Peter Martus

Migraine and tension headache in high-pressure and normal-pressure glaucoma

PURPOSEnTo analyze the association of normal-pressure glaucoma and migraine.nnnMETHODSnIn a prospective study, 154 patients with glaucoma (56 normal-pressure subgroup and 98 high-pressure glaucoma subgroup), 55 patients with ocular hypertension, and 75 control subjects were analyzed by means of a standardized questionnaire based on International Headache Society criteria.nnnRESULTSnAccording to the questionnaire, 46 patients (17%) were classified as suffering from migraine and 20 (7%) from tension headache (episodic and chronic). The prevalence of headache, migraine, and tension headache did not vary significantly among control subjects, patients with ocular hypertension, and patients with glaucoma, but migraine was significantly more common in patients with normal-pressure glaucoma (28%) compared with control subjects (12%; P<.05) and patients with high-pressure glaucoma (10%; P<.01).nnnCONCLUSIONnThe results suggest an association of normal-pressure glaucoma and migraine and a potential, common vascular etiology of both diseases.

Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation☆

PURPOSEnSeveral groups have reported the value of bladder preservation by a combined treatment protocol, including transurethral resection (TUR-B) and radiochemotherapy (RCT). As more experience is acquired with organ-sparing treatment, patient selection should be optimized. The purpose of this study was to investigate the role of several biologic markers that may predict response to RCT in muscle-invasive bladder carcinoma.nnnMETHODS AND MATERIALSnThe apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 70 patients treated for invasive bladder cancer by TUR-B and RCT. Expression of each marker was correlated with initial response, local control, and cancer-specific survival with preserved bladder. An exploratory multivariate analysis was also performed that included clinical and immunohistochemical variables.nnnRESULTSnA high AI (> median = 1.6%) and a high Ki-67 index (> median = 8.8%), but not the p53- and bcl-2 expression, were significantly related to initial complete response (CR) and local control with preserved bladder after 5 years. When the AI and Ki-67 expression were considered simultaneously, the association with initial CR (p < 0. 001), local control (p = 0.0002), and cancer-specific survival with preserved bladder (p = 0.008) was highly significant. In an exploratory multivariate analysis (final model), only AI, Ki-67, and the combined AI/Ki-67 variable retained significance for local control with preserved bladder at 5 years.nnnCONCLUSIONnPatients with a high spontaneous AI and a high pretreatment Ki-67 index should be considered preferentially for treatment with RCT, whereas tumors with low proliferation and low levels of apoptosis are less likely to respond to RCT.

Impact of short-term versus long-term topical steroids on corneal neovascularization after non-high-risk keratoplasty

Abstract.Purpose: To analyze incidence and extent of corneal neovascularization (CN) after non-high-risk keratoplasty and to find out whether duration of postoperative topical steroid therapy (6 vs 12 months) affects CN, corneal endothelial cell count, pachymetry, aqueous flare values, and best-corrected visual acuity at 1xa0year after keratoplasty. Methods: Patients of the prospective Erlangen non-high-risk keratoplasty study with available high-quality corneal photographs taken preoperatively and 1 year later were analyzed (n=136). Corneal photographs were evaluated by two independent observers in a standardized semiquantitative fashion. Slides were projected with 100× magnification and corneal vessels classified into five grades with regard to the limbus, sutures and host-graft junction in each of 12 corneal sectors. Incidence and extent of CN after keratoplasty and relation to short-term (0–6 months) versus long-term (0–12 months) postoperative topical steroid therapy were analyzed. The effect of duration of topical steroid therapy on corneal endothelial cell count, pachymetry, aqueous flare values, and best corrected visual acuity was also analyzed. Of the 136 patients, 69 (51%) were randomly assigned to short-term and 67 to long-term topical prednisolone acetate 1%. Results: Fifty-eight percent of patients (n=79) developed a CN within 1 year after keratoplasty in at least one corneal sector (mean 3.1±2.2, range 1–10). At 1 year after keratoplasty, only in 12% of these patients did at least one vessel reach the host-graft junction or grow into the donor cornea, whereas in 51% vessels were seen beyond the outer suture ends of the double running suture without reaching the host-graft junction. In 37%, capillaries were located between limbus and outer suture ends. New vessels usually pointed directly or indirectly to the outer suture ends and usually were located around the 12 oclock and 6 oclock positions. There was no significant difference regarding incidence and extent of CN 1 year after keratoplasty between the long-term and the short-term group. Duration of topical steroid therapy had no significant effect on corneal endothelial cell count and thickness, aqueous flare values and best-corrected visual acuity at 6 and 12 months postoperatively (only at 12 months, corneas in the long-term treatment group were slightly thicker; P=0.03). Interobserver correlation of vessel assessment was 0.77 (Kendalls tau B). Conclusions: CN is a common phenomenon after non-high-risk keratoplasty. New vessels rarely reach the host-graft junction, most commonly develop from the 6 oclock and 12 oclock positions and are usually located between epithelium and Bowmans layer (i.e., at the level of the superficial suture). The direction of vessel growth from the limbus towards the outer suture ends suggests release of angiogenic factors in this area. Prolongation of topical steroid therapy after non-high-risk keratoplasty beyond 6 months in this study did not significantly influence incidence and extent of CN, corneal endothelial cell count, aqueous flare values and best-corrected visual acuity observed 1 year after keratoplasty.

