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Biomedical subjects

A Heinemann

Publications and source records attributed to A Heinemann.

At least 19 recordsLinked to original sources
PubMed2005

Hypothalamic nitric oxide synthase in affective disorder: focus on the suprachiasmatic nucleus.

Depression is frequently associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which leads to repeated episodes of hypercortisolemia. Hypothalamic paraventricular neurons are believed to trigger these processes by aberrant generation and/or release of corticotropin releasing hormone, oxytocin, vasopressin, and nitric oxide (NO). Recent findings from two independent laboratories have demonstrated that the suprachiasmatic nucleus, which in part controls the cellular activity of paraventricular neurons (PVN), is also involved in affective disorder. The aim of the present study was to elucidate by stereological analysis, whether suprachiasmatic nucleus (SCN) nitric oxide synthase and neurophysin generating neurons are affected in neuropsychiatric disorders. We show that compared to controls the number of nitric oxide synthase immunoreactive neurons is greatly reduced both in depression and in schizophrenia. In subjects with affective disorder there was a correlation between the number of NOS-expressing cells and duration of treatment with antidepressants. The number of neurophysin-expressing SCN neurons was also fewer in cases with mood disorder. It is concluded that SCN-derived NO may be a relevant pathophysiological factor in neuropsychiatric disorders.

Adult↗
PubMed2004

Analysis of 683 drug packages seized from "body stuffers".

The wrappings and contents of 683 drug containers (bubbles) seized from 154 street dealers have been analysed since 2001, when the law enforcement policy in Hamburg, Germany, allowed the application of emetics to be used by so-called body stuffers for the recovery of swallowed drug packages. Of the bubbles recovered 96% contained cocaine. Cases of intoxication have not yet been observed but a 20-year-old man with a previously unknown toxic cardiomyopathy died 3 days after a sudden cardiac arrest which followed the forced application of ipecacuanha via correctly placed nasogastral tube.

Cocaine↗
PubMed2004

[High-grade pressure sores in frail older high-risk persons. A retrospective postmortem case-control-study].

Some old persons at risk do develop, but others, at comparable risk, do not develop high-grade pressure sores. To evaluate potentially different risk factors, we performed a post mortem case-control study in old persons who developed high-grade pressure sores within six months until 14 days before death. Consecutive cases with pressure sores grade >/=3 and potential controls at comparably high risk for pressure sores were examined before cremation. After written informed consent had been obtained by the next relatives, all available nursing and medical records of the deceased were thoroughly evaluated. Cases and controls were matched according to age, gender, immobility, and cachexia.A total of 100 cases with 71 pressure sores grade 3 and 29 pressure sores grade 4 were compared to 100 controls with 27 pressure sores grade </=2 and maximal risk as assessed by the Norton scale. The mean age was 86 years, 80% were females, 86% were bedridden, and cachexia was found in 66%. The cases were more often seriously disabled, had more often contractions of joints, and were on more drugs with intended or unwanted depressive/sedative effects (neuroleptics, benzodiazepines, centrally acting analgesics). Patient's impaired ability or low intention to comply/cooperate with preventive and/or therapeutic measures was more often recorded in cases than controls.A high degree of disablement and immobility, in particular, are risk factors for high-grade pressure sores in frail older high-risk persons. Sedative drug effects and impaired patient compliance with preventive and therapeutic measures may also be associated with the development of high-grade pressure sores in old persons at high risk.

Aged↗
PubMed2004

The CD63 basophil activation test in Hymenoptera venom allergy: a prospective study.

