CMV sinusitis as the initial manifestation of AIDS.

Cytomegalovirus (CMV) disease is a typical late-stage complication of AIDS. Only six cases of CMV sinusitis have been reported in the literature. This is the first case of CMV sinusitis leading to the diagnosis of HIV and CMV retinitis. Diseases of the sinonasal tract may represent an initial manifestation of HIV or AIDS.

Clinical efficacy of protease inhibitor based antiretroviral combination therapy--a prospective cohort study.

OBJECTIVES: To analyze virological and clinical efficacy of protease inhibitor based antiretroviral regimens in a cohort of unselected HIV-infected patients. METHODS: Prospective analysis of all HIV-infected patients started on protease inhibitor therapy until August 31, 1997 in two outpatient clinics. Partial viral suppression was defined as reduction of HIV-RNA at least 1log(10) below baseline and complete viral suppression as reduction below the limit of detection. Risk factors for clinical and virological failure were analyzed by a Cox proportional hazard model. RESULTS: 387 patients (median observation time 381 days) were analyzed. In 312 patients (81%) partial and in 265 (68%) complete viral suppression was observed. Secondary failure occurred in 75 patients and could be reversed in 11/75. The probability of virological failure at one year was 51% for complete and 47% for partial suppression. CD4-cells increased by a median of 101/microl overall and 39/microl for patients without partial virologic suppression. 57 clinical events or deaths occurred in 44 pts. Risk factors for virological failure were AIDS at baseline (RR 1.6) and use of Saquinavir vs. Indinavir or Ritonavir (RR 1.7), for clinical failure AIDS at baseline (RR 4. 9), CD4-cell count (0.74 for increase of 50/microl), degree of viral suppression (RR 0.1 for complete suppression) and PI used (Saquinavir vs. Indinavir or Ritonavir, RR 2.7). CONCLUSIONS: Virological failure of PI based combination therapy is common and associated with advanced HIV-infection. Clinical failure is associated with advanced HIV-infection and failure to suppress viral replication.

Salvage therapy with regimens containing ritonavir and saquinavir in extensively pretreated HIV-infected patients.

OBJECTIVE: To evaluate the efficacy and toxicity of salvage regimens containing ritonavir and saquinavir in patients failing highly active antiretroviral therapy (HAART), and to correlate outcome with plasma concentrations of protease inhibitors. DESIGN: Prospective, non-randomized interventional study. SUBJECTS AND METHODS: Thirty extensively pretreated HIV-infected patients with virological failure under HAART were treated with ritonavir (400 mg twice daily) and saquinavir (600 mg twice daily) and at least one reverse transcriptase inhibitor. HIV-RNA, CD4 cell counts and plasma concentrations of protease inhibitors were determined, and patients were monitored for toxicity at monthly intervals. RESULTS: Six patients showed complete virological success (HIV-RNA <200 copies/ml at week 12) which was sustained for a median follow-up of 6.3 months. Partial virological response (decrease of HIV-RNA of >1 log10 at week 12) was achieved by a further three patients. Patients with a virological response had significantly higher CD4 cell increases than patients without virological response (mean increase at week 12: 66x10(6) cells/l versus 6x10(6) cells/l; P = 0.01). No clinical events were observed during 6 months of follow-up. Neither the use of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nor the number of newly introduced drugs influenced the virological response. Plasma concentrations of protease inhibitors did not statistically differ between patients with and without success. Toxicity included gastrointestinal disturbances, lipid abnormalities and liver dysfunction. CONCLUSIONS: In extensively pretreated patients, salvage regimens containing ritonavir and saquinavir had only limited and short-term anti-HIV activity and were associated with substantial toxicity. Plasma concentrations of saquinavir were not predictive for virological response.

[Battle of odors: significance of pheromones for human reproduction]. / Der Krieg der Düfte: Bedeutung der Pheromone für die menschliche Reproduktion.

The significance of odours for human reproduction is partially neglected by medical sciences. Nevertheless, it can be shown that male pheromones (androstenol/androstenone) from male sweat have a direct impact on female menstrual cycles and ovulation. Furthermore, female pheromones (copulins), which are present in vaginal secretions, influence male perception of females and may induce hormonal changes in males. The mutual pheromonal influence between the sexes is discussed as a result of sex-specific reproductive interests which are a consequence of evolutionary constraints.

