[28-year-old patient with hypokalemic paralysis].
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Biomedical subjects
Publications and source records attributed to W Arnold.
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The gastrointestinal tracts of 76 free-living alpine marmots ( Marmota marmota) shot during a population control program in Switzerland were collected and analysed for patterns of change in morphology and function over the period from emergence from hibernation in April to just before re-entry into hibernation in September. Between first emergence and mid-summer (July) the fresh tissue mass of the stomach increased by 105%, the small intestine by 259% (among the largest recorded for a mammal), caecum by 185%, proximal colon by 138%, and distal colon by 144%. Mitotic activity was greatest in the small intestine; the mitotic index was high (40%) compared with indexes in the stomach and hindgut (approximately 4%) even at emergence, and increased to approximately 60% by mid-summer. Microbial activity in the caecum was also significant at emergence. The stomach (length) and caecum (length and fresh mass) increased in response to ingested food earlier than did the small intestine. Between mid-summer and September there were decreases in small intestinal tissue mass and mitotic activity. It is concluded that the gastrointestinal tract of alpine marmots probably continues to function throughout hibernation at a low level, with a mid-winter trough as part of an endogenous circannual rhythm. However, after emergence in spring, increases in size and activity of the tract appear to be a response to ingested food rather than to an endogenous signal. The early signs of down-regulation of the small intestine before re-entry into hibernation, together with its delayed up-regulation in response to food in spring, are consistent with the high costs of maintaining this section of the digestive system.
We investigated postnatal development of captive juvenile European hares (Lepus europaeus) with respect to growth, food intake and thermoregulation. Leverets increased their body weight on average 8.5-fold within 35 days, with a peak in relative growth rate on day 8. Although leverets started to take up solid food in the 2nd week of lactation, milk was the main energy source. Leverets of larger litters (two or three young) had less energy supply via milk than those of smaller litters (one young), and digested more energy in form of solid food. Weaning weight was positively correlated with body weight at birth and decreased with increasing litter size. Metabolic rates were largely determined by ambient temperature (Ta) and the increasing body weights. Leverets were able to maintain normothermic body temperatures from the Ist day of life during cold exposure down to Ta -8 degrees C. In their 1st week of life leverets showed reduced rates of heat loss in the cold, possibly by using peripheral vasoconstriction. Our results suggest that the precocial development of leverets is characterised by high maintenance costs due to rapid growth and thermoregulation, which may lead to negative energy balances when food supply is inadequate and T(a)s are low. We hypothesise that these physiological characteristics have played an important role in the recent decline of European hare populations.
The combination of ultrasound with atomic force microscopy (AFM) opens the high lateral resolution of scanning probe techniques in the nanometer range to ultrasonics. One possible method is to observe the resonance frequencies of the AFM sensors under different tip-sample interaction conditions. AFM sensors can be regarded as small flexible beams. Their lowest flexural and torsional resonance frequencies are usually found to be in a range between several kHz and several MHz depending on their exact geometrical shape. When the sensor tip is in a repulsive elastic contact with a sample surface, the local indentation modulus can be determined by the contact resonance technique. Contact resonances in the ultrasonic frequency range can also be used to improve the image contrast in other dynamic techniques as, for example, in the so-called piezo-mode. Here, an alternating electric field is applied between a conducting cantilever and a piezoelectric sample. Via the inverse piezoelectric effect, the sample surface is set into vibration. This excitation is localised around the contact area formed by the sensor tip and the sample surface. We show applications of the contact resonance technique to piezoelectric ceramics.
Changes in the materials microstructure caused by fatigue processes affect the ultrasonic absorption. Thus, quantitative measurement of the ultrasonic absorption should provide an indirect measure of fatigue damage. In this paper we present a study of the ultrasonic absorption in fatigue-damaged metals using the reverberation technique in combination with laser-based ultrasound. The reverberation technique allows one to measure absorption independently of scattering.
