PubMed Health⌕ Search

Biomedical subjects

H P Neumann

Publications and source records attributed to H P Neumann.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Pheochromocytoma as dominant manifestation of v. Hippel-Lindau syndrome].

A diagnosis of von Hippel-Lindau syndrome was made in two families originating from the same part of the Black Forest but apparently unrelated. Nine affected persons (seven males and two females) had a total of 17 tumours: retinal angioma (4), haemangioblastoma of the CNS (1), and phaeochromocytoma (12). Three of the affected persons and eight of the tumours (six phaeochromocytomas, two retinal angiomas) were diagnosed by family screening. Phaeochromocytoma was diagnosed in eight persons; in four it was the only symptomatic lesion. After extensive diagnostic tests the phaeochromocytoma was the sole tumour in four. Despite severe symptoms the diagnosis of von Hippel-Lindau syndrome had not been made prior to the screening examinations because either the common aetiology of the tumour was not known or there was insufficient exchange of information between the two families.--It is recommended that in each case of phaeochromocytoma von Hippel-Lindau syndrome should be excluded so that lesions can be discovered early in other organs and in other affected family members. If the syndrome is present, annual examinations are indicated because of asynchronous and multi-focal tumour growth.

Adolescent↗
PubMed1992

Central nervous system lesions in von Hippel-Lindau syndrome.

CNS manifestations were studied in 97 gene carriers of von Hippel-Lindau syndrome (HLS). Haemangioblastomas of the CNS were found in 43 patients (44%), 23 females and 20 males. The mean age at diagnosis was 39 years (12-73 years). A total of 93 haemangioblastomas were detected of which 74% were intracranial and 26% were located in the spinal cord; 75% were predominantly cystic and 25% presented as solid lesions. Multiple lesions were found in 42% of HLS-associated haemangioblastomas, but in none of 51 patients with CNS haemangioblastoma without HLS. Haemangioblastoma was the cause of death in 82% of patients with HLS. Although microsurgery has considerably improved post-operative results, multifocal tumour development and recurrence remain a serious problem in the clinical management of HLS gene carriers.

Adolescent↗
PubMed1991

Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus.

von Hippel-Lindau syndrome (HLS), an autosomal-dominant inherited disease, was studied in 92 affected subjects from 29 kindreds. In an initial survey to identify HLS gene carriers, all patients treated at the University of Freiburg for angiomatosis retinae (22), haemangioblastoma of the central nervous system (CNS) (63), and phaeochromocytoma (54) were examined as potential HLS gene carriers. HLS was diagnosed in 86% of the patients with angiomatosis retinae, 19% of the patients with haemangioblastoma of the CNS, and 19% of the patients with phaeochromocytoma. Based on these and on an additional 49 newly diagnosed cases (24 by clinical examination and 25 by pedigree analysis), the calculated prevalence of the disease in the district of Freiburg, Germany, with a population of 1.909 million is 1/38 951. There was a striking tendency for familial clustering of HLS features in affected kindreds. Both angiomatosis retinae and haemangioblastoma of the CNS occurred in most families, whereas renal lesions and/or pancreatic cysts and phaeochromatocytoma were mutually exclusive. This finding suggests that HLS is caused by different mutations within a complex genetic locus, or additional genetic lesions, which cooperate with the HLS gene on chromosome 3p. The data point to a linear sequence of features as follows: phaeochromocytoma, angiomatosis retinae, haemangioblastoma of the CNS, renal lesions, pancreatic cysts, and epididymal cystadenoma.

Adolescent↗
PubMed1991

Cytogenetics of renal cell carcinomas associated with von Hippel-Lindau disease.

To establish the chromosome pattern, we have analyzed short-term cultures of 24 renal cell carcinomas (RCC) from four patients with von Hippel-Lindau disease (VHL). We evaluated the results together with those for 16 RCCs from two VHL patients karyotyped previously in our laboratory and those of 6 tumors published by others. In all 46 RCCs, the cells had lost the shortest overlapping region of the 3pl3-pter chromosome segment. The rearrangement of 3p was the only karyotype change in 20 tumors. In more than 50% of the tumors, a gain of the shortest overlapping region of the 5122-qter segment was detected. Comparative analysis showed that the chromosome aberrations in RCCs associated with VHL are similar to those found in sporadic RCCs. These results indicate that non-papillary sporadic and VHL-RCCs have common genetic mechanisms that result in the loss of the 3p13-pter region containing one or more putative suppressor genes.

Aneuploidy↗
PubMed1991

Pancreatic lesions in the von Hippel-Lindau syndrome.

