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Biomedical subjects

M Hahn

Publications and source records attributed to M Hahn.

At least 109 records · Page 6Linked to original sources

[Basic molecular biology of colon and rectal carcinoma--when differential diagnosis?].

Colorectal cancer (CRC) is one of the most common cancers in Western populations, striking both women and men at approximately equal rates. A genetic basis for the development of cancer has already been suggested by Karl Heinrich Bauer in 1928 but only since the advancement of molecular biology direct evidence has been obtained to support the notion that cancer is a genetic disease. Recent progress in our understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Identification of genetic risk factors for the development of adenomas and associated carcinomas of the colon and rectum results in predictive molecular diagnosis of malignant disease and enables preventive treatment.

Adenomatous Polyposis Coli↗

The putative tumor suppressor gene FHIT at 3p14.2 is rarely affected by loss of heterozygosity in primary human brain tumors.

To elucidate the role of the recently identified FHIT gene, located at 3p14.2 in human brain tumor carcinogenesis, a total of 259 tumors were analyzed for loss of heterozygosity (LOH) at microsatellite loci D3S1313, D3S1234, D3S1300, and D3S1481. In primary brain tumors, LOH was detected at a frequency of 8.4% (n = 214). Low-grade gliomas exhibited insignificantly lower LOH rates in comparison to high-grade gliomas (5.3%, n = 19, versus 11.1%, n = 90). Notably, no allelic loss was observed in 12 recurrent glioblastomas analyzed in comparison to their corresponding primary tumor lesions and in two astrocytomas with progression to higher grades of malignancy. Our data indicate that allelic loss of the FHIT gene is neither a critical event in carcinogenesis of primary brain tumors nor tumor grade-associated in astrocytic tumors. In contrast, observed LOH rate for brain metastases was as high as 54.5% (n = 45), in accordance with data thus far accumulated from analyses of corresponding primary tumors.

Acid Anhydride Hydrolases↗

Multiple chemical sensitivity syndrome and porphyria. A note of caution and concern.

Growing numbers of patients suffering from many symptoms believe that they have a condition called multiple chemical sensitivity syndrome (MCSS). It has been suggested that this syndrome can be triggered by exposure to any of a large and usually incompletely defined number of natural and synthetic chemical substances. Major medical organizations, including the National Research Council and the American Medical Association, have not recognized MCSS as a clinical syndrome because of a lack of valid, well-controlled studies defining it and establishing pathogenesis or origin. Lately, some have proposed that many patients with MCSS suffer from hereditary coproporphyria. However, this purported association is based chiefly on results from a single reference laboratory of a fundamentally flawed assay for erythrocyte coproporphyrinogen oxidase. Although patients with MCSS may, at times, have modest increases in urinary coproporphyrin excretion, this is a common finding found in many asymptomatic subjects or patients with diverse other conditions (eg, diabetes mellitus, heavy alcohol use, liver disease, and many kinds of anemia). Such secondary coproporphyrinuria does not indicate the existence of coproporphyria. To our knowledge, there is no scientifically valid evidence to support an association between MCSS and coproporphyria, nor is there any unifying hypothesis for rationally linking these 2 disorders.

Adolescent↗

Comparative study of CD26 as a Th1-like and CD30 as a potential Th2-like operational marker in leprosy.

In the last years we have been able to establish CD26 as an operational marker for a human Th1-like reaction in various granulomatous diseases. Recently, CD30 was described as a marker for a Th2-type reaction, where CD30 is preferentially expressed and its soluble form released by human T cell clones producing Th2-type cytokines. To evaluate the possibility of CD30 as an eventual operational marker for a human Th2-like reaction in vivo, we performed immunohistological stainings on frozen sections of skin biopsies from patients with lepromatous and tuberculoid leprosy. A maximum of three to four CD30-positive cells was found per section, and there was no difference in the accumulation of CD30-positive cells between the tuberculoid and the lepromatous form of leprosy. With respect to CD26-positive cells, a high number was found in tuberculoid leprosy in contrast to a greatly reduced expression of CD26 in lepromatous leprosy. We conclude that, while CD26 was confirmed as an operational marker for a Th1-like reaction in leprosy, CD30 does not represent an operational Th2 marker in this disease.