Clinical evaluation of contrast-enhanced color Doppler sonography in the differential diagnosis of liver tumors.

We investigated the value of contrast‐enhanced color Doppler sonography in the differential diagnosis of liver tumors.

Somatization as a core symptom of melancholic type depression. Evidence from a cross-cultural study

The study questions whether different types of somatization may be a core symptom of melancholia, thus, being invariable across cultures and being a candidate for neurobiological research and diagnostic criteria. 51 Turkish patients and 51 education-matched German patients with melancholic depression were compared for two types of somatization. Turkish patients had higher frequencies of somatic preoccupation and hypochondriasis but they were not different in the perception and experience of somatic symptoms. It is concluded that: (1) somatization has to be differentiated psychopathologically; (2) it may be a neurobiological core symptom of melancholia in the well-defined sense of perceiving abnormal somatic symptoms; and (3) it may be a culture-bound symptom in the sense of being abnormally concerned with somatic symptoms or hypochondrial fears.

Aqueous flare in retinitis pigmentosa.

Abstractu2002· Background: The purpose of this study was to quantify blood-ocular barrier impairment by measuring aqueous flare in retinitis pigmentosa (RP) and to search for clinical correlations. · Methods: Forty-nine patients (94 eyes) with RP and 85 normal controls were examined. Aqueous flare was quantified with the noninvasive laser flare-cell meter (FC-1000, Kowa, Japan). Degrees of cystoid macular edema (CME), vitreous pigment dusting (VPD), intraretinal migration of retinal pigment epithelium, and waxy pallor of the optic nerve head were determined semiquantitatively by biomicroscopy. Data were analyzed using the t-test the Mann-Whitney U-test, the chi-squared test and regression analysis by taking into account the dependency of data from two eyes of the same patients. · Results: Aqueous flare (photon counts/ms) was significantly higher in RP (mean 10.11±3.53) than in normals (3.89±0.94; P<0.001). Clinically significant CME was present in 26% of eyes with RP, being significantly more frequent in autosomal dominant RP (11 of 16 eyes, 69%) than in other variants (17%; P<0.005). Multivariate analysis revealed that CME was most strongly associated with flare values (r=0.84, P<0.01), whereas – after adjusting for CME – correlations between aqueous flare and other clinical findings did not reach significance. · Conclusion: RP eyes show increased aqueous flare values, indicating impairment of blood-ocur barriers. This appears to be associated with CME and with autosomal dominant RP.

Concomitant radiochemotherapy with 5-FU and cisplatin for invasive bladder cancer. Acute toxicity and first results.