BACKGROUND: The basophil activation test (BAT), which relies on flow cytometric quantitation of the allergen-induced up-regulation of the granule-associated marker CD63 in peripheral blood basophils, has been suggested to be a useful approach in detecting responsiveness to allergens. The purpose of this study was to establish the usefulness of the BAT with regard to the clinical history and current diagnostic tools in Hymenoptera venom allergy using a prospective study design. METHODS: Fifty-seven consecutive patients allergic to Hymenoptera venom as defined by a systemic reaction after an insect sting, and 30 age- and sex-matched control subjects with a negative history were included. The degree and nature of sensitization was confirmed by skin testing, specific immunoglobulin E (IgE), serum tryptase levels and BAT. In the nonallergic control group only analysis of specific IgE and BAT were performed. Correlation of BAT, skin test and specific IgE, respectively, with the clinical history in the allergic group was termed as sensitivity and in the control group as specificity. RESULTS: Twenty one of 23 (91.3%) bee venom allergic patients and 29 of 34 (85.3%) patients allergic to wasp and hornet venom tested positive in BAT. The overall sensitivity of BAT, specific IgE and skin tests were 87.7, 91.2 and 93.0%, respectively. The overall specificities were 86.7% for BAT and 66.7% for specific IgE. No correlation between the severity of clinical symptoms and the magnitude of basophil activation was observed. CONCLUSION: The BAT seems to be an appropriate method to identify patients allergic to bee or wasp venom with a comparable sensitivity to standard diagnostic regimens. The higher specificity of BAT as compared with specific IgE makes this test a useful tool in the diagnosis of Hymenoptera venom allergy.

Animals↗
PubMed2003

[Deaths due to mechanical restraint in institutions for care].

The state of confusion in patients with severe disorientation and brain damage symptoms presents particular problems in gerontologic psychiatry. Six fatalities at different institutions due to improperly employed physical restraint and deficient surveillance are described. The causes of death involved strangulation which was accidentally caused by patients who become stuck between bedrails and mattress or who were fixed in an abdominal restraint belt or in a special protective blanket (mostly used for serious pre-conditions). The reconstruction of the scene of death was based in almost all the cases on the autopsy findings. We assume a considerable number of unreported emergency or fatal cases. The legal, psychiatric and nursing-related issues are discussed in this paper. Furthermore the precise documentation of the on-site appearance of the situation at discovery of death is called for. The indication for physical restraint should be limited as far as possible. Further studies in nursing homes and hospitals should focus on structural conditions with respect to the frequency of physical restraint in order to optimize the protection by quality standards.

Accidents↗
PubMed2003

Acid challenge delays gastric pressure adaptation, blocks gastric emptying and stimulates gastric fluid secretion in the rat.

Functional dyspepsia can be associated with impaired gastric relaxation in response to food intake and delayed gastric emptying. In this study, we investigated whether luminal hydrochloric acid (HCl) may reproduce these motor alterations in phenobarbital-anaesthetized rats via activation of extrinsic neural pathways. Intragastric pressure (IGP) changes induced by a 2-mL fluid bolus were recorded with an oesophageal catheter, and gastric emptying was determined via the fluid volume recovered from the stomach 30-min post-bolus. Experiments involving acute nerve transections or pharmacological blockade of nitric oxide synthesis revealed that the initial increase of IGP after a 0.35 mol L(-1) HCl bolus is dampened by duodenogastric and gastrogastric relaxation reflexes depending on vagal and splanchnic pathways as well as nitric oxide. Compared with saline, HCl (0.15-0.5 mol L(-1)) delayed the subsequent decrease (adaptation) of IGP, inhibited gastric emptying and stimulated gastric fluid secretion as seen in stomachs with ligated pylorus. The acid-evoked delay in IGP adaptation and inhibition of gastric emptying involved duodenogastric and duodenopyloric extrinsic nerve reflexes, whereas the gastric fluid secretion was independent of the extrinsic innervation. It is proposed that the gastropyloric motor changes induced by luminal acid challenge have a bearing on the motor disturbances underlying functional dyspepsia.

Animals↗
PubMed2003

Inhibition of prostaglandin biosynthesis in human endotoxin-stimulated peripheral blood monocytes: effects of caffeine.

