-dependent, and the mechanisms underlying these effects remain incompletely understood. Both in vitro and in vivo studies have provided ample evidence of their immunomodulary and anti-inflammatory actions. Importantly, this class of antibiotics is efficacious with respect to controlling exacerbations of underlying respiratory problems, such as cystic fibrosis, asthma, bronchiectasis, panbrochiolitis and cryptogenic organising pneumonia. Macrolides have also been reported to reduce airway hyper-responsiveness and improve pulmonary function. CONCLUSION: This review provides an overview on the properties of macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin), their efficacy in various respiratory diseases and their adverse effects.

Mean Platelet Volume and Platelet Distribution Width in non-diabetic subjects with obstructive sleep apnoea syndrome: new indices of severity?

UNLABELLED: To evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in non-diabetic subjects, according to obstructive sleep apnoea syndrome (OSAS) severity and the associations of these indices with anthropometric characteristics and parameters of breathing function during sleep. MATERIALS AND METHODS: We included 610 non-diabetic subjects with suspected OSAS, evaluated by polysomnography. According to their apnoea-hypopnoea index (AHI), patients were divided into Group A (n=148) with AHI<5/h; Group B (n=121) with AHI: 5-14.9/h; Group C (n=85) with AHI: 15-29.9/h and Group D (n=256) with AHI ≥ 30/h. MPV and PDW were measured using an automated blood cell counter. RESULTS: MPV was significantly higher in group D (mean value 12.1 ± 1.3 fl) than in groups A (9.8 ± 1.1 fl), B (9.8 ± 1.6 fl), and C (11.5 ± 1.3 fl) (p<0.001). The same pattern was observed in PDW values (15.9 ± 2.2 fl for group D and 13.2 ± 2.2 fl for group A, 14.1 ± 2.8 fl for group B, and 15 ± 2.2 fl for group C, p<0.001). Significant correlations were seen between MPV and AHI (p<0.001), average pulse oxygen saturation (SpO(2)) (p<0.001), minimum SpO(2) (p<0.001) and percent of the total sleep time with SpO(2) lower than 90% (t<90%) (p<0.001) during sleep, Arousal Index (p<0.001) and Epworth sleepiness scale (ESS) (p=0.028). Similarly, PDW was correlated with AHI (p<0.001), average SpO(2) (p=0.001), minimum SpO(2) (p<0.001), t<90% (p=0.002), and Arousal Index (p<0.001). CONCLUSIONS: MPV and PDW are higher in non-diabetic patients with severe OSAS and are correlated with different parameters of breathing function during sleep.

Carotid endarterectomy in patients with foetal-type posterior circle of Willis: is there an indication for local anaesthesia?

Foetal-type posterior circle of Willis is a common anatomical variation with a variable degree of vessel asymmetry. In patients with this abnormality, carotid endarterectomy (CEA) may create cerebral hypo-perfusion intraoperatively, and this may be underestimated under general anaesthesia. There is currently no evidence that anatomical variations in the circle of Willis represent an independent risk factor for stroke. Moreover, there is a paucity of data on treating patients with such anatomical variations and co-existing ICA stenosis. We present a case of CEA under local anaesthesia (LA) in a 52-year-old female patient with symptomatic stenosis of the right ICA and coexistent foetal-type posterior circle of Willis. There were no post-operative complications and she was discharged free from symptoms. She was seen again 3 months later and was free from complications. This case higlights that LA should be strongly considered to enable better intra-operative neurological monitoring in the event of foetal-type posterior circle of Willis.

Letters to the editor: definitely not children of a lesser god.

Letters to the editor are brief texts that are published in a special section of medical journals. There are two types of letters to the editor: the observation and the comment. The former presents original work, while the latter constitutes criticism on work already published in the same journal. Although short, letters to the editor require as much effort and discipline in writing as, indeed, any other manuscript. Clarity and brevity should be their principal values. It is also important to comply with the journals' instructions for correspondence. Thus, eloquent letters to the editor may promote knowledge and enable fruitful exchange of ideas.

Changes in the epidemiology of hepatitis B virus infection following the implementation of immunisation programmes in northeastern Greece.

