Biomedical subjects
J Müller
Publications and source records attributed to J Müller.
[Systematic analysis of local growth behavior and cervical lymph node metastasis of nasopharyngeal carcinoma--a clinical and computerized tomography examination].
BACKGROUND: Assessment of the incidence and patterns of cervical lymph node involvement according to the location, extension, and histological subtype of nasopharyngeal carcinoma. PATIENTS AND METHODS: The findings of the clinical and CT examinations of 80 patients with histological evidence of nasopharyngeal carcinoma (9T1-, 20 T2-, 17 T3-, 34 T4-carcinomas, lymph node involvement in 59 cases) were evaluated retrospectively. The histological subtype, local tumor spread, relation of the primary to the parapharyngeal fascias, compartments, and skull base structures were analysed and related to the cervical lymph node involvement. RESULTS: Two main types of nasopharyngeal carcinomas with different patterns of cervical lymph node involvement were identified: the posterior wall type, which spreads into the retropharyngeal and spinal accessorial neck node chains and the ventral type, which is located which is located at the roof, anterior, and lateral walls of the nasopharynx and spreads into the jugular neck node chains, preferring the neck side in which the main part of the primary is located. The border of lymph drainage via retropharyngeal-spinal accessorial or via jugular neck node chains is localised ventral of the origin of the m. capitus longus at the skull base. If the primary involves the prestyloidal compartment, the tumor may spread into the ipsilateral submaxillary lymph nodes. Combinations of the different types are frequently found with the neck node spread following the described directions. CONCLUSIONS: Knowledge of the regular patterns of spread of nasopharyngeal carcinoma is important for treatment procedures, especially for planning 3-dimensional radiotherapy.
Quantified testicular histology in boys with sex chromosome abnormalities.
Testicular histology in adult men with Klinefelter's syndrome (KS) is characterized by degenerative changes of the seminiferous epithelium. In contrast, limited changes have been reported in XXY fetuses. However, knowledge about the natural history of the degeneration of testicular histology in KS is scarce, and similarly testicular histology in prepubertal individuals with XY/XXY and XYY karyotypes is described incompletely. We have performed a qualitative and quantitative study of testicular histology in 11 XXY, one XY/XXY mosaic and two XYY boys between the neonatal period and 13 years of age using stereological methods and control data from normal XY boys and XY boys undergoing surgery for testicular maldescent. Testicular specimens were obtained at autopsy (n=2) or at time of surgery for malposition of the testis (n=10) or for inguinal hernia (n=2). The seminiferous tubules showed no sign of degeneration in any of the specimens. The volume density of seminiferous tubules was normal at all ages, whereas mean tubular diameter was reduced in all but three XXY boys. Germ cell numbers were only normal in XXY and XYY infants as well as in the 12 year old mosaic. No germ cells were observed in any XXY boy age 2 years or more. Leydig cells were observed in the infants and in a 13 year old XXY boy. The changes were comparable to what has been found in the most severely affected XY boys with testicular maldescent. We conclude that testicular histology in individuals with sex chromosome aneuploidy seems to be near normal during infancy, after which time degenerative changes occur.
The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide.
Serum concentrations of growth hormone-dependent insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), the carboxy terminal propeptide of type I procollagen (PICP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the amino terminal propeptide of type III procollagen (PIIINP) were studied in 14 prepubertal children with asthma (mean age 9.7 years) during treatment with inhaled budesonide. The study design was a randomized, crossover trial with two double-blind treatment periods (200 and 800 micrograms) and one open, non-randomized treatment period (400 micrograms). All periods were 18 days' duration. Budesonide treatment was associated with a dose-related suppressive trend in serum concentrations of PIIINP when the 400 micrograms period was included (p < 0.01; z = -2.7) and when it was excluded from the calculations (p < 0.01; z = -2.6), indicating reduced synthesis of type III collagen. A similar trend was observed in ICTP levels when the 400 micrograms period was excluded from the calculations (p = 0.05; z = -1.9). No other statistically significant variations were seen.
vpr deletion mutant of simian immunodeficiency virus induces AIDS in rhesus monkeys.
