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Biomedical subjects

G Wiesner

Publications and source records attributed to G Wiesner.

At least 19 recordsLinked to original sources

Brain leptin resistance in human obesity revisited.

Leptin is a 16 kDa peptide predominantly produced by adipocytes. Leptin and its receptor are known to be involved in the regulation of energy balance. The data from animal studies as well as our own observations of leptin overflow from the brain suggest that the central nervous system is a site of leptin synthesis. Using simultaneous arterio-venous blood sampling we here confirm that leptin is released from the brain into the internal jugular vein, and that release is greater in overweight men and in females compared to lean men, 467.3 ng/min+/-160.4 and 1426 ng/min+/-769.3 vs 80.0 ng/min+/-29.3, respectively (P<0.05). Furthermore, we have examined the gene expression of leptin and its receptor isoforms by reverse transcription-polymerase chain reaction (RT-PCR) in human cadaver hypothalami across a broad range of adiposity. Leptin gene expression was detected in a number of donors; the presence of detectable leptin mRNA was related to the mode of death rather than BMI or gender. We have also demonstrated gene expression of the three leptin receptor isoforms in the human hypothalamus. No relation was observed between the levels of hypothalamic expression of the long signaling form of the leptin receptor and BMI. In summary, this study indicates that it is very difficult to explain human obesity on the basis of central nervous system "leptin resistance", in that leptin is released in the brain, and at a higher level in the obese, and brain leptin receptor gene expression is not impaired in obesity.

Adult↗

[Multiple chemical sensitivity (MCS) -- a case series].

BACKGROUND AND OBJECTIVE: The phenomenon of Multiple Chemical Sensitivity which generally cannot be explained organically is frequently associated with psychic impairment. This case series deals with the question if in addition to a standardized interview a routine psychiatric-psychosomatic examination alters the classification if a patient suffers from symptoms compatible with MCS or not. METHODS: Nine consecutive outpatients (m = 3, f = 6, mean age 44 yrs) of the environmental medicine centre were investigated. Somatic diseases were evaluated by standard medical procedures and emotional disturbances were assessed by the Munich Composite International Diagnostic Interview (M-CIDI) and a psychiatric-psychosomatic examination. RESULTS: In all but one patients emotional disturbances (F-codes of the ICD-10) were diagnosed by the M-CIDI and the psychiatric-psychosomatic examination. The diagnoses of the M-CIDI and the psychiatric-psychosomatic examination often did not match. MCS was ruled out in seven patients. CONCLUSIONS: According to the criteria defined by Cullen (5), emotional disturbances must be ruled out before MCS is diagnosed. Therefore, an examination by a specialist in psychiatry or psychosomatics is mandatory because evaluation solely based on the M-CIDI is insufficient. Performing a routine psychiatric-psychosomatic examination, MCS could be ruled out much more often than previously.

Adult↗

[Exposure of hospital personnel to sevoflurane].

BACKGROUND: Occupational exposure to volatile anaesthetics cannot be completely avoided even in modern operating theatres. In 1997, the staff exposure during balanced anaesthesia in our hospital was low (sevoflurane 0.49 ppm; N(2)O 11.5 ppm). In 1999, N(2)O was completely omitted at our hospital, therefore, exposure to volatile anaesthetics, namely sevoflurane, might have increased. METHODS: Environmental exposure was measured by photoacoustic infrared spectrometry. To determine the personal exposure and to compare it with environmental exposure, 14 anaesthetists wore diffusion samplers near their breathing zones for 1 week. RESULTS: The median environmental concentration of sevoflurane was between 0.09 and 0.21 ppm in central operating theatres and between 0 and 24.8 ppm in intervention rooms. The median personal concentration was 0.19 ppm. CONCLUSION: The occupational exposure to volatile anaesthetics is not higher using sevoflurane alone compared to the combination of sevoflurane and N(2)O. In addition, the data acquired from environmental and personal measurements showed similar results.

Air Pollutants, Occupational↗

[Life expectancy, potential years of life lost (PYLL), and avoidable mortality in an East/West comparison].

