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Biomedical subjects

S Wolf

Publications and source records attributed to S Wolf.

At least 181 records · Page 10Linked to original sources

[Retinal hemodynamics in patients with hyperviscosity syndrome].

BACKGROUND: The hyperviscosity syndrome (e.g. plasmacytoma, cryoglobulinaemia and Waldenström's macroglobulinaemia) leads through the polymerisation of macro-molecules to an increased blood viscosity. This may result in microcirculatory disturbances in various organs. In the retina the hyperviscosity produces a pattern of retinal changes including dot and blot hemorrhages, retinal and optic nerve head edema and increased diameters of the veins. In the present study we quantified the retinal hemodynamic in patients with hyperviscosity syndrome. PATIENTS AND METHODS: Fifteen patients aged between 35 and 72 years were included in the study. Ten presented with Waldenström's macroglobulinaemia, two with cryoglobulinaemia and three with plasmacytoma. All patients underwent video fluorescein angiographic studies. The arteriovenous passage time (AVP) representing the retinal microcirculation and the arm retina time (ART) were quantified from the angiograms. In addition, hematocrit (Hct) and the plasma viscosity (ETA) were measured. RESULTS: The AVP was significantly prolonged in patients with hyperviscosity syndrome in comparison to healthy volunteers (AVP: 2.6 +/- 1.5 s vs. 1.6 +/- 0.4 s; p < 0.05). The ART showed no significant differences. Plasma viscosity was doubled in the patients as compared with reference values (ETA: 2.54 +/- 2.23 mPas vs. 1.24 +/- 0.08 mPas; p < 0.01). CONCLUSIONS: The simultaneous rising of plasmaviscosity and arteriovenous passage time suggests that the increase of plasmaviscosity causes retinal circulatory disturbance. All this may result in the typical fundus changes in patients with hyperviscosity syndrome.

Adult↗

CO2 dependence of retinal arterial and capillary blood velocity.

OBJECTIVE: Blood flow to the brain is extremely sensitive to changes in PCO2. While animal studies show a similar potent PCO2 dependence in retinal and choroidal vessels, the PCO2-retinal blood flow relationship has never been adequately studied in humans. METHODS: Video scanning laser ophthalmoscopy after fluorescein angiography was used to analyze retinal arterial and capillary blood velocity under conditions of mild hypercapnia and hypocapnia. Control conditions (end-tidal PCO2 = 38.3 +/- 0.4 mmHg) were contrasted with hyperventilation-induced hypocapnia (PCO2 = 34.0 +/- 0.4 mmHg) and hypercapnia (PCO2 = 42.3 +/- 0.5 mmHg) created by PCO2 addition to inspired gas. RESULTS: Both larger vessel and macular capillary blood velocity was dependent upon PCO2: arteriovenous passage time fell as PCO2 rose, and both mean arterial dye velocity and capillary blood velocity rose as PCO2 rose (all p < 0.05). These changes in flow velocity occurred despite unchanged heart rate, arterial systolic and diastolic blood pressure, intraocular pressure, and calculated ocular perfusion pressure. Contrast sensitivity was also unchanged by PCO2 variation. CONCLUSIONS: The human retinal circulation, like the whole cerebral circulation, may be strongly dependent upon PCO2 in a manner that is unrelated to perfusion pressure and apparently outside strict autoregulatory controls.

Adult↗

Macular microcirculation in cystoid maculopathy of diabetic patients.

BACKGROUND: In patients with diabetic macular oedema and central cysts ischaemia of the retina appears to be an important contributing factor in the pathogenesis of cysts. This study was performed to further elucidate the role of the inner retinal microcirculation in diabetic cystoid macular oedema (CMO). METHODS: Video fluorescein angiography allows visualisation of the macular microvasculature and measurements of the capillary blood velocity (CBV), foveal avascular zone (FAZ), and perifoveal intercapillary area (PIA, characterising capillary density). RESULTS: Twenty three diabetic subjects with CMO, matched diabetic patients without macular oedema (n = 23), and healthy subjects (n = 23) were included. CBV, PIA, and FAZ did not differ significantly among diabetic groups regardless of presence of cystoid changes. CBV was significantly reduced (p < 0.0001) and PIA was more than doubled in both diabetic groups (p < 0.0001) when compared with healthy subjects. Furthermore, FAZ showed a nearly doubled size in diabetic patients without macular oedema (p < 0.01) and a less pronounced enlargement (by 29%) in diabetics with CMO (p < 0.05). CONCLUSION: The results indicate that the retinal microcirculation in diabetic patients is markedly altered when compared with healthy subjects, regardless of CMO presence. In CMO patients the microcirculatory changes are similar to those of diabetic patients without macular oedema. Thus inner retinal perfusion does not contribute to tissue ischaemia leading to cystoid formations in diabetic maculopathy.

