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Biomedical subjects

W Aulitzky

Publications and source records attributed to W Aulitzky.

At least 37 records · Page 2Linked to original sources
PubMed1991

Physiology of the prostate.

The presence of the prostate is universal in mammals; when compared among species the prostate is marked by variations in its anatomy, biochemistry and pathology. The epithelial cells provide secretions that empty through ducts into the urethra to form a major component of the seminal plasma of the ejaculate. The prostate is stimulated to grow and is maintained in size and function by the presence of serum testosterone. Several protein-type growth factors, such as urogastrone and prostatropin, may also affect prostatic growth. After testosterone from the plasma has entered the prostatic cell through diffusion it is metabolized to other steroids by a series of enzymes. Over 95% of testosterone is converted to the most important prostatic androgen dihydrotestosterone. DHT then binds to the activated androgen receptor. The hormone receptor complex undergoes transformation and translocation into the nucleus. In the nucleus RNA-polymerase is activated followed by the synthesis of mRNA. The noncellular stroma and connective tissue compose the extracellular matrix. The extracellular matrix plays an important role in development and control of cellular functions.

Androgens↗
PubMed1991

Acute hematologic effects of interferon alpha, interferon gamma, tumor necrosis factor alpha and interleukin 2.

This study was designed to investigate acute effects of various doses of the cytokines IFN-alpha, IFN-gamma, Interleukin 2 and tumor necrosis factor alpha on white blood cell differential counts. Before initiation of phase II trials, a dose-determination phase was performed, where three different dose levels of each cytokine were applied as a single dose. White blood cell differential counts were assessed immediately before and 2, 12, 24, 48 and 168 h after injection. Patients enrolled suffered from metastatic cancer or chronic active hepatitis. In addition, IFN-alpha was administered to five healthy volunteers. Results indicate that cytokines cause rapid and transient changes in the numbers of leukocyte subsets. Hematologic changes were cell-type- and cytokine-specific: transient lymphopenia was observed after administration of all four cytokines, reaching a nadir 12 to 24 h after subcutaneous injection. Administration of TNF-alpha and IFN-gamma also caused transient monocytopenia. Neutrophilia developed after administration of Interleukin 2, IFN-alpha and TNF-alpha. We conclude that cytokines play a key role in the regulation of peripheral blood cell traffic by their capacity to influence homing patterns of peripheral blood leukocytes.

Female↗
PubMed1991

Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-gamma).

In order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-gamma (rIFN-gamma) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 micrograms rIFN-gamma three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of rIFN-gamma. Beta-2-microglobulin was assessed in parallel using a commercially available radioimmunoassay. Significant induction of soluble HLA class I protein serum levels was observed after treatment with 100 and 500 micrograms rIFN-gamma. The increments peaked after 2-4 days and remained elevated for up to more than 7 days. A significant correlation between increments of soluble HLA class I proteins and beta-2-microglobulin was observed. We conclude that measurement of soluble HLA serum levels is practical for monitoring induction of HLA class I synthesis in patients treated with rIFN-gamma. The correlation observed between induction of beta-2-microglobulin and soluble HLA class I proteins indicates that measurement of beta-2-microglobulin might be sufficient for the biological response monitoring in clinical studies.

Carcinoma, Renal Cell↗
PubMed1991

Increasing infertility in myotonia dystrophica Curschmann-Steinert. A case report.

A 26-year-old male came to our andrologic out-patient clinic because of his desire to have children. Preliminary examinations revealed a varicocele left and a subclinical varicocele right. Testicular volume was smaller than normal, and spermiogram values were already poor (vitality, motility and morphology). Basic hormones were normal. The anamnesis gave no information on hereditary disorders. Surgical treatment of the varicocele did not bring the desired outcome. A testicular biopsy showed Leydig cell hyperplasia with strongly reduced spermiohistogenesis. In a renewed and extensive anamnesis, the patient revealed that he suffers from myotonia dystrophica Curschmann-Steinert. This disorder causes sclerosis of the tubuli seminiferi contorti, which can ultimately lead to azoospermia.