There is an ongoing debate about possible advantages of the coadministration of caffeine with cyclooxygenase (COX) inhibitors in the treatment of pain. There are results suggesting interference by caffeine with COX expression and activity in rat immune cells. In the present study, we have used, therefore, human endotoxin-stimulated monocytes to investigate a possible influence of caffeine on indometacin-induced inhibition of prostaglandin E(2) (PGE(2)) formation. Endotoxin caused a concentration- and time-dependent increase in immunoreactive PGE(2) that was dependent on CD14-mediated mechanisms. In order to investigate pharmacological inhibition of the COX activity, a submaximal concentration of 1 ng/ml endotoxin (4 h exposure time) was used. Indometacin caused a concentration-dependent inhibition of PGE(2) with an apparent IC(50) of 8.9 +/- 1.4 x 10(-9) mol/l and an I(max) of 1 x 10(-7) mol/l. Caffeine (5 x 10(-6) to 1.5 x 10(-4) mol/l) on its own produced no statistically significant effect on endotoxin-induced PGE(2) formation. In the presence of caffeine (5 x 10(-6) to 1.5 x 10(-4) mol/l), inhibition of PGE(2) biosynthesis by indometacin (1 x 10(-8) mol/l) was not significantly altered. These results show that, in human monocytes, caffeine, up to concentrations severalfold higher than those reached in patients, has no significant effect on endotoxin-induced PGE(2) formation nor on its inhibition by indometacin.

Caffeine↗
PubMed2002

[Agreement on the Barthel Index. A rapid analysis of other and self-assessment in elderly stroke patients].

The relationship between staff and patient ratings of activity restrictions (Barthel Index, BI) was investigated in 120 elderly stroke patients (on average 78 years old) using the Rasch model and the rating scale analysis. In addition, the relationship between the rated activity restrictions and measures from the Geriatric Assessment was analyzed. We found good patient-staff agreement (r = 0.90) with the poorest agreement in the item "bathing" of the BI. There was also a highly significant correlation between staff and patient ratings and the Tinetti Gait and Balance Scales (r = 0.72 and r = 0.76, respectively). Correlations between other measures of the Geriatric Assessment and the rated activity restrictions were low explaining less than 8% of variance. Our findings merit the use of patient ratings of activity restrictions in stroke outcome research. However, self-ratings of activity restrictions were measured by an unstructured interview and it cannot be ruled out that this method had an influence on the correlation between self-rating and staff rating.

Activities of Daily Living↗
PubMed2001

Sodium salicylate enhances the expression of cyclooxygenase-2 in endotoxin-stimulated human mononuclear cells.

The effects of salicylate on the expression of cyclooxygenases, and on prostaglandin E(2) biosynthesis were examined in human peripheral blood mononuclear cells. Peripheral blood mononuclear cells were incubated in the presence of endotoxin, which induced expression of cyclooxygenase-2 protein, and caused a time-dependent increase of immunoreactive prostaglandin E(2) in the supernatant. The cycooxygenase-2 selective inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS-398, 1 microM) suppressed the endotoxin-induced increase of prostaglandin E(2), without significantly affecting the expression of cyclooxygenase-1 or cyclooxygenase-2. In peripheral blood mononuclear cells exposed to endotoxin (18 h), 1.0 and 3.0 mM sodium salicylate reduced the prostaglandin E(2) concentration of the supernatant, and, at the same time, stimulated cyclooxygenase-2 expression. After a subsequent 2 h incubation of peripheral blood mononuclear cells in drug-free medium, prostaglandin E(2) concentrations in samples that had been exposed to endotoxin together with 1.0 or 3.0 mM salicylate were significantly higher than in samples exposed to endotoxin alone. These results show that salicylate can enhance the expression of cyclooxygenase-2 in endotoxin-exposed peripheral blood mononuclear cells and at the same time reduce prostaglandin E(2) formation. After washout and removal of salicylate-induced cyclooxygenase inhibition, increased cyclooxygenase-2 expression resulted in enhanced prostaglandin E(2) formation. It seems possible that under certain conditions salicylate-induced stimulation of cyclooxygenase-2 expression may contribute to its clinical pharmacological profile.

