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Biomedical subjects

W Saeger

Publications and source records attributed to W Saeger.

At least 91 records · Page 5Linked to original sources
PubMed1994

Morphological and immunohistochemical studies of the pituitary in sudden infant death syndrome (SIDS).

The morphological structure and immunohistochemical reactions of 100 pituitaries from cases of SIDS children (58 males and 42 females, average age 5.34 +/- 3.12 months) were studied. Controls consisted of 19 pituitaries from children (14 males and 5 females, average age 5.63 +/- 2.52 months) with a clearly identifiable cause of death e.g. drowing or strangulation. The microscopical and immunohistochemical studies for identifying pituitary cell types revealed normally developed organs. Unspecific necroses and haemorrhages were observed in 2 cases of SIDS but in none of the controls. Hyperaemia was detected in 51 (30 male/21 female) cases of SIDS. No significant differences were found in the distribution of microfollicles (54%), cysts of the intermediate zone (14%), persistency of the Rathke's pouch (44%), Erdheim's squamous epithelium (8%) or heterotopic salivary glands (3%). The semiquantitative immunohistochemical evaluations of the different cell types showed no significant variations from the control group. The pattern of distribution of the intracytoplasmic vacuolisations of the ACTH and gonadotropic cells showed no significant differences. Folliculo-stellate cells were either not demonstrable--commensurate with age--or showed a normal distribution. The results for both study groups may be defined as consequences of terminal agony, but failed to reveal the cause of the sudden infant death.

Cause of Death↗
PubMed1994

The anterior pituitary lobe in patients with cystic craniopharyngiomas: three cases of associated lymphocytic hypophysitis.

Specimens of the anterior pituitary lobe were investigated histologically in 28 craniopharyngioma patients operated on trans-sphenoidally. The pituitary glands in 3 patients revealed lymphocytic invasion giving a histological appearance typical of lymphocytic hypophysitis (incidence: 11%). At follow-up examination all three patients with associated lymphocytic hypophysitis had complete pituitary insufficiency, whereas only 36% of the craniopharyngioma patients without associated lymphocytic hypophysitis were in this poor postoperative endocrine state. The phenomenon of associated lymphocytic hypophysitis in craniopharyngioma patients has not been reported so far. This might be due to the fact that investigators have failed to systematically examine the anterior pituitary lobe in craniopharyngioma patients. The 60 cases of lymphocytic hypophysitis reported in the literature occurred, for the most part, in women during late pregnancy or shortly after delivery. An auto-immune origin is assumed in this type of inflammation. In contrast to this pathophysiological mechanism, we assume a local induction of inflammation resulting from the craniopharyngioma cyst in our 3 patients.

Adult↗
PubMed1994

Venous thromboses and pulmonary embolisms in post-mortem series: probable causes by correlations of clinical data and basic diseases.

In a continuous series (1979-1989) of autopsies (n = 4,077) acute venous thromboses or pulmonary embolisms were found in 966 cases (23.7%). Fresh pulmonary embolisms were present in 758 cases (18.6%) and thromboses without embolisms were demonstrated in 208 (5.1%) autopsies. Fulminant fatal embolism leading to death was found in 598 cases (14.6%). In some cases with embolism (n = 56; 7.4%) a vein thrombosis was not demonstrable. In 62.1% of embolisms thromboses originated from pelvic or femoral veins and in 22.8% from calf veins. A comparison of the series of thromboses with a control group free of thromboses showed significant (p < 0.05) differences: a) thromboses are more frequent in females; b) patient's weight was higher in group with thromboses (59.4 kg versus 56.7 kg); c) the period of rest in hospital was longer in group with thrombosis (19.0 days versus 101.4 days); d) malignancies were more frequent in study group (54.5% versus 47.1%); e) hematocrit was higher in group with thrombosis (39.1% versus 37.5%); f) cases treated with heparin (15,000 IE sc daily) and patients with hepatic insufficiency are overrepresented in control group.