Common manifestations of the von Hippel-Lindau syndrome, an autosomally dominant inherited cancer-prone disorder, include retinal angiomatosis, hemangioblastoma of the central nervous system, renal cysts, renal cancer, pheochromocytoma, and epididymal cystadenoma. Multiple cysts and microcystic (serous) cystadenomas of the pancreas have also been reported occasionally in patients afflicted with this syndrome. In the large Freiburg study of the von Hippel-Lindau syndrome composed of 66 affected individuals, pancreatic lesions were systematically studied. Fifty-five living individuals were examined by abdominal ultrasound imaging. Abnormal findings were confirmed by computed tomographic scan and/or magnetic resonance imaging. For an additional 11 decreased patients autopsy data were available. Cystic lesions of the pancreas were found in 10 patients (15%). One of these patients presented with multiple pancreatic cysts as the only manifestation of the syndrome. In one patient, a malignant islet-cell tumor was found at autopsy. Because multiple pancreatic cysts did not cause major clinical symptoms and because follow-up examinations over an average period of 5 years did not show significant progression of the lesions, it is concluded that these patients usually do not require surgical treatment. Abdominal ultrasound screening is recommended for patients at risk as a tool to identify potential von Hippel-Lindau syndrome gene carriers with pancreatic manifestations. In all patients with multiple pancreatic cysts, the von Hippel-Lindau syndrome should be included in the differential diagnosis.

Adolescent↗
PubMed1991

Ultradian variations of chromogranin A in humans.

Chromogranin A (CgA) is an acidic soluble protein exocytotically released from virtually all neuroendocrine secretory vesicles. Here we examined spontaneous variations in CgA and catecholamine concentrations in humans. In normal subjects, basal CgA showed no day-to-day, week-to-week, or diurnal variability. Plasma CgA had significant ultradian variation in normotensives and hypertensives, and in bilaterally adrenalectomized subjects. Gender, but not age or blood pressure, influenced CgA variations, males having fewer (P less than 0.05) peaks per 8 h. Plasma catecholamines had significant ultradian variations in both controls and bilaterally adrenalectomized subjects. Within individuals, neither basal nor peak plasma CgA correlated with catecholamines, nor was there concordance between plasma CgA and catecholamine peaks. Somatostatin, a widespread inhibitor of nonsympathoadrenal neuroendocrine secretion, diminished both the frequency and amplitude of plasma CgA peaks. Thus spontaneous variations in basal CgA are not directly linked to alterations in sympathoadrenal catecholamine secretion. Furthermore, neuroendocrine secretion at sites other than the sympathoadrenal system contributes to spontaneous variations in CgA concentration.

Activity Cycles↗
PubMed1991

Suppression of chromogranin-A release from neuroendocrine sources in man: pharmacological studies.

Chromogranin-A (CgA) is an acidic soluble protein with a virtually ubiquitous occurrence in normal human neuroendocrine tissues. Of the many potential tissue sources of CgA immunoreactivity, which contribute to basal (unstimulated) circulating CgA? To explore this question we studied the effects of selective and nonselective suppression of secretion at several sites within the neuroendocrine system. Selective disruption of sympathetic outflow by trimethaphan decreased basal CgA by 25%, suggesting that sympathetic neurons contribute to circulating CgA. Plasma CgA in patients with unilateral and bilateral adrenalectomy fell within the range observed in normal subjects, weighing against the adrenal medulla as a major source of basal circulating CgA. Selective suppression of a variety of anterior and posterior pituitary cell types decreased plasma levels of the usual resident peptide hormones, but left plasma CgA unperturbed. After propranolol treatment, plasma CgA remained unaltered. Secretin suppressed plasma PTH and calcitonin, but did not alter plasma CgA levels. On the other hand, widespread nonselective suppression of a variety of neuroendocrine secretory cells by somatostatin decreased plasma CgA by 48%. Plasma catecholamines were unaltered by somatostatin infusion, suggesting that somatostatin inhibited CgA release from nonsympathoadrenal sources. During the infusion of somatostatin, the plasma epinephrine increment in response to insulin-induced hypoglycemia was maintained, and plasma CgA did not fall, nor did it rise after somatostatin cessation. Taken together, these findings suggest that somatostatin did not inhibit transport of stimulation-released CgA from the adrenal medulla to the circulation. In conclusion, although the adrenal medulla is the major tissue source of CgA immunoreactivity in man, other neuroendocrine sites, including sympathetic axons and multiple endocrine glands, appear to influence the basal circulating concentration of CgA.

Adrenal Glands↗
PubMed1990

Chromogranin A in familial pheochromocytoma: diagnostic screening value, prediction of tumor mass, and post-resection kinetics indicating two-compartment distribution.

