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.

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.

[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.

[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.

[Microcirculation disturbances at the onset of diabetic retinopathy. New therapeutic procedures? (author's transl)]. / Mikrozirkulationsstörungen bei beginnender diabetischer Retinopathie. Neue Wege in der Therapie?

The generalized capillary dilatation demonstrable at the early stage of diabetic retinopathy can now, on the basis of recent results in biochemistry, be assessed as an attempt at autoregulation in relative hypoxia of tissue. In patients with diabetic retinopathy, an elevated HbA1c concentration in the blood can be observed. The DPG level, however, is reduced. Both facts cause reduced oxygen transmission from blood to tissue. Rheologic changes such as augmented aggregation of erythrocytes, decreased deformability of erythrocytes and increased viscosity of blood and plasma finally lead to disturbances of microcirculation in the terminal vascular system. From these latest findings concerning the development of microcirculation disorders in diabetic retinopathy possible consequences for new therapeutic procedures can be derived.

[How effective is photocoagulation? (author's transl)]. / Was vermag die Fotokoagulation und was bewirkt sie?

Six hypotheses relating to the mode of action of photocoagulation, based on comprehensive data gathered from the literature, are put forward and discussed. Particular emphasis is given to the question of achieving a lasting break through of the barrier represented by Bruch's membrane and the pigment epithelium and thus to the altered diffusion conditions between the choriocapillaries and the retina. In addition a peculiar marginal fluorescence in fluorescein serial angiograms of old light coagulation foci is described and compared with data from the literature. The authors put forward a new hypothesis concerning the mode of action of light coagulation; they believe that particularly in the marginal areas affected by photocoagulation, completely new conditions are created for the metabolic exchange between choroid and retina, including the formation of anastomoses and shunts.

[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.

[Principal possibilities and limitations of fluorescent angiographic procedures for the measurement of the flow-physical magnitudes of the retinal circulatory system (author's transl)]. / Möglichkeiten und Grenzen fluoreszenzangiographischer Verfahren zur Messung strömungsphysikalisch definierter Grössen der Netzhautdurchblutung.

Flow-physical magnitudes are presented that describe the retinal circulatory system. The principal possibilities and limitations of fluorescent angiographic procedures for the measurement of these magnitudes are discussed. On this basis, we compare fluorescentophthalmoscopic measurements of time, serial angiography, and cinematography with densitometric evaluation of the negatives, integral fluorophotometry, 'two point' photometry, and the application of television with evaluation of the video signal.

[Experiences with the 32P test in tumor diagnosis]. / Erfahrungen mit dem 32P-Test bei der Tumordiagnostik.

A report on results of 186 32P tests is given. Radiation increases of more than 30%, compared with tumor-free areas, were considered as positive. 95 eyes were histologically examined. The 32P test gave 90 correct positive answers and 1 correct negative answer. Faulty positive results were found in 2 cases; faulty negative results were also found in 2 cases. This means that the diagnosis was correct in 95%. The literature is discussed concerning reliability and methods. The dangers of the use of 32P are stressed, and the development of noninvasive nuclear-medical diagnostic methods is suggested.

[ 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.

[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.

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.

[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.

[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.