The dynamics of convergence between East and West Germany in the life-prolonging process continued undiminished from 1990 until 2001. The regional differences in premature and avoidable mortality were clearly reduced, both between East and West and between the individual federal states. In the East and in the West there was an increase in life expectancy in all age groups and for both sexes, whereby the increase in life expectancy was considerably greater in East Germany and in all of the East German federal states. Also, the standardized potential years of life lost before the age of 65 decreased more intensively in East Germany. The women in East Germany achieved a lower premature mortality due to illness in the year 2001 than those in West Germany. In the initial year of 1990, the years of life lost were 27.2% greater. Unnatural premature mortality (especially due to accidents) was also relatively high in East Germany in the year 2001, but it is clearly being reduced. The avoidable mortality has been more than cut in half in all East German federal states since 1990. An almost complete alignment between East and West in regard to avoidable mortality was achieved in the year 2001. The phase of economic stagnation that can be observed in East Germany since 1997 has up to now not led to a worsening in the constitutive health references presented above.

Adolescent↗

[Suicidal methods--a comparison between East and West Germany. Epidemiological, forensic and sociomedical aspects].

A comparative study of the means of suicide in West and East Germany is extremely difficult both because of the data stock and the methodological questions that arise. This examination analyses means of suicide used during the following years: 1962-1964, 1987-1989 and 2000-2002. Accordingly, there is a similar pattern in both East and West for type of suicide committed and distinct developmental parallelism in applying the suicide methods. Certain means of suicide are more prominent (e. g. "hanging", "falling from a height") while others decrease in significance (e. g. "drowning"). No link was found between means of suicide and "society order". The use of a certain means of suicide depends on "availability", "existence" or "accessibility" of opportunities to commit suicide in the everyday environment. The same trend towards an increase of "hard" means of suicide was noted. The ways in which suicide is committed are becoming increasingly alike, but in the East it is apparent that people adhere more to "traditional" means of suicide.

Adolescent↗

A follow-up study on occupational exposure to inhaled anaesthetics in Eastern European surgeons and circulating nurses.

OBJECTIVE: Although no dose-response relationship exists for the health risks associated with the occupational exposure to inhaled anaesthetics, public health authorities recommend threshold values. The aim of the present study was to assess whether and to what extent these threshold values are exceeded in surgeons and circulating nurses of an Eastern European university hospital, before and after measures had been taken to reduce occupational exposure. METHODS: At nine workplaces, occupational exposure to nitrous oxide and the volatile anaesthetic used (halothane or isoflurane) was measured within the breathing zones of surgeons and circulating nurses by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces, and an air-conditioning system at one workplace. RESULTS: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared with that of 1996. In 1996, 89% of the nitrous oxide values were above the European threshold value of 100 ppm, whereas in 1997 approximately 50% were above this limit. In 1996 the majority of the measurements for the volatile anaesthetics were already below 5 ppm halothane and 10 ppm isoflurane and the number of measurements exceeding these limits was further reduced in 1997. CONCLUSION: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach Western European standards and to minimise possible health risks. These efforts comprise the installation of (active) scavenging devices, air-conditioning systems and new anaesthesia machines at all workplaces, the use of low-flow anaesthesia, the replacement of inhaled anaesthetics by intravenous anaesthetics and an appropriate working technique.

Anesthetics, Inhalation↗

Sympathetic nervous system and insulin resistance: from obesity to diabetes.

