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J Hensen

Publications and source records attributed to J Hensen.

At least 37 records · Page 2Linked to original sources

[Augmentation of the immune response to islet cell antigens with development of diabetes mellitus caused by interferon-alpha therapy in chronic hepatitis C].

We report on a 36-year-old patient suffering from chronic hepatitis C. Because of elevated liver enzymes and histology showing chronic inflammation and periportal fibrosis, interferon-alpha (IFN) therapy was started with a dosage of 5 Mio units three times a week. Four months later the patient hat to be hospitalized due to the typical clinical features of a recent onset type 1 diabetes (BG > 300 mg/dl, HbA1c 9.6%, ketonuria). In serum samples prior to and following interferon therapy, we analyzed titers of diabetes-related autoantibodies responding to GAD65 (glutamic acid decarboxylase), IA2c (tyrosine phosphatase) and ICA (islet cell autoantibodies). While ICA were negative before starting therapy, IA2c-antibodies were highly elevated. In contrast. GAD65-antibodies were elevated only slightly over the cut-off of the assay before therapy (controlled by a second different RIA assay) and increased 100 fold during IFN-alpha treatment. Additionally thyroid antibodies appeared. After the end of the IFN therapy, GAD65- and IA2c antibodies remained on high levels and also ICA could now be found. The patient was positive for HLA-DR4. This case supports the hypothesis that IFN-alpha therapy may lead to an augmented autoimmune reaction against islet cell antigens resulting in the development of diabetes mellitus type 1, especially if there are other predisposing factors before IFN treatment. We further discuss the possible involvement of interferon-alpha in the pathogenesis of autoimmune diabetes with reference to recent studies.

Adult↗

[Reduced incidence of side-effects of growth hormone substitution in 404 patients with hypophyseal insufficiency. Results of a multicenter indications study].

BACKGROUND: Substitution of pituitary insufficient patients with recombinant human growth hormone (rhGH) in addition to the conventional substitution with glucocorticoids, L-thyroxine and sex hormones has been approved by the regulatory authorities in 1995 with the imposition to conduct surveillance studies to monitor drug safety. RESULTS: 24% of all patients were within their 2nd treatment year, 15% within their 4th year, maximum treatment period was 6 years. There were 2 peaks within the patients age distribution: 30 to 39 years (24%) and 50 to 59 years (24%). The causes for pituitary disease were as follows: pituitary adenomas (47%), idiopathic (16%), craniopharyngeomas (16%) and others (21%). Mean GH dose was 1.5 IU/d s.c. (range 0.4 to 4 IU/d). Serum-IGF-1 increased by 159 and 192% in females and males. Waist circumference decreased by 2% and serum cholesterol was lowered by 5.5% in males. There were 2 cases with new carcinomas, 1 diabetes mellitus II and 1 death. Adverse events (AEs) within KIMS were compared to those of the treatment (GH) and placebo (PI) groups of the previous admission trials (in percent): edema: KIMS 10, GH 37, Pl 3; arthralgia: KIMS 8, GH 19, Pl 2; muscle pain: KIMS 3, GH 16, Pl 3; dizziness: KIMS 2, GH 1, Pl 3; headache: KIMS 2, GH 3, Pl 2; others: KIMS 2, GH 22, Pl 13. The reported incidence of AEs in KIMS was lower than in previous clinical trials. There might be 3 reasons for this: 1. under-reporting, particularly those AEs not likely to be related to GH treatment; 2. doses used in trials were 2-fold higher than in KIMS; 3. dose titration for individual patients. CONCLUSION: Surveillance programs are important for monitoring of drug long-term efficacy and safety.

Adolescent↗

[Endocrine orbitopathy: comparison of the long-term result and classification after radiotherapy].

