The effect of latanoprost and influence of changes in body position on patients with glaucoma and ocular hypertension.

BACKGROUND AND OBJECTIVES: Some patients have an elevation of intraocular pressure (IOP) in the supine position (IOPSP). It has been suggested that topical latanoprost 0.005% (LP) has an attenuating effect on these IOP elevations. The Authors report a simple procedure to evaluate the change in the IOPSP. This paper presents the results of the change in the IOPSP in normals, in patients with ocular hypertension (OH) and in patients with primary open angle glaucoma (POAG). The study also evaluates the effect of the addition of topical LP on those patients with an elevation of their IOPSP. PATIENTS AND METHODS: Part 1 evaluated the change in the IOPSP in the morning in 40 eyes of normals, 82 eyes in patients with OH and 77 eyes in patients with POAG. The IOP was measured before and after lying in the supine position (SP) for 90 minutes. In part 2 the patients with OH or POAG with an increase in their IOPSP were selected and the test was repeated again after the addition of topical LP. RESULTS: When compared with normals, the patients with OH and POAG had significantly greater IOPSP increases. The patients with POAG had significantly greater IOPSP increases than did those with OH. The addition of LP partially decreased but did not eliminate the IOP increases in the SP. CONCLUSIONS: Patients with OH and POAG have a larger increase in their IOPSP than do normals. The addition of topical LP partially decreased but did not totally eliminate these pressure increases.

Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy individuals and in hypertensive patients.

This study was conducted with the aim of showing the effects of Pycnogenol on controlling jet-lag symptoms. Oral Pycnogenol, 50 mg tablets 3 times/die, for 7 days starting 2 days prior to the flight was used. The study was divided into two separate parts. In study 1 the most common complaints of patients with jet-lag were evaluated with a rating scale consisting in of a scoring system. In study 2 a brain CT scan was performed after the flight in order to assess minimal brain edema (MBE) in association with typical signs and symptoms, observed in previous published flight studies. Study one included 38 subjects treated with Pycnogenol and 30 controls. The symptomatic jet-lag related total score was significantly lower (indicating a lower level of jet-lag) in the Pycnogenol group. The average duration of any jet lag symptom following the flight was significantly reduced from 39.3 (SD=0.8) hours in controls to an average of 18.2 (SD=3.3) hours in the Pycnogenol group (P<0.05). Study 2 included 34 subjects treated with Pycnogenol and 31 controls. The main observation was the brain CT scan performed within 28 hours after the end of the flight. The difference between the Pycnogenol and the control groups was statistically significant (P<0.05) for all items assessed including the cerebral edema score obtained by CT scan. The short-term memory was significantly altered in the control group and associated to edema and swelling of the lower limbs. The score (and the level of edema) was comparatively higher in a subgroup of hypertensive subjects in the control group. Minor alterations of cardiac function were observed in association with de-stabilisation of blood pressure. Fatigue was also significantly higher in the control group in comparison with the Pycnogenol group. A number of spontaneously reported symptoms was also scored and there was a statistically significant difference (P<0.05) between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to control jet-lag and minimal brain edema.

Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document.

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb, Lipohep, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anticoagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation.

Purification of putative insulin-sensitive cAMP phosphodiesterase or its catalytic domain from rat adipocytes.

Insulin acutely inhibits the catecholamine-stimulated rise in cAMP levels in fat, liver, and muscle primarily through stimulation of the enzyme cAMP phosphodiesterase (PDE). Adipocytes from rat epidydimal fat pads were exposed to insulin and fractionated by centrifugation. Whereas the cytosolic fraction contained a low-affinity cAMP PDE that was unaffected by insulin, the activity of a high-affinity enzyme residing in a particulate fraction was increased by insulin. This enzyme activity could be solubilized with nonionic detergent and chromatographed on ion exchange followed by chromatofocusing. The resulting enzyme preparation was subjected to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Silver staining revealed a single band with a molecular weight of 60,000. This apparent molecular weight was verified by calculation of the hydrodynamic properties of the enzyme. Evaluation of its kinetic properties indicated that the enzyme activity residing in this solubilized 60,000-Mr protein exhibited lower affinity than the membrane-bound enzyme but was still specific for cAMP. Activation of this enzyme may be one of the primary mechanisms by which insulin counteracts the effects of adenylate cyclase-stimulating hormones.