Adult↗
PubMed1990

Recombinant interferon-alpha-2C in chronic myelogenous leukaemia: relationship of sensitivity of committed haematopoietic precursor cells in vitro (BFU-E, CFU-GM, CFU-Meg) and clinical response.

In an ongoing phase-II trial we aimed to predict clinical responsiveness of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML) to recombinant IFN-alpha-2C (rIFN-alpha-2C) by pretesting in vitro. From five normal controls and 14 CML patients in chronic phase, bone marrow samples were taken before treatment and tested for antiproliferative activity by rIFN-alpha-2C, using a microagar culture system for BFU-E, CFU-GM, and CFU-Meg. Light-density nucleated bone marrow cells were stimulated for BFU-E and CFU-Meg colony formation with Alpha medium containing 20% serum obtained from a patient with severe aplastic anaemia. CFU-GM growth was induced with conditioned medium from the cell line GCT. In normal controls BFU-E, CFU-GM and CFU-Meg colony formation was inhibited by rIFN-alpha-2C in a dose-dependent manner. BFU-E proved to be the most sensitive cell lineage (IC50: 65; range: 53-116 U/ml) whereas CFU-GM was about 20 times less sensitive (IC50: 643; range: 480-897 U/ml). The sensitivity of CFU-Meg ranged between these two colony types with 50% growth inhibition at an IFN concentration of 160 (range: 68-246 U/ml). A heterogeneous response to rIFN-alpha-2C in vitro was seen in CML patients. Three of the 14 patients were 'resistant' to rIFN-alpha-2C in vitro with IC50 values for BFU-E, CFU-GM and/or CFU-Meg colony formation greater than 10(4) U/ml. Patients were subsequently treated with a daily dose of rIFN-alpha-2C of 5 x 10(6) U. Four patients achieved a complete and six achieved a partial haematological response. Of the four non-responders three rapidly progressed into blastic crisis. Thus it was seen that treatment failure to interferon was accompanied by IFN-resistance in vitro of BFU-E, CFU-GM and/or CFU-Meg colony formation by bone marrow precursors (p less than 0.01). These results suggest a predictive value of IFN-sensitivity testing in vitro in Ph1 + CML.

Adult↗
PubMed1990

Endogenous IFN-gamma during human bone marrow transplantation. Analysis of serum levels of interferon and interferon-dependent secondary messages.

Serum levels of interferon-gamma and the IFN-dependent marker molecules neopterin and beta 2-microglobulin were assessed in BMT recipients. Concentrations of the latter two markers were corrected for creatinine levels in order to eliminate the impact of alteration of kidney function. Serum levels were assessed daily using commercially available radioimmunoassays. Twelve patients were studied during the early phase of allogeneic bone marrow transplantation and eleven additional patients during complications of BMT. Results indicated that both the conditioning regimen for BMT as well as major clinical complications such as infection and acute graft-versus-host disease strongly influence the endogenous patterns of the lymphokine and its secondary messages. During allogeneic BMT IFN-gamma and neopterin levels exhibited a biphasic pattern with a first peak during conditioning with high-dose cyclophosphamide and a second still higher peak at the time of hemopoietic regeneration. beta-2-microglobulin ratios increased during conditioning and remained elevated throughout observation. Serious infections of bacterial and viral origin as well as GvHD were accompanied by elevated levels of all three serum parameters studied. The kinetics of enhanced endogenous production, however, differed between infectious complications and GvHD. Increasing concentrations were observed during infections subsequent to clinical manifestation, whereas they preceded disease manifestation in GvHD.

Biopterins↗
PubMed1989

Acute effects of single doses of recombinant interferon-gamma on blood cell counts and lymphocyte subsets in patients with advanced renal cell cancer.

