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Biomedical subjects

H Schmitz

Publications and source records attributed to H Schmitz.

At least 91 records · Page 5Linked to original sources
PubMed1996

Loss of antibody reactivity directed against the V3 domain of certain human immunodeficiency virus type 1 variants during disease progression.

We have previously shown that in AIDS patients a predominant species of infectious virus can be found which is not neutralized by homologous serum. The presence of the infectious virus was associated with the lack of type-specific antibody directed against the V3 domains of these virions. In contrast to this lack of V3-specific antibody, the other V3 domains of non-infectious virions were well recognized by antibody. To determine whether the lack of a V3-specific antibody response is due to a progressive loss of antibody during human immunodeficiency virus type 1 (HIV-1) infection, we monitored the anti-V3 antibody response in 90 patients over time. Anti-V3 antibodies were monitored by a V3-specific ELISA using 21 different V3 domains as a fusion with glutathione S-transferase (GST-V3) based upon sequences from 11 HIV-1 patient isolates and 10 sequences from an HIV-1 B subtype consensus-like GST-V3 expression library. This strictly heterologous screening showed a loss of V3-specific antibodies in 20 out of the 90 patients tested. To study the in vivo relevance of these findings we analysed V3 antibody loss in two patients. This strictly autologous antibody screening was performed based upon V3 sequences of the patients' cell-free virions. In both patients the loss of a V3-specific antibody could be detected in parallel to a decline of CD4+ T cells. Moreover, the escape of a distinct V3 variant was shown to correlate closely with the loss of the V3-specific antibody.

Amino Acid Sequence↗
PubMed1996

Tumor necrosis factor-alpha induces Cl- and K+ secretion in human distal colon driven by prostaglandin E2.

Increased levels of tumor necrosis factor-alpha (TNF-alpha) have been found in, for example, inflammatory bowel disease (IBD) and human immunodeficiency virus (HIV) infection. To investigate a possible contribution of TNF-alpha to the pathogenesis of diarrhea in these diseases, ion transport of human distal colon was studied in the Ussing chamber in vitro. Serosal addition of TNF-alpha increased short-circuit current (Isc) of partially stripped tissues in a dose-dependent manner. Maximum Isc increase of 1.8 +/- 0.2 mumol.h-1.cm-2 was reached after 60 +/- 9 min at 200 ng/ml TNF-alpha. Bidirectional tracer flux measurements revealed that TNF-alpha induced an increase in 36 Cl serosal-to-mucosal flux, a decrease in 36Cl- mucosal-to-serosal flux, and a slight increase in K+ secretion indicated by an increased secretory 86Rb net flux. In the highly differentiated colonic epithelial cell line HT-29/B6, TNF-alpha had no effect on Isc, suggesting a mediation step located in the subepithelium. This supposition was supported by measurements on totally stripped human tissues, since removal of subepithelial layers by total stripping reduced the TNF-alpha effect by 40%. Experiments with tetrodotoxin (10(-6)M) indicated that the TNF-alpha effect was not mediated by the enteric nervous system. The specific 5-lipoxygenase blocker ICI-230487 (5 x 10(-8)M) also had no effect on TNF-alpha action. In contrast, inhibition of cyclooxygenase by indomethacin (10(-6)M inhibited the effect of TNF-alpha. Radioimmunoassay of prostaglandin E2 (PGE2) in the serosal bathing solution revealed an increase in PGE2 production/release after addition of TNF-alpha, which paralleled the Isc response. We conclude that TNF-alpha changed Cl- and K+ transport toward secretion in human colon. This effect was mediated by PGE2 produced by subepithelial cells. Thus TNF-alpha could be a mediator of diarrhea during intestinal inflammation, e.g., in IBD and HIV infection.

Biological Transport↗
PubMed1996

Rift Valley fever in Nigeria: infections in domestic animals.

