Relief of pain induced by varicella-zoster virus in a rat model of post-herpetic neuralgia using a herpes simplex virus vector expressing enkephalin.

Acute and chronic pain (post-herpetic neuralgia or PHN) are encountered in patients with herpes zoster that is caused by reactivation of varicella-zoster virus (VZV) from a state of neuronal latency. PHN is often refractory to current treatments, and additional strategies for pain relief are needed. Here we exploited a rat footpad model of PHN to show that herpes simplex virus (HSV) vector-mediated gene delivery of human preproenkephalin (vHPPE) effectively reduced chronic VZV-induced nocifensive indicators of pain. VZV inoculated at the footpad induced prolonged mechanical allodynia and thermal hyperalgesia that did not develop in controls or with ultraviolet light-inactivated VZV. Subsequent footpad administration of vHPPE relieved VZV-induced pain behaviors in a dose-dependent manner for extended periods, and prophylactic vector administration prevented VZV-induced pain from developing. Short-term pain relief following low-dose vHPPE administration could be effectively prolonged by vector re-administration. HPPE transcripts were increased three- to fivefold in ipsilateral ganglia, but not in the contralateral dorsal root ganglia. VZV hypersensitivity and its relief by vHPPE were not affected by peripheral delivery of opioid receptor agonist or antagonist, suggesting that the efficacy was mediated at the ganglion and/or spinal cord level. These results support further development of ganglionic expression of enkephalin as a novel treatment for the pain associated with Zoster.

The digital library: an oxymoron?

"Virtual libraries" and "digital libraries" have become stock phrases of our times. But what do they really mean? While digital refers to a new form of document encoding and must be approached from that perspective, virtual resonates with aspects that modern philosophy treats with benign neglect at best. The word virtual harbors the notion of potential, and therein lies its hidden strength. Although strong commercial interests try to use the shift to a digital environment to redefine the political economy of knowledge, and thus virtualize libraries into a state of almost complete impotence, all hope is not lost. Librarians of virtualized libraries may well discover that they have re-empowered institutions if they place human interaction at the heart of their operations. In other words, rather than envisioning themselves as knowledge bankers sitting on treasure vaults of knowledge, they should see themselves as "hearts" dynamizing human communities. They should also see themselves as an essential part of these communities, and not as external repositories of knowledge. In this fashion, they will avoid the fate of becoming an oxymoron.

Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo.

OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.

[Management of a first antihypertensive treatment]. / Mise en place d'un premier traitement antihypertenseur.

The first prescription for high blood pressure should be the fruit of clear thinking about the goals of the treatment and the best means to achieve these goals for each individual patient. The aim of treatment is not only to lower arterial blood pressure, but also to ensure the best possible prevention against cardiovascular risks in the hypertensive patient. Several factors are involved, notably metabolic factors. In addition, the relationships between high blood pressure and structural disorders in the heart, the brain and the kidneys causing hypertension-related lethality and mortality result from a complex interrelationship between genetic phenomena. The socioeconomic aspect of high blood pressure cannot be ignored due to the high prevalence of the disease. The patient's quality of life during treatment directly affects his compliance to a therapeutic regimen. The general practitioner thus plays a predominant role in caring for the hypertensive patient, justifying the importance clinicians attach to continuing medical education on hypertension.

[Management of hypertensive patients while searching for a "thread of Ariadne" in the labyrinth of recommendations]. / La prise en charge de l'hypertendu à la recherche d'un "fil d'Ariane" dans le Dédale des recommandations.

The abundance of "recommendations" concerning the management of hypertension reflects the Public Health importance of this problem. This abundance and the absence of any real consensus concerning all aspects of this management can leave readers somewhat disconcerted. In this context, the authors attempt to define the guidelines adopted by the various Expert Committees in their approach in order to improve diagnostic performance and treatments, which are still very insufficient, in the field of hypertension.

Bandlimited and Haar filtered back-projection reconstructions.