Adult↗

Clozapine treatment in Russia: a review of clinical research.

OBJECTIVE: This paper is intended to help American clinicians and investigators further their understanding of the clinical use of clozapine by reviewing experience with the drug in Russia, where it was introduced 17 years before it became available in the United States. METHODS: Key articles on clozapine from the Russian clinical research literature were reviewed by the first two authors, former Russian clinical investigators. The third author comments briefly about the implications of this work from a contemporary American perspective. FINDINGS AND CONCLUSIONS: The review found that although clozapine was not widely distributed in Russia, it was investigated at several large psychiatric research institutions and hospitals. It was not reserved for neuroleptic-resistant disorders but instead was used with some success as a first-line treatment in acute disorders. Although no controlled clinical trials were conducted, results of long-term outcome studies of treatment-resistant schizophrenia were largely in agreement with those of controlled trials and clinical follow-up studies in the U.S. The studies found short-term gains for previously refractory patients as well as improvements in social functioning that continued for extended periods in some cases. Russian investigators described clozapine as an effective antipsychotic agent that lacked the extrapyramidal side effects of other neuroleptics.

Clinical Trials as Topic↗

Digital imaging of central serous retinopathy using infrared illumination.

When used with an infrared laser, scanning laser technology allows imaging of subretinal structures. In the indirect mode (scattered light), drusen, subretinal edema, and other changes in the retinal pigment epithelial complex can easily be visualized as pseudoprominent structures. This study was undertaken to determine the role of infrared imaging in central serous retinopathy. A total of 22 patients affected by acute central serous retinopathy were recruited for the study. All patients underwent fluorescein angiography (488 nm) and infrared imaging (788 nm) using a scanning laser ophthalmoscope (SLO 101; Rodenstock). The confocal mode was used for the fluorescein angiography, but the indirect mode was applied for infrared imaging. In all patients, serous detachment could be visualized by infrared imaging as pseudoprominent, oval-shaped structures. The size was at least one disk diameter and correspondend very well to the clinical appearance. In all patients, late-phase (20 min) fluorescein studies revealed the typical focal leakage with progressive hyperfluorescence. In six patients (27%) the extent of the serous detachment could be seen in a slightly hyperfluorescent rim. Digital image analysis showed that the extent of the serous detachment in the fluorescein angiogram was similar to the size of the thickened structures in the infrared image (r2 = 0.94). This initial study suggests that noninvasive infrared imaging can be a very useful indicator of serous detachment. Further studies regarding the influence of medical or laser treatment must be carried out to prove the clinical relevance.

Acute Disease↗

Indocyanine green angiography in traumatic choroidal rupture: clinicoangiographic case reports.

Blunt trauma to the eye can cause choroidal ruptures. Often localization is obscured by hemorrhages, edema, and pigmentary changes. The use of indocyanine green (ICG) angiography to supplement fluorescein angiography in visualizing retinal and choroidal tissues was investigated. Three patients with acute traumatic choroidal ruptures received a retinal examination, including fluorescein and ICG angiography study. Choroidal ruptures were well localized in ICG angiograms in both early and late phases. In fluorescein angiograms, the defects were underestimated in early phases and overestimated in the later phases. In one patient with severe traumatic changes, ophthalmoscopy and fluorescein angiography identified all superficial splits, whereas ICG angiography readily detected deeper changes as well. ICG angiography is helpful in diagnosis major and minor ruptures of the choriocapillaris and the choroid, in defining the extent of traumatic ruptures, and in furthering the understanding of the pathology of traumatic ruptures, and in furthering the understanding of the pathology of traumatic tears.

Adolescent↗

Retinal hemodynamics in patients with chronic open-angle glaucoma.