BACKGROUND: This study compares 4 classifications in patients with progressive refractory Graves orbitopathy (GO) and examines their prognostic value in long-term follow-up. PATIENTS AND METHODS: From 1984 to 1994, 60 consecutive patients (49 female, 11 male) received 20 Gy (10 x 2 Gy) radiotherapy with 6 MV Linac photons. Ocular symptoms and functional impairment was evaluated according to 4 GO-classification systems: Werner-, modified ATA- and Stanford-Score and Ophthalmopathy-Index (OI) according to Grussendorf. In addition, all patients noted their subjective response on a linear scale (0 to 100%). RESULTS: Improvement was achieved within 1 year after radiotherapy according to the Werner-Score in 28 (47%) patients in > or = 1 symptom category, according to the modified ATA-score in 48 (80%), the Stanford-score in 47 (78%) and the OI-Score in 55 (92%) patients (reduction of > 2 points). The Werner-Score correlated less to the other scores (coefficient r < 0.5) than the other scores among themselves (r approximately 0.9). The ATA-Score improved in the different symptom categories between 47% (stage VI) and 87% (stage V). The OI-Score was reduced by a mean of 6 points. The patients reached a mean subjective improvement of +70 +/- 25%. Acute or chronic side effects were not observed. In multivariate analysis the "male gender" (p = 0.08), a "symptom duration prior to radiotherapy > 1 year" (p = 0.14) and a "high symptom category" (p = 0.11) indicated a negative prognostic trend. CONCLUSIONS: External radiotherapy is effective for severe, progressive GO after pretreatment. A minimum follow-up of at least 12 months and standardized classification and success criteria are required.

Adolescent↗

[Radiotherapy only in severe, progressive endocrine orbitopathy: long-term results and comparison of various classification systems].

BACKGROUND: Therapeutic results after radiotherapy in thyroid associated orbitopathy (TAO) often are not comparable, because either different therapeutic methods at the same time or different scores were used in the evaluation. This study focuses on radiotherapy alone by means of different evaluation scores. PATIENTS AND METHODS: 60 patients (49 women, 11 men) received standard external beam radiotherapy (20 Gy: 10 fractions of each 2 Gy) as ultima ratio after failing different other therapies of thyroid associated orbitopathy. The mean interval from beginning of the symptoms to the radiotherapy was 17 +/- 36 months (between 6 and 240 months). The follow up was documented--classified by means of 4 different scores--before radiotherapy, 6-12 weeks, 1 year after radiotherapy and at last follow up. The changes of symptom categories or grades of the different scores were analysed. RESULTS: Significant changes of the ophthalmic scores were observed when comparing the endpoints at 6-12 weeks, and at 1-year follow up after radiotherapy. The "classical" Werner score at 12 months follow up did not correlate well with the other TAO scores: American thyroid association (ATA) scoring system, Stanford scoring system, International ophthalmopathy index, while all other TAO scores revealed a high correlation among each other. According to the Orbitopathy Index (OI) of Grussendorf an improvement from 14.2 points to 6.0 points was achieved. Soft tissue involvement and corneal involvement demonstrated the highest response rate (83/87%), extraocular muscle involvement and proptosis a good response rate (69/70%). No long-term complications were observed. CONCLUSION: According to this study there are indications that external beam radiotherapy is a suitable therapy even after pretreatment and a longer course of TAO. The OI, the ATA and the Stanford scoring systems lead to similar results in the assessment of thyroid orbitopathy.

Adolescent↗

Severe hyponatremia after transsphenoidal surgery for pituitary adenomas.

Severe hyponatremia has been described after elective surgery with subsequent permanent brain damage. Other authors, however, have noted that morbidity and mortality rates of severe hyponatremia have been greatly overestimated. We retrospectively examined 19 patients (8 male, 11 female) who developed severe hyponatremia (100 to 124 mmol/liter) after transsphenoidal surgery for pituitary adenomas. Eight patients had hormonally inactive adenomas, 5 ACTH-secreting adenomas, 2 GH-secreting adenomas and 4 prolactin-secreting adenomas. The mean age of the patients was 47.5 years, with a range from 16 to 71 years. The mean preoperative serum sodium level was 137.8 mmol/liter. The timing of hyponatremia showed two different patterns. Five patients developed early postoperative hyponatremia (mean 114.0 mmol/liter +/- 4.85) and 14 patients showed the lowest mean serum level one week after surgery (118.1 mmol/liter +/- 6.86). Patients with early hyponatremia had fewer and less severe symptoms than patients with delayed hyponatremia. None of the patients developed seizures or a demyelination syndrome. Despite severe degree of hyponatremia for most of our patients treatment with water restriction and oral sodium supplementation was sufficient.

Adenoma↗

[Neuro-MR-findings in primary panhypopituitarism].