Cyclooxygenase 2↗
PubMed2001

[Severe decubitus ulcer: risk factors and nursing requirements in the terminal life phase].

UNLABELLED: We present an analysis of the risk factors, the origin and the nursing and medical practice of 140 deaths with high-grade pressure sores which had been detected by post-mortem examination before cremation. METHODS: All available nursing and medical records from nursing homes and hospitals were screened; in addition, relatives and head nurses were interviewed. The data sources were screened for individual risk factors, information about pressure sore prevention and treatment activities by nursing staff and general practitioners. Moreover, the utilization of pressure relieving devices for patients before and after development of the final decubitus was analyzed. RESULTS: More than 50% of the pressure ulcers had been incident in nursing homes. The mean duration of the disease was 307 days (median duration 123 days); the maximum duration ranged up to about 6 years. As far as it could be judged from the nursing records, there was a shortfall of nursing quality in terms of prevention efforts which appeared to be frequently inadequate in relation to the risk profile of the residents. Standardized pressure sore record files were missing in most of the cases. General practitioners were not involved in the treatment in 20% of all cases; some of them prescribed an obsolete wound management. In this study 52% of the patients had been classified into the maximum grade within the three-stage German nursing care insurance scheme. In cases of private care information about utilization of financial support and of professional help should be enforced. DISCUSSION: Being an indicator of nursing quality, shortfalls of prevention measures should be combatted by a broad pattern of quality management strategies which could be adapted from the clinical sector.

Adult↗
PubMed2001

Vagal afferent signaling of a gastric mucosal acid insult to medullary, pontine, thalamic, hypothalamic and limbic, but not cortical, nuclei of the rat brain.

Although gastric acid is a factor in upper abdominal pain, the signaling and processing of a gastric mucosal acid insult within the brain are not known. This study examined which nuclei in the rat brain respond to challenge of the gastric mucosa by a noxious concentration of hydrochloric acid (HCl) and whether the central input is carried by vagal afferent neurons. Activation of neurons in the brain was mapped by in situ hybridization autoradiography of messenger ribonucleic acid (mRNA) for the immediate early gene c-fos 45 min after intragastric administration of saline or HCl. Following intragastric HCl (0.5 M) challenge, many neurons in the nucleus tractus solitarii, lateral parabrachial nucleus, thalamic and hypothalamic paraventricular nucleus, supraoptic nucleus, central amygdala and medial/lateral habenula expressed c-fos mRNA as compared to intragastric treatment with saline (0.15 M). However, c-fos transcription in the insular cortex was not enhanced by the gastric acid insult. Hypertonic saline (0.5 M) caused only a minor expression of c-fos mRNA in the hypothalamus and amygdala. The acid-evoked c-fos induction in subcortical nuclei was depressed by at least 80% five days after bilateral subdiaphragmatic vagotomy. Collectively, these observations indicate that vagal afferent input from the acid-threatened gastric mucosa does not reach the insular cortex but leads to activation of subcortical brain nuclei that are involved in emotional, behavioral, neuroendocrine, autonomic and antinociceptive reactions to a noxious stimulus.

Animals↗
PubMed2001

Disturbance of peristalsis in the guinea-pig isolated small intestine by indomethacin, but not cyclo-oxygenase isoform-selective inhibitors.