Age Factors↗
PubMed1994

Gastrointestinal amyloid deposits in old age. Report on 110 consecutive autopsical patients and 98 retrospective bioptic specimens.

The prevalence of gastrointestinal amyloid was determined in 110 consecutive autopsy patients aged 85 years and older. Paraffin sections from the esophagus, stomach, small intestine, colon and rectum were stained with Congo red and inspected in polarized light. Amyloid was found in 38 patients (36%). Four patients had generalized amyloidosis and the remaining 34 revealed more localized varieties of amyloid. Immunohistochemical classification with a panel of antisera directed against five major amyloid fibril proteins displayed at least four different types of amyloid. Twenty cases exhibited amyloid of transthyretin origin, five cases were of lambda light chain origin and one case was of amyloid A-type. Thus far, unclassifiable amyloid deposits were found in 18 cases, 16 of which were strictly localized in subserosal veins. This consecutive autopsy series was compared with 98 randomly-selected bioptical gastrointestinal tissues with amyloid according to distribution pattern, sex, frequency of the various types of amyloid and associated diseases.

Aged↗
PubMed1994

Preoperative octreotide treatment of growth hormone-secreting and clinically nonfunctioning pituitary macroadenomas: effect on tumor volume and lack of correlation with immunohistochemistry and somatostatin receptor scintigraphy.

The factors that determine the hormone and volume responses of pituitary adenomas to the somatostatin analog octreotide are poorly understood. We, therefore, studied the correlation between 111indium-pentetreotide somatostatin receptor scintigraphy (SRS) and the clinical and immunohistochemical classification of pituitary adenomas, on the one hand, and hormone and volume responses, on the other hand. Ten patients with GH-secreting (6 females and 4 males; age, 31-67 yr) and 14 patients with clinically nonfunctioning (NF) macroadenomas (5 females and 9 males; age, 22-79 yr) were preoperatively treated with 300 micrograms/day octreotide, which was increased to 600 and 1500 micrograms/day at weekly intervals and then continued for at least 3 months until surgery. SRS was performed before therapy. A sellar magnetic resonance imaging scan was performed before therapy; 1, 2, and 3 weeks and 3 months after start of therapy; and after surgery. Acromegalics also had an 8-h GH profile, insulin-like growth factor-I determination, and a 100-g oral glucose load at these time points. An attempt was made to identify NF adenomas as gonadotroph adenomas using their LH, FSH, and alpha-subunit responses to TRH. In acromegalic patients, octreotide suppressed mean GH (8-h profile) and insulin-like growth factor-I concentrations from 34.9 +/- 9.7 to 8.1 +/- 3.6 micrograms/L and from 2122 +/- 1025 to 701 +/- 208 micrograms/L, respectively, after 3 months. Significant (26-85% decline) tumor shrinkage occurred in 5 of 10 patients, mainly within the first week. Tumor shrinkage and GH suppression were not correlated. Four of 7 patients had increased pituitary 111indium-pentetreotide uptake, but this did not predict GH suppression or tumor shrinkage. Of the NF adenomas, 2 responded with shrinkage (57% and 96% decline). Four of 12 adenomas had increased 111indium-pentetreotide uptake, but this did not correlate with tumor shrinkage (2 adenomas; 1 gonadotroph and 1 null cell adenoma), immunohistochemistry, or clinical classification. We conclude that preoperative octreotide therapy suppresses GH in most patients and reduces tumor volume in up to 50% of acromegalic patients. It also induces shrinkage in some NF adenomas, although less frequently. SRS does not predict shrinkage of either tumor type. Shrinkage does not correlate with clinical classification or immunohistological characteristics. Further studies are needed to identify the factors that determine the hormone and volume responses of pituitary adenomas to octreotide therapy.

Acromegaly↗
PubMed1994

Hypothalamic hamartomas: with special reference to gelastic epilepsy and surgery.

