Biomedical subjects

K Heim

Publications and source records attributed to K Heim.

At least 19 recordsLinked to original sources

PubMed2000

Spontaneous regression of CIN and delayed-type hypersensitivity to HPV-16 oncoprotein E7.

We investigated delayed-type hypersensitivity to human papillomavirus (HPV) in women with cervical dysplasia or cancer. Women were challenged by skin tests with synthetic HPV-16 E7 oncoprotein peptides. 11 women were regressors (cleared disease without treatment) and 37 were progressors (required surgery). Antibodies to early antigens (markers for progression) were detectable in a higher proportion of cancer patients than all other patients, particularly progressors with cervical intraepithelial neoplasia (CIN). By contrast, cellular immunity to HPV-16 E7, measured by skin test, was significantly (p=0.0001) associated with clinical and cytological resolution of HPV-induced CIN, indicating that E7-specific T-helper cells have a role in control of HPV.

Female↗

PubMed2000

Specific serum IgG, IgM and IgA antibodies to human papillomavirus types 6, 11, 16, 18 and 31 virus-like particles in human immunodeficiency virus-seropositive women.

To evaluate the humoral immune response to human papillomavirus (HPV) in women infected with human immunodeficiency virus (HIV), serum samples of 83 HIV-positive individuals were analysed by ELISA for specific antibodies of the isotypes IgG, IgA and IgM recognizing HPV-6, -11, -16, -18 and -31 L1 virus-like particles (VLPs). Papillomavirus-related lesions were present in 30 of 83 HIV-positive women. Twenty-one women (25%) presented with high-/intermediate-grade anogenital squamous intraepithelial lesions. PCR analysis and sequencing for HPV typing was done from biopsy specimens of 18 women; PCR-positive results were obtained in 90% of cases. In addition, HPV DNA hybrid capture assays were performed from cervical swabs of 58 HIV-positive women, 53% of whom had a positive result for high-risk HPV. Overall, positive IgG reactivity to HPV-6/-11 and HPV-16/-18/-31 was seen in 19%/31% and 49%/30%/24% of HIV-positive women, respectively. HPV-seropositivity was even higher than in 48 HIV-negative cervical intraepithelial neoplasia/cancer patients with percentages as follows: 8%/2% and 31%/15%/15%. This difference was significant for HPV-16 (P=0.046). IgA responses were comparable to IgG. IgM responses were low. The extraordinarily high rate of antibodies to the capsid protein L1 of high-risk HPVs (HPV-16, -18 and/or -31) in 58% of HIV-positive women compared to 19% (P=0.00001) of 102 healthy HIV-negative control women suggests a high lifetime cumulative exposure to HPV and increased expression of capsid proteins due to cellular immunodeficiency in HIV-infected women.

Adult↗

PubMed2000

Multiple blue nevi of the vagina. A case report.

BACKGROUND: Melanotic lesions of the vagina are very rare; clinically, most are suspected to be malignant melanomas. Occasional benign cases, however, require differential diagnostic consideration. We report a case of multiple (benign) blue nevi of the vagina. CASE: A 51-year-old woman presented with bluish black macules irregularly distributed throughout the vagina. Biopsies revealed pigmented cells in the dermis that proved to be melanocytes. The patient received no therapy. The lesions remained unchanged in the follow-up period. CONCLUSION: Multiple blue nevi could be a differential diagnosis for malignant melanoma of the vagina. Our patient showed no malignant transformation over a 29-year period. Therapy for blue nevi in the vagina does not require complete excision.

Diagnosis, Differential↗

PubMed1999

Early postnatal depressive mood: associations with obstetric and psychosocial factors.