Between 1986 and 1989, 2,255 sera collected from six domestic animal species in Nigeria were tested for antibodies to Rift Valley fever (RVF) virus. In addition, a longitudinal study was carried out from July 1987 to December 1988, using ten sentinel flocks on four farms at Ibadan and Ile-Ife, to determine the activity of RVF virus (RVFV). All samples were tested for haemagglutination-inhibiting antibodies and positive sera were further screened, using the plaque reduction neutralisation test. Of 2,255 samples, 259 (11.5%) had haemagglutination-inhibiting and neutralising antibodies, as follows: sheep (18.7%), goats (10.4%), cattle (10.2%), horses (9.8%) and camels (3.3%). The highest prevalence of RVFV antibody was found in the plateau area (18.4%). Animals aged three years or more had a higher prevalence of antibodies to RVFV. Longitudinal studies showed seroconversion to RVFV in ten of the 210 animals which were kept under observation (4.8%). All seroconversions occurred during the wet season. The results of this study indicate that the infection of animals with RVFV is widespread in Nigeria.

Abattoirs↗
PubMed1996

Rift Valley fever in Nigeria: infections in humans.

Between 1985 and 1989, a total of 3,121 human sera collected from different population groups in six ecological zones of Nigeria were tested for the presence of antibodies to Rift Valley fever (RVF) virus by the haemagglutination-inhibition test. All reactive sera were further tested by the plaque reduction neutralisation test and specific RVF immunoglobulin M (IgM) assay. A total of 461 sera (14.8%) demonstrated haemagglutination-inhibiting antibody and 390 of the 461 initially reactive sera (84.6%) revealed neutralising antibodies. A significantly higher exposure to the virus was found among livestock workers and wildlife rangers than in other categories of people tested. The rate of positive reactions was higher in adults of 30 years or more than in younger age groups. Of 461 sera tested for specific RVF IgM, 107 gave positive results (23.2%). The highest prevalence of RVF IgM was found among livestock and forestry workers. In the longitudinal survey, an RVF virus infection rate of 6.7% was demonstrated. The infection rate was significantly higher during the wet season than during the dry season of the same year.

Adolescent↗
PubMed1996

Learning test on expressive phonetic symbolism.

We asked 249 students to learn three different vocabulary lists, each containing 19 word pairs (Indonesian, Suaheli, and one mixed list composed of items from 13 different languages) in three versions: "normal" (factual classification), "reversed" (opposite classification), and "disarranged" (word meaning imputed in a completely different dimension). That those word-pairs with "normal" classification would lead to best learning was not generally confirmed but was corroborated for favourable learning conditions (items at the top of the list, items at the beginning of the questioning, easy to learn items), whereas the effect of phonetic symbolism combined with "normal" presentation proved rather abstruse. We assume that in the latter cases encoding worked rather automatically, and additional information used energy. The encoding process uses so much energy that further information is not useful under unfavourable learning conditions. We found a relation between performance on each mode of presentation and sex. Independent of presentation mode, learning depends on age, sex, membership in a seminar, and subject matter studied. Therefore, we examined the distribution of these in our nine groups (three languages by three versions). Since no statistically relevant differences in distribution arose, our results do not have to be qualified.

Adult↗
PubMed1996

Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea.

In this population-based study, we correlated possible risk factors for rodent-to-human transmission of Lassa virus with markers of Lassa fever in two different regions of the Republic of Guinea (Prefectures of Pita and Gueckedou). Antibody prevalence was 2.6% (6 of 232) in Pita compared with 14.0% (105 of 751) in Gueckedou, with up to 35.0% seropositivity in selected villages of the higher prevalence area. We observed three major risk factors in Gueckedou favoring Lassa virus transmission: rodent infestation was much higher, food was more often stored uncovered and most strikingly, peridomestic rodents were hunted as a protein source by 91.5% of the population as opposed to 0% in Pita. To control for the confounding effects of differences in rodent infestation and food storage, rodent consumption was analyzed as a risk factor for transmission of Lassa virus comparing rodent consumers (RC) and nonconsumers (NC) in Gueckedou only: 14.6% of RC had Lassa virus antibodies versus 7.4% of NC (P = 0.1) and 23.0% of RC reported a history of a febrile illness with hearing loss (the most common sequel of Lassa fever) versus 6.1% of NC (P = 0.003).

Adolescent↗
PubMed1996

Ex-vivo in-vitro inhibition of lipopolysaccharide stimulated tumor necrosis factor-alpha and interleukin-1 beta secretion in human whole blood by extractum urticae dioicae foliorum.

