Search PubMed⌕ Search

Biomedical subjects

P Kann

Publications and source records attributed to P Kann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Confocal laser scanning microscopy: A nondestructive subsurface histotomography of healthy human bone.

Microscopy of bony tissue usually requires special treatment for decalcification and processing of thin sections. Confocal laser scanning microscopy (CLSM) allows the nondestructive histotomography of organic hard tissue. The aim of this study was to visualize healthy human bone structures and to correlate identical areas in CLSM and conventional light microscopy. Each sample of healthy human lower jaw (n = 20) was divided into three parts: (1) fresh, untreated bony blocks studied by CLSM; (2) MMA-embedded thin sections (without decalcification), HE stained and studied by CLSM and conventional light microscopy (correlation of identical areas); (3) decalcificated, HE stained, histological sections studied by conventional light microscopy. In untreated bony blocks, microstructures such as osteocytes and lamellae were identified by CLSM. These structures could be correlated with conventional light microscopy. In CLSM, subcellular structures cannot yet be interpreted, whereas cytoplastic processes of osteocytes were seen with high contrast. With CLSM, nondestructive histology of cortical bone can be obtained. The risk of artifacts due to pretreatment is minimized, and subsurface visualization does not affect the interpretation.

Histological Techniques↗
PubMed1999

Germline mutations in the MEN1 gene: creation of a new splice acceptor site and insertion of 7 intron nucleotides into the mRNA.

The MEN1 tumor predisposition syndrome is caused by mutations in the MEN1 gene on human chromosome 11q13. We screened MEN1 gene exons 1-10 and flanking intron sequences from four different MEN1 families for mutations. In three families, heterozygous germline mutations within the exons were found, two of these representing novel mutations. In another family, all clinically affected members were heterozygous for a point mutation Gright curved arrow A within intron 4. Sequence analysis of cDNA from lymphocytes of the affected patients revealed that the intron mutation created a new acceptor splice site, leading to the inclusion of 7 bp of intronic sequence into the mRNA. The resulting frameshift generates a premature stop in codon 271. Intron borders should thus be screened for mutations in MEN1 diagnostics and cDNA sequence analysis is helpful in identifying pathophysiological consequences of intron mutations.

Alternative Splicing↗
PubMed1998

[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↗
PubMed1998

[Confocal laser scanning microscopy (CLSM) for validation of non-destructive histotomography of healthy bone tissue].

OBJECTIVES: Fixation (formalin), decalcification (sections) or mechanical treatment (grinding) all bear the risk of artifacts occurring during hard-tissue histology. Because studies on the etiology of pathological changes mostly focus on subclinical lesions, artifacts can simulate early changes or even be superimposed on existing changes. The objective of this study was to determine how artifacts can be reduced. MATERIAL AND METHODS: In confocal laser scanning microscopy (CLSM) a focused laser beam scans the surface of the specimens and penetrates into the tissue. The intensity of the remitted light is recorded. The confocal effect is due to an extremely small aperture (pin-hole), excluding light from out-of-focus planes of the sample. By stepwise movement of the object table, a tomographic series of tomographic images is obtained. Sound cortical bone samples of the lower jaw (n = 20) were studied by light microscopy and by CLSM, visualizing identical areas of a ground sectioned sample after H&E staining. Additionally, embedded and fresh blocks of tissue of the same bone sample were studied histotomographically in the CLSM. RESULTS: (1) Light microscopic micromorphology of cortical bone can be visualized adequately in the CLSM; (2) many structures that can be visualized by light microscopy only after special staining (e.g., osteozyte processes) can be visualized by the CLSM using sample blocks without pretreatment. CONCLUSION: (1) Nondestructive subsurface histotomography by CLSM totally excludes mechanical artifacts; (2) physicochemical artifacts can be handled more easily because fresh samples can be studied; (3) pseudo-three-dimensional imaging allows histological interpretation of the tissue that is equivalent to macroscopic tomographic techniques (CT, MRT).

Artifacts↗
PubMed1998

Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH-deficient adults.

OBJECTIVE: Adults with GH deficiency (GHD) commonly have subnormal bone mineral density (BMD), and have been reported to have an increased risk of fractures. It has been suggested that GH replacement therapy may have beneficial effects on bone in such patients. The aim of this study was to investigate the effects of long-term GH replacement therapy on bone metabolism, BMD and bone elasticity in adults with GHD. DESIGN: At the start of the study, 20 adults with GHD were randomized to receive either GH, 0.25 IU/kg/week (the 'GH group') or placebo (the 'placebo group'). After 6 months, patients in the placebo group were switched to GH therapy, and all patients received GH for a further 42 months. PATIENTS: Of the 20 patients included in the study, 11 were male and nine were female. Mean age at the start of the study was 42.5 +/- 10.1 years. All patients had been GH-deficient for at least 2 years before the start of the study. MEASUREMENTS: Rates of bone resorption and formation were assessed by measuring serum levels of type I collagen carboxyterminal cross-linked telopeptide (ICTP) and carboxyterminal propeptide of type I procollagen (PICP), respectively. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the non-dominant forearm by single-photon absorptiometry (SPA). Bone elasticity was assessed by measuring apparent phalangeal ultrasound transmission velocity (APU). RESULTS: The main results in the GH group were as follows. The rate of bone resorption increased significantly during the first 6 months of treatment and remained significantly elevated above its baseline level thereafter. The rate of bone formation also rose during the first 6 months of treatment and remained elevated thereafter, but was significantly higher than at baseline only after 24 months of treatment. At both sites measured, BMD was subnormal at baseline, decreased during the first 6 months of treatment, and increased progressively for the rest of the study, eventually rising well above its baseline level. Bone elasticity decreased during the first 6 months of treatment, but had returned to its baseline level after 24 months. CONCLUSIONS: Our results support previous findings that BMD is subnormal in adults with GHD, that GH replacement therapy can stimulate bone turnover in such adults and that, in the long term, such stimulation results in a significant increase in BMD. In addition they show, for the first time, that BMD may continue to rise even after GH replacement therapy has been administered for 4 years, and indicate that bone elasticity is not adversely affected by long-term GH therapy.