Congenital panhypopituitarism is a rare disease. It may be a complication of tumors, craniocerebral trauma, infection, granulomatous diseases, vascular pathologies, etc. In many cases no primary disease causing panhypopituitarism is found (idiopathic form). A potential reason is interruption of the pituitary stalk due to ischemic etiology in patients with cord encirclement and/or other birth injuries leading to interruption of the axonal transport of ADH and oxytocin as well as hypothalamic releasing hormones. This explains the ectopy of the neurohypophysis without diabetes insipidus and the hypoplasia of the adenohypophysis. GH-deficiency causes short stature and metabolic disturbances, LH-FSH-deficiency amenorrhoea/oligomenorrhoea, loss of libido and secondary sexual characteristics, TRH-deficiency hypothyroidism and ACTH-deficiency hypotonia, weakness, loss of pigmentation. We report a case of congenital panhypopituitarism. MR imaging of the brain revealed a hypoplastic adenohypophysis and a hypoplastic pituitary stalk which was interrupted in its superior segment. An ectopic neurohypophysis was found located in the area of the hypothalamus ("hypothalamic hot spot"). The ectopic neurohypophysis showed strong enhancement after intravenous application of Gd-DTPA. MR imaging of the hypothalamic-hypophyseal axis is well suited for the differentiation between congenital and acquired forms of panhypopituitarism in clinically uncertain cases.

Adult↗

[Aquaretic drugs--a new therapeutic principle in treatment of hyponatremia?].

The antidiuretic hormone (vasopressin) is involved, either directly or indirectly, in the pathogenesis of almost all forms of hyponatremia. This means that blockage of the ADH effect at the renal ADH receptor represents a rational approach in the treatment of hyponatremia, in particular in difficult-to-treat and symptomatic forms. Recently, orally absorbable, non-peptidergic competitive ADH antagonists (aquaretics) have been introduced, which bind with high affinity to renal ADH receptor subtypes. Initial investigations in humans show that the substance is well tolerated. Numerous studies on patients with hyponatremia of varying genesis have since been started. It is to be expected that the availability of this new dass of substances will result in marked improvements in the treatment of acute and chronic forms of hyponatremia.

Antidiuretic Hormone Receptor Antagonists↗

[Mineralocorticoid-induced hypertension].

Several important advances have been made in the pathogenesis of mineralocorticoid induced hypertension. A hybrid gene was found to be responsible for glucocorticoid remediable hypertension. This extra gene contains fragments of 11-beta-hydroxylase and aldosterone synthase. The hybrid gene is the result of an unequal crossing-over of the two genes located in close proximity on chromosome 8, and leads to the production of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol. These hybrid steroids are also detected in patients with aldosterone producing adenoma but not in patients with hyperaldosteronism due to bilateral adrenal hyperplasia. In Apparent "Mineralocorticoid Excess", inherited as an autosomal recessive disorder, an increased ratio of urinary cortisol metabolite to cortisone is diagnostic. The syndrome is due to a deficiency of the renal enzyme 11-beta-hydroxysteroid dehydrogenase type II, which protects the mineralocorticoid receptor against cortisol that binds to the mineralocorticoid receptor like aldosterone. Liddle's syndrome is a rare entity and due to a constitute activation of an aldosterone dependent protein which triggers the amiloride sensitive sodium channel in the kidney. This results in hypokalemic hypertension with suppressed aldosterone and renin levels.

17-Hydroxysteroid Dehydrogenases↗

Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract.

BACKGROUND: Experimental evidence suggests a role of endothelin-1 (ET) in the regulation of intraocular pressure (IOP). METHOD: Therefore, in patients undergoing cataract surgery, ET-like immunoreactivity (ETIR) was measured by radioimmunoassay in pooled samples of aqueous humor of eyes with primary open-angle glaucoma (POAG) and normotensive eyes with cataract only. RESULTS: ETIR was significantly (P < 0.05) higher in patients with cataract and POAG (20.5 +/- 1.8 pg/ml, n = 12; preoperative IOP 21.4 +/- 1.1 mmHg, n = 33) than in patients with cataract only (15.8 +/- 1.6 pg/ml, n = 15; preoperative IOP 16.0 +/- 0.6 mmHg, n = 77). CONCLUSION: This finding may indicate a role of ET in POAG or ocular antihypertensive treatment, and its relevance should be further investigated.

Administration, Topical↗

Octreotide scintigraphy and catecholamine response to an octreotide challenge in malignant phaeochromocytoma.