Recently it has been demonstrated that retinal hemodynamics are disturbed in patients with chronic open-angle glaucoma. As the underlying cause a reduction in perfusion pressure due to increased intraocular pressure (IOP) and deficiencies of retinal autoregulation has been discussed. The present study was undertaken to clarify the influence of filtering surgery on retinal hemodynamics in patients with chronic open-angle glaucoma. A total of 17 patients with chronic open-angle glaucoma aged between 37 and 86 years were included in this prospective study. All patients underwent digital fluorescein angiography before and 10 days after fistulating procedures. From the angiograms the arteriovenous passage time (AVP) and arterial mean dye-bolus velocity (MDV) were quantified by means of digital picture analysis. At baseline the AVP was significantly prolonged in the patients as compared with reference values (AVP, 2.5 +/- 0.8 versus 1.6 +/- 0.4 s; P < 0.01). After the fistulating procedure (IOP: before, 29 +/- 5 mmHg; after, 16 +/- 4 mmHg) the AVP was significantly reduced as compared with baseline values (AVP, 2.5 +/- 0.8 versus 2.0 +/- 0.4 s; P < 0.05), whereas the MDV showed only a slight increase (MDV, 5.70 +/- 0.89 versus 5.99 +/- 0.92 mm/s; P > 0.05). This study confirms a disturbance of retinal hemodynamics in patients with chronic open-angle glaucoma. The significant reduction in AVP observed after lowering of the IOP by fistulating procedures demonstrates the positive influence of IOP reduction on the retinal circulation. The improvement in retinal circulation may prevent the occurrence of further glaucomatous damage after fistulating procedures.

Adult↗

Microperimetry in patients with central serous retinopathy.

In patients with acute central serous retinopathy (CSR), evaluation of visual acuity alone may not represent visual function. In patients with acute CSR, visual function may be disturbed by localized scotomas, distortion, and waviness. For the assessment of localized light sensitivity and stability of fixation, patients with CSR were evaluated by fundus perimetry with a scanning laser ophthalmoscope (SLO 101, Rodenstock Instruments). In all, 21 patients with acute CSR and 19 healthy volunteers were included in the study. Diagnosis of CSR was established by ophthalmoscopy and digital video fluorescein angiography. All patients and volunteers underwent static suprathreshold perimetry with the SLO. Light sensitivity was quantified by presenting stimuli with different light intensities (intensity, 0-27.9 dB above background; size, Goldmann III; wavelength, 633 nm) using an automatic staircase strategy. Stimuli were presented with simultaneous real-time monitoring of the retina. Fixation stability was quantified by measuring the area encompassing 75% of all points of fixation. Light sensitivity was 18-20 dB in affected areas, whereas in healthy eyes and outside the affected area, values of 22-24 dB were obtained. Fixation stability was significantly decreased in the affected eye as compared with normal eyes (33 +/- 12 versus 21 +/- 4 min of arc; P < 0.01). Static perimetry with an SLO is a useful technique for the assessment of localized light sensitivity and fixation stability in patients with macular disease. This technique could provide helpful information in the management of CSR.

Acute Disease↗

Renal hemodynamics in essential hypertensives treated with losartan.

ACE-inhibitors are known to have special renal effects, i.e. they increase ERPF, decrease the filtration fraction and lower proteinuria. These effects can be due to a decrease in angiotensin II (AII) levels as well as an increase in bradykinin. New and more specific AII-receptor antagonists may help to distinguish between effects exerted by angiotensin II and those exerted by bradykinin. We investigated the effects of losartan in 9 patients with essential hypertension (sitting mean diastolic blood pressure 95-120 mmHg). Renal hemodynamics were measured by continuous inulin-and PAH-clearance (GFR and RPF) after stopping antihypertensive therapy for 1 week, followed by a 2-week placebo period and after a 4-week treatment phase with losartan (50 mg/die) followed by a therapy with an ACE-inhibitor (ramipril 5mg/die). Additionally, urine albumin excretion (UAE) was measured. Treatment of patients with essential hypertension with losartan resulted in a significant decrease of MAP after three weeks of treatment (121 +/- 8 mmHg under placebo and 114 +/- 10 mmHg under losartan; * = p < 0.05). MAP after four weeks of losartan treatment was 115 +/- 11 mmHg. Regarding changes in renal hemodynamics we could not demonstrate a significant change for neither losartan nor the ACE-inhibitor. Urine albumin excretion was reduced by both treatment regimens in correlation to the magnitude of blood pressure reduction. Our data indicate that losartan induced a significant reduction in MAP in patients with essential arterial hypertension with only moderate effects on renal hemodynamics.