The central purpose of this investigation was to detect incidence and influencing factors on early postnatal depressive mood in a large hospital sample. By means of an interview we acquired information on sociodemographic data, physical and psychiatric anamnesis, and obstetric and psychologic variables. The Edinburgh Postnatal Depression Scale (EPDS) served to determine the depressive mood of our patients. The interview was carried out on 1250 women at two postnatal wards 5 days after delivery. According to the results of the German validation of the EPDS, where a cutoff of 9/10 indicates at least mild depressive disorder, the whole sample was divided into group A (EPDS score < or = 9; n = 996, 79.7%) and group B (EPDS score > or = 10; n = 254, 20.3%). Early postnatal depressive mood, as assessed by the EPDS, appeared with 20% of all women taking part in our investigation on the fifth postnatal day. Subjective measurements such as high childbirth burden, elevated trait anxiety, low life satisfaction and lower social class, and low birth weight of the infant seem to be of predominant relevance for early postnatal depressive mood.

Adult↗

PubMed1999

Neopterin is an independent prognostic variable in females with breast cancer.

BACKGROUND: Neopterin, produced by human monocytes/macrophages upon stimulation by interferon-gamma, is a sensitive marker for monitoring Th1-cell immune response in humans. In malignant diseases, the frequency of increases in neopterin in the serum and urine of patients depends on tumor stage and type. METHODS: In a retrospective study comprising 129 females with breast cancer, urinary neopterin/creatinine ratios were measured at the time of diagnosis. Tumor characteristics were determined concomitantly. RESULTS: Urinary neopterin was increased in 18% of the patients. It did not correlate with tumor size or lymph node status, but it was influenced by the presence of distant metastases (P <0.05) and by tumor differentiation (P = 0.01). When product-limit estimates were calculated after follow-up for up to 13 years (median follow-up, 56 months), the presence of distant metastases (P <0.001), neopterin (P <0.001), tumor size (P = 0.001), and lymph node status (P <0.01) were significant predictors of survival. By multivariate analysis, a combination of the variables presence of distant metastases (P <0. 001), neopterin (P <0.01), and lymph node status (P <0.05) was found to jointly predict survival. In lymph node-negative patients without distant metastases, the relative risk of death associated with increased neopterin concentrations was 2.5 compared with patients with neopterin concentrations within the reference interval. CONCLUSION: Urinary neopterin provides additional prognostic information in patients with breast cancer.

Adult↗

PubMed1998

[Coping with anger and the premenstrual syndrome].

OBJECTIVE: Investigations in recent years confirm the importance of "anger coping-behaviour" for women suffering from different diseases such as migraine, high blood pressure and coronary heart disease. The hypothesis for this investigation was that "anger-in" coping (anger-suppression) is a possible causal factor in the premenstrual syndrome. METHODS: Data analysis was undertaken on 38 patients (average age 32 years) fulfilling the inclusion criteria. The Menstrual Distress Questionnaire (MDQ) was used for measuring the intensity of premenstrual symptoms. As a result of a cluster analysis of MDQ scores, the 38 patients were divided into 3 subgroups (group 1: mild symptoms, n = 16; group 2: moderate symptoms, n = 10; groups 3: severe symptoms, n = 12). The 3 groups were compared by using different questionnaires regarding the variables anger, attitudes to menarche and menstrual bleeding, anxiety and depression. Additionally, sociodemographic data were obtained and a daily record taken for 2 days premenstrually and 5 day postmenstrually of subjective replies to a standardized protocol. RESULTS: Contrary to our expectations the results showed no significant differences for "anger coping" between the 3 subgroups. Increased daily stress (professional and familial double load) statistically significantly influenced the intensity of premenstrual symptoms. Additional significant factors were a general tendency towards somatization disorder, a negative attitude toward menarche and menstrual bleeding, as well as a tendency to depressive mood in patients with severe premenstrual symptoms. CONCLUSION: Emotional disorders (anger, anxiety) showed less influence on the premenstrual syndrome in the investigated women than daily stress and medical anamnesis.

Adaptation, Psychological↗

PubMed1998

[German language version and validation of the Edinburgh postnatal depression scale].