PURPOSE: Chromogranin A, co-released with catecholamines from the adrenal medullary and sympathetic neuronal vesicles, is elevated in plasma from patients with pheochromocytoma. We assessed its diagnostic screening value, its plasma level in correlation with tumor mass, and its disposition kinetics in familial pheochromocytoma and sporadic pheochromocytoma. PATIENTS AND METHODS: The sensitivity and specificity of chromogranin A's diagnostic value for pheochromocytoma were established through one kindred with familial pheochromocytoma associated with von Hippel-Lindau syndrome (13 available members) and in seven subjects with sporadic pheochromocytoma. Serial postoperative plasma samples were also obtained (5 minutes to 4 days) from eight subjects with pheochromocytoma in order to study chromogranin A post-resection kinetics. Chromogranin A was measured by radioimmunoassay based on purified pheochromocytoma chromogranin A. RESULTS: In this kindred, elevations of chromogranin A (greater than 52 ng/mL) were sensitive (83%, five of six) and specific (100%, 10 of 10) in detecting familial pheochromocytoma; these diagnostic values comparable to those achieved by conventional evaluations for pheochromocytoma, such as urinary catecholamines, urinary catecholamine metabolites or imaging methods. Elevated levels of plasma chromogranin A specifically indicated pheochromocytoma, rather than von Hippel-Lindau syndrome gene carrier status. In 13 preoperative subjects with either familial or sporadic pheochromocytoma, plasma chromogranin A concentration predicted tumor size (r = 0.81, p less than 0.01). The change in chromogranin A plasma concentration after pheochromocytoma resection best fit a two-compartment model, with an initial rapid half-life time of 16 minutes, followed by a longer half-life time of 520 minutes. The model also predicted a 23.8:1 compartmental ratio of extravascular/intravascular chromogranin A, suggesting substantial tissue sequestration or binding of chromogranin A. CONCLUSIONS: (1) Plasma chromogranin A is a valuable (sensitive and specific) diagnostic tool in detecting both familial and sporadic pheochromocytoma. (2) The concentration of plasma chromogranin A predicts the size of the pheochromocytoma. (3) Chromogranin A post-resection kinetics suggest extravascular sequestration of chromogranin A.

Adolescent↗
PubMed1990

Neuroendocrine sources of chromogranin-A in normal man: clues from selective stimulation of endocrine glands.

Chromogranin-A (CgA), as measured in the circulation by RIA, has emerged as a useful probe of exocytotic sympathoadrenal activity in man as well as of the presence and extent of neuroendocrine neoplasia. Here we studied, using a sensitive RIA, the distribution of CgA immunoreactivity in normal human neuroendocrine tissues. Furthermore, to investigate whether these normal tissue sources measurably contribute to plasma CgA, we measured plasma CgA, catecholamine, and other polypeptide hormone responses to selective stimuli of secretion at several sites within the neuroendocrine system. Immunoreactive CgA was ubiquitous in human neuroendocrine tissues, in rank order of concentration (micrograms per g wet wt): adrenal medulla greater than pituitary greater than pancreas greater than stomach greater than small intestine (jejunoileum) greater than brain (frontal cortex) greater than parathyroid greater than thyroid. Quantitatively, neuroendocrine tissues other than the adrenal medulla possessed only 0.04-25% of the immunoreactivity found in the adrenal medulla. Insulin-induced hypoglycemia, a potent stimulus of adrenomedullary secretion, resulted in 1.7- and 14-fold rises in plasma CgA and epinephrine, respectively. However, insulin-induced hypoglycemia failed to perturb plasma CgA in three bilaterally adrenalectomized patients, suggesting that the adrenal medulla is the source of plasma CgA elevation during hypoglycemia in normal subjects. Cell type-selective secretagogue stimulation of normal endocrine secretory cells other than the adrenal medulla (pituitary, pancreas, gut, thyroid, and parathyroid) induced measurable increments in the concentrations of the resident peptide hormones, but left plasma CgA unperturbed. Nonselective stimulation of a wide variety of endocrine secretory cells with pentagastrin elevated plasma CgA 1.4-fold. However, restriction of pentagastrin's targets by coinfusion of calcium abolished the effect on plasma CgA. Hence, within the normal human neuroendocrine system, only selective stimulation of the adrenal medulla is likely to elevate plasma CgA under physiological or pharmacological circumstances. This is consistent with our finding of the adrenal medulla as the quantitatively major normal neuroendocrine tissue source of CgA immunoreactivity.

Adrenal Medulla↗
PubMed1990

[Diagnosis of multiple endocrine neoplasms type IIa using DNA analysis].

The gene causing MEN IIa has recently being assigned to the pericentromeric region of chromosome 10. We performed linkage analysis using DNA-markers closely related to the chromosomal locus at chromosome 10: MCK II, retinol binding protein cDNA and cTBIRBP-9. Available for the study were EDTA blood from two families. The analysis was positive in two asymptomatic offsprings in one family (B), whereas the markers were not informative in the other family (A). Genetic distance of the informative marker of family A to MEN IIa gene is 2 cM, i.e. a likelihood of 98% (95% up a confidence limit with 5%) for the gene carrier status of two children aged 11 and 7 y old. The following clinical investigation including pentagastrin test, plasma catecholamines and 24 hour urine catecholamines and parathormone was negative until now. We recommend early linkage analysis for establishing the genetic status in offspring of MEN IIa families to focus further screening to those, who are predicted to be gene carrier.

DNA, Neoplasm↗