A new way to discretize the filtered back-projection (FBP) algorithm is presented. The function basis is the Haar system (2D product of rectangular windows). This scheme allows one to derive the optimal shape of the apodisation window, which is angle varying, and the oversampling ratio between the pixel and the projection cell size. The discrete equivalent filter is also derived. The comparison of standard radial band-limited and separable Haar reconstructions shows that improvements, in terms of linearity, shift-invariance and aliasing, can be obtained even for the case of a limited number of views. Considerations of projection degradations are then analyzed according to a specific imaging device to derive the optimum oversampling ratio.

Comparative effects of antihypertensive drugs on systolic blood pressure.

Importance of systolic over diastolic blood pressure measurements: Systolic pressure is known to be a more important independent cardiovascular risk factor than diastolic pressure in subjects over 50 years of age; after that age, a high incidence of two types of systolic hypertension is observed, sustained essential hypertension with a disproportionate increase in systolic pressure and isolated systolic hypertension. Effects of lacidipine on blood pressure in the elderly: The effects of vasodilators on blood pressure have been studied extensively. Recently, lacidipine, nitrendipine and enalapril were compared in a multicenter, randomly allocated, double-blind trial in elderly hypertensive patients with a disproportionate increase in systolic pressure treated for 8 weeks (n = 278). In these patients, supine systolic pressure decreased to a greater extent with lacidipine and enalapril than with nitrendipine, the difference between lacidipine and nitrendipine reaching statistical significance. In another trial, lisinopril produced a greater reduction in systolic pressure than atenolol. Finally, in a study in elderly patients with systolic hypertension, long-acting isosorbide dinitrate induced a selective sustained decrease in systolic pressure. Mechanisms of action of vasodilators: A fall in systolic blood pressure may be produced by vasodilators through a reduction in peripheral resistance with or without an active change in arterial compliance. Dihydralazine-like substances do not increase arterial compliance whereas angiotensin converting enzyme inhibitors, calcium entry blockers and nitrates tend to increase arterial compliance for the same decrease in mean arterial pressure.

[Arterial hypertension and diabetic nephropathy]. / Hypertension artérielle et néphropathie diabétique.

A high incidence of renal lesions is observed in patients with insulin-dependent diabetes. In the early stages of the disease glomerular capillary hemodynamics is altered with, in particular, glomerular hyperfiltration related to several factors: enhanced glomerular capillary flow rate, capillary hypertension and increased filtration area. These hemodynamic changes could affect development of the glomerular microangiopathy: the final outcome of this is the glomerulosclerosis associated with a progressively worsening and ineluctable chronic renal insufficiency. Hypertension, frequent in the early stages, is practically constant when the neuropathy stage has been reached; it is well established that hypertension accelerates the development of glomerular lesions and the progression of the renal impairment. Experimental and clinical studies have clearly demonstrated that antihypertensive treatment slows down the degradation of renal function. All antihypertensive drugs appear to be effective, but converting enzyme inhibitors, by their effects on renal hemodynamics, could play a particular role in the prophylactic treatment of diabetic nephropathy. Determination of urinary excretion of albumin (microalbuminuria), the global evidence of the onset of a nephropathy is useful for the follow up of the renal disease, allows follow up of the renal lesion and evaluation of the efficacy of treatment.

[Isolated urethral amyloidosis. Case report and review of the literature]. / Amylose urétrale isolée. Etude d'un cas et revue de la littérature.

Localised amyloidosis of the urethra is an extremely rare condition and we report one case of induration of the corpus spongiosum. This one is painful and increasingly obstructive. The first differential diagnosis we think about was an inflammatory process or carcinoma. The diagnosis can only be done after biopsies and microscopic observation. Localized amyloidosis must be recognized and this lesion must be locally treated. Since 40 years, about 25 such cases were described.

[Renal effects of intravenous tertatolol in essential arterial hypertension]. / Effets rénaux du tertatolol intraveineux dans l'hypertension artérielle essentielle.