DNA base changes and RNA levels in N-acetoxy-2-acetylaminofluorene-induced dihydrofolate reductase mutants of Chinese hamster ovary cells.

Formerly, we isolated a series of dihydrofolate reductase-deficient Chinese hamster ovary cell mutants that were induced by N-acetoxy-2-acetylaminofluorene. Deletions and complex gene rearrangements were detected in 28% of these mutants; 72% contained putative point mutations. In the present study, we have localized the putative point mutations in the 25,000 base dhfr gene by RNase heteroduplex mapping. Assignment of a position for each mutation was successful in 16 of 19 mutants studied. We cloned DNA fragments containing the mapped mutations from nine mutants into a bacteriophage lambda vector. In the case of 11 other mutants, DNA was amplified by the polymerase chain reaction procedure. Sequence analysis of cloned and amplified DNA confirmed the presence of point mutations. Most mutants (90%) carried base substitutions; the rest contained frameshift mutations. Of the point mutations, 75% were G.C to T.A transversions in either the dhfr coding sequence or at splice sites; transition G.C to A.T mutations were found in two mutants (10%). In one of these transition mutants, the base substitution occurred at the fifth base of the third intron. Of the frameshift mutations, one was a deletion of G.C pair and the other was an insertion of an A.T pair. Of the mapped mutants, 38% exhibited greatly reduced (approximately 10-fold) steady-state levels of dhfr mRNA. All eight sequenced mutants displaying this phenotype contained premature chain termination codons. Normal levels of dhfr mRNA were observed in five missense mutants and in five mutants carrying nonsense codons in the translated portion of exon VI. Taken together with the results of other mutagens at this locus, we conclude that the low dhfr mRNA phenotype is correlated with the presence of nonsense codons in exons II to V but not in the last exon of the dhfr gene.

Optical coherence tomography findings in a case of acute multifocal posterior placoid pigment epitheliopathy (AMPPPE).

PURPOSE: To report the optical coherence tomography (OCT) findings in a case of acute multifocal posterior placoid pigment epitheliopathy (AMPPPE). DESIGN: Case report. METHODS: A 26-year-old woman was seen for a mild loss of visual acuity in both eyes. The fundus examination revealed yellow-white placoid lesions in the posterior pole suggesting AMPPPE. Fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT) were performed 2 days, 9 days, and 1 month after the first examination. RESULTS: In the acute phases the OCT revealed a mild hyperreflective area above the retinal pigmented epithelium (RPE) in the photoreceptor layer. In the later phases the OCT scan revealed a nodular hyperreflective lesion on the plane of the RPE with mild underlying backscattering. CONCLUSIONS: In AMPPPE, the OCT demonstrates hyperreflective lesions that may indicate inflammatory tissue and inflammatory cells or the presence of ischemic edema in the outer retinal layers.

Fusidic acid vs ofloxacin prophylaxis before cataract surgery.

PURPOSE: To evaluate the safety and efficacy of two self-administrated antibiotics in eliminating conjunctival microbial flora. METHODS: A total of 133 patients operated for cataract surgery were divided into three groups. The first group (A), 55 patients, received fusidic acid drops (1%) two times per day during the 3 days before the surgery; a second group (B), 55 patients, received ofloxacin (0.3%) four times per day during the 3 days before the surgery; and the third group (C), 23 patients, did not receive any topical antibiotic before the surgery. On the day of the surgery, cultures were taken from the lower fornix. RESULTS: In Group A, 28 cultures (50.9%) were sterile, and 27 (49.1%) were positive for the presence of microbial agents. In Group B, 25 cultures (45.4%) were sterile, and 30 (54.5%) were positive for the presence of microbial agents. In Group C, 5 cultures (21.7%) were sterile, and 18 (78.2%) were not. Staphylococcus epidermidis was the most common micro-organism isolated in all the groups. Statistical analysis does not reveal a significant difference between Groups A and B for the sterile cultures (p=0.7) (chi-square test), but a statistically significant difference is present between the treated and not treated patients (p= 0.05) (chi-square test). CONCLUSIONS: A preoperative prophylaxis is useful in eliminating conjunctival micro-organism, and both antibiotics (fusidic acid and ofloxacin) are efficient.

