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Biomedical subjects

M Graf

Publications and source records attributed to M Graf.

At least 91 records · Page 5Linked to original sources

Gonadal agenesis in a 46,XY female with multiple malformations and positive testing for the sex-determining region of the Y chromosome.

A full-term 46,XY female newborn presented with respiratory failure due to a right-sided diaphragmatic hernia. During surgical repair, exploration revealed isolated dextrocardia and hypoplasia of the right lung. Neither gonads nor wolffian or müllerian structures could be palpated. Cardiac catheterization demonstrated defects of the ventricular septum, hypoplasia of the right pulmonary artery, persistence of the left vena cava superior and a patent ductus arteriosus. Anthropometric data were normal at birth, but fell below the 3rd percentile during follow-up. Body proportions displayed a predominance of the upper compared to the lower segment. Endocrine studies indicated no defect of steroid biosynthesis and no functional gonadal tissue. Using genetic analyses of various loci within the testis-determining region of the Y chromosome, a mutation could not be detected. The patient died from pneumonia at the age of 19 months. Postmortem examination confirmed the diagnosis of gonadal agenesis.

Abnormalities, Multiple↗

[The startle response and epilepsy].

Startle responses (SR) are described as epileptic and non-epileptic attacks and their mechanisms are poorly understood. Long-loop reflexes and a satisfactory response to L-tryptophan treatment have only seldom been published in this condition. This prompted us to report a case with epilepsy and startle-induced tonic spasms, the latter refractory to all conventional medication except for L-tryptophan. Special emphasis is placed on the electrophysiological findings. Similar observations of non-habituation of SR in post-anoxic brain damage and in the case of startle epilepsy possibly suggest a deficit of cortical inhibition, probably in the supplementary motor area, rather than brain stem dysfunction in both instances.

Adult↗

[Benign Rolandic epilepsy in children. Topographic EEG analysis].

Topographic EEG investigation with instant voltage mapping showed maximal negativity of "Rolandic" spikes over central or midtemporal electrodes with spread to parietal or upper frontal areas with a dipol formation (centro-temporal negativity, frontal positivity). Spike amplitude or duration was not correlated with spread to adjacent areas. No other focal abnormalities, such as focal slowing, occurred. Spike activity was pronounced during light sleep and was often associated with generalized spike wave activity, which is more likely to be a sign of functional disturbance rather than the sequelae of brain damage. A review of literature shows that this pattern is helpful in the differentiation from focal abnormalities due to brain lesions.

Adolescent↗

Localization of basic fibroblast growth factor, a mitogen and angiogenic factor, in human brain tumors.

Fibroblast growth factor (FGF) is a potent angiogenic factor and a mitogen for a variety of mesoderm- and neuroectoderm-derived cell types (e.g., fibroblasts, endothelial cells, astrocytes, oligodendrocytes). After application of a monospecific polyclonal antiserum, we localized basic FGF on frozen sections of 73 human brain tumors using immunohistochemistry. FGF was present in a variable number of tumor cells (16/16 astrocytomas, 5/5 ependymomas, 0/3 benign and 4/7 anaplastic oligodendrogliomas, 11/12 glioblastomas, 11/11 meningiomas, 6/6 neurilemmomas, 0/3 pituitary adenomas, 2/2 choroid plexus papillomas, 0/1 neurocytoma, 2/2 benign fibrous histiocytomas, 2/5 metastatic carcinomas). FGF was detected in vascular cells of 59 tumors and in fibroblasts of connective tissue stroma from all papillomas and metastases. These results tend to indicate FGF involvement in the malignant progression of gliomas due to an autocrine or paracrine action. Histopathological aspects of malignant gliomas (e.g., pseudopalisading or pathological vessels) could be related to FGF activity.

Astrocytoma↗

[Cultural and serologic Chlamydia detection in diagnosis of sterility and increased risk of infection].

364 women were studied for the possible role of chlamydia trachomatis infection as a factor related to infertility. C. trachomatis was isolated from the cervix in 20% of our high-risk STD patients and in a much lower proportion in patients with tubal (5%) or unexplained (4%) infertility. IgG-antibodies to C. trachomatis were found in 75% of patients with tubal infertility, in 44% of women without gynaecological diseases and in 87% of the high-risk STD patients. By contrast, the difference was significant in the IgA-antibody tests. 67% of the women with tubal infertility and only 25% of the women with nontubal infertility were positive. From these data it appears, that antecedent infections with C. trachomatis, as measured by antibody prevalence, are an important factor in infertility of tubal origin.