As the world faces an obesity "epidemic," the mechanisms by which overweight is translated into insulin resistance, hypertension, and diabetes need to be better understood. Although the processes of transition remain uncertain, overactivity of the sympathetic nervous system appears pivotal. In obesity, there is stimulation of sympathetic outflow to the kidneys, evident in increased rates of spillover of noradrenaline into the renal veins, and to skeletal muscle vasculature, demonstrated with microneurography. The cause is unclear, but possibly involves the stimulatory action of leptin released from adipose tissue, or from within the brain, for which there is recent evidence in human obesity. The high renal sympathetic tone contributes to hypertension development by stimulating renin secretion and through promoting renal tubular reabsorption of sodium. Neurally mediated skeletal muscle vasoconstriction reduces glucose delivery and uptake in muscle. Impairment of glucose uptake by skeletal muscle is a hallmark of insulin resistance syndromes. Pharmacologic sympathetic nervous suppression within the central nervous system with imidazoline receptor-binding agents such as rilmenidine is a logical therapeutic approach for lowering blood pressure (BP) in patients with essential hypertension, in whom sympathetic activity is often increased. In addition, drugs of this class appear to have the capacity to favorably modify insulin sensitivity, which has particular relevance in the treatment of hypertensive diabetic patients. In the hypertension accompanying maturity onset obesity, with recent recommendations from advisory bodies setting lower goal BP, and with these lower targets often being reached only with combinations of antihypertensive agents, it is advisable that all drugs used in combination therapy have a favorable or at least a neutral effect on insulin resistance.

Antihypertensive Agents↗

Waste gas exposure to sevoflurane and nitrous oxide during anaesthesia using the oesophageal-tracheal Combitube small adult.

Exposure to sevoflurane (SEV) and nitrous oxide during ventilation using a Combitube (37Fr) small adult (SA) was compared with waste gas exposure using conventional endotracheal tubes. Trace concentrations of SEV and nitrous oxide were assessed using a direct reading spectrometer during 40 gynaecological laparoscopic procedures under general anaesthesia. Measurements were made at the patients' mouth and in the anaesthetists' breathing zone. Mean (SD) concentrations of SEV and nitrous oxide measured at the patients' mouth were comparable in the Combitube SA (SEV 0.6 (0.2) p.p.m.; nitrous oxide 9.7 (8.5) p.p.m.) and endotracheal tube group (SEV 1.2 (0.8) p.p.m.; nitrous oxide 17.2 (10.6) p.p.m.). These values caused comparable contamination of the anaesthetists' breathing zone (SEV 0.6 (0.2) p.p.m. and nitrous oxide 4.3 (3.7) p.p.m. for the Combitube SA group, compared with SEV 0.5 (0.2) p.p.m. and nitrous oxide 4.1 (1.8) p.p.m. for the endotracheal tube group). We conclude that the use of the Combitube SA during positive pressure ventilation is not necessarily associated with increased waste gas exposure, especially when air conditioning and scavenging devices are available.

Adult↗

High-level, but not low-level, occupational exposure to inhaled anesthetics is associated with genotoxicity in the micronucleus assay.

UNLABELLED: To minimize the possible health risks posed by waste anesthetic gases, the National Institute of Occupational Safety and Health (NIOSH) recommends exposure limits. We investigated the genotoxicity of a previously established occupational exposure exceeding these limits (high-level exposure) and of one within these limits (low-level exposure). Genotoxicity was assessed by the formation of micronucleated lymphocytes in 25 anesthetists and anesthetic nurses of an Eastern European (High-Level Exposure Group) and a German (Low-Level Exposure Group) university hospital. Each exposed group was compared with a group of nonexposed personnel of the same hospital. Compared with its Control Group, there was an increased fraction of micronucleated lymphocytes per 1000 binucleated cells in the High-Level Exposure Group (median 14.0, range 9.0-26.7 vs median 11.3, range 3.2-19.4; P < 0.05) but not in the Low-Level Exposure Group (median 9.8, range 4.2-20.0 vs median 10.5, range 5.0-20.5). We conclude that a high-level exposure to inhaled anesthetics is associated with an increase in chromosome damage, and measures are recommended to decrease exposure levels. As evidenced by the formation of micronucleated lymphocytes, the threshold values recommended by NIOSH appear to be safe. IMPLICATIONS: A high level of occupational exposure to inhaled anesthetics is associated with genotoxicity (as defined by formation of micronucleated lymphocytes), whereas a low-level exposure (within National Institute of Occupational Safety and Health limits) is not.

Adult↗

E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma.