The objective of this study was to investigate changes in the epidemiology of hepatitis B virus infection in the general population and selected groups of immigrants in the region of northeastern Greece over the last decade in relation to the introduction of hepatitis B vaccination programmes. Two population-based seroprevalence surveys were carried out during the years 1992-1994 and 1998-2006. In total, 25,105 individuals were tested for the presence of hepatitis B virus markers: HBsAg, anti-HBs and anti-HBc. Childhood/adolescence immunisation programmes began early in 1994 in selected groups of immigrants and were complemented by the national vaccination programme in 1998. Between 1992-1994 and 1998-2006, the HBsAg carrier rate declined from 5.4% [95% CI: 4.5-5.9] in adults (20-60 years old) and 1.9% [95% CI: 1.6-2.4] in children/adolescents (5-19 years old) of indigenous residents to 3.4% [95% CI: 2.9-3.8] and 0.6% [95% CI: 0.2-1.4] respectively (p<0.05). In spite of a decrease compared with 1992-1994, the percentage of HBsAg carriers was still relatively high in 1998-2006 among the Muslim religious minority group (8.2% [95% CI: 8.0-8.7] in adults and 2% [95% CI: 1.7-2.4] in children/adolescents) and in immigrants from the former Soviet Union (4.3% [95% CI: 3.6-4.7] in adults and 1.1% [95% CI: 0.8-2.4] in children/adolescents) (p<0.05 for both selected groups versus general population). The decline of the prevalence of HBsAg in the general population and selected groups of immigrants in northeastern Greece over the last decade supports the effectiveness of the ongoing immunisation programme although the information on the actual number of cases of acute HBV infection is not available.

Risk factors for ipsilateral reamputation in patients with diabetic foot lesions.

This study aimed to examine the rates and risk factors for ipsilateral re-amputation in 121 patients with diabetic foot and prior amputation. Twenty-six (21.5%) patients required re-amputation during a mean follow-up of 18 months. Most re-amputations were performed within the first 6 months of the initial amputation. Re-amputation was more common among patients in whom the initial amputation had only affected one or two toes. Age (hazard ratio: 1.06) and heel lesions (hazard ratio: 2.69) were significantly associated with re-amputation. There is a high risk of re-amputation in the diabetic foot, especially within the first 6 months of the initial amputation, mainly due to poor selection of the original amputation level in an effort to save a greater part of the lower extremity. Patients 70 years and those with heel lesions are at greatest risk of re-amputation.

Correlation of cardiac autonomic neuropathy with small and large peripheral nerve function in type 2 diabetes mellitus.

AIMS: To analyse the correlation of cardiac autonomic neuropathy (CAN), sympathetic and parasympathetic dysfunction with the different diagnostic tools for large and small peripheral nerve fibres in type 2 diabetes mellitus (T2DM). METHODS: We included 153 T2DM subjects (92 men) with mean age of 64.4 years. CAN, as well as sympathetic and parasympathetic dysfunction were diagnosed by the Ewing's cardiovascular reflex tests. Vibration perception threshold (VPT), monofilament, Ipswich Touch test, automated sural nerve conduction study and neuropathy disability score (NDS) evaluated large and small peripheral nerve fibre function. RESULTS: CAN (adjusted odds ratio [aOR]: 44.57), parasympathetic (aOR: 18.40) and sympathetic dysfunction (aOR: 5.50) correlated with measures of small fibre function evaluated by pinprick sensation and temperature perception. Among tools for large nerve fibres, positive correlation was shown between: (1) CAN and abnormal VPT (aOR: 16.78), (2) parasympathetic dysfunction and abnormal VPT (aOR: 39.47). CONCLUSIONS: CAN and parasympathetic dysfunction correlate with peripheral neuropathy, especially when the latter is assessed through VPT and measures of small fibre function as evaluated by pinprick sensation and temperature perception. The latter additionally correlate with sympathetic nervous system impairment.

Post-thyroidectomy thyroxine replacement dose in patients with or without compensated heart failure: the role of cytokines.