Biomarkers↗

[Monocondylar fractures of the femur. Therapeutic strategy and clinical outcome].

Twenty-nine unicondylar fractures of the distal femur were treated at the Trauma Center "Bergmannsheil", University of Bochum, Germany, between 1981 and 1994. All patients sustained their injuries from severe direct trauma. There were 16 lateral condylar fractures, 7 medial condylar fractures and 6 tangential posterior ("Hoffa-type") fractures. Twenty-eight closed injuries and 1 grade IIIB open fracture injuries to the skeleton. All fractures were treated with open reduction and internal fixation with screws within 8 h of admission. Postoperative management consisted of early continuous passive motion and minimal weight-bearing for 6-8 weeks, progressing to full weight-bearing. The mean follow-up was 68 months (18-120). The therapeutic outcome (clinical result, radiographs) was rated by the Neer score. Twenty-seven patients were available for follow-up examination. Of these, 23 were rated as excellent. 3 achieved satisfactory results, and 1 had an unsatisfactory result. All patients who did not achieve an excellent outcome had had accompanying injuries. Open reduction and internal screw fixation of unicondylar femur fractures provided overall excellent long-term results. The therapeutic outcome was significantly affected by associated injuries of the skeleton.

Adolescent↗

[Possibilities and limits of functional conservative therapy of acute Achilles tendon ruptures].

According to sonographic criteria, 55 patients underwent surgical treatment with mobilisation in a lower leg plaster or conservative treatment with early mobilisation in heel pad (3 cm) shoes when an acute Achilles tendon rupture (ATR) was diagnosed. The follow-up period in 51 patients was 2.4 years (operated group = 28 patients, conservative group = 23 patients) with clinical examination and testing of isokinetic muscle strength in knee joint flexion. After surgical treatment, minor wound infections occurred in 10.6%. Reruptures occurred in 13% of the conservative group. Following conservative treatment, the rate of stress-related achillodynia was significantly higher (P = 0.019). In the operated group mean isokinetic muscle strength was 13.7% lower than in the uninvolved leg and decreased significantly with non-operative treatment to 75.3% (P = 0.012). We recommend surgical treatment of acute ATR. The indications for conservative treatment depend on the extent of the rupture (measured by ultrasound in the equinus position), the desired level of daily activity and the patient's degree of compliance.

Achilles Tendon↗

[Vascular sports in ambulatory therapy of venous circulatory disorders of the legs. Diagnostic, therapeutic and prognostic aspects].

In 33 patients with chronic venous incompetence (CVI) caused by primary varicoses or postthrombotic syndrome stage I-III (according to Widmer) the therapeutic benefit of 6 months of medically supervised physical exercise training was documented. During the training penud there was an improvement in subjective complains such as pain and tendency for edema in the legs. Mobility in the upper ankle joint was improved asuss as venous drainage function. Clinical benefit was achieved in the reduction of ulcer size; 7 of the 10 ulcers completely healed. Medically supervised physical exercise training and optimized compression therapy are basic therapeutic approaches in conservative treatment in chronic venous insufficiency. Costs are covered by the patient's health insurance company in Germany, as long as the exercise training is medically supervised.

Adult↗

[Dynamic in vivo skin pressure measurement in quality control of compression stockings].

The well-documented positive effect of compression stocking therapy on the venous macro- and microhemodynamics of the legs can only be attained if the stockings fit well. In order to determine the effective pressure exerted by compression stockings, we usually deleted in US journals. One can get this out of journal and author's address have developed a new measuring method based on piezoresistant microprobes and a microprocessor unit. With our 2-mm-thick, 5-mm diameter probe, the pressure between the compression stocking and skin can be measured at any location desired. A temporal resolution of 50 Hz makes it possible to carry out dynamic measurements while the patient is walking or performing exercises on tiptoes. Here we present 4 typical cases out of a total of over 80 which we have evaluated. We have decided empirically that the pressure exerted by a class-2 compression stocking on the skin at the height of the ankles (b-position) should not exceed 70 mm Hg while resting and a peak of 110 mm Hg while exercising on tiptoes. At the middle of the calf (c-position) these values should not exceed 60 mm Hg at rest and 80 mm Hg on tiptoes. The pressure should decrease from the distal to proximal direction in order to produce a drainage gradient. We have found empirically that a pressure gradient of 30-40% from the b to the c measurement is favorable. Too high a proximal pressure or too high a pressure on a part of the lower leg causes pain and swelling. Too low a pressure, on the other hand, does not produce the desired vascular effect and alleviation of symptoms. Although dynamic pressure measurements take about 20-30 minutes per leg, they markedly improve patient compliance with compression therapy.