This study presents six patients with hypothalamic hamartomas diagnosed on the basis of magnetic resonance imaging. Histological confirmation was performed in three patients who underwent surgery. Immunohistological assays were used to determine the neurosecretory pattern. Four patients presented with epilepsy, including gelastic seizures. Other symptoms included behavioral abnormalities in four patients and precocious puberty and visual impairment in two patients. One patient presented associated developmental defects. Good results without morbidity were achieved with surgical resectioning in two patients with large hamartomas associated with behavioral abnormalities and gelastic epilepsy that was unresponsive to conventional medical treatment and in one patient with visual impairment. We propose a classification of the hypothalamic hamartomas based on topographical and clinical data obtained from 36 selected cases in the literature and six of our own cases. This classification should help to classify the various treatment methods and the surgical risks into four subgroups (Types la, lb, lla, and llb). We conclude that the surgical approach is a realistic alternative in certain cases, including large and broad-based Type llb hamartomas associated with gelastic epilepsy and behavioral disorders.

Adult↗
PubMed1993

Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para-adenomatous gland in Cushing's disease and Nelson's syndrome.

Pro-opiomelanocortin (POMC) mRNA was demonstrated in pituitary adenomas from 16 patients with Cushing's disease and 10 with Nelson's syndrome. The intensity of signal was significantly greater in Nelson's syndrome than in Cushing's disease and there was a trend towards a greater proportion of positive cells. This probably reflects inhibition of POMC gene expression by the high circulating levels of cortisol in Cushing's disease. In the para-adenomatous gland, the intensity of signal was variable in cells showing Crooke's hyaline change, ranging from negative to strongly positive, in keeping with the functional heterogeneity of corticotrophs. In one case, junctional corticotrophs were present and these were more intensely stained than anterior lobe corticotrophs in the same gland. This supports the concept that these cells are subject to different regulatory influences from corticotrophs in the anterior lobe. Whether this is related to differences in embryological origins or to local factors is at present unclear.

Adenoma↗
PubMed1993

Effects of octreotide on morphology of pituitary adenomas in acromegaly.

We studied the effects of the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz, Basel, Switzerland) on the morphology of pituitary adenomas in acromegaly. Of the 29 adenomas examined by light microscopy, 16 had been treated pre-operatively with octreotide. The treated adenomas were compared with the untreated adenomas. 14 adenomas were also studied by electron microscopy. In 23 cases we performed in-situ-hybridization for GH-mRNA. Under light microscopy, we found a decrease in amyloid deposits and a higher amount of cell necroses and fibroses after treatment, mainly in the tumors with shrinkage. Tumor shrinkage was diagnosed when the maximal diameter of the adenoma decreased for at least 1/3 during octreotide treatment in NMR examination. Immunohistochemical examinations showed that treated adenomas, especially those with tumor shrinkage, possessed more GH immunoreactive cells, and after in-situ-hybridization we found a higher content of GH-mRNA. On the ultrastructural level, rough endoplasmic reticulum appeared to be increased in treated adenomas. The increase of GH-mRNA and of rough endoplasmic reticulum suggests the likelihood of an increased secretory activity due to a rebound effect after short-term pre-operative omission of octreotide. Other findings are discussed.

Acromegaly↗
PubMed1993

Tumors of the sellar region mimicking pituitary adenomas.