BACKGROUND AND OBJECTIVE: There is no valid method in the German literature for assessing postpartum depressive disorders. This study was undertaken to translate into German, validate and test the reliability of the Edinburgh postnatal depression scale (EPDS). PATIENTS AND METHODS: Randomly selected women after childbirth (n = 110) underwent (on the fourth postpartum day) a semistructured interview after first having answered the translated EPDS questionnaire. The diagnosis of depressive disorder was made according to the the criteria for psychological disorders in the ICD-10. For validation the results of the EPDS were compared with the clinical diagnosis of depression. The calculation of sensitivity, specificity and positive prognostic value was related to the respective EPDS results. In addition the EPDS data were analyses as to their reliability. RESULTS: The average age of the tested women was 28.6 years; 72% were married and 45% were primiparae. For an EPDS total score threshold value of 9.5 the sensitivity was 0.96, the specificity 1.0, and a positive prognostic value of 1.0. In the reliability analysis for EPDS the Guttmann split-half reliability was 0.82 and the alpha-coefficient 0.81. CONCLUSIONS: The German version of the EPDS with ten questions is an "application friendly" as well as proven to be a valid and reliable method for supporting the diagnosis of postpartum depressive disorder. It is suitable for both clinical and research use.

Adult↗

PubMed1998

Vulval and vaginal adenosis.

Vaginal adenosis is defined by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, thought to be derived from persistent Müllerian (synonymous with paramesonephric) epithelium islets in postembryonic life. Spontaneous vaginal adenosis appears to be a fairly common (present in about 10% of adult women) but mostly insignificant coincidental finding. In women prenatally exposed to diethylstilboestrol (DES), vaginal adenosis may arise in up to 90% and is associated with a high risk of vaginal carcinoma. Since the withdrawal of DES from the market, vaginal adenosis has virtually disappeared from the medical literature. A case of vaginal adenosis is presented in a middle-aged woman who had not been prenatally exposed to DES. The lesions differed from the spontaneous type by their sudden appearance, their extent and their pronounced subjective symptoms. It is speculated that protracted oral contraceptive intake may have played a causative role.

Adult↗

PubMed1998

Childbirth as a biological model for stress? Associations with endocrine and obstetric factors.

OBJECTIVE: The aims of this investigation were to measure corticotropin-releasing hormone (CRH), corticotropin (ACTH) and cortisol before, during and after delivery searching for an endocrine intercorrelation of the hypothalamic-pituitary-adrenal (HPA) axis and to correlate these findings with obstetrical variables. METHODS: Blood was sampled from 50 women with singleton pregnancies at term without uterine contractions, during delivery (after full cervical dilatation) and on the 4th postnatal day. Hormones were measured by radioimmunoassay (RIA). The correlation between obstetric variables, sociodemographic and endocrine data were evaluated using the Spearman rank coefficient. Group comparisons for continuous variables were calculated using the Mann-Whitney U test and Kruskal-Wallis test. RESULTS: Maternal plasma ACTH and cortisol increased significantly during labor, declining toward the 4th postnatal day (p < 0.001) and showing a significant intercorrelation (p < 0.01). Compared to women without uterine contractions CRH rose during labor (p < 0.05) and decreased rapidly to the 4th postnatal day (p < 0.001). No correlations between CRH and ACTH or cortisol were observed. None of the obstetrical variables (parity, newborn's weight, duration of delivery) revealed any significant correlation with ACTH. Analgetic medication (pethidine hydrochloride) was not able to influence the endocrine response to labor stress. CONCLUSIONS: Stressful experience during childbirth has an impact on endocrine response. However, this is not fully evident along the HPA axis in a simple biological model with monocausal dependencies. This 'biological stress model' is not sensitive enough to detect different childbirth conditions and the hormones in the maternal compartment have partially fetal (placental) origin.

Adrenocorticotropic Hormone↗

PubMed1997

Detection of serologic neutralizing antibodies against HPV-11 in patients with condyloma acuminata and cervical dysplasia using an in vitro assay.