The object of this study was to investigate the effects of different single doses of recombinant interferon-gamma (rIFN-gamma) on white blood cell counts, differential blood counts, and the relative composition of T-cell subsets in the peripheral blood of cancer patients. Sixteen patients suffering from metastasizing renal cell carcinoma received 10, 100, or 500 micrograms of rIFN-gamma three times at weekly intervals. After a therapy-free interval of 2 weeks, the next dose level was applied. The order of dose levels was assigned randomly to each patient. White blood cells, differential blood counts, and the number of Leu1, Leu3, Leu2a, Leu7, and HLA DR+ cells were measured immediately before and at 4, 24, 48, 72, 96, and 168 h after the administration of single doses of rIFN-gamma. Results indicated that white blood cells were transiently removed from the blood circulation after administration of IFN-gamma. Monocytes, HLA DR+ cells, and Leu7+ cells were reduced to below 50% of pretreatment values 4 h after application of the cytokine. CD8+ cells and granulocyte counts declined to approximately 70% of pretreatment values 24 h after IFN therapy. The preferential reduction of CD8+ lymphocytes resulted in a temporary increase of the T4/T8 ratio in these patients.

Adult↗
PubMed1989

Pulsatile LHRH therapy in patients with oligozoospermia and disturbed LH pulsatility.

Pulsatile administration of LHRH can drive the pituitary to secrete LH and FSH in a pattern that closely mimics the physiological pattern of the hypothalamic-pituitary-gonadal axis. As there is evidence that infertility in some men is due to dysfunction of this axis, 14 men with reported infertility of more than 2 years duration were treated by long-term pulsatile LHRH therapy. They were 24-42 years of age, with variable degrees of oligozoospermia, elevated FSH levels but normal LH and testosterone levels. The number of endogenous LH pulses/24 h was less than eight in all 14 subjects. The degree of testicular damage was assessed semi-thin sections prepared from biopsies of both testes. Scores for spermatogonia per seminiferous tubule (SPT) were calculated from the actual number of Ad-spermatogonia/tubule. Patients were grouped according to sperm density and SPT score (groups I-III). Pulsatile LHRH therapy was administered by means of a portable infusion pump; 4 micrograms LHRH were administered subcutaneously every 120 min for a period of 6 months. This treatment restored the normal pattern of LH secretion to 12 LH pulses/24 h in all patients. A statistically significant decrease of mean FSH levels to normal, and an increase of mean LH levels was observed in most of the 14 patients. Testosterone values did not change in any group. Marked improvement of the sperm count was observed in eight out of 14 patients (groups I and II) and three pregnancies were reported during the treatment periods. These results suggest that some states of male infertility are due to hormonal dysregulation and that these patients may benefit from pulsatile LHRH therapy.

Adult↗
PubMed1989

Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.

Adult↗
PubMed1989

Comparison of clinical efficacy and toxicity of conventional and optimum biological response modifying doses of interferon alpha-2C in the treatment of hairy cell leukemia: a retrospective analysis of 39 patients.

Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.

Adult↗
PubMed1988

Treatment of advanced renal cell cancer with recombinant interferon alpha as a single agent and in combination with medroxyprogesterone acetate. A randomized multicenter trial.

The response rates in metastatic renal cell cancer (RCC) after chemotherapy, hormonal treatment, or immunotherapy rarely exceed 15%. Recently, interferon alpha (IFN alpha) was used for treatment of this disease in several studies which also demonstrated response rates of 15%. In order to test whether IFN therapy combined with hormones would result in higher response rates we compared single agent IFN therapy with a combined therapy of rIFN alpha 2C plus medroxyprogesterone acetate (MPA) in a randomized multicenter trial. The rIFN alpha 2C (2MU) was given s.c. 5 times per week for 8-12 weeks and subsequently once weekly until week 48. In the combined treatment, 750 mg MPA was given p.o. daily until week 48 in addition to the IFN as described. The overall response rate in 93 evaluable patients was 5.4% corresponding to 2 complete and 3 partial responses. Median survival was 7 months in both treatment groups. These data confirm the ineffectivity of low IFN doses for treatment of RCC. The low response rate is not increased by addition of MPA to IFN. The analysis of other IFN studies suggests that not only IFN doses but also IFN sources may influence response rates in metastatic RCC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Clinical microdose study of gossypol: effect on sperm motility and renal function.