Pycnogenol® and Centella asiatica in the management of asymptomatic atherosclerosis progression.

AIM: The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol® and total triterpenic fraction of Centella asiatica (TTFCA) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral stenosing plaques. METHODS: This was an observational pilot, substudy of the San Valentino epidemiological cardiovascular study. The study included 824 subjects aged 45-60 without any conventional risk factors who had a stenosing atherosclerotic plaque (>50-60%) in at least one carotid or common femoral bifurcation, allocated into 6 groups: Group 1 (Controls): management was based on education, exercise, diet and lifestyle changes. This same management plan was used in all other groups; group 2: Pycnogenol® 50 mg/day; group 3: Pycnogenol® 100 mg/day; group 4: Aspirin® 100 mg/day or ticlopidine 250 mg/day if intolerant to aspirin; group 5: Aspirin® 100 mg/day and Pycnogenol® 100 mg/day; group 6: Pycnogenol® 100 mg/day plus TTFCA 100 mg/day. The follow-up lasted 42 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed and on the number of subjects that had cardiovascular events. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 42 months. RESULTS: The ultrasonic score increased significantly in groups 1, 2, and 4 (>1%) but not in groups 3, 5 and 6 (<1%) suggesting a beneficial effect of Pycnogenol® 100 mg. Considering the percent of patients that progressed from class V (asymptomatic) to VI (symptomatic) there was a progression of plaques in 48.09% of controls. In the Pycnogenol® 100 (group 3, 10.4%) and in the Aspirin®+ Pycnogenol® (group 5, 10.68%) progression was half of what observed with antiplatelet agent (group 4, 20.93%); in the TTFCA+ Pycnogenol®group (group 6) progression was 7.4 times lower than in controls; 3.22 times lower than in the antiplatelet agents group (4). Events (hospital admission, specialized care) were observed in 16.03% of controls; there were 8.83% of subjects with events with Pycnogenol® 50 mg and 8% in group 3 (Pycnogenol® 100 mg). In group 4 (antiplatelets), 8.52% of subjects had events; in group 5, 6.87% of subjects had events and in group 6 (TTFCA+ Pycnogenol®) only 4.41% had events (this was the lowest event rate; P<0.05). All treatment groups had a significantly lower event rate (P<0.05) in comparison with controls. Considering treatments groups 2, 3, 5, 6 had a lower number (P<0.05) of subjects in need of cardiovascular management in comparison with controls. The need for risk factor management was higher in controls and lower in group 6 (P<0.05). In groups 2 to 6 the need for risk factor management was lower than in controls (P<0.05). Including all events (hospital admission, need for treatment or for risk management) 51.9% of controls were involved. In the other groups there was a reduction (from a -9.28% reduction in group 2 to a -26% in group 6) (P<0.002). The most important reduction (higher that in all groups; P<0.05) was in group 6. At 42 months, oxidative stress in all the Pycnogenol® groups was less than in the control group. In the combined group of Pycnogenol® and TTFCA the oxidative stress was less than with Pycnogenol® alone (P<0.001). CONCLUSION: Pycnogenol® and the combination of Pycnogenol® +TTFCA appear to reduce the progression of subclinical arterial plaques and the progression to clinical stages. The reduction in plaque and clinical progression was associated with a reduction in oxidative stress. The results justify a large, randomized, controlled study to demonstrate the efficacy of the combined Pycnogenol® and TTFCA prophylactic therapy in preclinical atherosclerosis.

Estrogen alters the effects of neuropeptide-Y on luteinizing hormone and follicle-stimulating hormone release in female rats at the level of the anterior pituitary gland.