Bacteriological Techniques↗

[The value of functional tests in diagnosis of prolactinoma].

The present study in 37 hyperprolactinaemic patients was performed, to investigate the relationship between radiographic changes of the pituitary region and serum prolactin levels, clinical signs and the results of dynamic tests. Prolactin responsiveness after metoclopramide- and TRH-injection and the nocturnal profile of serum prolactin were examined in 25 women. The results of the dynamic tests did not correlate with the radiological diagnosis. However, serum prolactin concentrations correlated strongly with the radiographic evidence of a pituitary tumour. The results show, that prolactin stimulation tests and the evaluation of the nocturnal secretory pattern of prolactin are not useful for differentiating between adenoma and nonadenoma caused hyperprolactinaemia. However, determinations of prolactin serum levels are of great clinical importance in the diagnosis of prolactinomas.

Circadian Rhythm↗

Surgical treatment of epilepsy.

Seventy patients with intractable epilepsy were surgically treated. Thirty-three patients underwent a stereotactic procedure and in all as a first-stage operation fornicotomy was performed. Because of inadequate results in 14 patients, an additional stereotactic intervention was necessary; the targets were amygdala, thalamus, and Forel's H-field, and the final outcome of these patients was 9 (27%) seizure-free, 19 (58%) improved, and 5 (15%) unchanged. In 3 patients a selective amygdalo-hippocampectomy was performed with 2 seizure-free patients and one with improvement. Topectomy in focal epilepsy in 5 patients resulted in freedom from seizures in all cases. In 23 patients a lobectomy was performed; 10 (43%) were seizures-free, 8 (35%) were improved, and 5 (22%) were unchanged. In 6 patients only a pathological lesion was resected. Our results speak in favour of ablative surgery. However, stereotactic operations are indicated in cases with secondary generalization and dissipated foci on the dominant hemisphere.

Adult↗

[Clinical and endocrinologic aspects of treatment with pure FSH. A report of experiences].

Ovarian stimulation with pure urinary FSH (Fertinorm, Serono Freiburg, FRG) shows therapeutic efficacy in patients with chronic clomiphene-resistant anovulation and elevated androgen levels. In case of unsatisfactory ovarian response the rate of success can be improved by adding HMG. 20 patients were stimulated for a total of 36 cycles. Cycle monitoring was performed by transbdominal ultrasound and cervical mucus evaluation. Hormone determination (E2, LH, FSH, prolactin, testosterone, DHEAS) was carried out retrospectively. In 17 cycles HMG was added because of insufficient follicle maturation. Upon achieving a dominant follicle with a diameter of more than 1.6 cm (25 cycles, 14 of those with FSH stimulation only) HCG was applied for induction of ovulation. In 22 cycles ovulation occurred. 7 of those revealed sings of luteal phase deficiency. In anovulatory cycles (n = 3) there was a discrepancy between sonography and E2-levels. Premature increase in LH, partly with subsequent luteinization of follicles was observed in 7 of all 36 cycles (19.4%), 2 of those under sole FSH-stimulation. The number of dominant follicles on the day of HCG-application was 1.40 +/- 1.06 (n = 15) in cycles with FSH alone and 2.09 +/- 1.76 (n = 11) in cycles with additional HMG. Hyperstimulation (more than 4 leading follicles) was induced in 9 cycles (5 cycles with FSH only). In 7 (4) cases HCG had to be cancelled. Polyfollicular ovarian reaction and premature increase in LH preferentially occurred in cycles with high basel levels of LH and elevated LH/FSH-ratio.

Adult↗

[Diurnal beta-endorphin rhythm in relation to menstrual cycle phase].

Beta-endorphin (beta-EP) concentrations in hypophyseal portal blood are related to the menstrual cycle in primates. In women, changes in peripheral plasma beta-EP-concentrations were detected throughout the menstrual cycle. A similar circadian rhythm of beta-EP and ACTH was observed in males, suggesting a common mechanism of secretion at the pituitary level. We examined beta-EP, cortisol (F) and prolactin (PRL) levels in peripheral blood of regularly menstruating women. Samples were taken every 2 hours between 6 p.m. and 10 a.m. on days 3 and 4 of the menstrual cycle and 6 and 7 days after the rise of the basal body temperature. A diurnal rhythm of beta-EP could be seen between 6 p.m. and 10 a.m. in the luteal phase, but not in the follicular phase. An early morning rise of beta-EP was accompanied by increasing F-concentrations, suggesting a concomitant secretion of beta-EP and ACTH by the cells of the anterior pituitary. We therefore conclude, that ovarian steroids may influence beta-EP secretion at the pituitary level as well.