This study was designed to investigate if neutralizing antibodies against HPV-11 are detectable in the serum of patients with condyloma acuminata (CA) or cervical intraepithelial neoplasia (CIN) using an in vitro infectivity assay for HPV-11. Purified HPV-11 virions were extracted from xenografted condyloma tissues implanted into athymic mice and used to infect cultured neonatal human foreskin keratinocytes (HFK) and an immortalized adult skin cell line (HaCaT). The presence of HPV-11-specific E1--E4 mRNA as detected by reverse transcriptase-polymerase chain reaction was indicative of early infection. Sera previously characterized for reactivity to HPV-11 and HPV-11 VLP (virus-like particles) by ELISA were tested for the ability to prevent HPV-11 in vitro infectivity. Neutralizing antibodies against HPV-11 were demonstrated when monoclonal antibodies or patient serum preincubated with HPV-11 virions prevented the infection of either of the two cell cultures, as shown by the absence of the E1--E4 mRNA transcript. Eleven (of 20) patients with CA were strongly ELISA reactive against HPV-11 virus-like particles. Five of these 11 patients also had detectable levels of neutralizing antibodies in their serum. It was also demonstrated that the neutralizing properties of the serum were titratable by endpoint dilution. None of 15 patients with CIN had detectable neutralizing antibodies against HPV-11. Neutralizing antibodies against HPV-11 can be detected in some patients with CA and the neutralizing effects of the patient sera can be titrated by endpoint dilution. The in vitro assay for the detection of neutralizing antibodies against HPV-11 may have utility for investigating the natural history of HPV infection and resolution, as well as assessing the efficacy of any putative HPV vaccine.

Animals↗

PubMed1997

Spontaneous or interferon-gamma-induced T-cell infiltration, HLA-DR and ICAM-1 expression in genitoanal warts are associated with TH1 or mixed TH1/TH2 cytokine mRNA expression profiles.

The purpose of the study was to investigate the cytokine gene expression patterns and immunohistochemical characteristics of genitoanal warts in order to obtain a clue as to the immunological mechanisms possibly relevant for wart regression or persistence. We analysed surgically removed warts from 11 patients, 2 of whom were immunosuppressed. Lesions of five of the nine otherwise healthy individuals were additionally treated with intralesional interferon-gamma (IFN gamma) prior to surgery. Invasion of CD4+ T cells into the papillomas and HLA-DR and ICAM-1 expression on keratinocytes were found in two otherwise healthy patients and were intensified by intralesional IFN gamma in four of five patients. The mRNA expression patterns in seven of eight non-recurrent warts were compatible with a predominant TH1 or mixed TH1/TH2 cytokine profile. In contrast, in recalcitrant warts of three patients (one healthy, two immunocompromised) histological signs of immunore-activity and TH1-like cytokine mRNA expression were not detected. In recurrent warts of a renal transplant patient, IL-4 and IL-5 mRNA expression was repeatedly found suggesting a predominant TH2 response. In conclusion, immunoreactivity to genitoanal warts such as T-cell infiltration, HLA-DR and ICAM-1 expression was associated with a predominant TH1 or mixed TH1/ TH2 cytokine mRNA expression profile.

Adult↗

PubMed1997

Evidence for role of transforming growth factor-beta in RRR-alpha-tocopheryl succinate-induced apoptosis of human MDA-MB-435 breast cancer cells.

MDA-MB-435 human breast cancer cells treated with 10 micrograms/ml of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for one, two, three, and four days exhibit 9%, 19%, 51%, and 73% apoptotic cells, respectively. Likewise, cells cultured for one, two, and three days with conditioned media (CM) obtained from MDA-MB-435 cells treated with VES exhibit 10%, 36%, and 74% apoptosis, respectively. A quantitative luciferase-based assay showed CM from VES-treated cells collected at 24 and 48 hours after treatment initiation to contain 75 and 32 pg of active transforming growth factor-beta (TGF-beta), respectively, per 10(6) cells. Although purified TGF-beta 1 is not an effective apoptotic agent for MDA-MD-435 cells, cotreatment of the cells for three days with suboptimal levels of VES (2.5 and 5 micrograms/ml) + 10 ng/ml of purified TGF-beta 1 enhanced apoptosis by 66% and 68%, respectively. Interference of the TGF-beta-signaling pathway by transient transfection of MDA-MB-435 cells with antisense oligomers to TGF-beta type II receptor (TGF-beta R-II) blocked VES-induced apoptosis. Likewise, addition of neutralizing antibodies to TGF-beta 1 or to all three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) blocked VES- and CM-induced apoptosis. Furthermore, inhibitors of TGF-beta conversion from an inactive latent form to a biologically active form inhibited VES-induced apoptosis. In summary, the ability to reduce apoptosis by blocking TGF-beta or the TGF-beta receptor-signaling pathway with antisense oligomers or ligand-neutralizing antibodies or prevention of activation of TGF-beta indicates a role for TGF-beta signaling in VES-induced apoptosis.