This study is part of a series designed to identify the smallest effective gossypol dose for male fertility control. Three men, aged 31-35 years, were administered gossypol, 10 mg/day, orally for 3 months. Urinalysis and assays for plasma hormone values, including cortisol, beta 2-microglobulin, potassium, and BUN, showed no changes during treatment. Forward sperm motility, however, was severely affected by the end of the treatment period (less than 4% forward motility). Sperm density also showed a marked decrease. The subjects developed no undue side effects.

Adult↗
PubMed1988

Pulsatile luteinizing hormone-releasing hormone treatment of male hypogonadotropic hypogonadism.

Luteinizing hormone-releasing hormone (LH-RH) secretion from the hypothalamus follows a rhythmic pattern, inducing pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from the pituitary gland. Consideration of this physiologic principle led to the introduction of pulsatile LH-RH therapy via infusion pump for the treatment of different forms of hypogonadotropic hypogonadism. We report on 10 male patients, 16 to 28 years of age, suffering from idiopathic hypogonadotropic hypogonadism (IHH) including Kallman's syndrome (n = 2) and delayed puberty (n = 2). All presented with complete eunuchoidism and had undergone no treatment for their conditions during the previous 2 years. LH-RH was administered in subcutaneous pulses of 4 to 16 micrograms, with a portable infusion pump (ZYKLOMAT, Ferring Corp., Kiel, FRG); treatment periods ranged from 6 to 24 months. With therapy, the subjects improved secretion of LH, FSH and testosterone. Testicular volumes and penis size increased; all patients developed normal secondary sexual characteristics. Spermatogenesis was induced in all patients. The time to onset of spermatogenesis ranged from 3 to 15 months. No major side effects were observed, and no patient dropped out of the study. The results indicate that pulsatile LH-RH therapy is an highly effective treatment for IHH and delayed puberty.

Adolescent↗
PubMed1988

Cytokines in the control of beta-2 microglobulin release. II. In vivo studies with recombinant interferons and antigens.

The influence of in vivo application of recombinant interferon-alpha 2c (IFN-alpha 2c) and recombinant interferon-gamma (IFN-gamma) on beta-2 microglobulin levels was studied in eight patients with chronic myelogenous leukaemia or advanced renal cell carcinoma. Data indicated enhanced beta-2 microglobulin biosynthesis in close temporary association with injection of both types of interferons. The influence of in vivo stimulation by allogenic leukocytes and the influence of renal allografts or cytomegalovirus infection on serum beta-2 microglobulin and IFN-gamma levels were also studied. Increased beta-2 microglobulin concentrations were observed again in each of these clinical situations and were closely associated with enhanced endogenous interferon production. From these in vivo data and the in vitro data presented in the preceding publication, (1) we conclude that endogenous interferon levels are crucial for the regulation of beta-2 microglobulin release in vivo.

Antigens↗
PubMed1988

Male contraception.

To share contraceptive measures between partners is a goal which should be reached in the future. The possibilities on the male side are still limited in comparison with the techniques available for women. During the last 20 years many efforts have been undertaken to study and evaluate possible methods for fertility control in the male, based on interaction with the hormonal axis, sperm maturation and sperm transport. The requirements for such a method in the male are the same as in female: high efficacy, little or almost no side-effects, high practicability and compliance and the possibility for easy reversibility in a high percentage of men. Despite their increasing acceptability worldwide, the existing male methods, condom and vasectomy, do not fully meet these requirements and therefore a search for alternative male methods is warranted. At present, the following medical approaches to male fertility control have been tested or are under consideration: (i) selective inhibition of FSH: antibodies, inhibin; (ii) inhibition of pituitary-gonadal axis: steroids such as testosterone, progestin-testosterone combinations, LHRH analogues with and without testosterone substitution; and (iii) selective inhibition of spermatogenesis by gossypol, a phenolic compound from cotton plant. Whether one of these methods will reach the desired goal for male fertility control has yet to be determined.

Contraception↗