[Multivariate analysis for the understanding of typical diabetic hemostasis criteria. 1: Plasma markers]. / Multivarianzanalyse zur Erfassung diabetestypischer Hämostasekriterien. Teil 1: Plasmatische Merkmale.

In 309 patients investigations were made into the functions of blood coagulation with special consideration of numerous metabolic criteria. They referred to 111 healthy control persons and 198 patients with diabetes mellitus, 67 of them being of type I and 131 of type II. From a variety of metabolic characteristics and haemostasis optimal criteria were determined by means of the statistical method of multivariance analysis, which enables a distinction to be made between diabetics of type I, type II and healthy persons. Among those 13 characteristics detected as optimal amount there were thrombin time, thrombin coagulase time as parameter of haemostasis both before and after venous congestion, reptilase time prior to venous congestion and fibrinogen concentration after it. Thus, these coagulation factors indicate a different behaviour in both types of diabetes and in healthy control persons.

[Multivariate analysis for the understanding of typical diabetic hemostasis criteria. 2. Prevalent thrombocytic markers]. / Multivarianzanalyse zur Erfassung diabetestypischer Hämostasekriterien. Teil 2: Vorwiegend trombozytäre Merkmale.

Various thrombocyte functions and metabolic criteria were investigated in 309 test persons, among them 198 Patients affected with diabetes mellitus, 67 of type I and 131 of type II as well as 111 healthy control persons. From the variety of these factors an optimal amount was determined by means of the statistical method of multivariance analysis separating both types of diabetes and healthy control persons. In addition to haemoglobin A1 concentration, thrombocyte parameters have been found together with the degree of capillary fragility, adrenalin-induced aggregation, platelet aggregation test and clot retraction, which allow individuals to be assigned diagnostically to various groups of test persons. Thus, thrombocyte functions found in both types of diabetes and normal persons exhibit differences which may contribute to a diagnostic classification.

[Multivariate analysis for the understanding of typical diabetic hemostasis criteria. 3. Determination of a typical retinopathy parameter-constellation]. / Multivarianzanalyse zur Erfassung diabetestypischer Hämostasekriterien. Teil 3: Ermittlung einer retinopathietypischen Parameter-Konstellation.

Features of metabolism and haemostasis which are different in diabetics of both types in comparison with normal subjects were covered by the statistical method of multivariance analysis depending on the severity of diabetic retinopathy. In 29 diabetics without retinopathy, 46 patients with stage I or II, and 36 patients with stage III the following parameters could be found as optimal criteria for characterizing the extent of vascular changes: blood sugar concentration, concentration of sialic acid and HDL cholesterol in the serum, serum protein, sialic acid per protein volume, total cholesterol in the serum and capillary fragility and number of large spreading forms of platelets features of hemostasis. Thus, diabetic retinopathy is characterized by a wide spectrum of different features containing the parameters of hemostasis. Thrombocytic vascular interactions are characterized by platelet spreading and capillary fragility which are significant for the development of diabetic retinopathy.

[Platelet spreading in diabetes mellitus]. / Untersuchungen der Thrombozytenausbreitung bei Diabetes mellitus.

In 162 test persons divided into healthy control persons and diabetics of type I and type II the thrombocyte spreading was investigated according to the method of Breddin. Age, sex, degree of seriousness of retinopathy, duration of diseases, present level of blood sugar and HbA1 concentration were taken into account. Spread thrombocyte forms were increasingly found in old age, in diabetics of both types and a close relation to the extent of retinopathy was evident. As diabetic retinopathy became evident and with growing degree of seriousness, spread forms of thrombocytes were increasingly found, so that the increased spreading capacity may be interpreted as a disturbed metabolic and blood vessel situation in diabetes mellitus.

[Clinical interpretation of retinal circulatory measurements. I. Technical measurement possibilities and clinical interpretation aid]. / Klinische Interpretation retinaler Durchblutungsmessungen. I. Messtechnische Möglichkeiten und klinische Interpretationshilfe.

The present possibilities to measure blood flow and other magnitudes of retinal microcirculation in vivo are discussed. On this basis, a simple model designed for retinal microcirculation is presented as a tool for the clinical interpretation of measuring results. Based on the experience of over 200 measurements of retinal microcirculation magnitudes, subsequent reports give a clinical interpretation of measuring results, utilizing the measuring models presented. Thus, it is intended to demonstrate the actual clinical significance of such measurements.