In the sellar region most tumors of our collection (n = 1937) are pituitary adenomas, followed by craniopharyngiomas, chordomas and meningiomas. Difficulties in morphological differential diagnosis by light microscopy may occur in meningiomas, plasmacytomas, chordomas and germinomas. In these cases, immunohistological investigations and sometimes even electron microscopy are helpful in solving the problems. Meningiomas can sometimes resemble pituitary adenomas. Of diagnostic value in these cases is the expression of vimentin and S-100-protein in the meningioma cells. Plasmacytomas may also mimic pituitary adenomas. In these cases, the positive reaction with antibodies against LCA and immunoglobulins or against kappa-light-chains and lambda-light-chains leads to the diagnosis. Chordomas, too, can sometimes be hardly distinguished from pituitary adenomas. In these cases, the expression of S-100-protein, vimentin and CEA by the chordoma cells and the typical electron microscopic features of chordomas are helpful for the differential diagnosis. Germinomas may sometimes be indistinguishable from lymphocytic hypophysitis. Of diagnostic importance are here the expression of HCG and placental alkaline phosphatase by germinoma cells. In the above mentioned cases, it is also important to perform immunohistochemical examinations for pituitary hormones including alpha-subunit. All these tumors do not express these hormones.

Adenoma↗
PubMed1993

Cushing's disease in a child caused by a corticotropin-releasing hormone-secreting intrasellar gangliocytoma associated with an adrenocorticotropic hormone-secreting pituitary adenoma.

Cushing's disease resulting from intrasellar corticotropin-releasing hormone (CRH)-secreting gangliocytomas is very rare, and only two such cases have been reported in the literature to date. The authors present a third case in which an adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms of Cushing's disease. Computed tomographic and magnetic resonance imaging scans showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor and a small adenoma were removed transsphenoidally. Histological examination revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor causing Cushing's disease in a child. It might exemplify induction of an ACTH-secreting pituitary adenoma by means of chronic overstimulation of CRH.

Adenoma↗
PubMed1993

Detection of growth hormone, prolactin and human beta-chorionic gonadotropin mRNA in growth hormone-secreting pituitary adenomas and in prolactin-secreting pituitary adenomas by in situ hybridization using a non-isotopic detection method.

A non-isotopic in situ hybridization method with digoxigenin-labelled probes was used to examine growth hormone (GH), prolactin (PRL) and human beta-chorionic gonadotropin (beta-hCG(LH)) gene expression in 63 pituitary tumours in acromegaly and 20 adenomas in hyperprolactinaemia. hCG and LH were detected simultaneously because of the extensive homology (more than 90%) of their mRNA sequences (1). A comparison with former results obtained with 35S-labelled probes shows the value of the easier and faster non-isotopic method. Additionally, immunohistochemical data are included to give even more evidence for the synthesis of the respective hormones by the tumour cells. In all 63 adenomas in acromegaly, GH mRNA was revealed in 59 PRL mRNA and in 36 beta-hCG(LH) mRNA. A positive immunostaining for GH was found in all, for PRL in 40, and for beta-hCG(LH) in 34 adenomas. The comparison of the two in situ hybridization methods revealed no differences concerning GH mRNA detection, but not all tumours positive after non-isotopic PRL and beta-hCG(LH) mRNA detection showed signals with the radioactive method. Referring to the 20 PRL-secreting adenomas, PRL gene expression was demonstrable in all, GH mRNA in 12, and beta-hCG(LH) mRNA in 2 cases. Comparing the positive results of immunohistochemistry with those of in situ hybridization, correspondence was found in 19 cases for PRL, in 5 cases for GH and in no case for beta-hCG(LH).

Acromegaly↗
PubMed1993

Cerebral amyloid angiopathy. Frequency, significance and immunohistochemistry.