Antihypertensive Agents↗

Quantification of cystoid changes in diabetic maculopathy.

PURPOSE: In patients with diabetic macular edema and cysts, quantification of the extent of the cystoid formation has been difficult. This study was performed to introduce reliable measurements of cysts, the quantification of the extent, and its relation to visual acuity. METHODS: Fluorescein angiography generated with a scanning laser ophthalmoscope provided detailed recognition not only of the foveal microvasculature, but also of well-demarcated cystoid formations in the early phases. The sampling area included the central 2.5 degrees of the fovea. Using digital image analysis, two independent observers estimated the area covered by cysts, the number of cysts, and the foveal avascular zone (FAZ). RESULTS: Twenty-three subjects with diabetes and macular cysts were enrolled in the current study. The mean area of the cysts was 0.315 +/- 0.241 mm2 (0.05 mm2 to 0.9 mm2), and the number of cysts ranged from 1 to 7. Both parameters, area of cysts (r2 = 0.61), and number of cysts (r2 = 0.48) showed a significant correlation with visual acuity (P < 0.01), whereas FAZ (0.08 to 0.58 mm2) showed no significant correlation with visual acuity. CONCLUSIONS: Fluorescein angiography allows a reproducible quantification of the extent of macular cysts. The relation of visual acuity to the number of cysts and to the area covered by the cystoid formation is highly significant. Thus, both these measures can provide an objective criterion for the estimation of visual prognosis and an outcome for evaluation therapy techniques.

Adult↗

Protein C, protein S, and antithrombin III in acute ocular occlusive diseases.

Hereditary and acquired deficiencies of protein C, protein S, and antithrombin III are important risk factors of thrombosis, especially in peripheral veins. In a prospective study, concentrations of these factors were measured to determine the prevalence of deficiencies of these proteins in ocular vascular occlusive disease. A total of 167 patients with acute retinal arterial (28%) or venous occlusion (55%) or ischemic optic neuropathy (17%) were included. Exclusion criteria were anticoagulant therapy, renal insufficiency, and hepatic disease. The mean values obtained for all patients were in normal range (protein C, 102 +/- 25%; protein S, 109 +/- 22%; antithrombin III, 23.6 +/- 3.1 IU/ml). Antithrombin III was pathologically reduced in one patient with branch venous occlusion. Proteins C and S were severely altered in two patients with central venous occlusion, in one individual with ischemic optic neuropathy, and in one patient with branch arterial occlusion. Subnormal values were found in 21 patients for antithrombin III (16.1-19.9 IU/ml), in 7 patients for protein C (55-65%). Two of these five patients with pathologic findings showed severe vascular manifestations in the form of current deep-vein thrombosis and multiple retinal occlusions. Their age was 30 and 53 years, respectively, and differed considerably from the mean age of the entire group (65 +/- 12 years). This study suggests that these proteins were important factors for the development of ocular vascular occlusive diseases in single patients. Although the prevalence is low, measurement of these parameters in young patients may be useful in preventing other vascular complications.

Acute Disease↗

[The effect of angiotensin-converting enzyme inhibitors on proteinuria in chronic glomerulonephritis].

The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and captopril, on proteinuria and renal haemodynamics was investigated in 11 hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5 g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial the patients received, each time for six weeks, either lisinopril (5 mg/d, sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg, sometimes increased to twice 25 mg after 3 weeks). Initially and between the individual treatment phases they were on a placebo phase for 4 weeks. The following were measured: protein excretion, including fractional clearance of albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d; lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and fractional albumin clearance were significantly decreased only by lisinopril (P < 0.05), not by captopril. Plasma-renin activity was increased more by lisinopril than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was only slightly influenced by either drug, but captopril significantly decreased the filtration fraction in the presence of chronic glomerulonephritis and renal failure. - Resulting from their influence on the renin-angiotensin-aldosterone system, ACE inhibitors have, in addition to their known action on renal haemodynamics, an independent effect on the loading barrier of the basal membrane of the kidney.