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and post-thyroidectomy thyroxine replacement dose in patients with or without compensated heart failure. PATIENTS AND METHODS: The study included 42 patients (group A: 20 men, mean age of 54.5+/-6.8 years) with NYHA I or II heart failure and 54 patients (group B: 25 men, mean age of 52.9+/-7.1 years) without heart failure. All patients had undergone total thyroidectomy and were euthyroid on a stable thyroxine replacement dose. Serum Interleukin-1b (IL-1b), Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-6 (IL-6), TSH, T3, T4, fT3 and fT4 were measured. RESULTS: Both groups exhibited a significant positive correlation between IL-6 and levothyroxine replacement dosage (group A: r=0.708, p<0.001; group B: r=0.345, p=0.012) and a negative correlation between IL-6 and T3 (group A: r=-0.342, p=0.023, group B: r=-0.294, p=0.035). Significant independent predictors of levothyroxine replacement dosage were IL-6 (p<0.001) and TNF-alpha (p=0.007) in group A (58.3% of dosage variation) and only IL-6 (p=0.012) in group B (10.1% of dosage variation). CONCLUSIONS: In both groups, a significant positive correlation was observed between IL-6 and levothyroxine replacement dosage, but this correlation was stronger in group A. In the same group, there was evidence for a more pronounced influence of cytokines on levothyroxine dosage.

A comparison of the new indicator test for sudomotor function (Neuropad) with the vibration perception threshold and the clinical examination in the diagnosis of peripheral neuropathy in subjects with type 2 diabetes.

UNLABELLED: Peripheral neuropathy remains a major cause of morbidity and is a cardinal factor in the pathogenesis of diabetic foot ulceration. The aim of the present study was to compare the new indicator test for sudomotor function (Neuropad) with the vibration perception threshold (VPT) and the clinical examination in the diagnosis of peripheral neuropathy in subjects with type 2 diabetes. This study included 154 type 2 diabetic patients (76 men) with a mean age of 64.3+/-7.3 years and a mean diabetes duration of 12.8+/-4.3 years. Neuropathy was diagnosed clinically using the Neuropathy Disability Score (NDS). The VPT was measured with a neurothesiometer, values > 25Volts being classified as abnormal. Sudomotor function was evaluated by the indicator test. Sensitivity of the indicator test for neuropathy was 97.8% and specificity was 67.2%. Sensitivity and specificity of VPT for neuropathy were 78.9% and 85.9% respectively. A significant correlation was shown between time to colour change of the indicator test and VPT (rs=0.889, p<0.001). CONCLUSIONS: Both the indicator test and the VPT have a high sensitivity for neuropathy. Sensitivity is higher with the indicator test, but specificity is higher with VPT. Time until complete colour change of the indicator test shows a positive correlation with VPT. Thus, the indicator test appears to be a useful additional diagnostic tool of neuropathy, particularly suitable for screening and self-examination, in type 2 diabetes. The correlation between time to colour change of the indicator test and VPT is interesting and merits investigation in a prospective study.

Double gall-bladder--two pathologies: a case report.

True gall-bladder duplication is a rare biliary anomaly, which is usually discovered as an incidental finding. There are reports of double gall-bladders missed during the first operation. We present the case of a double gall-bladder which, albeit suspected during the operation, was confirmed post-operatively. The patient underwent successful laparoscopic cholecystectomy and the examination of the resected gall-bladder revealed two chambers, only one containing stones. Predisposing factors for the development of gall-stones in one gall-bladder only, as well as surgical options, are briefly discussed.

An insertion/deletion polymorphism in the alpha2B adrenoceptor gene is associated with peripheral neuropathy in patients with type 2 diabetes mellitus.

UNLABELLED: Alpha2B adrenoceptor (alpha2B-AR) mediates a variety of functions in humans. An insertion/deletion (I/D) polymorphism of the alpha2B-AR gene located on chromosome 2 has been described. The aim of the present study was to investigate the potential association between alpha2B gene I/D polymorphism and peripheral neuropathy in Greek patients with type 2 diabetes mellitus. The study included 130 patients (70 men) with diabetic neuropathy (group A) and 60 patients (34 men) without diabetic neuropathy (group B). There was no difference in age, gender and diabetes duration between the groups. Diabetic neuropathy was diagnosed by clinical examination using the Diabetic Neuropathy Index (DNI). Genotyping of I/D polymorphism was performed by PCR. Frequency of the D allele was significantly higher (p=0.001) in group A (26.9%) as compared to group B (11.7%). DNI score differed significantly (p=0.001) between the three genotype groups (I/I, I/D, D/D). It was significantly higher (p=0.04) in patients with I/D (3.7+/-1) than in those with I/I (2.5+/-0.9) and significantly higher (p=0.001) in patients with D/D (5.6+/-1.3) than in those with I/D (3.7+/-1). CONCLUSIONS: Patients with neuropathy exhibit a significantly higher frequency of the D allele in comparison to those without neuropathy. Presence of the D allele is also associated with a higher neuropathic score. These results provide evidence for an association of the D allele with both presence and severity of neuropathy in patients with type 2 diabetes mellitus.