OBJECTIVE: Octreotide scintigraphy has been reported to visualize chromaffine tumours. This study in patients with malignant phaeochromocytoma was designed to assess octreotide in comparison with standard m-iodobenzylguanidine (MIBG) scintigraphy and to study functional activity of somatostatin receptors. Finally, two cases of octreotide treatment are reported. DESIGN: Open, prospective clinical trial. PATIENTS: In 12 patients with histologically proven malignant phaeochromocytoma, 111In-octreotide scintigraphy, 123I-MIBG scintigraphy and computed tomography were performed. In ten patients plasma catecholamine response to a single dose of octreotide (200 micrograms i.v.) was monitored up to 5 hours after injection. Two patients were treated with octreotide over several months. MEASUREMENTS: Plasma catecholamines were measured by high performance liquid chromatography (HPLC). Scintigraphy was performed using a large field gamma camera and SPECT technique where appropriate. RESULTS: At least one metastatic lesion was visualized by octreotide scintigraphy in eight patients while the remaining four patients had negative findings. In total, 43 out of 54 known metastases (79.6%) were detected by MIBG, 24 (44.4%) by octreotide. Nevertheless, octreotide scintigraphy detected six metastases that were negative by MIBG. There was no correlation between the results of octreotide scintigraphy and catecholamine suppression after i.v. octreotide. In two patients on octreotide treatment, symptomatic improvement, but not mass reduction, could be documented. CONCLUSIONS: Octreotide scintigraphy behaves in part complementary to MIBG, thus, increasing diagnostic sensitivity. Presence of somatostatin receptors, as demonstrated by octreotide scintigraphy, does not necessarily predict functional activity or therapeutic response.

3-Iodobenzylguanidine↗

Atherosclerosis, aortic stenosis and sudden onset central diabetes insipidus.

The majority of cases of central diabetes insipidus are still pathogenetically unclear (idiopathic). Atherosclerotic cholesterol emboli might be partly responsible for some of these idiopathic cases. A 54-year-old woman with known aortic valve stenosis and a history of a transitory ischemic attack presented with sudden-onset polyuria and polydipsia of up to eight l/d, which had started acutely with headaches. She had been treated with lithium for 3 years because of cyclothymic depression. Plasma sodium was in the upper normal range (142-148 mmol/l). Hypertonic saline infusion during lithium therapy revealed a normal threshold of thirst and resetting of vasopressin secretion (osmotic threshold > 300 mosmol/l), whereas vasopressin reserve was normal. Lithium withdrawal led to an even greater delay of vasopressin release upon hypertonic saline infusion (> 310 mosmol/l). Pituitary function tests revealed a normal anterior pituitary function. MR imaging of the hypothalamo-hypophyseal region showed a normal hypothalamic region and a highly intensive neurohypophyseal signal in the T1-weighted image. The patient responded well to desmopressin. We suggest that in this rare case clinical symptoms as well as biochemical findings like impairment of AVP release might be related to a minor structural hypothalamic damage by a vascular lesion, caused, for example, by an atheromatous (cholesterol) embolism in the hypothalamic region responsible for integration of osmoreceptor function and AVP-secretion. The patient's atherosclerosis and aortic stenosis might be responsible for this event.

Aortic Valve Stenosis↗

Lymphocytic and granulomatous hypophysitis: experience with nine cases.

OBJECTIVE: Lymphocytic hypophysitis and granulomatous hypophysitis are rarely encountered. The aim of this study was to demonstrate their clinical peculiarities among pituitary disorders and to provide an approach for their clinical management. METHODS: In a retrospective study, we reviewed our surgical experience with nine patients harboring hypophysitis. The series included six cases of lymphocytic hypophysitis, two cases of granulomatous hypophysitis, and one case with evidence of coexisting lymphocytic and granulomatous hypophysitis. RESULTS: A striking similarity of clinical signs was found for our nine patients. Headache or aseptic meningitis, thickening of the sphenoid sinus mucosa, pituitary stalk enlargement, and tongue-shaped extension of the lesion along the basal hypothalamus were characteristic signs. Lymphocytic hypophysitis was not associated with pregnancy in any of the seven cases. No recurrence has been observed in six cases with total removal of the inflammatory tissue. CONCLUSION: Lymphocytic hypophysitis and granulomatous hypophysitis represent related inflammatory disorders. Their conspicuous clinical features frequently allow preoperative diagnosis of hypophysitis. In view of their sometimes insidious clinical course, early surgical exploration is justified.

Adolescent↗

Antigastric autoantibodies in Helicobacter pylori infection: implications of histological and clinical parameters of gastritis.

BACKGROUND: It has recently been shown that humoral antigastric autoreactivities occur in a substantial number of Helicobacter pylori infected patients. AIMS: To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course. METHODS: Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies. RESULTS: H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer. CONCLUSION: The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy.

Adolescent↗

Absence of angiotensin II type 1 receptor gene mutations in human adrenal tumors.