Antibodies↗

PubMed1997

Spontaneous abortion and psychosomatics. A prospective study on the impact of psychological factors as a cause for recurrent spontaneous abortion.

A group of 36 patients who had had at least two consecutive spontaneous abortions and who desired to have children was subjected to a psychosomatic investigation before a biomedical diagnostic screening programme was started. A semi-structured interview regarding sociodemographic data, current relationship, social support, education, occupation and medical anamnesis was carried out. In addition, all women completed four standardized questionnaires on the topics of anxiety, somatization disorder, life satisfaction and depression. A control group of 36 women, matched for age and occupation, was subjected to the same psychosomatic investigation. The findings of the diagnostic screening programme showed that 16 women had abortions because of physical abnormality, and 15 women had no physically confirmed cause (in five women, the investigations were not completed). Following recurrent spontaneous abortion, 18 women had a successful pregnancy within 2 years, and 18 women were still childless. The comparison between patients and the control group revealed that patients with recurrent abortion were significantly more satisfied with their life quality regarding leisure time, financial situation and occupation. No significant differences were observed in any other variables. Patients who suffered spontaneous abortions due to a physical disorder showed partner relationship of longer duration, and more frequent miscarriages. Women with successful pregnancy within 2 years after recurrent miscarriage were significantly younger and had fewer physically related abortions compared with women who remained childless. In summary, psychological factors seem to be of subordinate importance as a cause for recurrent spontaneous abortion. Moreover, physical abnormalities in the reproductive system have a predominant impact on the prediction of a future successful pregnancy.

Abortion, Habitual↗

PubMed1996

[Immunologic aspects of infections with papillomaviruses. Prospects for a vaccine].

Human papillomaviruses induce benign or malignant epithelial proliferations in both skin or mucosa and are involved in the development of anogenital cancer. One can consider two approaches towards vaccine development: prevention of infection by prophylactic induction of virus neutralizing antibodies or therapeutic vaccination which would lead to regression of already existing lesions. Neutralizing antibodies are directed against 3-dimensional structures on intact virions. Such antibodies which are protective in model systems can be induced safely by DNA-free "virus-like-particles". These constructs are candidates for a prophylactic vaccine. A further approach to optimize the vaccination strategy concentrates on immunotherapy of precancerous or malignant lesions by induction of a specific cell-mediated immune response. Hypothetically the transforming papillomavirus proteins which are expressed in basal layers of the epidermis could be used as a therapeutic vaccine in the form of synthetic peptides.

Animals↗

PubMed1996

RRR-alpha-tocopheryl succinate enhances TGF-beta 1, -beta 2, and -beta 3 and TGF-beta R-II expression by human MDA-MB-435 breast cancer cells.

