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Biomedical subjects

D Nagel

Publications and source records attributed to D Nagel.

At least 73 records · Page 4Linked to original sources

Ultra-long-distance running and the liver.

During an ultra-long-distance race (1000 km in 20 days) the influence of running was examined on the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyl-transferase (GGT), and glutamate dehydrogenase (GLDH) with regard to their release from the liver cells or their induction. Furthermore the liver synthetic capacity was assayed by measuring the enzyme activity of cholinesterase and the concentration of serum albumin during the race. Of the 110 participants, 55 finished the race and only the results of these runners were used in our study. AP increased continuously from day 0 (mean = 102 U/L) to day 19 (mean = 120 U/L). A fivefold increase of AST and a twentyfold increase of CK up to day 3 was followed by a significant decrease towards the end of the race. ALT rose as well up to day 6 from a mean value of 8 U/L to 24 U/L but remained at this level. Surprising was the individual increase of the enzymes GLDH (up to twentyfold) and GGT (up to sixfold) in more than half of the finishers on various days indicating liver cell injuries. The activity of CHE and the concentration of serum albumin decreased during the race, both were significantly correlated.

Adult↗

The use of cluster analysis in clinical chemical diagnosis of liver diseases.

Diagnostic judgement is usually based on recognition of patterns. Unfortunately more than three quantitative data cannot be judged simultaneously without help of mathematical methods. Working on laboratory reports, a clinician usually goes linearly through the columns and reduces quantitative to qualitative data. Therefore the medical decision process should be improved if data reduction is performed with the aid of mathematical methods for pattern recognition. A total of 191 consecutive outpatients with a tentative or proven diagnosis of hepatobiliary disease were examined clinically, clinically chemically and partly histologically. Nineteen clinical chemical parameters were determined. Prior to pattern cognition, a principal component analysis was performed. Using six factors, accounting for 72.4% of total variance, cluster analysis was done, applying a hierarchical algorithm for ascertaining a starting partition, followed by the k-means algorithm. The validity of the solution was scrutinized, and a stable structure was found with nine clusters. Patients with a rejected suspect of liver disease were mainly located in clusters 1, 6 and 7. Cluster 1 also contains patients with compensated cirrhosis without inflammation, idiopathic hyperbilirubinaemia, focal nodular hyperplasia and haemangioma of the liver. In contrast, one third of cirrhoses, all with inflammatory activity were assigned to cluster 5. Patients with primary biliary disease were distributed among clusters 2, 3 and 4. All malignant neoplasias were assigned to cluster 9. More than 50% of fatty livers were classified to cluster 7. Cluster 2 and 8 contain only one patient with primary biliary cirrhosis (cluster 2) and fatty liver hepatitis (cluster 8). The follow-up of 66 patients also showed clinically meaningful changes of cluster assignment.

Cluster Analysis↗

The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine by isolated hamster pancreas cells.

The activation of 3H-labeled N-nitrosobis(2-oxopropyl)amine [( 3H]BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro was measured as DNA alkylation. Hamster tissue was incubated with [3H]BOP (0.1 mM; 20 microCi/ml) for 2 h. Initial levels of alkylation were similar, 41.7 +/- 3.7 (acinar) and 51.5 +/- 7.8 (duct) dpm/micrograms DNA. Alkylation persisted for longer in duct (t/2 greater than 46 h) than in acinar tissue (t/2 = 6 h). The faster repair of alkylation in acinar tissue was not due to acinar cell death. In rat duct tissue the level of alkylation 2 h after incubation (38.9 +/- 4.5 dpm/micrograms DNA) was similar to that in hamster ducts but declined more rapidly (t/2 = 27 h). Hamster and rat acinar and duct tissue was incubated with BOP followed by [3H]thymidine to measure DNA synthesis. BOP stimulated DNA synthesis in hamster but not in rat duct tissue or hamster acinar tissue. These data support the hypothesis that the duct tissue is the target tissue for BOP in Syrian hamsters.

Alkylation↗

Effects of an ultra-long-distance (1000 km) race on lipid metabolism.