The E-cadherin mutation has been identified in a subset of families with multiple cases of diffuse gastric carcinoma. However, the true penetrance of this mutation and its association with other carcinomas in such families remains elusive. We aim to show the importance of DNA-based genetic counseling in hereditary diffuse gastric carcinoma. The proband was self-referred after three of his siblings died of diffuse gastric carcinoma. Medical and pathology records confirmed diagnoses. The family was educated about diffuse gastric carcinoma. Analysis for the 70G-->T mutation was performed by sequencing genomic DNA from lymphocyte pellets. DNA results and genetic counseling were provided individually to those tested. Twenty-four family members were tested for the E-cadherin mutation. Nine were found to be positive and 15 were negative. Three who tested positive and were affected are now deceased. None of the 19 patients counseled wanted results sent to their physicians once they recognized the potential for insurance discrimination. None had undergone endoscopic ultrasound. Three who were positive for the E-cadherin mutation expressed strong interest in prophylactic gastrectomy. The E-cadherin mutation strongly predicts susceptibility to diffuse gastric carcinoma. Emotional stress in at-risk patients, the limited knowledge of the mutation's penetrance, and limitations of available screening mandate patient-centered genetic counseling.

Cadherins↗

Occupational exposure to inhaled anaesthetics: a follow-up study on anaesthetists of an eastern European university hospital.

BACKGROUND: Although no dose-response relationship for the health risks associated with the occupational exposure to inhaled anaesthetics exists, public health authorities recommend threshold values. The aim of the present study was to assess if and to what extent these threshold values are exceeded in an eastern European university hospital before and after measures had been taken to reduce occupational exposure. METHODS: At nine workplaces occupational exposure of anaesthetists to nitrous oxide and halothane or isoflurane was measured by means of photoacoustic infrared spectrometry. The measurements were carried out in 1996 and were repeated in 1997 after the installation of active scavenging devices at five workplaces and an air-conditioning system at one workplace. RESULTS: Occupational exposure to nitrous oxide and halothane or isoflurane was lower in 1997 compared to 1996. In 1997 most of the nitrous oxide values still exceeded the threshold value of 100 ppm, whereas most of the halothane and isoflurane values were already below the threshold values of 5 ppm and 10 ppm in 1996. CONCLUSION: The measures taken were effective in reducing waste gas exposure. Nevertheless, further efforts are necessary, especially for nitrous oxide, to reach western European standards. These efforts comprise structural measures such as active scavenging devices and air-conditioning systems at all workplaces, the use of total intravenous anaesthesia, low-flow anaesthesia and an appropriate working technique.

Anesthesiology↗

Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer.

Aberrant promoter methylation and the associated loss of gene expression is a common accompaniment of human cancers. Nonetheless, it has been challenging to demonstrate in any given tumour that methylation of a specific gene was causal and not consequent to malignant transformation. In this regard, our attention was drawn to the genesis of gastric cancers in individuals with hereditary diffuse gastric cancer (HDGC). These individuals harbour germline mutations in the gene encoding E-cadherin, CDH1, but their cancers have consistently demonstrated absence of loss of heterozygosity at the CDH1 locus. These findings suggested the hypothesis that CDH1 promoter methylation might function as the 'second genetic hit' in the genesis of these cancers.

Alleles↗

A cytogenetic study on the teaching staff of a polluted school with a questionable increased incidence of malignancies.

Exposure to pollutants, in particular polychlorinated biphenyls (PCB), was established at a school built in 1966. Because of a statistically conspicuous increased frequency of breast cancer observed in the teachers of the school this study was performed to ascertain whether the teachers in the polluted school have an increased level of micronucleated cells (MN) or sister chromatid exchanges (SCE) as an expression of a raised cytogenetic risk. Teachers in a directly adjacent school served as one control group and those from a school about 30 km away as a second one. Each teacher had to answer a questionnaire and after venous blood samples had been taken, the number of MN and SCE in peripheral lymphocytes were determined. For the teachers in the polluted school, in addition, the length of stay in the building during the last month and year was recorded. Thereby no correlation with the number of MN and SCE was proven. In comparison with the two control groups, neither the number of MN nor SCE was increased in the teachers of the polluted school. Even if their predictive value for cancer risk assessment is disputed, MN and SCE have a high rating as standard procedures in the proof of an exposure to genotoxic agents. This study thus does not provide any evidence that, for the teachers in the polluted school, a relevant exposure to genotoxic agents exists.