Use of the new indicator test (Neuropad) for the assessment of the staged severity of neuropathy in type 2 diabetic patients.

UNLABELLED: The new indicator test for sudomotor function (Neuropad) has been shown to represent a highly sensitive and reproducible tool for the diagnosis of diabetic peripheral neuropathy. This study aimed to examine the utility of the indicator test in the assessment of the staged severity of neuropathy in patients with type 2 diabetes mellitus. The study included 120 type 2 diabetic patients (58 men) with a mean age of 67.3+/-5.9 years and a mean diabetes duration of 13.1+/-3.2 years. Neuropathy was diagnosed and staged by clinical examination and nerve conduction study, according to the Michigan classification system. Patients were also examined with the indicator test, applied on the plantar aspect of the feet. Time until complete colour change of the test was recorded and stratified into deciles according to the spread of measurements in the study population. Neuropathy was staged as class 0 in 37 patients, class 1 in 44 patients, class 2 in 28 patients and class 3 in 11 patients. Time until complete colour change was 436.5+/-62.9, 740+/-88.1, 1192.5+/-161 and 1817.3+/-127.4 seconds in patients staged as class 0, 1, 2 and 3 respectively (p=0.001). Use of a threshold lower than 530 seconds until complete colour change had 97% sensitivity and 100% specificity for diagnosis of class 0 neuropathy. Use of a threshold lower than 1000 seconds until complete colour change had 100% sensitivity and 97% specificity for class 1 neuropathy. A threshold lower than 1440 seconds had 93% sensitivity and 100% specificity for class 2 neuropathy. A threshold above 1440 seconds had 100% sensitivity and 99% specificity for class 3 neuropathy. A highly significant (Kendall's tau-b=0.848, p=0.001) correlation was shown between time until complete colour change of the test and Michigan class of neuropathy. CONCLUSIONS: It appears that the indicator test contributes substantially to the assessment of the staged severity of neuropathy in patients with type 2 diabetes mellitus. There is excellent agreement between the indicator test and the Michigan classification system. These results suggest a role for the indicator test in the assessment of diabetic neuropathy.

Changes in blood flow of anterior and middle cerebral arteries following carotid endarterectomy: a transcranial Doppler study.

AIM: The aim of the present study was to evaluate the changes in blood flow of anterior and middle cerebral arteries following carotid endarterectomy, using transcranial Doppler (TCD) flow studies. PATIENTS AND METHODS: This study included 100 patients (72 men, mean age 65 years) who underwent carotid endarterectomy because of high-grade carotid stenosis or symptoms of ischemic stroke. Endarterectomy was performed by a distal shunt between the common carotid and internal carotid arteries. Blood flow in the anterior and middle cerebral arteries was assessed by TCD preoperatively and also in the postoperative period (1st and 4th day; 1st, 6th, and 12th month). Collateral circulation in the Willis circle was evaluated by common carotid compression. RESULTS: Patients with bilateral carotid stenosis > or =70% exhibited a significantly increased flow velocity in the ipsilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), and in the contralateral ACA. Patients with entirely occluded contralateral internal carotid artery showed the most pronounced changes in cerebral hemodynamics. Blood flow velocities returned to the preoperative values at 1 to 12 months following endarterectomy. Hyperperfusion syndrome was manifested in 14 patients, who exhibited significantly higher flow velocities in the ipsilateral MCA compared with asymptomatic patients. CONCLUSIONS: A transient bilateral increase of blood flow velocity in the anterior part of the Willis circle may often occur in the immediate postoperative period following carotid endarterectomy. Although its clinical significance is not entirely understood, this increase may be associated with cerebral hyperperfusion syndrome.

Ankle-brachial index: a surrogate marker of microvascular complications in type 2 diabetes mellitus?