An extract of Urtica dioica folium (IDS 23, Rheuma-Hek), monographed positively for adjuvant therapy of rheumatic diseases and with known effects in partial inhibition of prostaglandin and leukotriene synthesis in vitro, was investigated with respect to effects of the extract on the lipopolysaccharide (LPS) stimulated secretion of proinflammatory cytokines in human whole blood of healthy volunteers. In the assay system used, LPS stimulated human whole blood showed a straight increase of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion reaching maximum concentrations within 24 h following a plateau and slight decrease up to 65 h, respectively. The concentrations of these cytokines was strongly positively correlated with the number of monocytes/macrophages of each volunteer. TNF-alpha and IL-1 beta concentration after LPS stimulation was significantly reduced by simultaneously given IDS 23 in a strictly dose dependent manner. At time 24 h these cytokine concentrations were reduced by 50.8% and 99.7%, respectively, using the highest test IDS 23 assay concentration of 5 mg/ml (p < 0.001). After 65 h the corresponding inhibition was 38.9% and 99.9%, respectively (p < 0.001). On the other hand IDS 23 showed no inhibition but stimulated IL-6 secretion in absence of LPS alone. Simultaneously given LPS and IDS 23 resulted in no further increase. In contrast to described effects on arachidonic acid cascade in vitro, tested Urtica dioica phenol carbon acid derivates and flavonoides such as caffeic malic acid, caffeic acid, chlorogenic acid, quercetin and rutin did not influence LPS stimulated TNF-alpha, IL-1 beta and IL-6 secretion in tested concentrations up to 5 x 10(-5) mol/l. These further findings on the pharmacological mechanism of action of Urticae dioica folia may explain the positive effects of this extract in the treatment of rheumatic diseases.

Adult↗
PubMed1996

[Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid].

Urtica dioica extract is a traditionary used adjuvant therapeutic in rheumatoid arthritis. The antiphlogistic effects of the urtica dioica folia extract IDS 23 (Extractum Urticae dioicae foliorum) and the main phenolic ingredient caffeic malic acid were tested concerning the inhibitory potential on biosynthesis of arachidonic acid metabolites in vitro. The caffeic malic acid was isolated from Urtica folia extract using gel exclusion- and high performance liquid chromatography and identified by mass spectroscopy and nuclear magnetic resonance. Concerning the 5-lipoxygenase products IDS 23 showed a partial inhibitory effect. The isolated phenolic acid inhibited the synthesis of the leukotriene B4 in a concentration dependent manner. The concentration for halfmaximal inhibition (IC50) was 83 microns/ml in the used assay. IDS 23 showed a strong concentration dependent inhibition of the synthesis of cyclooxygenase derived reactions. The IC50 were 92 micrograms/ml for IDS 23 and 38 micrograms/ml for the caffeic malic acid. Calculating the content in IDS 23 the caffeic malic acid is a possible but not the only active ingredient of the plant extract in the tested assay systems. It is demonstrated that the phenolic component showed a different enzymatic target compared with IDS 23. The antiphlogistic effects observed in vitro may give an explanation for the pharmacological and clinical effects of IDS 23 in therapie of rheumatoid diseases.

Animals↗
PubMed1996

Experimental infection of three Nigerian breeds of sheep with the Zinga strain of the Rift Valley Fever virus.

Experimental infection of three indigenous breeds of sheep in Nigeria, namely the West African Dwarf (WAD), Yankasa and Ouda resulted in fatal disease with the Zinga Rift Valley Fever virus. Infected sheep of the three breeds responded by pyrexia within 24 h of infection, that lasted 6 to 7 days, but peaked between day 2 and 4 post-infection. Viraemia coincided with pyrexia and peaked (10(9) PFU/ml) 3 days p.i. in Yankasa and WAD sheep, but with highest titre (10(7.5) PFU/ml) in Ouda sheep. Zinga Rift Valley Fever virus infection of sheep was characterised by hyperactivity, watery and mucoid nasal discharges, projectiles and bloody diarrhoea, external haemorrhage and clinical manifestations of nervous disorders. Viraemia was followed by low level of antibody development in all the infected sheep. Haemotological changes included a sharp fall in the PCV, Hb concentration and total RBC count during the course of the disease. These changes were most severe in the Yankasa, followed by WAD and Ouda breeds. There were thrombocytopaenia, prolongation of prothrombin and clotting times in all the infected sheep. There was also progressive leucopaenia associated with lymphopaenia. The total protein and albumin levels were depressed, but the globulin level rose from day 5 p.i. The changes in the serum biochemical constituents included sharp and progressive increase in the level of alanine aminotransferase and aspartate aminotransferase. The sodium level decreased gradually while that of potassium was initially stable but later increased until the infected animals died. There was a significant increase in the level of blood urea nitrogen from day 3 p.i. that continued until the infected animals died. Gross and microscopic examinations of the carcasses of the infected sheep showed significant lesions in many organs, including disseminated intravascular coagulation.