Adult↗

Protein binding of piritramide: influence of various protein concentrations and the postoperative acute phase response.

OBJECTIVE: Piritramide is a lipophilic opioid, which is widely used for postoperative analgesia and analgosedation in Europe. In this study we investigated the influence of various protein concentrations (total protein, alpha1-acid glycoprotein, albumin) and the postoperative acute phase response on the protein binding of piritramide. METHODS: The influence of various protein concentrations on the protein binding of piritramide was investigated by either diluting the serum samples of five volunteers with isotonic saline or by adding different amounts of alpha1-acid glycoprotein. Albumin binding was measured in a 5% human albumin solution. The impact of the postoperative acute phase response was investigated by obtaining daily serum samples from 18 surgical patients until the third postoperative day, and measuring piritramide protein binding, alpha1-acid glycoprotein, total protein and albumin. RESULTS: There was a significant relationship between piritramide protein binding and the concentrations of total protein and alpha1-acid glycoprotein. The binding to albumin was 88%. During the postoperative acute phase response, the protein binding of piritramide did not change. Serum concentrations of alpha1-acid glycoprotein increased, whereas total protein and albumin decreased. CONCLUSION: Although there were significant changes in the piritramide-binding proteins, alpha1-acid glycoprotein and albumin, during the postoperative acute phase response, the protein binding of piritramide did not change. Therefore, a change in protein binding, which might be one factor to be considered in determining piritramide dosage in the postoperative period, does not have to be taken into account.

Acute-Phase Reaction↗

Sister chromatid exchange in human lymphocytes exposed to isoflurane and nitrous oxide in vitro.

The question of whether or not inhalation anaesthetics are genotoxic remains controversial. Therefore, we have studied the in vitro genotoxic potential of isoflurane and nitrous oxide in human lymphocytes. Blood samples were obtained from eight healthy male, non-smoking volunteers, which were incubated and exposed to increasing concentrations of isoflurane (0.0, 0.3, 0.6 and 1.2 mmol litre-1) or 50% nitrous oxide in oxygen. Baseline sister chromatid exchange (SCE) rate per cell was mean 7.65 (SD 1.5) which increased to 9.15 (1.0), 9.55 (1.4) and 9.95 (1.8) SCE/cell during exposure to isoflurane 0.3, 0.6 and 1.2 mmol litre-1, respectively. During 50% nitrous oxide exposure, SCE rate was 9.26 (1.4). The difference between the control and exposed cells was statistically significant (P < or = 0.05). We conclude that exposure to nitrous oxide and subanaesthetic concentrations of isoflurane can produce genetic damage in peripheral lymphocytes in vitro.

Adult↗

Waste anaesthetic gases induce sister chromatid exchanges in lymphocytes of operating room personnel.

Genotoxicity related to waste anaesthetic gas exposure is controversial. We have investigated the frequency of sister chromatid exchanges in peripheral lymphocytes of operating room personnel exposed to trace concentrations of isoflurane and nitrous oxide. Occupational exposure was recorded using a direct reading instrument. Frequencies of sister chromatid exchanges were measured in lymphocyte cultures of 27 non-smokers working in the operating room and 27 non-smoking controls. Personnel were exposed to an 8-h time-weighted average of nitrous oxide 11.8 ppm and isoflurane 0.5 ppm. After exposure, sister chromatid exchange frequency was increased significantly (mean 9.0 (SD 1.3) vs 8.0 (1.4) in exposed and control personnel, respectively) (P < 0.05). We conclude that exposure to even trace concentrations of waste anaesthetic gases may cause genetic damage comparable with smoking 11-20 cigarettes per day.

Adult↗