PurposeTo evaluate acute toxicity and efficacy of simultaneous radiochemotherapy for invasive urothelial cancer of the bladder.Patients and MethodsFrom September 1993 to July 1997,61 patients with invasive bladder cancer were treated with a transurethral resection (TURB) followed by radiochemotherapy (RCT). Twenty-five received a combination of 5-FU and cisplatin. The prescribed doses were 600 mg/m2 5-FU daily as continuous infusion over 5 days each in the 1st and 5th treatment week and 20 mg/m2 cisplatin daily at the same days as a short infusion. The pelvis was irradiated with 54 Gy, the bladder with 59.4 Gy and the paraortic nodes in 7 cases with 45 Gy, respectively. Six to 8 weeks after RCT a second TURB was performed for reasons of restaging.ResultsTwenty out of 25 patients received at least 80% of the prescribed chemotherapy, in 13 cases the full dose could be given. Gastrointestinal toxicity of Grade I and II occurred in 10 cases, 1 patient developed severe diarrhea (Grade VI). After the 1st course of chemotherapy 7 patients had leucoor thrombopenia of Grade III. One patient had a leucopenia of Grade IV. After the 2nd course 4 patients developed Grade III leuko- and thrombopenia, 1 of Grade IV. Two Grade II anemia were found. All more severe toxicities and necessary dose reductions were related to radiation of the paraaortic nodes. No life threatening infections, bleedings or cardiotoxicity was found. Restaging TURBs resulted in 22 complete remissions, 1 patient had a de-novo-carcinoma (Tis) at this time, 2 were non-responders (8%). After a median follow-up of 38 months 20 patients are alive (80%).Conclusions1. If irradiation of paraaortic nodes is necessary, 5-FU should not be applied, because the gastrointestinal toxicity is too extensive. In all other cases side effects are tolerable and can be managed by supportive care. 2. The first results are promising and should be evaluated in a prospective study.ZusammenfassungZielsetzungDie Bestimmung der akuten Toxizität und Evaluation erster Ergebnisse bei der Behandlung des invasiven Harnblasenkarzinoms mit simultaner Radiochemotherapie unter Verwendung von 5-FU und Cisplatin.Patienten and MethodeVon September 1993 bis Juli 1997 wurden insgesamt 61 Patienten mit invasivem Harnblasenkarzinom mit transurethraler Resektion (TURB) und anschließender Radiochemotherapie (RCT) behandelt. 25 Patienten erhielten eine Kombination aus 5-FU und Cisplatin. Die vorgesehenen Dosen waren 600 mg/m2 5-FU täglich als Dauerinfusion über fünf Tage in der ersten und fünften Behandlungswoche und 20 mg/m2 Cisplatin täglich an denselben Tagen als Kurzinfusion. Der pelvine Lymphabfluß wurde bis 54 Gy, die Blase bis 59,4 Gy und die paraaortalen Lymphknoten in insgesamt sieben Fällen bis 45 Gy bestrahlt. Sechs bis acht Wochen nach Beendigung der RCT wurde zum Restaging eine zweite TURB durchgeführt.Ergebnisse20/25 Patienten erhielten mindestens 80% der beabsichtigten Dosis, in 13 Fällen konnte die volle Dosis gegeben werden. Gastrointestinale Toxizität der Grade I und II traten in zehn Fällen auf. Ein Patient entwickelte eine schwere Diarrhö (Grad IV). Nach dem ersten Chemotherapiekurs hatten sieben Patienten eine Leukobzw. Thrombopenie vom Grad III. Ein Patient wies eine Grad-IV-Leukopenie auf. Nach dem zweiten Kurs fanden sich bei vier Patienten Leukooder Thrombopenien vom Grad III, bei einem vom Grad IV. Es gab zwei Grad-II-Anämien. Alle schwereren Toxizitäten und in der Folge notwendigen Dosisreduktionen waren verbunden mit der Bestrahlung der paraaortalen Lymphknoten. Es traten keine lebensbedrohlichen Infektionen, Blutungen oder kardialen Komplikationen auf. Bei der zweiten TURB konnten 22 Vollremissionen nachgewiesen werden, ein Patient hatte ein De-novo-Kar-zinom (Tis). Zwei Patienten waren Nonresponder (8%). Nach einem medianen Follow-up von 38 Monaten leben 20 Patienten (80%).Schlußfolgerungen1. Bei Bestrahlung der paraaortalen Lymphknoten sollte wegen erhöhter Gefahr gastrointestinaler Komplikationen kein 5-FU appliziert werden. In allen anderen Fällen scheint die Toxizität tolerabel. 2. Die ersten Ergebnisse sind vielversprechend und sollten in einer prospektiven Studie weiter evaluiert werden.

Quantification of aqueous melanin granules in primary pigment dispersion syndrome