Absorptiometry, Photon↗
PubMed1998

Endosonography of the adrenal glands: normal size--pathological findings.

Transabdominal sonography of the adrenal glands frequently is non-successful. It was the aim of this project to improve the imaging of the adrenal glands using high resolution sonography in order to obtain information about even small changes in these organs. Therefore, endosonographic imaging was investigated using an endosonoscope PENTAX FG32UA. The correct identification of the adrenal glands was examined in five human cadavers. A total of 58 patients with 113 adrenal glands (in 3 cases history of unilateral adrenalectomy) were investigated. 109 adrenal glands (97%) were identified and evaluated. Healthy adrenal glands are slightly hyperechoich and regarding their echogeneity comparable to other endocrine organs such as the testes or the thyroid. Adrenal size can be determined as largest cross sectional area and was found to be 216 +/- 93 mm2 right and 231 +/- 98 mm2 left. In the adrenal glands which could be imaged by endosonography, all findings detected by CT (n = 33) or MRI (n = 19) could also be demonstrated endosonographically. Additional information as compared to CT/MRI was obtained in 7 out of 33 and in 6 out of 19 patients. This concerns in particular differentiation between tumor and hyperplasia and detection of small adrenal adenomas. High resolution endosonography of the adrenal glands can provide information about adrenal gland morphology which cannot be obtained by any other diagnostic approach.

ACTH Syndrome, Ectopic↗
PubMed1998

[Endosonographic imaging of the adrenal glands: a new method].

UNLABELLED: In contrast to the reliable imaging of the adrenal gland in infants and children, transabdominal sonography of the adrenal glands is often unsuccessful. AIM: To improve the imaging of the adrenal glands with high resolution in order to obtain information on even small changes in these organs. METHOD: Adrenal glands taken from human cadavers were investigated using a 7.5 MHz transducer. Thereafter, endosonographic imaging was investigated in 5 human cadavers using an endosonoscope PENTAX FG32 UA (longitudinal sector scanning. 7.5 MHz). Furthermore, the adrenal glands were imaged in a total of 30 patients with different indications for endosonography. RESULTS: The adrenal glands in 5 human cadavers could be identified in each case. This was proved in one human cadaver by endosonographically guided fine needle puncture with consecutive preparation of the tissue damage caused by the needle. In a total of 30 patients with 56 adrenal glands (in 4 cases preview history of unilateral adrenalectomy), 55 adrenal glands were correctly identified and evaluated. The only exception was the left adrenal gland of a patient with Billroth-II-stomach, which was slightly pulled to the right and very small. Healthy adrenal glands are slightly hyperechoic as compared to the parenchyma of the kidney and have echogeneity comparable to other endocrinal organs such as the testicles or the thyroid. Endosonographic imaging of the adrenal glands is far superior in resolution and determination to transabdominal sonography. In 18 of 30 patients (60%) endosonography provided additional diagnostic information compared to conventional sonography. CONCLUSION: Endosonography of the adrenal glands enables imaging of these organs with high resolution using a 7.5 MHz transducer from a distance of 1-2 cm.

Adenoma↗
PubMed1998

Establishment of a quantitative RT-pCR for detection of vascular cell adhesion molecule-1 transcripts in endothelial cells after stimulation with advanced glycation endproducts.

Advanced glycation endproducts (AGE) are supposed to increase endothelial expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1) by inducing an intracellular stress with subsequent activation of nuclear transcription factor NF-kappa-B. Quantitative analysis of VCAM-1-transcription has not been demonstrated concerning this topic. Thus, the aim of this study was to establish quantitative reverse transcription polymerase chain reaction (RT-PCR) assays using a spacer gene in order to measure the amounts of specific mRNA for VCAM-1 in human umbilical vein endothelial cells (HUVEC) which were stimulated with AGE-albumin (AGE-BSA). A recombinant RNA-standard was synthesized and used as internal RT-PCR standard. The amount of VCAM-1-mRNA in unstimulated HUVEC was found to be 2.2 +/- 2.7 copies per cell. After stimulation with AGE-BSA, mRNA-levels were elevated to 38.9 +/- 10.9 copies per cell. Positive controls (stimulated with lipopolysaccharide) revealed mRNA-levels of 78.7 +/- 27.5 copies per cell. We conclude that quantitative RT-PCR using the spacer gene technique is a valid and reliable method for the measurement of small amounts of specific

Cells, Cultured↗
PubMed1997

Bone mineral density and bone metabolism in diabetes mellitus.