For the assessment of the anatomical distribution of cerebral amyloid angiopathy (CAA) as well as that of amyloid plaques (AP), 955 post-mortem brain specimens from 653 patients (aged 14 to 95 years) were made available from a general hospital. Using histological and immunohistochemical techniques, we demonstrated amyloid angiopathy chiefly in the occipital, parietal and temporal regions. Senile plaques were mostly found in parietal, temporal and occipital areas. In our cases, neurofibrillary tangles were rarely prominent in the regions examined. There was often a significant difference in the frequency of amyloid angiopathy and of plaques in distinct areas between men and women. Congophilic angiopathy was associated with senile plaques in 82.3%, and neurofibrillary tangles with plaques in 76.9%. In comparison, the correlation of amyloid plaques with CAA (32.5%) and of plaques with neurofibrillary tangles (11.5%) was less pronounced. There was a strong association of cerebral vascular amyloid with age in both sexes, it was more pronounced in women than in men. Unexpectedly, CAA showed a decrease in frequency in men in the 7th and 8th decade of life. In addition, there was a positive correlation between the amount of CAA and spontaneous hemorrhages, but no correlation with ischemic encephalopathy. Immunohistochemistry showed that cerebral amyloid was neither amyloid of the AA- nor of the ATTR-(Antitransthyretin-, formerly anti-AF)-type. An antibody to the beta-protein (anti-A beta) showed cerebral vascular deposits to be congruent with the Congo red method, whereas senile plaques stained weakly and neurofibrillary tangles could not be stained at all with these antibodies.

Adolescent↗
PubMed1993

[Ectopic ACTH- or CRH-secreting tumors in Cushing's syndrome].

A collection of 13 tumors causing an ectopic Cushing's syndrome was composed of four bronchial carcinoids, one small cell carcinoma of the bronchus, one thymic carcinoid, two islet cell tumors of the pancreas, one pheochromocytoma, two medullary carcinomas of the thyroid, one prostatic cancer and one intrasellar choristoma. By immunohistochemistry, ACTH in combination with CRH was found in one bronchial carcinoid and in one islet cell carcinoma. ACTH but not CRH was demonstrable in one bronchial carcinoid, in both medullary carcinomas of the thyroid, in the thymic carcinoid and in the pheochromocytoma. CRH without ACTH was present in the small cell carcinoma of the bronchus, one bronchial carcinoid, the prostatic cancer and the choristoma of the sellar region. Neither ACTH nor CRH could be found in one islet cell carcinoma. In the pituitary (n = 7) Crooke's cells were found except in one case with islet cell carcinoma which was treated with adrenostatic drugs. The pituitary besides the intrasellar choristoma harbored an ACTH cell adenoma. The pathophysiological correlations are discussed.

Adenoma, Islet Cell↗
PubMed1992

Effect of drugs on pituitary ultrastructure.

Various drugs and hormones influence the light microscopic and especially the electron microscopic structure of the anterior pituitary and its tumors. Many structural effects are known only from animal experiments since specimens from human pituitaries are mostly not available. The structure of growth hormone (GH) cells is relatively stable. A massive GH cell hyperplasia is known only in rare cases with growth hormone releasing factor (GRF) excess from tumors. Prolactin cells can be stimulated by drugs, neurotransmitters, and hormones which decrease the dopamine inhibition. Adrenocorticotropic hormone (ACTH) cells are stimulated by stress, some hormones, loss of adrenals, and drugs which activate the alpha 1- and beta-receptors or inhibit the alpha 2-receptors. They are suppressed and changed into Crooke's cells by treatment with glucocorticoids. Thyroid-stimulating hormone (TSH) cells increase in number and size in states for overstimulation especially by thyrotropin releasing hormone (TRH). A decrease results from hyperthyroidism and possibly from somatostatin, L-dopa, and dopamine. Gonadotroph cells transform into castration cells in strongly hyperactive states (gonadectomy, antiandrogens, gonadotropin releasing hormone [Gn-RH]agonists, aminoglutethimide). Special types of pituitary adenomas can be treated with drugs which suppress hormone production and proliferation. Dopamine agonists and somatostatin reduce the tumor size of varying proportions of GH secreting adenomas in acromegaly. Ultrastructurally, a decrease of cytoplasmic and nuclear volume and an increase of lysosomes are found. Bromocriptine and other dopamine agonists are established in the treatment of prolactin secreting adenomas. They induce a shrinkage in many cases. Ultrastructurally, a reduction of cellular and nuclear size, an increase in number of secretory granules and of lysosomes, and a reduction of rough endoplasmic reticulum can be demonstrated.

Adenoma↗