Adult↗

[Treatment of venous ulcers with low frequency pulsed current (Dermapulse): effects on cutaneous microcirculation].

Chronic venous insufficiency (CVI) is characterised by stage-dependent microangiopathy. With increasing severity there is a decrease in the number of skin capillaries and the oxygen partial pressure. The cutaneous vascular reserve, which is measured by laser-doppler fluxmetry, is reduced. Cutaneous microangiopathy is one of the main causes of the trophic disturbances associated with CVI. Low frequency pulsed current improves cutaneous microcirculation and thus nutrition as well as accelerating the formation of granulation tissue. In a open prospective pilot study, 15 patients suffering from CVI with persistent leg ulcers were treated with low frequency pulsed current (Dermapulse), which is thought to improve particularly the tissue microcirculation. The average age of the patients was 70.3 years and the average duration of ulceration was 79.1 months. The patients were treated over a period of 38 days. With this treatment, 2 ulcers healed completely and 13 showed a reduction of size of on average 63%. Capillary density increased by 43.5%, while transcutaneous oxygen partial pressure increased by 82.4%. Electrostimulation is a treatment with few or no side effects.

Aged↗

An intronic germline transition in the HNPCC gene hMSH2 is associated with sporadic colorectal cancer.

The aim of this study was to determine whether an intronic germline substitution in the hereditary non-polyposis colorectal cancer (HNPCC) gene hMSH2 represents a genetic risk factor for sporadic CRC. Possible effects of this substitution were investigated by assessment of microsatellite instability and hMSH2 cDNA sequencing. Constitutional DNA from patients with sporadic CRC and healthy controls from the same region in Germany was analysed for the intronic germline T-->C transition six bases upstream of exon 13 of hMSH2. 29 of 106 patients (27%) were found to harbour the germline T-->C transition as opposed to only 13 of 125 controls (10%; P < 0.001; OR 3.2, CI 1.58-6.63). CRCs from patients with the substitution displayed neither clinical HNPCC-like features nor an increased rate of microsatellite instability. No abnormal cDNA sequence was found at the exon 12-13 border. These data suggest a 3.2-fold increased risk of sporadic CRC for individuals with the intronic hMSH2 transition. However, this substitution might not be pathogenic itself, but may be linked to a locus nearby that is.

Adult↗

Characteristics of the cancellous bone of edentulous mandibles.

Trabecular bone volume and trabecular connectivity (trabecular bone pattern factor) of edentulous mandibles were examined using undecalcified bone sections from the region of the 1st premolar to investigate atrophy-related changes in mandibular cancellous bone. The mean trabecular bone volume was 21.8% in female mandibles and 36.6% in male mandibles. The mean trabecular bone pattern factor was -0.22 mm-1 for female mandibles and -2.29 mm-1 for male mandibles. The difference between the sexes was statistically conspicuous for both parameters, but did not attain statistical significance. A notable fact was the extreme range of variation in both trabecular bone volume and trabecular connectedness. A difference of 65% between the highest and the lowest trabecular bone volumes measured in the present study (min, 7.6%; max, 73.6%, both male) reflects the possible variation in trabecular density of edentulous mandibles.

Aged↗

Effect of calcitriol in combination with corticosterone, interleukin-1beta, and transforming growth factor-beta1 on nerve growth factor secretion in an astroglial cell line.