The effect of diabetes mellitus on bone metabolism and bone mineral density is discussed controversially. Diabetes mellitus due to an autoimmune process seems to be associated with low turnover osteopenia either in the animal model or in children and adolescents. A number of factors are discussed as being involved, but in this age group clinical symptoms are missing. Adult patients of either sex with IDDM show a reduced bone mineral density when measured at peripheral sites such as the distal forearm or the femoral neck, diabetic complications such as neuropathy and microangiopathy seem to pronounce the deficit of bone mass. In these patients, osteopenia is accompanied by a high turnover situation of bone metabolism, possibly due to microvascular complications. In contrast, patients with NIDDM and here especially overweight women have a normal or even increased bone mineral density. Up to now, there is no convincing evidence for an increased incidence of osteoporotic fractures in diabetic patients. Systemic diabetic osteopenia therefore does not seem to be of great epidemiological relevance.

Animals↗
PubMed1996

Growth hormone substitution in growth hormone-deficient adults: effects on collagen type I synthesis and skin thickness.

Growth hormone stimulates collagen type I synthesis. Collagen type I is a common matrix compound in a large number of connective tissues. The aim of our study was to prove whether a stimulation of collagen type I synthesis might be accompanied by a deposition of collagen type I in the skin (cutis). Twenty growth hormone-deficient hypopituitary patients were included in a randomised, double-blind, placebo controlled, prospective, twelve-month study (eighteen patients assessable at the end of the study). The patients were treated with recombinant human growth hormone 0.25 U/kg/week subdivided in daily subcutaneous injections beginning with half the dosage during the first four weeks. During the first six months half of the patients were treated with placebo. PICP, the indicator of collagen type I synthesis, was increased after six months of therapy when compared to placebo. Skin thickness measured by ultrasound at the forearm and mechanically at the dorsum of the hand with strong compression of the skin both increased significantly following growth hormone substitution. Our data indicate that the stimulation of collagen type I synthesis by growth hormone substitution is followed by a deposition of collagen type I in the skin.

Adult↗
PubMed1995

In-vivo investigation of material quality of bone tissue by measuring apparent phalangeal ultrasound transmission velocity.

The square of ultrasound transmission velocity in a material is related to the modulus of elasticity, which is known to be an indicator of stability in bone. The aim of our study was to use ultrasound transmission velocity to obtain information about the material properties of bone tissue, keeping other factors possibly influencing ultrasound transmission as constant as possible. Apparent phalangeal ultrasound transmission velocity (APU) measured in 54 isolated, fresh pig phalanges was shown to be independent of bone mineral density (BMD) measured by SPA. Fastest sound transmission led exclusively through cortical bone so that intertrabecular connectivity in spongious bone could not influence the result. In humans APU was measured in the mediolateral direction at the midphalanx of the middle finger. In 53 healthy subjects (15-81 years old; 27 women, 26 men), there was a decrease of APU with age (r = -0.30, p < 0.05). Further, when comparing the results of both hands intraindividually almost identical values indicated constant intraindividual architecture of bone at this location. There was no evidence for a relation of APU to physical load comparing dominant and nondominant hand and relating the results to subjectively estimated physical load. In a second group of 43 perimenopausal women (47-60 years old), APU, which again decreased with age (r = -0.33, p < 0.05), was found not to be correlated to BMD measured by SPA at the distal forearm (cortical bone).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Association between diabetic-autonomic-C-fibre-neuropathy and medial wall calcification and the significance in the outcome of trophic foot lesions.

The role of peripheral autonomic nerve failure in the development of medial arterial calcification is discussed controversially in the literature. In addition, the influence of medial wall calcification in the development of trophic foot lesions is still not fully understood. We have compared 28 diabetic patients with cardiac autonomic failure and/or decreased acetylcholine-induced sweat response with 22 diabetic patients without evidence of diabetic neuropathy and 27 healthy control subjects. A strong association was found between medial wall calcification and diminished heart rate variation (p.001) or diminished peripheral sweat response (p < 0.001). Only one subject in the control group exhibited a calcification of the tunica media in the lower limb. Medial calcinosis was accompanied by a significant rise of systolic ankle blood pressure (p < 0.05). In addition, there was a strong relationship between medial wall calcification and trophic foot lesions (p < 0.0001). Our results demonstrate a strong association between sympathetic C-fibre neuropathy and the development of medial wall calcification, as well as between calcification of the tunica media and trophic foot ulceration. Further investigation is necessary to determine whether there is a causal connection between medial arterial sclerosis and diabetic foot ulceration, or whether both are independent consequences of diabetic neuropathy.

Acetylcholine↗