AIM: The aim of this study was to investigate the potential role of ankle-brachial index (ABI) as a marker of microvascular disease in patients with type 2 diabetes mellitus. METHODS: This study included 126 type 2 diabetic patients (64 male and 62 female) with an age of 66.6+/-5.3 years (mean+/-SD) and diabetes duration of 13.2+/-4.1 years. ABI was measured with a Doppler device. The exclusion criterion was the medial arterial calcification. Patients were also examined for microalbuminuria, retinopathy and peripheral neuropathy. RESULTS: ABI was significantly lower in patients with microalbuminuria than in those without microalbuminuria (0.91+/-0.17 vs 1.05+/-0.13, P=0.004), in patients with retinopathy than in those without retinopathy (0.91+/-0.18 vs 1.06+/-0.1, P=0.005), as well as in patients with neuropathy than in those without neuropathy (0.94+/-0.17 vs 1.06+/-0.11, P=0.001). Sensitivity and specificity of ABI <0.9 were 48.8% and 87.9% respectively for microalbuminuria, 39.1% and 93% respectively for retinopathy and 47% and 90.7% respectively for neuropathy. In multiple regression analysis, significant predictor of microalbuminuria was diabetes duration (P=0.0014), significant predictor of retinopathy was diabetes duration (P=0.001), while significant predictors of neuropathy were diabetes duration (P=0.001), male sex (P=0.001) and presence of retinopathy (P=0.047). CONCLUSION: ABI is significantly lower in patients with than in those without microvascular complications of type 2 diabetes. An ABI <0.9 has a low to modest sensitivity, but a high specificity for the diagnosis of these complications. Our results suggest a potential role for ABI as a surrogate marker of microvascular complications in type 2 diabetic patients.

Could sustained monomorphic ventricular tachycardia in the early phase of a prime acute myocardial infarction affect patient outcome?

OBJECTIVES: Sustained monomorphic ventricular tachycardia (SMVT) in the course of a prime acute myocardial infarction is not a common arrhythmia and its prognostic significance has not been specifically elucidated. The aim of the study was to estimate the prognostic implications of the occurrence of sustained monomorphic ventricular tachycardia in the early phase (<72 h) of a prime acute myocardial infarction. METHODS: We studied 690 consecutive patients admitted to the coronary care unit with a diagnosis of a prime myocardial infarction. SMVT was observed in 18 (2.6%) patients and we followed these patients for establishing the prognostic value of the arrhythmia according to the clinical characteristics. RESULTS: Patients with SMVT had a more extensive myocardial infarction based on the peak of the CK-MB isoenzyme activity (480+/-290 IU/L, vs 270+/-190 IU/L, P < .01), and higher mortality rate (40% vs 9%, P < .001). The independent predictors of SMVT were CK-MB (odds ratio [OR] 12.4), presence of complex ventricular arrhythmias (OR = 5.7), a wide QRS complex > or =130 milliseconds (OR = 4.8) and Killip class (OR = 4.8). The SMVT was itself an independent predictor of mortality (OR = 5.0). Compared with patients with ventricular fibrillation or polymorphic ventricular tachycardia, those with SMVT had a higher CK-MB activity, higher rate of wide QRS > or =130 milliseconds (33% vs 8%, P < .002), had a worse hemodynamic condition (Killip class >I:58% vs 23%, P < .04) and higher recurrence rate of ischemic events (68% vs 16%, P < .05). During the one year follow-up period, 4 patients (36.3%) of the 11 survivors from those with SMVT died of cardiac related causes. CONCLUSIONS: SMVT during the first 72 h of a prime myocardial infarction is an index of a larger healing myocardium with acute very complexed electrophysiological changes and it is an independent predictor of in-hospital mortality and a prognostic factor of a poor one year outcome.

Growth factors in the treatment of diabetic foot ulcers: new technologies, any promises?

Foot ulcers remain a common problem, leading to increased morbidity in patients with diabetes. Despite the progress that has been achieved in revascularization techniques as well as in off-loading to relieve high-pressure areas, diabetic foot wounds remain a clinical challenge. Growth factors are a major technological advance that promised to change the face of wound healing. The most important of growth factors are recombinant human platelet-derived growth factor-BB and granulocyte colony-stimulating factor. The former has been approved by the FDA for the treatment of neuropathic ulcers when there is adequate blood supply. The latter is less demonstrably useful. Advances include methods of delivering growth factors.