In previous experiments, animals infected with SIVmac239 containing a point mutation in the vpr and nef genes developed AIDS-like symptoms after early reversion of the vpr and nef genes. Here we show that two animals in which the nef gene but not the vpr gene had reverted in the first few months did not develop disease during a 3-year observation period even after reversion to a functional vpr gene 70 weeks postinfection. To study the influence of a stable vpr mutation on virus load and pathogenesis, a 43-bp deletion was introduced into the vpr gene of SIVmac239on, a nef-open mutant of SIVmac239. Four rhesus monkeys were inoculated with the vpr deletion mutant (SIV delta vpr), and two control animals were infected with SIVmac239on. Both control animals had persistent antigenemia, high cell-associated virus loads, and elevated neopterin levels. They had to be euthanized 20 and 30 weeks postinfection because of AIDS-related symptoms. However, all four rhesus monkeys inoculated with SIV delta vpr showed only transiently detectable antigenemia. The cell-associated virus loads were high in three of the four animals. Two animals with AIDS-like symptoms had to be euthanized 71 and 73 weeks postinfection. The two remaining monkeys infected with SIV delta vpr were still alive 105 weeks postinfection. In contrast to the SIVmac239on-infected animals, SIV delta vpr-infected animals had strong humoral immune responses and intermittent cellular immune responses to SIV antigens. Our data show that a functional vpr gene is not necessary for pathogenesis. However, vpr-deficient SIVmac239 variants might be slightly attenuated, allowing some animals to resist progression to disease for an extended period of time.
Diminished concentrations of insulin-like growth factor I in cystic fibrosis.
Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.
Metabolic effects of GH: a rationale for continued GH treatment of GH-deficient adults after cessation of linear growth.
GH deficiency in children has been treated for decades with GH in order to normalize growth and final height. After cessation of linear growth GH treatment has traditionally been stopped. However, adults with GH deficiency have increased mortality due to cardiovascular disease and share several clinical signs, such as reduced muscle strength, reduced exercise capacity, reduced sweating ability and thermoregulation, subnormal kidney function, reduced myocardial function, reduced energy expenditure, abnormal thyroid hormone metabolism, impaired psychosocial well-being, decreased lean body mass and decreased bone mineral content. Several studies have shown unanimously that GH replacement therapy in GH-deficient adults have improved all the above-reported clinical symptoms. We conclude that GH deficiency in adults is associated with a number of subnormal features. GH treatment improves (normalizes) these symptoms and we therefore believe that GH replacement therapy of a GH-deficient individual should be continued after cessation of linear growth. However, treatment of such patients should be carefully monitored since data from follow-up studies are still lacking.
Severe insulin-resistant diabetes mellitus in patients with congenital muscle fiber type disproportion myopathy.
Congenital muscle fiber type disproportion myopathy (CFTDM) is a chronic, nonprogressive muscle disorder characterized by universal muscle hypotrophy and growth retardation. Histomorphometric examination of muscle shows a preponderance of smaller than normal type 1 fibers and overall fiber size heterogeneity. Concomitant endocrine dysfunctions have not been described. We report the findings of altered insulin secretion and insulin action in two brothers affected with CFTDM and glucose intolerance as well as in their nonconsanguineous glucose-tolerant parents. Results are compared with those of six normoglycemic control subjects. All study participants underwent an oral glucose tolerance test to estimate insulin secretion. The oldest boy and his parents volunteered for studies of whole-body insulin sensitivity consisting of a 4-h euglycemic hyperinsulinemic clamp in combination with indirect calorimetry. Insulin receptor function and glycogen synthase (GS) activity and expression were examined in biopsies of vastus lateralis muscle. Despite a 45-90-fold increase in both fasting and postprandial serum insulin levels, both CFTDM patients had diabetes mellitus. Clamp studies revealed that the oldest boy had severe insulin resistance of both liver and peripheral tissues. The impaired insulin-stimulated glucose disposal to peripheral tissues was primarily due to reduced nonoxidative glucose metabolism. These changes were paralleled by reduced basal values of muscle GS total activity, allosterical activation of GS by glucose-6-phosphate, GS protein, and GS mRNA. The father expressed a lesser degree of insulin resistance, and studies of muscle insulin receptor function showed a severe impairment of receptor kinase activity. In conclusion, CFTDM is a novel form of severe hyperinsulinemia and insulin resistance. Whether insulin resistance is causally related to the muscle disorder awaits to be clarified.
Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty: effects of two different treatment regimens with gonadotropin-releasing hormone agonists, without or in combination with an antiandrogen (cyproterone acetate).
Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term treatment with GnRH in combination with an antiandrogen (cyproterone acetate) to block the possible effect of adrenal androgens has not previously been evaluated. We, therefore, studied 40 patients with idiopathic CPP that were treated for 24 months with either GnRH analog (Buserelin) in combination with cyproterone acetate (Androcur; n = 23) or with long acting GnRH analog (Decapeptyl Depot; n = 17). We found that serum IGF-I levels were increased before treatment in both groups (mean +/- SE, 446 +/- 35 and 391 +/- 35 micrograms/L; P < 0.0001, respectively) compared to those in normal age-matched prepubertal children. Similarly, IGFBP-3 levels were significantly elevated (4675 +/- 209 and 4305 +/- 162 micrograms/L, respectively; P < 0.0001) in the two groups. Treatment with GnRH analog in combination with cyproterone acetate significantly decreased height velocity and serum IGF-I and IGFBP-3 levels to normal levels after 2 yr of treatment (P < 0.0001). Serum IGF-I levels remained unchanged during monthly im treatment with long acting GnRH analog, whereas IGFBP-3 levels significantly increased during the first year of this treatment despite unmeasurable estradiol levels. Thus, in both groups, the molar ratio between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P < 0.0001 and r = 0.24; P = 0.003, respectively). Six of the patients with a subnormal GH response to clonidine had similar IGF-I and IGFBP-3 serum levels and growth velocity compared to the other 34 girls with CPP and a normal GH response.(ABSTRACT TRUNCATED AT 400 WORDS)
Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation.
Circulating IGF-I and -II are bound to specific insulin-like growth factor (IGF)-binding proteins (IGFBPs), of which IGFBP-3 binds the majority of the IGFs. IGFBP-3 levels are regulated by GH and have been suggested to provide additional information on GH secretory capacity compared to IGF-I. However, the diagnostic value of IGFBP-3 is still controversial, perhaps because the quality of the available normative data for IGFBP-3 varies. It has recently been shown that a large number of individuals is required to establish reference ranges for IGF-I that take into account age, sex, body mass index (BMI), and pubertal stage. Therefore, we measured IGFBP-3, IGF-I, IGF-II, IGFBP-1, and IGFBP-2 levels by RIA in 907 healthy children to establish well characterized normative data on IGFBP-3 according to age, sex, and pubertal stage and to study the complex relationship between IGFs and their BPs in puberty. We found that IGFBP-3 levels increase with age in children, with maximal levels in puberty; girls experience peak values approximately 1 yr earlier than boys. Age, sex, height, BMI, and pubertal maturation were all important factors in determining the circulating levels of IGFBP-3, whereas IGF-I levels were unaffected by BMI. Comparison of IGFBP-3 with IGF-1 concentrations revealed that they did not exhibit the same developmental pattern in puberty. IGF-I levels increased to relatively higher levels than IGFBP-3, leading to an increasing molar ratio between IGF-I and IGFBP-3 in puberty, when growth velocity is high. Concomitantly, IGF-II and IGFBP-2 levels were unchanged throughout puberty, whereas IGFBP-1 levels declined with age in prepubertal children, with lowest values in puberty. There was a highly significant correlation between IGF-I and -II and IGFBP-3 on a molar basis (r = 0.84; P < 0.0001). Thus, we speculate that IGFBP-3 is pivotal for circulating IGF bioactivity and that the increase in the molar ratio between IGF-I and IGFBP-3 reflects an increase in free, biologically active IGF-I. In conclusion, we have provided normative data on a large group of healthy individuals and conclude that age, sex, height, BMI, and pubertal maturation have to be taken into account before a single IGFBP-3 value in a growth-retarded child can be evaluated properly.
Function of the Polycomb protein is conserved in mice and flies.