Adult↗

[The segmented phantom insert for the formation of a neovagina according to Vecchietti].

Formation of a neovagina by surgical cavitation with an olive-shaped plastic form following Vecchietti, yields good functional and cosmetic results. By replacing the olive with a motile model consisting of a variable number of single segments, complications can be reduced. The newly developed model leads to better dilatation and stabilization of the newly-formed vagina. Wound secretion is drained by an interior canal and by lateral perforations. Through this canal, catheter irrigations and drug application are possible. 15 cases of this novel surgical technique are reported.

Adolescent↗

Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome.

We have investigated the hypothesis that hyperinsulinemia may cause the polycystic ovary syndrome (PCO) by directly stimulating gonadal steroidogenesis and/or gonadotropin secretion. 10 insulin-resistant women with PCO and 5 age- and weight-matched ovulatory normal women had pulsatile gonadotropin release, gonadotrope sensitivity to gonadotropin-releasing hormone, and sex hormone levels studied on two consecutive study days, basally and during the infusion of insulin (mean +/- SEM steady state insulin levels, 1,254 +/- 63 microU/ml PCO vs. 907 +/- 92 microU/ml normal, P less than or equal to 0.01). Insulin acutely increased mean delta (6 h minus prestudy) levels of androstenedione (A) (P less than or equal to 0.001) and estradiol (E2) (P less than or equal to 0.05) and decreased mean plasma pool (0-6 h) levels of testosterone (T) (P less than 0.05), nonsex hormone binding globulin-bound T (P less than 0.05), and dihydrotestosterone (P less than or equal to 0.01) in the PCO women. Insulin also decreased mean plasma 6 h A to estrone (E1) ratios and increased 6 h E1 levels (both P less than or equal to 0.05) in the PCO women. There were significant sequence effects (insulin + day) in the PCO women on T/E2 ratios, indicating a carryover action of insulin. Insulin had no effects on gonadotropin release in the PCO women. In the normal women, the only significant change was an insulin or study day effect that increased mean 6 h E2 levels (P less than or equal to 0.01). There were significant spontaneous decreases in mean luteinizing hormone (p less than 0.05) and follicle-stimulating hormone levels (p less than or equal to 0.01) in the PCO but not the normal women on the second day of study. This study indicates that insulin can directly alter peripheral sex hormone levels independent of changes in gonadotropin release in insulin-resistent PCO women. Insulin decreased the levels of potent androgens in PCO women and did not increase androgen levels in normal women, arguing against a simple, direct causal relationship between hyperinsulinemia and hyperandrogenism in PCO.

Adolescent↗

A novel rat carboxypeptidase, CPA2: characterization, molecular cloning, and evolutionary implications on substrate specificity in the carboxypeptidase gene family.

A new member of the carboxypeptidase gene family, carboxypeptidase A2 (CPA2), has been identified from the predicted amino acid sequence of a rat pancreatic cDNA clone. In vivo recombination and in situ hybridization techniques employing the CPA2 cDNA resulted in the isolation of two genomic clones spanning the 25-kilobase pair rat CPA2 gene. Evolutionary trees built from the amino acid sequences of the known pancreatic carboxypeptidases show that CPA2 and carboxypeptidase A1 (CPA1) are the products of genes which duplicated before the mammalian radiation, and that bovine CPA is of the A1 type. The substrate specificities of CPA1 and CPA2 isolated from rat pancreas are similar to bovine CPA in that carboxyl-terminal amino acids with aromatic or branched aliphatic side chains are preferred. However, the substrate preference of rat CPA1 is skewed toward smaller amino acids, while that of rat CPA2 is skewed toward bulkier amino acids as compared to bovine CPA. The differences in the substrate specificities of these three carboxypeptidases are compatible with the nature of the amino acid replacements in their binding pockets for the carboxylterminal amino acid of the substrate.

Amino Acid Sequence↗

[Discrimination between epileptic and non-epileptic seizures using defined prolactin studies].