In recent years, several studies have shown that neuropeptide-Y (NPY) is involved in the control of LH secretion. We determined the effects of estrogen on NPY-induced LH and FSH release in the absence or presence of LH-releasing hormone (LHRH) at the level of the anterior pituitary gland (APG). Adult female rats were ovariectomized. Fifteen to 20 days later, they were given a blank or estrogen-filled capsule subdermally and killed 17-19 h later. APG cells were isolated and cultured for 3 days in medium containing 12.5% rat serum collected at death from the same rats used to make the respective APG cell pools. The cells were then challenged for 3 h with vehicle, NPY (10(-12)-10(-6) M), LHRH (10(-9)-10(-6) M), or combinations of NPY (10(-9)-10(-7) M) and LHRH (10(-9) M). LHRH stimulated LH and FSH release from nonestrogen and estrogen-primed cells. NPY at 6.7 x 10(-8)-10(-6) M increased (P < 0.05) LH release and at 10(-6) M increased (P < 0.05) FSH release from estrogen-primed cells, but was without effect on nonestrogen-primed cells. In contrast, NPY at 10(-9)-10(-7) M potentiated the action of LHRH (10(-9) M) to increase the release of LH and FSH from nonestrogen-primed cells, but was without potentiating effects in cultures of estrogen-primed cells. The results demonstrate that 1) NPY can release LH and FSH by a direct action on estrogen-primed APG cells; and 2) NPY can potentiate the action of LHRH to increase the release of LH and FSH by a direct action on nonestrogen-primed APG cells.

Binding specificity of the mouse cerebral cortex receptor for small cholecystokinin peptides.

Prior studies have shown that the cerebral cortex cholecystokinin (CCK) receptor can bind CCK and gastrin analogs with high affinity. In the present work the brain CCK receptor had approximately a three times greater affinity for CCK8 than its C-terminal tetrapeptide (CCK4) while the C-terminal tripeptide (CCK3) was 1000-fold less potent than CCK4. Thus the C-terminal tetrapeptide appears to be the minimal C-terminal CCK sequence required for high affinity binding. Since brain membranes degrade various peptides including CCK, we also evaluated the stability of CCK analogs under the conditions used to measure receptor binding by the following three methods: (1) Studies of degradation-resistant analogs in binding assays; (2) analysis of analog degradation by high performance liquid chromatography (HPLC); and (3) determination of the change in potency of CCK analogs in competitive binding studies subsequent to preincubation with brain membranes. These studies indicated that degradation of analogs by the brain membranes although significant did not account for the differences in potency of analogs in competitive binding studies. Therefore, the observed differences in potencies of the analogs tested are due to the receptor affinity and not sensitivity of the analog to degradation.

Characterization of cholecystokinin receptors in bullfrog (Rana catesbeiana) brain and pancreas.

The binding of biologically active 125I-Bolton-Hunter-CCK-33 to bullfrog brain and pancreatic membrane particles was characterized. Both tissues exhibited time-dependent, saturable, reversible, and high affinity binding without evidence for cooperative interaction. Both bullfrog CCK receptors resembled their mammalian counterparts in having acidic pH optima for tracer binding and a Kd of about 0.5 nM. However, the receptors differed from their mammalian counterparts in that (1) the bullfrog brain membranes bound more tracer per mg protein than did the pancreatic membranes, (2) both bullfrog CCK receptors were relatively insensitive to dibutyryl cGMP, and (3) both bullfrog brain and pancreatic CCK receptors exhibited the same general specificity toward a variety of CCK and gastrin peptides. For both tissues, the relative order of receptor binding potency was CCK-8 greater than caerulein = CCK-33 greater than gastrin-17-II greater than CCK-8-ns = gastrin-17-I greater than caerulein-ns greater than gastrin-4 with the sulfated CCK peptides being 1000-fold more potent than their nonsulfated analogs. Sulfated gastrin was also relatively potent, being only 10-fold weaker than CCK-8. Gastrin-4 was 20 000-fold weaker than CCK-8 in interacting with the brain CCK receptor. The latter finding is in sharp contrast to the mammalian brain CCK receptor. We conclude that the bullfrog brain and pancreas contain similar CCK receptors of probable physiological significance and may represent an ancestral condition from which the two distinct CCK receptors present in mammalian brain and pancreas have evolved.

Absorption and disposition of 14C-labelled Kathon biocide, a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, following intravenous or dermal administration to male Sprague-Dawley rats.

