Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Relationship between peripheral diabetic neuropathy and microvascular reactivity in patients with type 1 and type 2 diabetes mellitus -- neuropathy and microcirculation in diabetes.

The aim of the study was to evaluate differences in the relationship between peripheral diabetic neuropathy and microvascular reactivity in type 1 and type 2 diabetic patients. Twenty-eight type 1 and 37 type 2 diabetic patients were included in the study. Control groups consisted of 18 and 25, age and body mass index matched healthy persons. The presence of peripheral neuropathy was estimated by vibration perception threshold higher than 20 V evaluated by biothesiometry. Microvascular reactivity was examined by laser doppler fluxmetry using postocclusive reactive hyperemia and thermal hyperemia. The following variables of vascular reactivity were examined: peak flow after occlusion as a difference between maximal and basal perfusion (PORH (max)), mean velocity increase during postocclusive hyperemia (PORH (max)/t (1)), peak flow during thermal hyperemia (TH (max)) and the mean velocity increase in the perfusion during thermal hyperemia (TH (max)/t (2)). These parameters are expressed in perfusion units (PU) or in perfusion units per second (PU . s (-1)). The microvascular reactivity in type 1 diabetic patients without evidence of peripheral neuropathy was comparable with that in healthy persons and it was significantly higher than in type 1 diabetic patients with peripheral neuropathy in all tested parameters (PORH (max): 64 [40; 81] PU vs. 24 [17; 40] PU, p < 0.001, PORH (max)/t (1): 5.41 [2.69; 8.18] PU/s vs. 1.21 [0.69; 2.5] PU/s, p < 0.001, TH (max): 105 [77; 156] PU vs. 56 [46; 85] PU, p < 0.001 and TH (max)/t (2): 2.48 [1.67; 3.33] PU/s vs. 0.87 [0.73; 1.06] PU/s, p < 0.001). On the contrary, no difference in the microvascular reactivity parameters was found between type 2 diabetic patients with and without neuropathy (PORH (max): 48 [30; 60] PU vs. 49 [36; 57] PU, NS, PORH (max)/t (1): 3.46 [2.15; 5.19] PU/s vs. 3.29 [2.45; 4.8] PU/s, NS, TH (max): 95 [78; 156] PU vs. 97 [73; 127] PU, NS and TH (max)/t (2): 1.45 [0.95; 2.84] PU/s vs. 1.37 [1.12; 1.95] PU/s, NS). In both these groups microvascular reactivity was comparable with that estimated in the age and BMI matched healthy persons. An inverse relationship was observed between microvascular reactivity and vibratory perception threshold in type 1 diabetic patients, but it was not true in type 2 diabetic patients. We suppose that the pathogenesis of neuropathy and impaired microvascular reactivity may be differently influenced by metabolic factors in type 1 and type 2 diabetic patients.     

Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.     

Left pulmonary artery evaluation through transesophageal echocardiography.

INTRODUCTION: Transesophageal echocardiography (TEE) has become increasingly useful in the study of patients with suspected pulmonary thromboembolism. OBJECTIVE: The aim of this study was to prospectively evaluate the usefulness of TEE in the study of the distal part of the left pulmonary artery (LPA) as well as the influence of this procedure on total echocardiographic exam duration. METHODOLOGY: A prospective study in two groups of consecutive patients referred for TEE with a one- year interval between evaluation of Group A: 33 patients, 17 male, mean age 54 +/- 24 years, and Group B: 42 patients, 20 male, mean age 48 +/- 27 years (p = NS). The procedure was considered long when it took more than 3 min to evaluate the distal part of the LPA. RESULTS: In group A we were able to visualize the distal part of the LPA in 24 patients (73%) without significant prolongation of total exam duration in 16 patients (48% of group A). In one of the patients with suspected pulmonary thromboembolism thrombi were only observed in the distal part of the LPA. In group B we were able to visualize the distal part of the LPA in 36 patients (86%) without significant prolongation of total exam duration in 26 patients (61% of group B). CONCLUSIONS: 1. Visualization of the distal part of the LPA was possible in more patients, and with TEE time prolongation in less patients, in group B. These differences can be accounted for by the training of the operator in this technique. 2. The importance of visualization of this part of the LPA in guiding treatment in the subset of patients with pulmonary thromboembolism confirms the usefulness of this specific procedure.     

Modeling in Frequency Domain Used for Assessment of In Vivo Dissolution Profile

Purpose. To present a model-dependent approach for the assessment of the in vivo drug dissolution profile based on in vitrodata for the multiple unit dosage form, as an alternative to the numerical method proposed in the study by Hayashi et al, Pharm. Res. 12:1333–1337 (1995). Methods. The data for aspirin granules administered to healthy subjects obtained in the above mentioned study were re-evaluated. The subject dissolution system was considered to consist of two subsystems connected in series, i.e. the subsystem describing the gastric-emptying process and the subsystem describing the intestinal dissolution process. The frequency response method was used to model the subject dissolution system. Results. The model in vivodissolution profile of aspirin, assessed as the integral of the model weighting function of the subject dissolution system, was in agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method. Conclusions. Comparison of dynamic properties of the subject dissolution system with the subsystem describing the gastric-emptying process yielded quantitative confirmation of the decisive role of the gastric-emptying process in the in vivodrug dissolution after administration in the multi unit dosage form.     

Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion.

This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.