The influence was examined of ultra-long-distance running (1000 km race lasting 20 days) on changes in serum lipids. The 110 participants received two types of diet, a conventional Western diet and a wholesome vegetarian diet. Of the 55 finishers the serum concentration of total cholesterol, low density lipoprotein (LDL)-cholesterol, apolipoprotein B and triglycerides decreased significantly during the first 8 days of the run, but rose again towards the end of the race without reaching pre-race levels. The high density lipoprotein (HDL)-cholesterol increased initially but decreased in the final days of the run. The values for apolipoprotein A-I were not correlated with HDL-cholesterol. The free fatty acids and free glycerol showed marked increases (five times the prerace concentration), falling towards the end of the run. Changes in serum lipids showed no correlation with changes in body mass. Similar changes were observed in both dietary groups.

Adult↗

Effects of long-distance running on iron metabolism and hematological parameters.

In 110 well-trained participants of a 1000-km running competition lasting for 20 days hematological parameters, iron metabolism, and their respective changes during the race were investigated. Thirty-nine men and 11 women were accustomed to wholesome vegetarian food (lacto-ovovegetarian), 52 men and 8 women consumed a conventional western diet. In each group 50% of the runners finished the race. Before the competition started red blood cell count, hematocrit, and hemoglobin were on average below the values observed in the normal population in all groups. Both male and female runners consuming the wholesome diet showed significantly lower ferritin values than those on a western diet. During the first days of the competition hemolysis occurred leading to increased serum concentrations of bilirubin and iron and decreased haptoglobin levels. Hb concentrations showed a constant decrease during the race. Serum ferritin concentration rose about twofold within the first days and then decreased again without reaching pre-race levels. Serum iron concentrations showed a significant decrease between days 3 and 6. Iron loss was caused by hematuria (25% of all urines tested), gastrointestinal blood loss (10% of all stool specimens tested), and by sweating (4.5 micrograms iron/dl sweat). Our results suggest that especially in female long-distance runners it may be difficult to supply sufficient quantities of iron with the diet.

Adult↗

[Epidemiologic studies of tinnitus aurium].

The prevalence of tinnitus was examined in a group of 270 persons from an average cross-section of the population of Ulm. For statistical reasons we selected eight groups aged exactly 10, 20, 30, 40, 50, 60, 70, and 80 years. Thirty-one percent of those examined have already noted the presence of tinnitus at some point in time. Temporary tinnitus lasting not longer than 5 min. was reported in 19.5% and longer lasting tinnitus in 11.5% of cases. The highest incidence of 55% was found at the age of 20. The previously assumed age dependent increase in the incidence of tinnitus was seen only in the longer lasting type (5 min). The age dependent incidence of tinnitus was statistically correlated to audiogram, blood pressure, grade of physical activity, noise stress, and vertigo. The low incidence of tinnitus in presbyacusis (11%) differs from previous studies. Hypertension was associated with a lower incidence of tinnitus than normotension or hypotension.

Adult↗

Biochemistry of fusion mass consolidation in the sheep spine.

We report here the biochemistry of fusion mass consolidation in sheep spines during a 1-year period following autogenous cortical-cancellous bone grafting and stabilization with Harrington distraction rods. Biochemical analysis of vertebral fusion mass included determination of wet weight and dry weight and quantification of glycosaminoglycan, collagen, calcium, and phosphate following extraction with neutral EDTA and proteolytic hydrolysis with papain. Our results showed that at 1 week after surgery, the fusion mass consisted of original cortical and cancellous bone graft material. The cortical bone graft was partially resistant to EDTA-papain treatment, resulting in a residue containing hydroxyproline and mineral. At 12 weeks after surgery, the fusion mass had become a homogeneous material, which, like cancellous bone graft, was completely susceptible to treatment by EDTA-papain. Collagen content of consolidating fusion mass was highest at 16 weeks after surgery when normalized to dry weight; glycosaminoglycan content was highest within 6 weeks after surgery. Mineral content was lowest at the 6-week stage but by 12 weeks after surgery, it was comparable with original bone grafting material. At 24 and 52 weeks after surgery, fusion mass consolidation was characterized by an increase in the proportion of organic and mineral components resistant to EDTA-papain. The appearance of the EDTA-papain-resistant material in the fusion mass coincided with formation of lamellar bone and successful consolidation.