Kathon biocide (KB), a 75:25 mixture of 5-chloro-2-methyl-4-isothiazolin-3-one (KI) and 2-methyl-4-isothiazolin-3-one (KII), is a broad-spectrum antimicrobial agent. The absorption and disposition of 14C label were studied in male Sprague-Dawley rats following iv or dermal administration of KB 14C labelled in the carbonyl carbon of either KI or KII. KI-labelled Kathon was distributed rapidly following an iv dose (0.8 mg/kg). Total 14C label in the plasma was rapidly eliminated, with the data best described by a three-compartment model. Total 14C label concentration in the blood, however, remained constant at 3 ppm from 6 to 96 hr after administration and represented 29% of the dose, indicating that KI-labelled Kathon and/or metabolites was sequestered by the cellular fraction of blood. Elimination of 14C label from the tissues examined was biphasic, with a terminal half-life of more than 4 days; by 96 hr, faeces, urine and CO2 accounted for 35, 31 and 4% of the dose, respectively. Following a single 24-hr dermal application of 0.2 ml of an aqueous solution containing 2000 ppm [14C]KB (400 micrograms), rats absorbed 94% of KI-labelled KB and 82% of KII-labelled KB. However, the systemic bioavailability of KB was substantially less than this, since approximately half of the absorbed KB was associated with the skin at the application site 24 hr after the application. Percutaneous absorption was not affected by concentration over the range 500-4000 ppm. As the concentration of KI-labelled KB in the applied solution increased from 500 to 4000 ppm, the relative amount of 14C label associated with the skin decreased, while that in the excreta increased, indicating greater systemic penetration at higher concentrations. Low amounts of 14C label were found in the testes (less than 2 ppb) and blood (24 ppb) 28 days after a single dermal application of KI-labelled KB. Four consecutive daily applications of KI-labelled KB did not influence the proportion of the dose absorbed from the skin. However, the proportion of the dose excreted was higher than after a single application of an equivalent amount of KB.

Ocular and orbital blood flow velocity in patients with peripheral vascular disease and diabetes treated with intravenous prostaglandin E1.

The purpose of this study was to evaluate the effect of intravenous prostaglandin E1 (PGE1) on the flow velocity of the ophthalmic artery and the central retinal artery in patients with peripheral vascular disease manifested by intermittent claudication. The flow velocity of these vessels is frequently decreased in vascular patients. Since these patients were already being treated with PGE1 for their intermittent claudication, the authors wanted to evaluate the effect on the flow velocity of the ocular vessels as well. A randomized 21-week study of two groups of vascular patients was performed. The first group had intermittent claudication. The second group had intermittent claudication and were also diabetics. Both groups were treated with intravenous PGE1 for their intermittent claudication. Using the color Doppler, the flow velocities of the ophthalmic artery and central retinal artery were measured before and after the intravenous treatment. Before treatment, the flow velocity of the ophthalmic artery and the central retinal artery was decreased when compared to that in the normals. After treatment, there was a significant increase in the systolic and diastolic phases of the flow velocity in both arteries. The systolic flow velocity increased by as much as 40%, and the diastolic flow velocity increased by as much as 80%. The flow velocities of the ophthalmic artery and the central retinal artery are frequently decreased in certain ocular diseases, and this decreased flow may contribute to the ocular pathology. If intravenous PGE1 is able to increase the flow velocity of these vessels in patients with peripheral vascular disease, it is possible that it is also able to increase the flow velocity of these vessels in patients with ocular disease as well. Intravenous PGE1 may prove to be a useful adjunct therapy in eyes when ischemia is part of the pathology.

Ocular and retrobulbar blood flow in ocular hypertensives treated with topical timolol, betaxolol and carteolol.

The purpose of this study was to evaluate the effect of topical timolol 0.5%, betaxolol 0.5% and carteolol 2% on the blood flow velocity of the central retinal artery (CRA), the posterior ciliary artery (PCA) and the ophthalmic artery (OA) in patients with ocular hypertension. A group of 14 patients with ocular hypertension and a group of 11 normals were studied. The color Doppler was used to measure the peak systolic flow velocity (PSFV) and the end diastolic flow velocity (EDFV) of the CRA, the PCA and the OA in the normals and in the patients. The normals were under no treatment, while the patients were studied before and after treatment with topical timolol 0.5%, betaxolol 0.5% and carteolol 2%. In the systolic phase, there was a significant increase in the flow velocity of the CRA with all three drugs. In the diastolic phase of the CRA, the increase was significant for timolol 0.5% and carteolol 2% but not for betaxolol 0.5%. The flow velocity of the PCA and OA remained unchanged. In this study of 14 patients with ocular hypertension, topical timolol 0.5%, betaxolol 0.5% and carteolol 2% led to a significant increase in the flow velocity of the CRA without creating a steal or decrease in the flow velocity of the PCA.