Animals↗
PubMed1996

[Cytokine secretion in whole blood of healthy subjects following oral administration of Urtica dioica L. plant extract].

Twenty healthy volunteers ingested for 21 days 2 capsules b.i.d. of an IDS 23/1 containing nettle leaf extract (Rheuma-Hek). Before and after 7 and 21 days the basal and the lipopolysaccharide (LPS) stimulated tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) concentrations were measured ex vivo. In vitro the effects of IDS 23/1 on the release of these cytokines were determined. Additionally basal interleukin-4 (IL-4) and interleukin-10 (IL-10) levels were recorded. Orally taken the test drug has ex vivo no effect on basal levels of TNF-alpha, IL-1 beta, IL-4, IL-6 or IL-10 which were always below detection limits. After 7 and 21 days ingestion ex vivo a decrease of LPS stimulated TNF-alpha release of 14.6 and 24.0%, respectively, was observed. IL-1 beta was reduced for 19.2 and 39.3%. In vitro IDS 23/1 added to whole blood resulted in an exceeded inhibition of LPS stimulated TNF-alpha and IL-1 beta secretion which correlated with the duration of the drug ingestion. Using the highest tested IDS 23/1 concentration the inhibition reached 50.5 (day 0) to 79.5% (day 21) for TNF-alpha and 90.0 (day 0) to 99.2% (day 21) for IL-1 beta, respectively. IDS 23/1 induced a pronounced release of IL-6 in absence of LPS only in vitro. The detected IL-6 concentrations were comparable to those after LPS stimulation, additive effects could not be observed. The absence of detectable IL-6 concentrations in whole blood ex vivo after oral ingestion of the tested drug as well as the differences in the inhibition patterns for TNF-alpha and IL-1 beta ex vivo and ex vivo in vitro suggest that the extract contains different pharmacological effective compounds with varying bioavailabilities.

Adult↗
PubMed1996

[The in vitro induction of monocyte chemotactic protein-1 and interleukin-8 in whole human blood by low molecular weight thymus peptides].

Thymic peptides show immunoreconstitutive und tumor suppressive effects. They are used in oncology to improve the immunological status of patients. Chemokines are able to activate immune cells and inhibit tumor growth. In this study it was proved whether low molecular thymic peptides are able to increase the secretion of the chemokines monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), macrophage inflammatory protein-1 alpha (MIP-1 alpha) and macrophage inflammatory protein-1 beta (MIP-1 beta) as well as the cytokine tumor necrosis factor-alpha (TNF-alpha) which is not related to chemokines using cell cultures of human whole blood. The thymic peptides induced a significant (p < 0.05) elevated secretion of MCP-1 and IL-8 whereas for MIP-1 alpha, MIP-1 beta and TNF-alpha no significant chances were seen. MCP-1 and IL-8 showed divergent dose-dependent effects and a different time kinetic of their secretion. The MCP-1 concentration correlated positively with the count of monocytes in whole blood of the volunteers while the IL-8 concentration in dependence with the incubation time correlated positively with the count of granulocytes or monocytes of the volunteers. The results indicate an activation of monocytes and/or granulocytes by low molecular thymic peptides followed by selective elevated secretion of MCP-1 and IL-8.

Adult↗
PubMed1995

Investigations on autologous T-cells for adoptive immunotherapy of AIDS.