A key aspect of determination--the acquisition and propagation of cell fates--is the initiation of patterns of selector gene expression and their maintenance in groups of cells as they divide and develop. In Drosophila, in those groups of cells where particular selector genes must remain inactive, it is the Polycomb-Group of genes that keep them silenced. Here we show that M33, a mouse homologue of the Drosophila Polycomb protein, can substitute for Polycomb in transgenic flies. Polycomb protein is thought to join with other Polycomb-Group proteins to build a complex that silences selector genes. Since members of this group of proteins have their homologues in mice, our results suggest that the molecular mechanism of cell determination is widely conserved.
Growth hormone treatment during pregnancy in a growth hormone-deficient woman.
Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 25-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she became pregnant after donor insemination. The GH treatment was continued until variant GH production from the placenta was evident. Serum levels of GH, IGF-I and IGFBP-3 were measured monthly during pregnancy after 3 days off GH therapy. Abdominal ultrasound was performed five times. Hormonal levels were measured immediately after delivery and during the following days. Serum GH and IGF-I levels increased during the second half of pregnancy; serum IGFBP-3 remained constant throughout pregnancy at a normal level. Serum levels of GH fell within 1 h after delivery, and levels of IGF-I and IGFBP-3 decreased into the range of GH-deficient women 4 days after. The fetal biparietal diameter increased normally, and birthweight was 3.564 kg, length 52 cm. No adverse events were recorded. We conclude that the role of GH replacement during pregnancy of GH-deficient women should be investigated further.
Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells.
BACKGROUND: It has been hypothesized that carcinoma in situ of the testis (CIS), which is the precursor of invasive testicular germ cell tumours, may arise from fetal germ cells during fetal development rather than later in life. In order to corroborate this hypothesis, we undertook the present study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester, and the decrease continued with the fetal age. CONCLUSIONS: The expression of adult carcinoma in situ markers in normal fetal germ cells is consistent with the hypothesis that CIS cells may arise from fetal germ cells, although re-expression of the antigens in postnatally arising CIS cells could provide an alternative explanation. However, we speculate that a transformation of normal fetal germ cells into CIS cells may take place before the end of the 9th week of fetal development. Furthermore, the expression of c-kit in early human fetal germ cells indicates that the c-kit and its ligand play a role in the early human testicular development.
[Adolf Bengel--the second inventory of lumbar pneumoencephalography].
In 1918, Walter Dandy reported contrasting liquor-filled spaces by air for the first time. He published the results in eight pneumencephalographies after lumbar air application in 1919. Without knowing about Dandy's papers Adolf Bingel performed his first lumbar encephalography in 1919. In contrast to Dandy, based on this experience Bingel developed ventricular imaging, improved the technique of lumbar puncture and did a scientific evaluation of the results.
Are implantable hearing devices really necessary?
Indications, advantages and disadvantages of different types of bone-anchored hearing aids and middle ear implants are discussed and compared with conventional hearing devices. The hearing results obtained at the University of Würzburg in 4,195 middle ear surgeries, from January 1988-August 1993, are presented. In those cases where tympanoplasty wasn't able to provide a good hearing result, the additional use of a conventional hearing aid was sufficient. If the gain and maximum output of the implantable hearing aid is improved in the future, the implant may be able to provide intelligible hearing also to patients with a profound sensorineural hearing loss. At this point implantable hearing aids will become really necessary, irreplaceable devices.
Noninvasive assessment of hepatobiliary and renal elimination of cysteinyl leukotrienes by positron emission tomography.
N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolf Bingel, the second inventor of lumbar pneumencephalography.
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[Psychiatrist--psychiatric critic--"Pazjent". The anti-psychiatry concept of Oskar Panizza (1853-1921)].
Most of the works of the physician and author Dr. med. Oskar Panizza were confiscated. Panizza himself was locked up and persecuted because of his works. Panizza was a well-educated psychiatrist working with Bernhard von Gudden and Emil Kraepelin at the "Oberbairische Kreisirrenanstalt München". When his family was afflicted with cases of mental disorders Panizza himself felt threatened from insanity. He broke off and became critic of the contemporary psychiatry. He drew up a kind of a psychistic psychiatry that anticipated important contents of the Anti-psychiatry of the 1970s.