Doppler ultrasonography in giant cell arteritis.

A patient with biopsy negative giant cell arteritis was examined and treated by our group. Since in some cases the visual loss in this disease is due to a central retinal artery occlusion, a technique to evaluate the blood flow velocity in this artery would be useful. The Duplex scanner was utilized by us in this patient to study the blood flow velocity of the central retinal artery. The flow velocity was reduced. The patient was treated with systemic steroids which lead to clinical and symptomatic improvement. After the treatment with steroids the Duplex scanner was again used to study the flow velocity of the central retinal artery. The blood flow velocity improved. We think that Doppler ultrasonography may be useful in the diagnosis of and in monitoring the treatment of some cases of giant cell arteritis.

Treatment of vascular retinal disease with pentoxifylline: a controlled, randomized trial.

The aim of this study was to evaluate the effect of PXF (1800 mg daily) in patients with sudden loss of vision (SLV) in a 4-week trial, evaluating clinical outcome and retinal flow parameters. Inclusion criteria were SLV associated with thrombosis of the retinal artery; decrease in retinal blood flow (PSF: peak-systolic flow; EDF: end-diastolic flow velocity) and asymmetry between the two retinal arteries (>40%) documented by duplex scanning. All 10 included patients completed the study. The groups were comparable. No side effects were reported. A significant improvement in flow velocity (p<0.05) and a decrease in analogue score in both groups were observed. PSF increase was 550% in the PXF group vs 288% in the placebo group (262% difference). EDF increase was 400% in the PXF group vs 200% in the placebo group (200% difference). There was a significant difference in the analogue score decrease (33.3% difference larger in the PXF group; p<0.05). In conclusion, PXF treatment improved retinal flow after retinal artery occlusion better than placebo and should be considered as an important option in this condition.

Treatment of retinal vein thrombosis with pentoxifylline: a controlled, randomized trial.

The aim of this study was to evaluate PXF (pentoxifylline; 1600 mg daily vs placebo) in patients with retinal vein thrombosis (RVT) in a 4-week trial, evaluating clinical outcome and retinal flow. Inclusion criteria were sudden loss of vision (SLV); retinal vein thrombosis (RVT); decrease in retinal vein flow; asymmetry between retinal veins (>40%) documented by duplex scanning (retinal vein thrombosis flow = RVTF). All 18 included patients completed the study. The groups were comparable. No side effect was observed. An improvement in arterial flow (p<0.05) and a decrease in analogue score (p<0.05) were observed in both groups (due to the spontaneous evolution with partial thrombus lysis in 4 weeks). The increase in arterial flow (PSF and EDF) were greater (p<0.05) in the PXF group. The RVFV increase was better in the PXF group (350% increase vs 200% increase in the placebo group; p<0.05). There was a significant difference in the analogue score decrease (4 vs 7) in the PXF group (p<0.05). In conclusion, PXF improved retinal flow after RVT better than placebo. It should be considered as an important treatment option.

Pressure and microcirculatory effects of treatment with lercanidipine in hypertensive patients and in vascular patients with hypertension.

The aim of this study was to evaluate the macrocirculatory and microcirculatory effects of treatment with lercanidipine, a new antihypertensive agent acting both on blood pressure and microcirculation in patients with moderate essential hypertension and without vascular disease and in patient with hypertension and vascular disease. In hypertensive subjects target-organ damage associated with high blood pressure may now be objectively documented by noninvasive tests. These alterations constitute a model to evaluate not only the pressure effects of antihypertensive treatment but also the normalization of the peripheral microcirculatory network. With color duplex scanning, flow velocity in the central retinal artery and retinal flow velocity can be measured and with use of laser-Doppler-flowmetry, it is also possible to evaluate microcirculation alterations in hypertensive subjects. These evaluation methods are completely noninvasive and may be used to assess the microcirculatory effects of antihypertensive drugs.

Shock waves in vascular diseases: an in-vitro study.