The acute renal effects of intravenous tertatolol were studied in eight patients with moderate essential hypertension: the study included a 100 mmol/day sodium intake during 3 days. Then, tertatolol was infused after a water load during 2 consecutive periods of 30 min (priming dose followed by constant infusion) in order to obtain plasma concentrations of tertatolol at 2 different levels: 10 ng/ml, then 40 ng/ml successively; the measurements were obtained at 15, 30, 45 and 60 min. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were calculated from the 131I-Hippuran clearance and the 125I-Iothalamate clearance respectively; a bladder catheter allowed a precise urine collection. The results indicate that intravenous tertatolol, at low dose, induced a marked and early renal vasodilatation; higher dose of tertatolol attenuated the vasodilator response, probably because of a decrease in cardiac output (suggested by the decrease in heart rate); thus, the systemic effects would hide the direct renal hemodynamic effects of tertatolol. Natriuresis and kaliuresis were unchanged by intravenous tertatolol.

[Renal effects of captopril in hypertension with renal artery stenosis. Comparison between Tc-99m-DTPA scintigraphy and clearance method]. / Effets rénaux du captopril dans l'hypertension avec sténose d'artère rénale. Comparaison entre scintigraphie au Tc-99m-DTPA et méthode des clairances.

In eleven hypertensive patients with renal artery stenosis, the acute renal effects of captopril were investigated using two methods: 1) the Tc99m-DTPA renography with determination of an index of renal perfusion (IP), an index of glomerular filtration (IF) and the ratio of these indices (F/P); 2) the renal hemodynamics obtained by the clearance method using a continuous infusion of I131-hippuran and I125-iothalamate for calculation of renal blood flow (RBF), glomerular filtration rate (GFR) and filtration fraction (FF). The studies were performed before and after captopril treatment. Patients were classified according to the acute response to captopril as responders (R; n = 6) and non responders (NR; n = 5). Results are as follows: (B: basal, C = captopril). (table; see text) These data confirm that captopril produced a significant decrease in F/P and FF in R whereas these indices did not change in NR; it was found that IF and GFR decreased in R whereas IF increased and GFR did not change in NR; a significant correlation was observed between delta IF and delta GFR in R (r = 0.834, p less than 0.05). These results indicate that 1) data obtained before and after captopril by renography and by clearance methods are in good correlation either in Ror in NR patients; 2) Captopril test including renography or renal hemodynamic measurements is useful for selection of R patients.

Effects of perindopril on renal haemodynamics and natriuresis in essential hypertension.

Renal haemodynamics and natriuresis were studied before and 6 h after oral intake of perindopril (8 mg) in eight hypertensive patients without renal failure. The patients were then treated with perindopril (8 mg per day) and renal haemodynamics were measured on the fifth day, 6 h after the morning intake. Sodium intake was controlled during the study (100 mmol sodium per day). Renal blood flow and the glomerular filtration rate were measured by the clearance method using 131I-hippuran and 125I-iothalamate, respectively. Mean blood pressure decreased from 135 to 110 after 6 h, and was 118 mmHg on the fifth day (P less than 0.001, respectively). Renal vascular resistance decreased significantly after acute drug intake from 0.19 to 0.15 arbitrary units (P less than 0.001) and on the fifth day to 0.16 arbitrary units (P less than 0.001). Renal blood flow rose from 708 to 723 after 6 h, and to 750 ml/min per 1.73 m2 on the fifth day but the change was no significant. There was no alteration in the glomerular filtration rate so that the filtration fraction decreased from 0.27 to 0.26 (after 6 h), and to 0.25 on the fifth day (P less than 0.02). Natriuresis increased after the first intake between the first and tenth hours. On the fifth day, maximum natriuresis was observed between the fourth and sixth hours. Perindopril caused strong renal vasodilation after the first intake and during the following days, with no change in the glomerular filtration rate. There was a significant decrease in the filtration fraction, indicating efferent, as well as afferent, arteriolar vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Converting enzyme inhibitors in the treatment of arterial hypertension]. / Les inhibiteurs de l'enzyme de conversion dans le traitement de l'hypertension artérielle.

Angiotensin converting enzyme inhibitors, in comparison with other antihypertensive agents, offer unquestionable advantages in the treatment of hypertension. They do not alter cerebral blood flow. They improve cardiac function by decreasing postload, by preventing left ventricular hypertrophy and by decreasing myocardial excitability which engenders dysrhythmias. They increase compliance of large arteries and correct renal hemodynamic disturbances in hypertensive patients. Finally, they do not cause metabolic disturbances involving serum blood sugar, uric acid or lipids, and they help conserve potassium in patients on diuretics.