[ Fibrinolysis in diabetes mellitus]. / Untersuchungen zur Fibrinolyse bei Diabetes mellitus.

In 198 diabetic patients of type I and type II and in 111 healthy persons of a control group the activity of fibrinolysis was investigated before and after a venous occlusion test of ten minutes. Spontaneous fibrinolysis was significantly diminished in diabetics of both types in comparison to the control group. A relationship to the degree of seriousness of retinopathy could not be identified in type I. The activity of fibrinolysis decreased in all test persons in old age. In diabetics patients of type II as well as in that age group being more than 56 years old there were smaller activities of fibrinolysis at higher stages of retinopathy. A negative linear correlation of this spontaneous activity of fibrinolysis could be found for the duration of the disease as well as for age. Different forms of diabetic therapy and the sex allowed no influence of the activity of fibrinolysis to be recognized. An increase of the activity of fibrinolysis after congestion could be established in diabetics as well as in the control group. After venous congestion the fibrinolytic activity showed no differences any longer in diabetics and in the control group, with age, duration of the disease and form of therapy being taken into consideration. Before and after venous congestion a negative linear correlation could be revealed between the activity of fibrinolysis and the height of blood sugar level. Therefore, the real blood sugar concentration should be taken into account in evaluating the fibrinolytic activity.

Measurements of retinal microcirculation in retinal vessel occlusion before and after treatment.

Blood flow, arterial velocity, and vascular diameter were measured in patients with retinal vessel occlusion before and after treatment, especially after light coagulation. The mean values in the patient group showed significantly reduced blood flow and velocity compared to the normal group. The mean group difference before and after therapy revealed that while there is an increase in blood flow after treatment, the normal value is not reached. Individual patient values indicated both increased and decreased blood flow and velocity after treatment as compared with the values before therapy. There are various stages in microcirculatory disease and the microcirculation also behaves differently after treatment, which could be observed by measurement in vivo of the physiological flow parameters.

[Clinical interpretation of retinal circulatory measurements. IV. Photocoagulation in diabetic retinopathy and venous occlusive diseases]. / Klinische Interpretation retinaler Durchblutungsmessungen. IV. Fotokoagulation bei diabetischer Retinopathie und venösen Verschlusserkrankungen.

Based on the pathomechanism of diabetic retinopathy, the effect of photocoagulation on retinal microcirculation as assessed by measurements of retinal microcirculation magnitudes is discussed. The clinico-experimental results support the opinion that an essential effect of photocoagulation is due to an improvement in the flow conditions of the noncoagulated central retinal area with regard to metabolic exchange and stasis situation by the coagulation-induced occlusion of peripheral capillary areas. Further clinico-experimental measurements of retinal microcirculation magnitudes for the assessment of the behavior of microcirculation after photocoagulation in venous occlusive diseases of the retina are presented. It is shown that retinal microcirculation immediately after photocoagulation reacts by transitory instationary flow conditions; in this period it is quite possible that an additional blood flow reduction over several days will occur. In particular, the effect of photocoagulation in venous occlusive diseases with narrow arterial vessels is discussed. It is emphasized that with regard to the therapeutic effect of photocoagulation as well as to the discussion of pathomechanisms, apart from blood flow, the differentiated behavior of single retinal vascular areas, such as arteries, arterioles, capillaries, venules and veins, requires more attention. Particularly with this in mind, substantial improvements in differential diagnosis and treatment of retinal circulatory disturbances may be expected from measurements of retinal circulation magnitudes.

[Clinical interpretation of retinal circulatory measurements. II. Blood flow]. / Klinische Interpretation retinaler Durchblutungsmessungen. II. Blutfluss.

Beginning as early as the mid-4th decade of life, an age-dependent reduction in retinal blood flow has to be considered an essential risk factor for disorders of retinal microcirculation. Blood flow measurements are a valuable, but not the sole criterion of microcirculatory disorders. While in retinal occlusive diseases blood flow is a valuable indicator of the severity of microcirculatory disorders, the latter can also occur in the presence of normal and elevated blood flow values. Shifts of the metabolic activity of the retina and changes in the metabolic activity of the retina and changes in the metabolic conditions have to be taken into account when a clinical interpretation is given.