We report on the preclinical results of an immunotherapeutic approach of AIDS mediated by ex vivo propagated CD4+ and CD8+ T-cells. A mean yield of 6.23 x 10(9) lymphocytes, containing 1.82 x 10(9) CD4+, 3.23 x 10(9) CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral blood progenitor cells (PBPC) were be obtained by continuous flow cytapheresis (CFC) in 15 asymptomatic HIV infected patients (CD4-count > 350/mm3). The CD4/CD8 ratio (mean: 0.53, SD: +/- 0.15) in the cell concentrates reflected the distribution of the circulating lymphocyte subsets in vivo. Absolute lymphocyte counts decreased at a mean of 404/microliter (25%) immediately after CFC but were replaced from the extravascular pool within one hour. Neither the CD4/CD8 ratio nor p24-antigen and neopterin levels did change significantly after cell separation. No alteration of the number of proviral DNA copies (1/10(3)-1/10(6)) could be detected in peripheral T-helper cells by semiquantitative PCR after lymphapheresis. Cells were cryopreserved in liquid nitrogen without substantial loss of viability or function. Ex vivo propagation of T-cells in a strictly autologous manner in the presence of PHA + IL-2 for 14d resulted in a 50-fold expansion rate (140-fold in healthy controls, p < 0.001). Viral replication could be controlled but not completely eliminated by cocultivation with autologous CD8+ T-lymphocytes as measured by limiting dilution nested PCR (NPCR). The expanded cells showed the typical phenotype of highly activated memory type T-lymphocytes (CD3+ CD45RO+ CD25+ HLA-DR+). The distribution of CD4+ and CD8+ T-cells did not reveal significant changes before and after culture indicating that both subsets were equally expanded. Functionally important membrane or intracellular epitopes which were found to be decreased in HIV infected subjects (CD7, CD55, CD59) before culture were reconstituted after ex vivo propagation of T-cells. The functional importance of the up-regulation of complement regulating epitopes (CD55, CD59) after culture could be proven by a significant inhibition of cytolysis of T-cells in the presence of autologous complement. The majority (75%) of expanded CD8+ T-cells stained positive with mAb TIA-1 which is directed to intracellular granules within cytotoxic T-cells. Furthermore, programmed cell death of expanded T-cells could be prevented by cocultivation with fibroblasts which are believed to secrete a cytokine pattern preventing activated T-cells from apoptosis after withdrawal of IL-2 and other stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

Follicular dendritic cells productively infected with immunodeficiency viruses transmit infection to T cells.

Lymphoid organs have been proposed to function as the major reservoir for the human immunodeficiency virus type 1 (HIV-1). Within lymphatic tissues germinal centers represent foci of rapidly proliferating B cells governed by the interaction between B and T cells and follicular dendritic cells (FDC). Accumulating evidence suggests an important role of FDC in the pathophysiology of the acquired immunodeficiency syndrome. Direct proof for the infectibility of FDC with HIV-1 has been lacking until recently when we were able to demonstrate a CD4-independent infection of FDC in vitro. Here we report that in vitro HIV-1-infected human FDC do not only contain proviral DNA, but also produce the virus, and transmit the infection to T cells. Furthermore, electron microscopical studies on ex vivo isolated FDC from simian immunodeficiency virus (SIV)-infected rhesus monkeys revealed typical virus budding. In addition, FDC from SIV-infected rhesus monkeys transmitted the infection to T cells in vitro. Due to this central role within the immune response FDC may serve as preferential targets for HIV both by trapping of virions on their surfaces and by productive infection. During disease FDC become productively infected and may, thus, be regarded as crucial elements in viral dissemination.

Animals↗
PubMed1995

Determination of anti GAD65 autoantibodies with an ELISA before and after standardization with the new international reference serum.

The serum of a stiff-man syndrome patient was declared international GAD reference standard at the "1st GAD Antibody Workshop" held at the "12th International Immunology and Diabetes Workshop" in Orlando, Florida, USA 1993. A comparative study was performed with 123 diabetic and non-diabetic patients to evaluate whether standardization of this reference serum had changed the properties of a commercially available ELISA assay. All samples classified positive with the old test were confirmed with the new assay. Four additional samples with high "normal" values became positive with the new test. One of them was a control person having a family history of diabetes and genetic loci DR4/DR11. These findings might implicate a higher risk for the development of IDDM. The new standardization and adaptation of the ELISA seems to have influenced the sensitivity of the test positively.

Autoantibodies↗
PubMed1995

Enzyme- and mineralocorticoid receptor-controlled electrogenic Na+ absorption in human rectum in vitro.