BACKGROUND: The present study describes clinical and epidemiological data of patients with malignomas of the head and neck documented in the Munich Cancer Register. PATIENTS AND METHODS: Data of head and neck cancer patients treated at four departments of head and neck surgery and one of oral-maxillo-facial surgery in the area of Munich from 1978 up to now are reported. RESULTS: Incidence and mortality as a function of age, sex, and tumor localization are described in comparison to clinical and epidemiological data as specified in tumor registers of the Saarland and the USA. Moreover, TNM stages, survival, recurrence, and metastasis rates are presented. CONCLUSION: Based on the documentation of the Munich Cancer Register our study is the first to present a detailed description of clinical and epidemiological data of patients suffering from head and neck malignomas.
Despite an increasing incidence of acute sensorineural hearing loss, the pathogenesis of this disease remains uncertain. While viral infection of the stria vascularis, organ of Corti or spiral ganglion cells is discussed in the American literature, a vascular genesis with resulting impaired perfusion of the inner ear is favoured by European investigators. Although both hypotheses are supported by different therapeutic strategies to regain normal hearing, the influence of spontaneous remission remains unclear. This study aims at combining these seemingly opposing concepts with the assumption of an immunologically mediated vasculitis with consequent cochlear hypoperfusion. We already know from other organs that during viral vasculitis circulating immunoglobulins are deposited perivascularly, which leads to a local decrease in perfusion and tissue hypoxia. Also in autoimmune diseases, perivasculitis is common with the endothelium playing a major role at the initial stages of the disease. These endothelial cells promote vasculitis by secreting pro-inflammatory cytokines like IL-1, IL-6 or TNF-alpha in addition to the expression of adhesion molecules. Due to the persistence of these immunopathological mechanisms stenosis or atresia with ischaemic necrosis results. To examine whether this pathomechanism is also important in inner ear dysfunction, the immunological response after stimulation of the cochlear endothelium of guinea pigs was determined. In addition, the influence of corticosteroids on this immune cascade was examined.
BACKGROUND: Treatment of sudden sensorineural hearing loss (SSNHL) consists of administration of blood flow-promoting drugs with or without the addition of glucocorticoids. General guidelines based on scientific data do not currently exist. OBJECTIVE: To investigate the effect of glucocorticoids on the treatment of SSNHL. SETTING: Academic medical center. PATIENTS AND METHODS: We retrospectively analyzed the audiograms of 603 patients with SSNHL: 301 patients (cared for between January 1, 1986, and December 31, 1991) received intravenous blood flow-promoting drugs without glucocorticoids and 302 patients (cared for between January 1, 1992, and December 31, 1998) received intravenous blood flow-promoting drugs with glucocorticoids (intravenous +/- oral application). The age distribution of patients with SSNHL in lower, middle, and higher frequencies was similar in both groups. RESULTS: Patients with SSNHL in lower and middle frequencies (250-2000 Hz) who received glucocorticoids (prednisolone-21-hydrogen-succinate) showed significantly better recovery of hearing levels compared with those who did not receive glucocorticoids (P<.05). There was no significant difference at higher frequencies between the 2 groups. Patients with SSNHL throughout all frequencies (pancochlear hearing loss) who received glucocorticoids also had significantly better recovery of hearing levels compared with those who received blood flow-promoting drugs alone (P<.05). Also, patients with elevated blood sedimentation rates had better improvement of their hearing levels after receiving glucocorticoids. CONCLUSIONS: Administration of glucocorticoids should be recommended for treatment of patients with SSNHL. In particular, patients with SSNHL in the lower and middle frequency range and pancochlear hearing loss have significantly better recovery of hearing levels.
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The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.