1. Since the cyclo-oxygenase (COX) isoform-nonselective inhibitor indomethacin is known to modify intestinal motility, we analysed the effects of COX-1 and COX-2 inhibition on intestinal peristalsis. 2. Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a rise of the intraluminal pressure and recorded via the pressure changes associated with peristalsis. 3. The COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398 (both at 0.1 -- 1 microM) and the isoform-nonselective inhibitors flurbiprofen (0.01 - 10 microM) and piroxicam (0.1 - 50 microM) were without major influence on peristalsis, whereas indomethacin and etodolac (0.1 -- 10 microM) disturbed the regularity of peristalsis by causing nonpropulsive circular muscle contractions. 4. Radioimmunoassay measurements showed that SC-560, NS-398, indomethacin and etodolac (each at 1 microM) suppressed the release of 6-keto-prostaglandin F(1 alpha) (6-keto-PGF(1 alpha)) from the intestinal segments. 5. Reverse transcription - polymerase chain reaction tests revealed that, relative to glyceraldehyde-3 phosphate dehydrogenase ribonucleic acid, the expression of COX-1 mRNA increased by a factor of 2.0 whereas that of COX-2 mRNA rose by a factor of 7.9 during the 2 h experimental period. 6. Pharmacological experiments indicated that the action of indomethacin to disturb intestinal peristalsis was unrelated to inhibition of L-type calcium channels, adenosine triphosphate-sensitive potassium channels or phosphodiesterase type IV. 7. These results show that selective inhibition of COX-1 and COX-2 does not grossly alter peristaltic motor activity in the guinea-pig isolated small intestine and that the effect of indomethacin to disturb the regular pattern of propulsive motility in this species is unrelated to COX inhibition.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Basophil responses to chemokines are regulated by both sequential and cooperative receptor signaling.

To investigate human basophil responses to chemokines, we have developed a sensitive assay that uses flow cytometry to measure leukocyte shape change as a marker of cell responsiveness. PBMC were isolated from the blood of volunteers. Basophils were identified as a single population of cells that stained positive for IL-3Ralpha (CDw123) and negative for HLA-DR, and their increase in forward scatter (as a result of cell shape change) in response to chemokines was measured. Shape change responses of basophils to chemokines were highly reproducible, with a rank order of potency: monocyte chemoattractant protein (MCP) 4 (peak at <1 nM) >/= eotaxin-2 = eotaxin-3 >/= eotaxin > MCP-1 = MCP-3 > macrophage-inflammatory protein-1alpha > RANTES = MCP-2 = IL-8. The CCR4-selective ligand macrophage-derived chemokine did not elicit a response at concentrations up to 10 nM. Blocking mAbs to CCR2 and CCR3 demonstrated that responses to higher concentrations (>10 nM) of MCP-1 were mediated by CCR3 rather than CCR2, whereas MCP-4 exhibited a biphasic response consistent with sequential activation of CCR3 at lower concentrations and CCR2 at 10 nM MCP-4 and above. In contrast, responses to MCP-3 were blocked only in the presence of both mAbs, but not after pretreatment with either anti-CCR2 or anti-CCR3 mAb alone. These patterns of receptor usage were different from those seen for eosinophils and monocytes. We suggest that cooperation between CCRs might be a mechanism for preferential recruitment of basophils, as occurs in tissue hypersensitivity responses in vivo.

Basophils↗
PubMed2000

Methadone-related fatalities in Hamburg 1990-1999: implications for quality standards in maintenance treatment?

Drug-related fatal poisonings were analysed in Hamburg from 1990 to 30th June 1999 with special attention to the role of methadone. The first methadone-related fatalities were observed in Hamburg three years after methadone maintenance treatment (MMT) was introduced in 1990. Meanwhile more than half of all fatal poisonings among drug addicts are monovalent or polydrug intoxications with evidence for methadone. From January 1997 until June 1999 methadone was the predominant cause of death in about 39% of all drug-related fatal poisonings while the proportion of mixed heroin/methadone intoxications was about 10%. The rising problem of methadone-related fatalities goes with a decline of monovalent heroin intoxications which decreased in the last 9 years from 60% to 11%. Sixty-five per cent of those who died of fatal methadone-related poisonings had no history of MMT (60% of those with methadone as predominant cause of death). Since take-home doses for up to 7 days are prescribed to the patient due to a change in the German Narcotics Act in 1998, the diversion of methadone into illegal markets may have been accelerated. This results in rising numbers of non-intentional methadone-related fatalities among addicts who have never been in MMT. The prerequisites for the prescription of take-home doses should be taken more serious. There is no doubt that MMT reduced the mortality rate among the great majority of patients in Hamburg but supreme efforts should be made to prevent or reduce fatal intoxications by methadone in the non-treatment group.