UNLABELLED: Three human aortic specimens were used for this in-vitro study on the effects of shock waves on the arterial wall. Specimen one was from a normal (for age) healthy aorta. The full abdominal length was used (including mesenteric and renal arteries and the aortoiliac bifurcation), divided into six pieces (3 cm). The pieces were placed and fixed into degassed water. Shock waves (SW) were focused onto the aortic wall by means of a B-mode ultrasound imager. An SW generator (Minilith SL1, Storz Medical AG, Kreuzlingen, Switzerland) was used for setting of energy flux density between 0.03 and 0.5 mJ/mm2. The six aortic pieces (excluding piece 1, placed in water and left untreated as control) were treated with SW at increasing energy levels. A second aortic specimen of a man with arteriosclerotic plaques was also used and the experiment repeated at energy levels 1, 5, and 8. Another specimen of normal thoracic aorta was exposed at energy levels 1 and 8 only. Energy levels delivered onto the aortic walls were selected from theoretically destructive levels to minimal levels known not to alter vascular tissues. High-resolution ultrasounds of the aortic segments were performed with a 10 MHz high-resolution, broad-band (ATL 3000, USA) probe in water before and after SW application to detect structural changes in the wall after SW. Histology was performed with a standard hematoxylin-eosin staining. RESULTS: The aortic pieces did not show macroscopic damages at visual examination, and at the ultrasound examination no visible changes were observed even at higher levels of SW energy. Also no effects were seen by histology. In conclusion, no damaging effects were observed, visually, by ultrasound, or by histology. At these energy levels SW appear to be safe and do not produce any damage to the aortic wall. Therefore, SW could be considered a safe, nondamaging procedure for potential treatment (ie, thrombolysis) in which vessel walls could be involved. Theoretically it is possible that functional changes could be observed in vivo including cell permeability modifications and other alterations (including changes in the potential of the cells in SW fields to modify themselves and to divide). At the energy levels described in this study SW could, theoretically be, safely used for vascular applications (ie, treating venous and arterial thrombi or in arterial plaques modification) without altering major, structural, arterial wall characteristics. Lesions or alterations that have a different density from the normal wall (thrombi or plaques) could be differently sensitive to the same dosage of SW. These differences in acoustic impedance characteristics could be used for potential treatments with SW without damaging the arterial wall.

[Edema tester. Assessment of edema of the legs]. / Edema tester. Valutazione dell'edema negli arti inferiori.

BACKGROUND: The aim of this study was the clinical evaluation of an original device produced to evaluate edema in a semi-quantitative way, the ACI Medical, Edema Tester (ET). ET1, is a soft plastic plate characterised by two parallel conic pyramidal protrusions. One side of the protrusion is rounded while the other side has an angular edge. The two protrusions are placed on the plate in inverse decreasing height. ET2 is characterised by two lines of 7 holes placed in the plate. The ET is applied at the internal perimalleolar region with the conic pyramidal protrusions in contact with the skin. A standard sphygmomanometer cuff is applied over the area and pressure is maintained at 50 mmHg for a period between 1 an 3 minutes. The cuff is then removed. ET1: skin marks are usually just visible in normal subjects without edema and disappear in a few minutes. When edema is moderate some half of each protrusion is visible as a skin mark. In limbs with severe edema the whole length of the protrusion is clearly visible. ET2: skin marks are usually just visible in normal limbs without edema and disappear in a few minutes. In limbs with edema the number of holes visible on the skin is increased and in severe edema all holes are visible. METHODS: To evaluate semi-quantitatively the level of edema the length of the two skin marks can be measured and for the ET2 the numbers of visible holes can be counted, as they are generally proportional to the degree of edema. The ET testers were evaluated in 22 normal subjects, 19 limbs with varicose veins, 22 patients with CVI and lipodermatosclerosis, 5 patients with initial primary lymphedema and in 8 subjects with severe, chronic, lymphedema and skin alterations. RESULTS: The results showed a significant difference between normal limbs an patients. CONCLUSIONS: In conclusion, the method of evaluating edema with ET can be used to supplement the clinical and noninvasive evaluation. In general practice the presence of edema measurable with ET indicate the need for treatment. The several degrees of skin marks visibility and disappearance time may be used as a general guideline to indicate the need for different types and length of treatment.