Animals↗

The production and repair of DNA damage by N-nitrosobis(2-oxopropyl)amine and azaserine in hamster and rat pancreas acinar and duct cells.

The activation of N-nitrosobis(2-oxopropyl)amine (BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro and in vivo was measured in terms of the production and repair of DNA damage. Hamsters were given BOP (1 X 10 mg/kg, s.c.). DNA single strand breaks (SSB) were measured over 2 weeks. Significantly more SSB were present in duct than in acinar tissue. Their persistence in the duct fragments was due to a slower rate of repair. In a related experiment, duct fragments were isolated from BOP-treated (1 X 10 mg/kg, s.c.) hamsters 24 h after exposure and cultured for 6 days, or were isolated 7 days after exposure. The extent of DNA damage was comparable in the two groups, indicating that the repair process(es) were still operative in cultured cells. Isolated duct fragments were exposed to either BOP or N-nitrosomethyl(2-oxopropyl)amine (MOP) in vitro. MOP produced significantly more DNA damage than BOP even at a 5-fold lower dose. This is consistent with the greater carcinogenicity of MOP in the pancreas. BOP produced significantly less DNA damage in the rat pancreas than in the hamster pancreas. The rate of repair was at least twice as fast in the rat pancreas as in the hamster pancreas. There did not appear to be any preference for acinar or duct tissue in rats as there was in hamsters. This procedure was validated in rats by the use of the rat pancreas carcinogen azaserine, which only produced DNA damage in rat acinar tissue.

Animals↗

[Dynamic properties of the ipsilateral tactile-elicited stapedius muscle reflex in probands with normal hearing].

We tested 94 male and female persons with normal hearing. From these persons we elicited from the external ear canal the ipsilateral tactile stapedius muscle reflex and examined its dynamic properties. The electric stimulus consisted of a series of electric impulses of a duration of 30 msec lasting for 1 sec. The intensity ranged from 2.0-8.0 mA increasing in steps of 0.5 mA. Statistical evaluation showed a significant reflex dependence on stimulus intensity and sex of the volunteers but not on the volunteer's age. Starting with a stimulus intensity of 3.5 mA all tested persons showed good reflex response. The average latency between the start of the stimulus and the beginning of the reflex was 130-200 msec diminishing with growing stimulus intensity. The best parameters describing the dynamic properties of the reflex seem to be the latencies L 1 and L 3 at a stimulus intensity of 3.5 - 6.0 mA.

Brain Stem↗

[Measurement of the acoustically evoked stapedius reflex in intubation anesthesia].

The threshold of the acoustically elicited stapedial reflex was measured in 45 persons with normal hearing aged 13-34 years. The intravenous barbiturate given for induction of general anaesthesia was found to raise the reflex threshold by an average of 15 dB. Ketanest and Halothane raise the reflex threshold by an average of 24 dB and 28 dB respectively. The ipsilateral reflex response was altered less by general anaesthesia than the contralaterally evoked response. The stapedial reflex can thus be measured under general anaesthesia if sedation fails to control disturbed and severely handicapped children.

Adult↗

Changes in cochlear microphonic response after Y-ray irradiation of the inner ear of the guinea-pig.

The effects of ionizing irradiation on the cochlear microphonic response of guinea-pigs were studied. The cochlear microphonics (CM) of both ears were recorded in a total of 36 animals. Recording was carried out by the differential electrode technique on the basal turn of the cochlea. One week prior to recording, the left ear of each animal had been exposed to 35-70 Gy radiation in increments of 5 Gy. Doses of 40 Gy and above led to a reduction in CM response. After doses of 60 Gy or more, no CM response could be detected. Damage most probably occurred in the outer and inner hair cells.

Animals↗

Comparative metabolism of beta-oxidized nitrosamines.

Several beta-oxidized nitrosamines have been shown to induce pancreatic cancer in Syrian hamsters. N-Nitrosobis(2-oxopropyl)amine (ND2OPA) is the most specific, but it also induces either colonic or prostatic tumours in MRC-Wistar rats. In-vivo and in-vitro metabolic studies show that N-nitrosomethyl(2-oxopropyl)amine is a metabolite of ND2OPA in hamsters but not in rats. ND2OPA is also present in higher concentrations in hamster pancreas than in the liver. No similar effect occurs in rats. These factors may explain, in part, the organotropism and species specificity of this nitrosamine.