The replacement of inactivated tumour suppressor genes is a promising approach in cancer therapy. The aim of this study was to evaluate the influence of technical determinants on the efficiency of adenoviral-mediated gene transfer into solid tumours. Therefore, we compared the efficacy of two different injection needle types, a conventional needle and a modified needle characterised by perforations at the side of the shaft in vivo. The total amount of adenoviral vector DNA and the activity of the transferred reporter gene were quantitatively analysed by polymerase chain reaction (PCR) specific for the E4 region of the Ad vector genome and the beta-galactosidase assay, respectively. The levels of adenoviral DNA, as well as the total beta-galactosidase activity, varied widely, but were not significantly different for the two groups. These results suggest, that the efficiency of intratumoral gene transfer cannot be improved by the design of the application device.
Osteoarthritis of the knee is considered to be the most common degenerative joint disease and finally ends up in a total knee replacement. Pain relief, restoration of a passive knee stability and improvement of functional ability are the primary goals of arthroplasties. But at the surgeons' closing, the patient for the present has just a knee "ready to function". Making the new joint function and recovering quality of life are the major outcome criteria for the rehabilitation process. This retrospective research was performed to evaluate three different rehabilitation programmes provided for patients receiving knee arthroplasties. Included were 124 patients with unilateral knee arthroplasty due to primary gonarthritis. All three rehabilitation clinics were able to improve the functional ability of the affected joints significantly, without any quantitative differences among them. The main influence factor in reaching the therapy aim (defined as: full extension and flexion > or = 90 degrees) seems to be the length of stay in the rehab clinic, which in turn is dependent on the presence of complications. On the other hand complications did not directly affect the achievement of the rehab goal, neither did age of patients, number of days between discharge (from acute care) and admission (to the rehab clinic), nor any accompanying illnesses. There, hence, have to be additional factors which influence the length of stay and so indirectly the rehab aim, factors which obviously are not accessible to quantitative objective measuring methods.
Using the HSV-tk/GCV system, complete remissions of tumors up to a size of 5 mm in diameter have been reported in mice and rats. In order to examine whether larger tumors of clinically relevant size can also be successfully treated, we established hepatic and peritoneal tumors consisting of retrovirally pretransduced tk-positive CC531 colon adenocarcinoma cells in syngenic Wag/Ola rats. In this model, we evaluated whether large tumors respond to therapy under the ideal condition of 100% gene transfer. Within 10 days, GCV treatment led to a marked regression of the adenocarcinomas. Tumors up to a size of 4000 mm3 could be completely eradicated. Passing through several stages of degeneration and cytolytic necrosis, a complete replacement by fibrous tissue was seen. There was no histological evidence for apoptosis and cell mediated immunity. These results suggest that complete regression of tumors of clinically relevant size can be achieved by direct toxic effects of the HSV-tk/GCV system if 100% of the cells are transduced.
Morphological and biochemical investigations have shown evidence of an association between measles virus and otosclerosis. Epidemiological analysis of age and gender distributions in the 1960s and 1970s revealed a higher incidence of otosclerosis in women, the average age of onset of clinical disturbances and need for surgery being between 15 and 40 years. In the late 1960s and early 1970s a campaign to vaccinate children against measles was started in Germany. The aim of our study was to evaluate whether this campaign has had any influence on the distributions of the age and gender of patients affected by otosclerosis over the past 20 years. The study included patients suffering from clinical otosclerosis who had undergone stapedectomy between 1978 and 1999 and whose clinical data were complete (n = 1351). Statistical analysis during the recruitment period indicated a significant increase in the average age of the otosclerosis patients (p = 0.012). With regard to the gender distribution it was found that the increase of otosclerosis in women compared to men was statistically insignificant (p = 0.418). These data strongly support the hypothesis of a measles virus involvement in otosclerosis and may reflect a decreased incidence of otosclerosis in the generation of patients vaccinated against measles virus.