In astrocytes, nerve growth factor (NGF) synthesis has been described to be stimulated by the cytokines interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) and inhibited by corticosterone. As all three factors are present in the brain under certain conditions, we investigated the effect of their combined application on NGF secretion in the astroglial cell line RC7 and, in addition, studied the effect of calcitriol (1alpha,25-dihydroxyvitamin D3). Calcitriol stimulated NGF secretion, whereas corticosterone reduced basal levels of NGF secretion as well as inhibited the NGF secretion induced by IL-1beta, calcitriol, and TGF-beta1. Calcitriol had an additive effect when applied together with IL-1beta and a synergistic effect when applied with TGF-beta1. Moreover, calcitriol not only counteracted the inhibitory effect of corticosterone on NGF secretion stimulated by TGF-beta1 but even augmented it to a level more than threefold higher than that reached with TGF-beta1 alone. Due to the trophic effect of NGF on basal forebrain cholinergic neurons, these findings might be of therapeutic relevance under conditions where cholinergic function is impaired and the endogenous levels of corticosterone, IL-1beta, or TGF-beta1 are elevated.

Animals↗

Characterization of in planta-induced rust genes isolated from a haustorium-specific cDNA library.

Rust fungi are plant parasites that depend on living host tissue for growth. For invasion of leaves, dikaryotic urediospores differentiate germ tubes and infection structures that penetrate through stomata. Biotrophic growth occurs by intercellular mycelia that form haustoria within host cells. A cDNA library was constructed from haustoria isolated from broad bean leaves infected by Uromyces fabae. Differential screening revealed that a high proportion (19%) of the haustorial cDNAs are specifically expressed in planta but are not expressed, or are much weaker, in germlings or infection structures produced in vitro. A total of 31 different in planta-induced genes (PIGs) were identified. Some of the PIGs are highly expressed in haustoria. The PIGs are single or low copy number genes in the rust genome. A variety of developmentally regulated expression patterns of PIG mRNAs were observed. Sequence analysis of PIG cDNAs revealed similarities to genes encoding proteins involved in amino acid transport, thiamine biosynthesis, short-chain dehydrogenases, metallothioneins, cytochrome P-450 monooxygenases, and peptidyl-prolyl isomerases.

Amino Acid Sequence↗

A putative amino acid transporter is specifically expressed in haustoria of the rust fungus Uromyces fabae.

A cDNA library constructed from haustoria of the rust fungus Uromyces fabae was screened for clones that are differentially expressed in haustoria. One family of cDNAs (in planta-induced gene 2 [PIG2] was isolated and found to encode a protein with high homologies to fungal amino acid transporters. A cDNA clone containing the complete coding region of PIG2 and the corresponding genomic clone were isolated and sequenced, revealing the presence of 17 introns in the PIG2 gene. Expression of PIG2 mRNA appeared to be restricted to haustoria. With antibodies raised against synthetic peptides, the PIG2-encoded protein was found in membranes fractions of isolated haustoria but not of germinated rust spores. With immunofluorescence microscopy, the putative amino acid transporter was localized to plasma membranes of the haustorial bodies, but not detected in the haustorial neck, haustorial mother cells, or intercellular fungal hyphae growing within infected leaf tissue. These data present for the first time molecular evidence that the rust haustorium plays a special role in the uptake of nutrients from an infected host cell.

Amino Acid Sequence↗

Airbag-induced lethal cervical trauma.

In a frontal collision of a car (taxicab) perpendicular into a streetcar with an impact speed of approximately 30 kph (20 mph), the driver survived with minor injuries. The front-seat passenger was extremely "out-of-position," with her seat positioned nearly fully forward. This in combination with her short stature led to fatal injuries resulting from the inflating airbag (U.S.-type) striking against her face and chin. At the scene, she was found essentially clinically dead, but was resuscitated and died finally 13 days later. Postmortem examination showed a complete disruption of all ventral ligaments between the base of the skull and the first and second vertebrae, a nearly complete ventral rupture of the medulla, and diffuse axonal injury of the brain.

Accidents, Traffic↗

Effects of new anticonvulsant medications on porphyrin synthesis in cultured liver cells: potential implications for patients with acute porphyria.