In vivo electrogenic Na+ absorption (JeNa) in the human rectum is controlled by acute variation of aldosterone in nanomolar concentration range. In this study we report both the induction of JeNa in human rectum epithelium by nanomolar aldosterone added in vitro and the enzymatic control of glucocorticoid action on JeNa. JeNa was measured as amiloride-sensitive short-circuit current 8 h after addition of the respective steroid. Aldosterone (10 nM) caused JeNa of 5.7 +/- 1.4 mumol.h-1.cm-2. Cortisol in the same concentration did not induce significant JeNa. Because cortisol is readily inactivated by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the true mineralocorticoid activity of cortisol was evaluated after inhibition of 11 beta-HSD by carbenoxolone. Carbenoxolone alone did not exhibit mineralocorticoid activity. If cortisol (10 nM) was given together with carbenoxolone (1 microM), the resulting JeNa (4.5 +/- 0.4 mumol.h-1.cm-2) was not significantly different from that after 10 nM aldosterone, indicating equal intrinsic mineralocorticoid activity of cortisol and aldosterone. The same mechanisms were found in rat late distal colon. Kinetic data of carbenoxolone at 10 nM cortisol resulted in a Michaelis constant of 0.3 microMs, maximal absorption of 8.4 mumol.h-1.cm-2, and a Hill coefficient of 1.8. The effects of carbenoxolone and glycyrrhetinic acid did not differ. We conclude that JeNa is under complete control of mineralocorticoid action. "Spontaneous" JeNa in the beginning of the in vitro period can be explained by elevated steroid levels before tissue removal.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Antibody-dependent complement-mediated cytotoxicity in sera from patients with HIV-1 infection is controlled by CD55 and CD59.

Various immune mechanisms have been reported to contribute to the progressive destruction of Th cells in HIV-1-infected patients. Among these, complement mediated lysis of infected cells has been suggested. An increased sensitivity of lymphocytes from HIV-1-infected patients to lysis by monoclonal antibodies directed to MHC class I antigen and complement has been directly correlated with a decreased expression of the decay accelerating factor (CD55). It also has been reported that the expression of the membrane inhibitor of reactive lysis (CD59) is decreased during HIV-1 infection. We examined the effect of antibodies in the serum of HIV-1-positive individuals and normal human serum (NHS) as source of complement on several HIV-1-infected cell lines differing in their expression of CD55 and CD59. When HIV-1-infected target cells without membrane expression of CD55 and CD59 were used, a highly significant cytotoxic effect was observed in the presence of heat inactivated anti-HIV-1-positive sera and NHS, while heat-inactivated anti-HIV-1-negative sera and NHS were unable to induce cytolysis. Similar results were obtained using purified IgG isolated from HIV-1-positive sera and either NHS or guinea pig serum as source of complement. Lysis of HIV-1-infected cells correlated with expression of viral antigens on the cell surface. HIV-1-infected CD55 and CD59 positive target cells showed specific lysis, when the function of these molecules was abrogated by blocking antibodies to CD55 and CD59. The finding of anti-HIV-1-specific cytotoxic antibodies in sera from HIV-1-infected patients should be considered in the pathogenesis of the HIV-1-infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Splenopeptides for climacteric complaints. Comparison of ovarian stimulation with transdermal estradiol substitution].

256 women aged 45 to 60 years with climacteric complaints participated in an open randomized clinical study comparing spleno-peptides (SPS 1187, Solcosplen) with transdermal estrogen (CAS 50-28-2, E2) substitution (4 mg) in respect of efficacy and tolerability. The primary criterion, defined as the Kupperman Index, and the safety parameter of the drugs were estimated prior to and after 1, 4 and 8 weeks of therapy. In the pre-, peri- and early postmenopause the results of treatment with the spleno-peptides were comparable to those with transdermal E2 substitution (4 mg). Pretreatment with estrogens impaired the results of treatment significantly. Although the menopausal status (in most cases < 3 years) did not influence the results essentially, the efficacy of SPS 1187 is expected to decrease 2 to 3 years postmenopause. Therefore SPS 1187 should be used in pre-, peri- and early postmenopause only. The tolerance of SPS 1187 was found to be significantly better than that of the E2 patch. With respect to the claimed indication, i.e. climacteric complaints in the pre-, peri- and early postmenopause, SPS 1187 having an equivalent efficacy compared to that of the E2 patch shows a better tolerability (total collectives) and better benefit/risk ratio.

Administration, Cutaneous↗