Regulatory actions of angiotensin II (AngII), which is involved in the pathophysiology of hypertension and also participates in cell proliferation and cell differentiation, are mainly mediated by AngII type 1 (AT1) receptor. Recently, activating mutations of receptors causing hyperfunctioning endocrine diseases have been described in the case of the TSH and LH receptors, implicating that such mutations might occur in other G-protein-coupled receptors. Furthermore it seems to be possible that genetic variations of AT1 receptor have an influence upon the action of AngII. Therefore, we searched by sequence analysis of the coding region of AT1 receptor gene for activating mutations and genetic polymorphisms in 56 human adrenal tumors (16 aldosterone-producing adenomas, 10 cortisol-producing adenomas, 1 aldosterone-producing carcinoma, and 29 incidentalomas). We were not able to identify any activating mutation in the coding region of AT1 receptor gene. We conclude that activating mutations of the AT1 receptor are not a major cause of the development of adrenal adenomas, if at all. In addition, polymorphic subtypes of AT1 receptor do not seem to play a major role in the pathogenesis of these tumors, even though a tendency towards a higher frequency of the polymorphic base substitution at position 573 (T573-->C) in cortisol-producing tumors needs to be further evaluated.

Adenoma↗

[Adrenal gland incidentaloma is not a "time bomb"--arguments for follow-up control].

Adrenal masses are nowadays more and more diagnosed incidentally. In the vast majority of cases these "incidentalomas" are benign adrenocortical adenomas which do not compel operative therapy. In about 12% of patients an endocrine activity is detected. With Increasing tumor size the risk of malignancy increases. This article summarizes recommendations, only to allow patients with endocrine activity or an increased risk of malignancy to be selected for surgery. A small uncertainty will always remain, but may be minimized by an individually tailored follow-up.

Adrenal Gland Neoplasms↗

[Clinical picture, diagnosis and therapy of acromegaly patients in Eastern and Western Germany].

Acromegaly, a chronic disease characterized by an excessive secretion of growth hormone (GH), is not commonly diagnosed timely enough. Therefore, investigations have been conducted through standardized questionnaires concerning the path to diagnosis, clinical data, therapy, and the patient care of 46 acromegalic patients. The acquired information has been compared in the former Eastern and Western German states. The mean duration of disease before diagnosis was estimated to be 6.1 +/- 5.3 years in the area surrounding Erlangen and 9.3 +/- 7.3 years in the Leipzig and Dresden areas. Despite current trends, a significant difference could not be established regarding the age in which the first symptoms are noted, time of diagnosis, and the delay between the two points in time General practitioners have diagnosed about 35 percent of the occurrences of acromegaly, 15 percent of the cases were accidentally found and about as many were discovered in hospitals. 11 percent of the occurrences were diagnosed by neurologists and another 11 percent by internists. The remaining cases were established by eye specialists. ENT departments, orthopedic specialists or gynaecologists. The most frequent symptoms are increased acral growth, coarse facial features and excessive sweating. For 91 percent of the acromegaly patients, surgery was voted as the therapy of choice. Acromegalic patients have learned the most about their disease through personal contact with doctors, especially endocrine specialists. Many patients are not informed enough about the possible complications of their disease. Through gathered data, it has been concluded that in Eastern and Western Germany the disease has not been identified soon enough. Interdisciplinary teamwork among doctors is a basis for early diagnosis, as well as better patient awareness and education.

Acromegaly↗

Antigastric autoantibodies in Helicobacter pylori gastritis: prevalence, in-situ binding sites and clues for clinical relevance.

Colonization of human gastric mucosa with Helicobacter pylori leads to chronic active gastritis and induces the occurrence of an acquired mucosa-associated lymphoid tissue (MALT) in the stomach. This remodelling of the gastric mucosa together with chronic antigen persistence may induce autoimmune reactions. The aim of this study was to investigate humoral autoimmune reactions to human gastric mucosa in H. pylori gastritis and their clinical relevance. Sera from patients with dyspeptic symptoms were tested for presence of IgG immunoglobulins against H. pylori. Gastric infection with H. pylori and alterations of gastric mucosa were demonstrated by histological examination of gastric biopsy specimens. All sera were tested for reactivity against human gastric mucosa by immunohistochemistry. Two different in-situ binding sites of antigastric autoantibodies were observed. Binding to canalicular structures within parietal cells was significantly correlated with antibodies to H. pylori, elevated basal gastrin levels and atrophy of gastric corpus glands. Our data indicate that autoimmune reactions to antigens in the human gastric mucosa occur in H. pylori gastritis and that they may play a role in the pathogenesis of the disease.

Adult↗