Adult↗

Interleukin-12 but not interferon-gamma production correlates with induction of T helper type-1 phenotype in murine candidiasis.

By means of polymerase chain reaction-assisted mRNA amplification, we have monitored message levels of interleukin (IL)-12 in splenic macrophages and of interferon-gamma (IFN-gamma), IL-4, and IL-10 in CD4+ and CD8+ T cells using Candida albicans/host combinations that result either in a T helper type-1 (Th1)-associated self-limiting infection ("healer mice") or in a Th2-associated progressive disease ("nonhealer mice"). The timing and pattern of message detection did not differ qualitatively by the expression of IFN-gamma or IL-10 mRNA in CD4+ and CD8+ cells from healer (i.e. PCA-2 into CD2F1) vs. nonhealer (i.e. CA-6 into CD2F1 or PCA-2 into DBA/2) mice. In contrast, IL-4 mRNA was uniquely expressed by CD4+ cells from nonhealer animals. IL-12p40 was readily detected in macrophages from healer mice but was detected only early in infection in mice with progressive disease. Cytokine levels were measured in sera, and antigen-driven cytokine production by CD4+ and CD8+ cells was assessed in vitro, while IFN-gamma-producing cells were enumerated in CD4- CD8- cell fractions. Overall, our results showed that (i) antigen-specific secretion of IFN-gamma protein in vitro by CD4+ cells occurred only in healing infection; (ii) IL-4- and IL-10-producing CD4+ cells would expand in nonhealer mice in the face of high levels of circulating IFN-gamma, likely released by CD4- CD8- lymphocytes; (iii) a finely regulated IFN-gamma production correlated in the healer mice with IL-12 mRNA detection, and IL-12 was required in vitro for yeast-induced development of IFN-gamma-producing CD4+ cells. Although the mutually exclusive production of IL-4/IL-10 and IFN-gamma by early CD4+ cells may be the major discriminative factor of cure and noncure responses in candidiasis, IL-12 rather than IFN-gamma production may be an indicator of Th1 differentiation.

Animals↗

A nonradioactive assay for microsomal cysteine-S-conjugate N-acetyltransferase activity by high-pressure liquid chromatography.

Microsomal cysteine-S-conjugate N-acetyltransferase, an enzyme specific for S-substituted cysteines, plays an important role in the detoxicative metabolism of xenobiotics by catalyzing the N-acetylation of cysteine-S-conjugates. Cysteine-S-conjugate N-acetyl-transferase activity is generally assayed by measuring the amount of N-[14C]acetyl-S-benzyl-L-cysteine generated from the model compound S-benzyl-L-cysteine and [14C]acetyl-CoA and subsequent extraction of the product. Although sensitive, this method is costly and time consuming. For safety and environmental reasons we developed a nonradioactive assay for cysteine-S-conjugate N-acetyltransferase activity. Our method depends upon the acetylation of the uv-sensitive model compound 4-nitro-S-benzyl-L-cysteine. The test mixture is separated by HPLC, guaranteeing that no by-products interfere with the determination of product formation. Radioactive and nonradioactive methods were compared using different porcine kidney samples. With the nonradioactive test we determined values of Km and Vmax of both 4-nitro-S-benzyl-L-cysteine and acetyl-CoA. In summary, this new nonradioactive assay is sensitive, less costly, safer, less time-consuming, and less laborious than radioactive assays for cysteine-S-conjugate N-acetyltransferase.

Acetyl Coenzyme A↗

Hemodilution therapy in central retinal vein occlusion. One-year results of a prospective randomized study.

Systemic hemorheologic abnormalities may play a part in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients compared with age-matched controls at baseline examination. We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and rheologic manipulation with parenteral pentoxifylline. We found a statistically significant improvement in visual acuity at 1 year post-treatment for the treated group compared with the control group (increase of visual acuity of 1.5 lines vs decrease of 1.5 lines). The retinal blood flow parameters were markedly improved soon after the institution of therapy, and this may have contributed to the improvement in visual acuity in the treated group. There was no statistically significant difference between the two groups in the progression to ischemic central vein occlusion.

Aged↗