Analgesics, Opioid↗
PubMed2000

[Decubitus ulcer in the terminal phase: epidemiologic, medicolegal and ethical aspects].

BACKGROUND AND OBJECTIVES: Pressure sores usually result from insufficient preventive measures. They are particularly omnipresent among dying persons in geriatric care. This study deals with prevalence, risk factors and the significance of the nursing environment. PATIENTS AND METHODS: The prevalence of pressure sores among the dead was analysed in a prospective cross-sectional study based on 10,222 postmortem examinations in a crematorium in Hamburg. RESULTS: The overall prevalence of pressure sores from grades I to IV was 11.2% (grade I: 6.1%, grade II: 3%, grade III: 1.1%, grade IV: 0.9%). A final logistic regression model showed that pressure sores of Grade III or IV were associated with female gender, date of death in the summer, marasmus, stroke history, neurological disease in general, kidney disease, preceding traumatic events and nursery home residence at the time of death. More than half of all the grade IV cases were diagnosed among nursing home residents whereas those who had died in hospitals contributed to only 11.5% of all the grade IV cases (dead from private homes 34.4%). Nursing home residence was associated with female gender, marasmus and stroke history which predisposed to a higher rate of pressure sores. CONCLUSIONS: Nursing homes are confronted with the highest proportion of pressure sores among dying people when compared to hospitals or private home care. Failure to meet the standards of preventive action against pressure sores point to the shortfalls in the present public health sector and nursing home regulations as well as the medical responsibility for supervision of nursing care. Apart from established standards of care, medicolegal assessment of high-grade pressure sores should also take ethical considerations into account when considering maximum therapy goals among dying persons.

Aged↗
PubMed2000

Pressure sores: epidemiology, medico-legal implications and forensic argumentation concerning causality.

The aim of the present investigation was to identify the frequency and grading of pressure sores in a large series of unselected consecutive deceased subjects before cremation and to discuss aspects of the forensic argumentation concerning causality. A total of 10,222 corpses were examined prospectively over a 1-year-period (1998) for the occurrence, localization and grading of pressure sores. Epidemiological aspects (e.g. age, sex, underlying and contributing causes of death, place of death etc.) were taken from the death certificate. The mean prevalence of pressure sores was 11.2% (87.1% isolated sores; predominant localization of advanced grades on the sacrum in 69.6%). There was a positive correlation between the prevalence of sores and advanced age resulting in a clear female predominance in the age group of 80 years and over because of differences in life expectancy. A significant correlation was found between the prevalence of pressure sores and certain underlying diseases, e.g. trauma, senile dementia, neurological diseases, apoplexy and marasmus. Pressure sores of all grades were more frequently found in the deceased when a senior citizen's or nursing home was given on the death certificate as the domicile in the last period of life. The forensic argumentation for the causal relationship of a pressure sore as the focus of fatal infectious complications or septicemia has to be based on the results of clinical expertises and forensic investigations (evaluation of the institutional documentation of the patient's course, autopsy findings, histology, immunohistochemistry). The vast majority of physicians seem to pay only little attention to the potentially fatal outcome of pressure sores and fatalities associated with this condition are clearly underreported. From the point of view of social medicine, the prevalence of pressure sores in a defined population can be seen as a parameter for the quality of nursing and medical care. In bringing these fatalities to light, the field of legal medicine contributes to a general quality control of standards of nursing and medical care.

Age Factors↗