Human papillomavirus in endometrial adenocarcinomas: infectious agent or a mere "passenger"?

AIMS: To investigate the possible association of human papillomavirus (HPV) with endometrial hyperplasias and neoplasia. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas? METHODS: Twenty-five endometrial adenocarcinomas of the endometrioid cell type, with and without squamous differentiation, and twenty-four endometrial hyperplasias of various forms (simple, complex, and atypical) were analyzed for the presence of type 16 and 18 HPV by the polymerase chain reaction (PCR). The results were related to histopathological features of the tumour, and the patients' age, and prognosis. RESULTS: Six of 25 endometrial adenocarcinomas were HPV 16-positive (24%), and 5 of 25 (20%) were HPV 18-positive. Simple endometrial hyperplasias was associated somewhat more commonly with HPV 16 and 18 (2/8 and 1/8 cases, resp.) than hyperplasias progressing to endometrial adenocarcinomas, namely, atypical endometrial hyperplasia (1/8 and 0/8 cases, resp.). None of the positive cases in the series, whether hyperplastic or neoplastic, demonstrated cytological evidence of HPV infection. There was no relation between HPV-positive cases and squamous differentiation, depth of myometrial invasion, lymphatic involvement, lymphocytic response, patients' age, or prognosis. CONCLUSION: It appears that the presence of HPV in the endometrium, as detected by PCR, does not play any role in the initiation or prognosis of endometrial adenocarcinoma.

Family History of Type 2 Diabetes: Does Having a Diabetic Parent Increase the Risk?

BACKGROUND: It is well established that there is an important genetic predisposition for type 2 diabetes mellitus (T2DM). OBJECTIVE: To summarise available epidemiological data regarding T2DM transmission in various populations. METHOD: Narrative review. RESULTS: The estimated risk for the diagnosis of T2DM increases approximately by 2-4 times, when father, mother or both have this condition. Conversely, many T2DM patients have family members with DM. Studies have suggested that the likelihood of T2DM in the next generation is higher in the event of a diabetic mother than father. Both genetic factors, such as mitochondrial DNA mutations, and environmental components, such as intra-uterine environment, have been implicated in the higher maternal transmission of T2DM. Despite the above findings, some studies in populations with high frequency of T2DM have not corroborated the predominantly maternal transmission. Such works have shown either an excess paternal or an equal transmission of T2DM. CONCLUSION: It appears that potential biases in reporting family history data, especially between the various racial groups, have contributed to the controversy over the existence of excess maternal transmission of DM.

Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions.

BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

Gliclazide treatment lowers serum ICAM-1 levels in poorly controlled type 2 diabetic patients.

OBJECTIVE: To investigate the potential effect of gliclazide on serum ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) levels in poorly controlled type 2 diabetic patients. PATIENTS AND METHODS: The study included 104 patients, randomly divided into two groups. Group A comprised 53 patients (26 men) treated with gliclazide with a mean age of 67.5+/-9.9 years, a mean diabetes duration of 13.4+/-5.4 years and a mean HbA1c of 8.6+/-1.1%. Group B comprised 51 patients (25 men) treated with glibenclamide with a mean age of 66.4+/-10.9 years, a mean diabetes duration of 13.2+/-6.1 years and a mean HbA1c of 8.4+/-1.3%. A third group of 30 healthy controls (15 men) with a mean age of 63.3+/-10.4 years was also included. Serum levels of ICAM-1 and VCAM-1 were measured at the beginning of the study and after six months of treatment. RESULTS: Pretreatment serum ICAM-1 and VCAM-1 levels did not differ between groups A and B, while they were significantly higher (P=0.0001) than in healthy controls. No significant difference in HbA1c, body mass index, blood pressure control and lipid profile between the two groups was observed after the sixth month of treatment. In group A, serum ICAM-1 levels after six months of treatment were significantly reduced from 623.12+/-61.17 ng/ml to 370.14+/-49.92 ng/ml (P=0,01), while no reduction was found in VCAM-1 levels. In group B, no reduction was found in serum ICAM-1 and VCAM-1 levels after the end of the study. CONCLUSIONS: Our results suggest that gliclazide treatment reduces serum ICAM-1 levels in poorly controlled type 2 diabetic patients. This reduction is independent of the hypoglycaemic action of gliclazide.