Some patients with acute hereditary porphyrias have seizures and require anticonvulsant therapy, but many anticonvulsants induce exacerbations of the hepatic porphyrias. Recently, several new anticonvulsants have become available. Among these are gabapentin, vigabatrin, felbamate, lamotrigine, and tiagabine. Little is known about their potential for induction of porphyric attacks. We used a cell culture model of primary chicken embryo liver cells, which maintain intact heme synthesis and regulation, to study the effects of these new anticonvulsants on porphyrin accumulation. Treatment of the cells with deferoxamine (250 microM) led to a partial block in heme synthesis, simulating the conditions encountered in human beings with porphyria. Concomitant exposure of these cells to phenobarbital (2 mM) strongly induced accumulation of porphyrins, serving as a positive control in this model. Cells were treated for 20 hours with increasing doses (3.2 to 1,000 microM) of the newer anticonvulsants, with or without deferoxamine. For most of these anticonvulsants 5 to 100 microM is representative of the concentrations achieved in humans with therapeutic doses. Porphyrins were measured spectrofluorometrically as uro-, copro-, and protoporphyrins. Results were confirmed by high-pressure liquid chromatography. Neither vigabatrin nor gabapentin treatment, with or without deferoxamine, led to any increase in porphyrin accumulation. Similar doses of felbamate (with deferoxamine) led to a marked increase in (mainly proto-) porphyrin levels, qualitatively and quantitatively almost identical to the accumulation produced by phenobarbital. Lamotrigine or tiagabine (with deferoxamine) caused similar porphyrin accumulation. Tiagabine treatment up to 100 microM (with deferoxamine) also resulted in very high levels of predominantly proto-porphyrin. In contrast to the other anticonvulsants tested, tiagabine without deferoxamine led to mild porphyrin accumulation. In the presence of deferoxamine, phenobarbital, felbamate, lamotrigine, or tiagabine, but not gabapentin or vigabatrin, increased levels of the mRNA of ALA synthase, the first and rate-controlling enzyme of porphyrin synthesis. Such enzyme induction is a sine qua non for acute porphyric attacks. We conclude that neither vigabatrin nor gabapentin is porphyrogenic, whereas felbamate, lamotrigine, and, especially, tiagabine lead to much accumulation of porphyrins. The latter three anticonvulsants, therefore, may precipitate or exacerbate acute porphyric attacks in humans. We recommend use of vigabatrin or gabapentin, but not felbamate, lamotrigine, or tiagabine, in patients with acute porphyria and seizures.

Animals↗

The thickness of human vertebral cortical bone and its changes in aging and osteoporosis: a histomorphometric analysis of the complete spinal column from thirty-seven autopsy specimens.

The object of this study was to analyze the cortical thickness (Ct.Th) of the ventral and dorsal shell of the vertebral bodies throughout the human spine in aging and in osteoporosis. Therefore, the complete front column of the spine of 26 autopsy cases (aged 17-90, mean 42 years) without diseases affecting the skeleton and of 11 cases (aged 58-92, mean 77 years) with proven osteoporosis were removed. A sagittal segment prepared through the center of all vertebral bodies was undecalcified, embedded in plastic, ground to a 1 mm thick block, and stained using a modification of the von Kossa method. The analysis included the measurement of the mean cortical thickness of both the ventral and dorsal shell, respectively (from the third cervical to the fifth lumbar vertebral body). The qualitative investigation of the structure of the cortical ring completed the analysis. The presented data revealed a biphasic curve for both the ventral and dorsal shell, skeletally intact with high values of the cortical thickness in the cervical spine (285 microm), and a decrease in the thoracic (244 microm) and an increase in the lumbar spine (290 microm). The mean thickness of the ventral shell is in general greater than the thickness of the dorsal shell in both skeletally normal and osteoporotic cases. The cortical thickness of the spine showed no gender-specific differences (p = NS). There was a slight decrease of the cortical thickness with aging; however, this decrease and the correlation of cortical thickness to age was only significant below vertebral body T8 (r = 0.225-0.574; p(r) < 0.05-0.005). Most interestingly, however, osteoporosis presents itself with a highly significant loss of cortical thickness throughout the whole spine. This decrease of cortical thickness was more marked in the dorsal shell (p < 0.05) than in the ventral shell (ventral from C3 to T6 [p < 0.05] below T6 [p = NS]). We therefore conclude that in osteoporosis the loss of spinal bone mass is not only a loss of trabecular structure but also a loss of cortical thickness. Furthermore, these results may explain the development of regions of least resistance within the spine in aging and the clustering of osteoporotic fractures in the lower thoracic and lumbar spine.

Adolescent↗