The location of nitric oxide (NO) in the structures of the cochlea is a topical issue. Nitric oxide synthase (NOS) has been detected previously in mammalian cochleae, but information on its presence in the human cochlea is still sparse. The location of NOS isoforms I, II and III in substructures of the human cochlea was studied by immunohistochemistry (fluorescein isothiocyanate technique) using monoclonal antibodies to NOS I, II and III. NOS I was the predominant isoform and staining could be observed in cells of the spiral ganglion (SG), in nerve fibres and in the outer hair cells (OHC). Furthermore, the supporting cells of the organ of Corti and the stria vascularis showed a fluorescent reaction to NOS I. Staining for NOS III was less intense and was located in the OHC, supporting cells and SG cells, while the stria vascularis remained unstained. By contrast, NOS II showed weak staining in a few neuron fibres only. The results imply that NO in the human cochlea could act as a neurotransmitter/neuromodulator at the level of neural cells and may be involved in the physiology of the supporting cells and stria vascularis. Moreover, because NO is both a mediator of excitotoxicity and a non-specifically toxic radical, it may also play a role in neurotoxicity of the human cochlea.
The mechanical performance of natural materials depends on the type, and especially the composition of the molecular constituents. They are almost without exception composite materials, whose characteristics are determined by the characteristics of the individual constituents, their shape, their interaction, and in particular their orientation within the natural material. One of the most impressive natural composites is the insect cuticle. This lightweight building material impresses one with its ability to withstand extremely heavy loading. Even the ultrathin (3-10 microm) membranes of insect wings add greatly to the structural stability of the wings. By means of acoustic microscopy, the present study also shows that the thin covering of wax on the membrane is not an accidental material arrangement. Contrary to that of locust wings, dragonfly wing membranes were found to have a criss-cross fiber-like density gradient within to the waxy layer. This density gradient proved to be mechanically relevant in stabilizing the wings.
The genetic characterization of a 5.5-kb chromosomal region of Sinorhizobium meliloti 2011 that contains lpsB, a gene required for the normal development of symbiosis with Medicago spp., is presented. The nucleotide sequence of this DNA fragment revealed the presence of six genes: greA and lpsB, transcribed in the forward direction; and lpsE, lpsD, lpsC, and lrp, transcribed in the reverse direction. Except for lpsB, none of the lps genes were relevant for nodulation and nitrogen fixation. Analysis of the transcriptional organization of lpsB showed that greA and lpsB are part of separate transcriptional units, which is in agreement with the finding of a DNA stretch homologous to a "nonnitrogen" promoter consensus sequence between greA and lpsB. The opposite orientation of lpsB with respect to its first downstream coding sequence, lpsE, indicated that the altered LPS and the defective symbiosis of lpsB mutants are both consequences of a primary nonpolar defect in a single gene. Global sequence comparisons revealed that the greA-lpsB and lrp genes of S. meliloti have a genetic organization similar to that of their homologous loci in R. leguminosarum bv. viciae. In particular, high sequence similarity was found between the translation product of lpsB and a core-related biosynthetic mannosyltransferase of R. leguminosarum bv. viciae encoded by the lpcC gene. The functional relationship between these two genes was demonstrated in genetic complementation experiments in which the S. meliloti lpsB gene restored the wild-type LPS phenotype when introduced into lpcC mutants of R. leguminosarum. These results support the view that S. meliloti lpsB also encodes a mannosyltransferase that participates in the biosynthesis of the LPS core. Evidence is provided for the presence of other lpsB-homologous sequences in several members of the family Rhizobiaceae.
The cause of otosclerosis is still unknown. Recently, measles virus involvement has been implicated. The aim of this study was to analyze the presence of measles virus RNA within the otosclerotic focus and to evaluate the perilymphatic antibody pattern. Bone and perilymph specimens from 40 patients with the spontaneous form of otosclerosis and from control patients were investigated by reverse transcription polymerase chain reaction (RT-PCR), Western blot techniques, and cell culture. By the use of RT-PCR, measles virus RNA could be detected in 32 patients, but not in controls. Analysis of perilymph revealed the presence of antibodies to N, F1, and M measles virus proteins in all cases, and antibodies against H protein in 2 additional cases. In preosteoblasts cultured from otosclerotic bone chips, no measles virus RNA could be amplified. We conclude that the spontaneous form of otosclerosis is, in the vast majority of cases, a measles virus-associated disease of the otic capsule.