Animals↗

[Acid phosphatase in blood (substrate: alpha-naphthylphosphate): reference values and diagnostic significance].

We report the results obtained with a modification of Hillmann's method (1) for determination of the catalytic concentration of acid phosphatase in serum using alpha-naphthylphosphate as the substrate. In a group of 158 males aged 16-85 years, the upper limit of the reference range (95th percentile) for the total acid phosphatase was established as 4.7 U/l (37 degrees C) and 4.2 U/l (30 degrees C), respectively; the corresponding values for the tartrate-inhibited acid phosphatase were 1.6 U/l (37 degrees C) and 1.5 U/l (30 degrees C). The upper limit of the reference range (95th percentile) for the total acid phosphatase determined in 60 females aged 18-80 years was 3.7 U/l (37 degrees C) and 3.0 U/l (30 degrees C). The catalytic concentrations in men and women did not show any age-related differences. The catalytic concentration of the tartrate-inhibited acid phosphatase was determined with the substrates alpha-naphthylphosphate and p-nitrophenylphosphate in a group of 89 patients with prostatic carcinoma (stages C and D). In 74 of these patients, the concentration of the prostatic specific acid phosphatase was assayed by enzyme-immunoassay and radioimmunoassay. The sensitivity of the method with p-nitrophenylphosphate was found to be unsatisfactory (66%), while that obtained with the other methods was superior and intercomparable (approx. 90%). The results obtained with the two substrates (p-nitrophenylphosphate vs. alpha-naphthylphosphate) differed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Carcinogenicity of N-nitrosomethyl(2-oxobutyl)amine and N-nitrosomethyl-(3-oxobutyl)amine in Syrian hamsters with special reference to the pancreas.

Studies with oxidized derivatives of N-nitrosodi-n-propylamine suggested a structure-activity relationship between pancreatic cancer induction in Syrian hamsters and position and degree of nitrosamine oxidation. To elucidate the importance of the position of the oxidized substituent relative to the N-nitroso group in pancreatic carcinogenesis, we compared the toxicity and carcinogenicity of two substituted methylbutylnitrosamines. N-Nitrosomethyl(2-oxobutyl)amine (M-2-OB) and N-nitrosomethyl(3-oxobutyl)amine (M-3-OB) were given in equitoxic doses to male and female Syrian hamsters. The 50% lethal doses for M-2-OB and M-3-OB in males and females, respectively, were 92 and 160 and 705 and 810 mg/kg body weight. M-2-OB, although given in significantly smaller doses (minimum dose, 2.3 mg/kg body weight) than was M-3-OB (minimum dose, 17.6 mg/kg body weight), induced a much broader spectrum of neoplasms (in 17 tissues), whereas M-3-OB induced tumors in only 5 tissues and had no carcinogenic effect in the pancreas. M-2-OB, however, produced pancreatic ductular-ductal adenocarcinomas in over 90% of the males and 67% of the females, even at the lowest doses (2.3 and 4.0 mg/kg, respectively). Although both compounds caused a similar incidence of morphologically equivalent neoplasms (mostly adenocarcinomas) in the nasal and paranasal cavities, the remaining distribution of affected tissues differed significantly. M-2-OB predominantly affected the lip (epitheliomas, squamous cell carcinomas), liver (cholangiomas and cholangiocarcinomas), and flank organ (epitheliomas, squamous cell carcinomas). The principal target organs for M-3-OB were the cheek pouch (papillomas, squamous cell carcinomas) and trachea (polyps). In contrast to M-2-OB, M-3-OB did not induce renal and urethral tumors. These findings indicate the importance of the 2-oxo group as a prerequisite for the carcinogenicity of methylalkylnitrosamines in the hamster pancreas; however, a methyl group in one aliphatic chain, alpha to the N-nitroso function, appears to cause the molecule to lose its selectivity for the pancreas.

Animals↗