Prolactin blood levels (HPRL) increase within 20 minutes postictally after generalized epileptic, especially generalized tonic-clonic seizures and return to normal values within one hour. Elevated HPRL levels were also observed after complex partial seizures, but usually in less extent, exceeding normal ranges only slightly. Therefore baselin HPRL measurements are necessary for estimation of spontaneous fluctuations in comparison to changes after seizures. Unchanged PRL levels after attacks do not support their epileptic origin. Rage attacke showed no clear pattern of PRL changes.

Adolescent↗

Heterogeneity of antigenic determinants on human spermatozoa: relevance to antisperm antibody testing in infertile couples.

Sera from 1074 male and 947 female partners of infertile marriages were tested by enzyme-linked immunosorbent assay for antibodies to motile sperm purified from ejaculates of the male partners or a donor. In men, 9.2% of the sera were positive for immunoglobulin A, 7.9% for immunoglobulin G, and 5.1% for immunoglobulin M antibodies to their own sperm. In women, immunoglobulin M antibodies to the husband's sperm predominated (10.1%), with immunoglobulins G (8.3%) and A (5.9%) following. Differences between men and women in the incidence of immunoglobulin A (p less than 0.01) and M (p less than 0.005) antibodies were significant. In both sexes only about two thirds of the antibody-positive sera remained positive when donor sperm was substituted for partners' sperm in the assay. The decreased occurrences of antisperm immunoglobulins A (p less than 0.025) and G (p less than 0.01) in men and of immunoglobulins G (p less than 0.025) and M (p less than 0.01) in women were significant. Incubation of donor sperm in the husband's cell-free seminal fluid before analysis led to the acquisition of sperm reactivity with husband-specific antisperm antibodies in only one of eight women. Women with husband-specific antisperm antibodies also exhibited differences in their cell-mediated immune responses to sperm from various men. Thus sperm from different individuals vary in their ability to react with the immune system of sperm-sensitized men or women.

Antibodies↗

[Flow measurements in extracranial carotid arteries by means of duplex sonography. Results in normal subjects].

Carotid arteries were examined by Duplex sonography in 116 healthy volunteers of between 16 and 78 years of age. We measured the internal carotid artery and common carotid artery peak systolic velocities and their ratio, the common carotid artery time-averaged velocity, the maximal diameter of the common carotid artery, and the common carotid artery volume flow (ml/min). Flow velocities and volume flow showed an age-dependent decrease.

Blood Flow Velocity↗

[Beta-endorphin in premature labor and in mature newborn infants following vaginal and abdominal delivery].

Umbilical venous plasma concentrations of beta-endorphin in 20 premature and 30 mature newborn infants after vaginal delivery or elective caesarean section were determined by specific RIA. In the premature infants the beta-endorphin levels after vaginal and abdominal delivery were significantly higher than in mature newborns. Our data indicate that for premature infants the delivery is more stressful and therefore most likely the release of beta-endorphin from the pituitary is more pronounced. Since high opioid levels can cause respiratory and circulatory difficulties, premature infants are exposed to risk of these problems.

Bradycardia↗

Circadian variation in response to CRF-41 and AVP.

The diurnal response to ovine corticotropin-releasing factor (CRF-41), arginine vasopressin (AVP), and adrenocorticotropic hormone (ACTH) was studied in rats in which the endogenous release of CRF was blocked by chlorpromazine, morphine sulfate, and pentobarbital sodium. This procedure resulted in a markedly attenuated circadian rhythm at base-line levels of plasma corticosterone and ACTH. Decreased pituitary responsiveness to CRF-41 and AVP at 0400 compared with 1600 was observed. The plasma corticosterone response 30 min after intravenous injection of ovine CRF-41 (0.1 microgram/kg) or AVP (5.0 micrograms/kg) remained nearly constant over the major portion of the 24-h light-dark cycle. However, in the early morning (0400), 2 h before lights on, there was an approximately threefold decrease in response. The time of this decrease in response coincided with the normal decline in the concentrations of plasma corticosterone and ACTH. Rats exposed to constant darkness for 10 days continued to show a significantly greater response to CRF or AVP at 1600 than at 0400. In contrast, rats exposed to constant light for 10 days failed to demonstrate a differential response to CRF or AVP at different times of the day. These results demonstrate that there is a diurnal rhythm in pituitary response to CRF and AVP.

Adrenocorticotropic Hormone↗