The proliferation of MDA-MB-435 human breast cancer cells was inhibited by RRR-alpha-tocopheryl succinate (vitamin E succinate, VES). Conditioned media (CM) from VES growth-inhibited cells contained potent antiproliferative activity, part of which is contributed by transforming growth factor-beta (TGF-beta) isoforms. Antibody neutralization analysis, employing TGF-beta isoform-specific antibody reagents, showed that TGF-beta 1, -beta 2, and -beta 3 were present in the CM from VES-treated cells. Culturing MDA-MB-435 cells with VES did not alter the levels of constitutively expressed 2.4-kb TGF-beta 1, 3.0- and 4.0-kb TGF-beta 2, or 1.2- and 3.5-kb TGF-beta 3 mRNA transcripts. Inhibition of DNA synthesis by MDA-MB-435 cells was increased by combinations of suboptimal levels of VES and purified TGF-beta 1. VES-treated MDA-MB-435 cells exhibited enhanced binding of radiolabeled TGF-beta 1, and Western immunoblotting analyses showed that VES treatment enhanced TGF-beta type II receptor protein expression. TGF-beta type I receptor protein levels were not modified by VES treatments. Although the mRNA transcript for the 5.5-kb TGF-beta type II receptor was upregulated after four hours of treatment with VES, this treatment did not modify the 6.5-kb TGF-beta type I or the 6.5-kb TGF-beta type II receptor mRNAs. Results demonstrate that biologically active TGF-beta 1, -beta 2, -beta 3 and levels of TGF-beta type II receptor expressed by human breast cancer cells are enhanced by VES treatment.

Blotting, Western↗

PubMed1995

[Special suction tube holder for a laser handpiece in effective smoke suction evacuation. On the problem of smoke suction in external CO2 laser therapy].

Treatment with a CO2 laser causes high smoke production, which leads to reduced view to the surgical field, to bad smell and has potential health hazards. Hitherto the problem of the external smoke evacuation had not been solved sufficiently. Therefore a special sucking-tube holder for a laser handpiece is presented. The end of the sucking tube exactly follows all movements of the handpiece and can be positioned close to the source of smoke. Through a defined angle the smoke can be removed quickly out of the way of the laser beam. According to the practical experiences so far, this special equipment on a laser handpiece guarantees an effective evacuation of smoke, allows the reduction of assisting staff, reduces irritation through bad smell and additionally minimizes the potential risks of smoke caused by an external CO2 laser application.

Condylomata Acuminata↗

PubMed1995

Serum IgG, IgM, and IgA reactivity to human papillomavirus types 11 and 6 virus-like particles in different gynecologic patient groups.

Serum samples from several groups of patients attending a gynecology clinic were analyzed by ELISA for specific antibodies recognizing surface epitopes on intact human papillomavirus (HPV) types 6 and 11 L1 virus-like particles (VLPs) that were synthesized in vitro. In these samples, positive IgG and IgM reactivities to HPV-11 L1 VLPs were, respectively, 12% and 6% for 87 controls, 46% and 67% for 79 condyloma patients, 30% and 64% for 72 cervical intraepithelial neoplasia patients, 16% and 19% for 63 pregnant women at time of delivery, and 5% and 0 in their 63 newborns. IgA reactivities were low and not significantly different. The prevalence of IgG-positivity in HPV-6/11 DNA-positive patients increased from 46% with HPV-11 L1 VLPs to 76% when the sera were additionally screened with HPV-6 L1 VLPs. These data show that HPV-6 and -11 L1 VLPs are effective antigens for serologic studies and they detect type-specific antibodies.

Adolescent↗

PubMed1995

[Specific serologic studies with a novel authentic HPV antigen (virus-like particles) for HPV-6 antibodies in gynecologic patient samples].

OBJECTIVE: A serological assay for genital HPV infection would provide important additional information to HPV DNA diagnostic methods, since it would evaluate prior exposure to the viruses, detect significant systemic immunologic response to virus infection, and could be performed in most clinical laboratories. METHODS: Serum samples from three groups of patients attending a gynecology clinic were analysed by direct ELISA for specific IgG antibodies to baculovirus-expressed HPV-6 and BPV-1-L1-VLPs. RESULTS: Positive IgG reactivity to HPV-6-L1-VLPs were 4/72 (6%) in a control group, 28/73 (38%) in a condyloma group and 17/62 (17%) in cervical intraepithelial neoplasia patients. Individual IgG ELISA values of condyloma and CIN patients for HPV-6-L1-VLPs demonstrated no correlation to results with BPV-1-L1-VLPs. CONCLUSIONS: These data show that HPV-6-L1-VLPs are effective antigens for serological studies and can detect species specific antibodies with important implications for diagnosis, epidemiology, insights to natural course of disease, prognosis and evaluation of vaccination.

Adolescent↗