[Clinical interpretation of retinal circulatory measurements. III. Blood flow velocity and vessel diameter in normal persons and in patients with venous occlusive diseases]. / Klinische Interpretation retinaler Durchblutungsmessungen. III. Blutgeschwindigkeit und Gefässdurchmesser bei Normalpersonen und bei Patienten mit venösen Verschlusskrankheiten.

Based on results from measurements of arterial blood velocity, arterial and venous diameters of major segmental retinal vessels in normal persons and in patients with venous occlusive diseases and in continuation of the two preceding parts of this series of articles, further possibilities for the differential diagnosis of measurements of retinal microcirculation magnitudes are discussed. Whereas the measurement of blood velocity is an important criterion for the assessment of the stasis conditions and the arterial involvement in an occlusive disease, the diameters of the vessels offer essential suggestions to local regulative processes. In this connection, a dependence on pH of the contraction state of the smooth vascular musculature detected in porcine coronary arteries is presented. By its transmission to the arterial retinal vessels, it is possible to unequivocally clarify the local regulative and pathological behavior of arterial retinal vessels in terms of flow physiology.

[Behavior of fibrinogen in diabetic patients in comparison with objective vascular measurements in the ocular fundus]. / Fibrinogenverhalten bei Zuckerkranken im Vergleich mit objektiven Gefässmessungen am Augenhintergrund.

Objective measurements of vessels were performed in vivo in 10 patients affected with diabetes mellitus, the fibrinogen concentrations in the venous blood being determined simultaneously. Whereas the ensured correlations with fibrinogen concentration could be recognized from the diameter of arteries and veins and from the flow velocity, a linear correlation could be found to exist between the fibrinogen level and the volume flowing through a retinal artery. These findings prove that the very existence of a hyperfibrinogen anemia does not justify the assumption of the blood volume flow being decreased. In patients with diabetes mellitus the enhanced volume flowing through retinal arteries is rather connected with an increased fibrinogen level.

Reflectance spectrophotometry in the human ocular fundus.

Spectrometric investigations were carried out in normal human maculae and optic discs and in those with pathological findings (50 eyes in total). Reflection spectra were measured by illumination of various points of the fundus, using a highly sensitive photon-counting technique. It is necessary to distinguish diffusely reflected light from regularly reflected light, as we found marked differences in the spectra of diffusely reflected light between normal eyes and those with pathological findings. In optic atrophy cases, the intensity of light reflected from the optic disc (510-600 nm) was remarkably higher than normal. In findings of proliferative diabetic retinopathy, the reflected light intensity showed a steeper slope, beginning at 580 nm, in comparison with normal findings.

Measurement of flow-physiologic parameters of retinal blood circulation in type 1 and 2 diabetics before and after photocoagulation.

In seven diabetics of type 1 and seven of type 2, the flow physiologic magnitudes were measured in a retinal quadrant before and after photocoagulation. The segmental blood flow, the arterial flow velocity, and the diameters of artery and vein are smaller after photocoagulation than before. Investigations into the time course of the flow-physiologic parameters following photocoagulation show that the flow-physiologic values are stationary about 2 weeks after photocoagulation.

[Evaluation of fluorescein angiograms using the multitemporal technic]. / Auswertung von Fluoreszenzangiogrammen mit Hilfe der Multitemporaltechnik.

If there are differences in the density of black-and-white photographs of the fundus oculi taken at different times, they may be transformed into color differences by means of the multitemporal technique. A multitemporal picture is obtained by additive color mixing of black-and-white photographs transilluminated at the same time with one primary color each. Since, in a serial angiogram, the interrelation between the film density and the passage of the fluorescein concentration in the fundus oculi is known, it is possible to draw conclusions from the multitemporal picture regarding phase differences and changes in the curve shape of the fluorescein concentration.

[Teaching and learning in ophthalmology]. / Lehren und Lernen in der Augenheilkunde.

The acoustic era is being transformed ever more rapidly into the audiovisual era. This development is also having an increasing effect on training methods in medicine. In ophthalmological training especially, "teaching to see" plays a decisive role. Every newcomer to the specialty first has to learn how to "see" correctly, to judge three-dimensional relationships. The dynamic processes in the retinal and choroidal circulation can easily be demonstrated to students and young ophthalmologists by fluorescein angiography and TV fundus photography. This study illustrates the importance of space and time and shows how they can be integrated into ophthalmological training.