PURPOSEnAqueous melanin granules are essential in the pathogenesis of pigment dispersion syndrome and pigmentary glaucoma. We quantified aqueous melanin granules with the laser flare-cell meter in patients with pigment dispersion syndrome, assessed the measurement reproducibility, and correlated the numbers with clinical findings.nnnMETHODSnAqueous melanin granules were counted by means of the cell count mode of the laser flare-cell meter (KOWA FC-1000; Kowa, Tokyo, Japan) in 42 eyes of 21 patients with primary pigment dispersion syndrome under three conditions (undilated pupils, dilated pupils, after exercise). The reproducibility of the measurements was determined with the intraclass correlation coefficient. A control group of 40 age- and sex-matched eyes was also examined after pupillary dilation. The results were correlated with biomicroscopic findings in eyes with pigment dispersion syndrome (retrocorneal Krukenberg spindle, iris transillumination, pigmentation of trabecular meshwork).nnnRESULTSnNumerous aqueous melanin granules were detected in eyes with pigment dispersion syndrome (mean, 2.9 +/- 3.7 granules/0.075 mm3) but only small numbers were counted in normal eyes (0.2 +/- 0.3, P < .001). Medical pupil dilation caused an additional increase of aqueous melanin granules in pigment dispersion syndrome (6.3 +/- 5.3, P < .001), but not undilated exercise (climbing stairs) (2.9 +/- 3.7, P > .5). The reproducibility of the measurements was very high (intraclass coefficient >0.92). The number of melanin granules correlated with the degree of Krukenberg spindle (r = .61, P = .004) and with iris transillumination (r = .69, P = .001).nnnCONCLUSIONSnQuantification of aqueous melanin granules yields reproducible results and shows increased numbers in pigment dispersion syndrome, especially after pupillary dilation. Aqueous melanin granule quantification may be useful for evaluating eyes with pigment dispersion syndrome and for assessing treatment effects.

HISTAMINE AND CUTANEOUS NOCICEPTION : HISTAMINE-INDUCED RESPONSES IN PATIENTS WITH ATOPIC ECZEMA, PSORIASIS AND URTICARIA

Having observed altered itch and flare reactions after histamine application in patients with atopic eczema, we tried to determine these reactions in patients with urticaria and psoriasis. We investigated 16 healthy non-atopic subjects, 16 atopics in an eczema-free interval, 16 with acute atopic eczema, 16 with urticaria and 16 with psoriasis. Histamine was iontophoretically applied. The resulting sensations were rated on a visual analogue scale. Flare areas were measured 6 min after stimulation. Itch ratings of urticaria and psoriasis patients did not differ significantly from controls, whereas both atopic groups, regardless of acute or symptom-free state, reported significantly reduced intensity of itching. Flares were significantly diminished in all subjects with acute skin disease (psoriasis, urticaria and atopic eczema), regardless of diagnosis. However, flares were normal in symptom-free atopics and were not significantly different from controls. In conclusion, all acute patients showed a diminished axon-reflex function, possibly due to a downregulation of C-fiber responsiveness to histamine or an increased turnover rate of inflammatory mediators. Both atopic groups reported weaker itching, suggesting altered central nervous processing of itch.

Quantification of aqueous melanin granules, intraocular pressure and glaucomatous damage in primary pigment dispersion syndrome☆

OBJECTIVEnAqueous melanin granules may be accurately quantified with the laser flare-cell meter and have been demonstrated to be increased in primary pigment dispersion syndrome (PDS). It was the aim of this study to correlate intraocular pressure, glaucomatous damage of the optic nerve head, and visual field defects with the number of aqueous melanin granules in PDS.nnnDESIGNnCross-sectional study.nnnPARTICIPANTSnThirty-nine eyes of 21 patients with PDS and either ocular hypertension or pigmentary glaucoma.nnnMAIN OUTCOME MEASURESnA 24-hour intraocular pressure (IOP) profile, automated perimetry (Octopus G1), and analysis of photostereographs and HRT (Heidelberg Retina Tomograph) images of the optic disc were performed. Aqueous melanin granules were quantified using the cell count mode of the laser flare-cell meter (KOWA FC-1000) with undilated and dilated pupils. Granule counts were correlated with maximum and mean IOP, maximum range (amplitude) of IOP, mean defect of automated perimetry (G1-program), and damage to the optic disc was measured with the HRT.nnnRESULTSnThe number of aqueous melanin granules showed a strong correlation with maximum IOP in both undilated (r = 0.72, P < 0.001) and dilated eyes (r = 0.5, P = 0.02). A marginal correlation was found with the IOP range (r = 0.43, P = 0.04) and the mean defect of automated perimetry (r = 0.41, P = 0.06) in undilated eyes. The mean IOP and HRT measurements of the optic disc (area, volume of the neuroretinal rim, third moment in contour) showed no statistically significant correlation with the number of aqueous melanin granules (r < 0.4, P > 0.2).nnnCONCLUSIONSnA larger number of aqueous melanin granules is strongly associated with high IOP and also with visual field loss, providing additional evidence of the relation between aqueous melanin dispersion and development of pigmentary glaucoma. Quantification of aqueous melanin granules with the laser flare-cell meter might be useful for evaluation of treatment effects, including laser iridotomy, in patients with PDS.