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Biomedical subjects

A Harmsen

Publications and source records attributed to A Harmsen.

At least 19 recordsLinked to original sources
PubMed2001

Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo.

Cyclic ADP-ribose is believed to be an important calcium-mobilizing second messenger in invertebrate, mammalian and plant cells. CD38, the best-characterized mammalian ADP-ribosyl cyclase, is postulated to be an important source of cyclic ADP-ribose in vivo. Using CD38-deficient mice, we demonstrate that the loss of CD38 renders mice susceptible to bacterial infections due to an inability of CD38-deficient neutrophils to directionally migrate to the site of infection. Furthermore, we show that cyclic ADP-ribose can directly induce intracellular Ca++ release in neutrophils and is required for sustained extracellular Ca++ influx in neutrophils that have been stimulated by the bacterial chemoattractant, formyl-methionyl-leucyl-phenylalanine (fMLP). Finally, we demonstrate that neutrophil chemotaxis to fMLP is dependent on Ca++ mobilization mediated by cyclic ADP-ribose. Thus, CD38 controls neutrophil chemotaxis to bacterial chemoattractants through its production of cyclic ADP-ribose, and acts as a critical regulator of inflammation and innate immune responses.

ADP-ribosyl Cyclase↗
PubMed2000

Pneumocystis carinii enhances soluble mannose receptor production by macrophages.

Phagocytosis of extracellular organisms in the alveolar spaces of the lungs represents the first-line of host defense against pulmonary pathogens. Disruption of this process is likely to interfere with the generation of appropriate specific immune responses, and lead to a delayed or inefficient clearance of the pathogen. Pneumocystis carinii, an opportunistic pathogen in immunodeficient individuals, is cleared from the lung by alveolar macrophages. In the absence of specific anti-Pneumocystis antibodies, phagocytosis is dependent on the non-opsonic macrophage mannose receptor (MR). Recent studies have demonstrated that alveolar macrophage MR activity is downregulated in individuals infected with HIV, and that functional MR is shed from the macrophage cell surface. Here we report that P. carinii enhances the formation of soluble MR by macrophages in vitro. Soluble MR was detected in cell-free alveolar fluid from humans infected with HIV and/or P. carinii, but not in alveolar fluid from healthy controls. Soluble MR was found in association with extracellular clumps of P. carinii in the lungs of mice with P. carinii pneumonia, and was associated with P. carinii organisms purified from these mice. When purified P. carinii organisms were incubated with soluble MR-containing supernatants, they were phagocytosed less readily by alveolar macrophages than were control organisms. Our results suggest that P. carinii organisms enhance the shedding of MR from the surface of alveolar macrophages, and that the resultant soluble MR binds to intra-alveolar organisms, thereby interfering with their non-opsonic uptake via the macrophage cell surface MR.

AIDS-Related Opportunistic Infections↗
PubMed1998

Induction of fibrinogen expression in the lung epithelium during Pneumocystis carinii pneumonia.

Pneumocystis carinii is an important pulmonary pathogen responsible for morbidity and mortality in patients with AIDS. The acute-phase response (APR), the primary mechanism used by the body to restore homeostasis following infection, is characterized by increased levels of circulating fibrinogen (FBG). Although the liver is the primary site of increased FBG synthesis during the APR, we unexpectedly discovered that FBG is synthesized and secreted by lung alveolar epithelial cells in vitro during an inflammatory stimulus. Therefore, we sought to determine whether lung epithelial cells produce FBG in vivo using animal models of P. carinii pneumonia (PCP). Inflammation was noted by an influx of macrophages to P. carinii-infected alveoli. Northern hybridization revealed that gamma-FBG mRNA increased two- to fivefold in P. carinii-infected lung tissue, while RNA in situ hybridization demonstrated increased levels of gamma-FBG mRNA in the lung epithelium. Immunoelectron microscopy detected lung epithelial cell-specific production of FBG, suggesting induction of a localized inflammatory response resembling the APR. A systemic APR was confirmed by a two- to fivefold upregulation of the levels of hepatic gamma-FBG mRNA in animals with PCP, resulting in a corresponding increase in levels of FBG in plasma. Furthermore, immunoelectron microscopy revealed the presence of FBG at the junction of cell membranes of trophic forms of P. carinii organisms aggregated along the alveolar epithelium. These results implicate FBG in the pathogenesis of PCP in a manner similar to that of the adhesive glycoproteins fibronectin and vitronectin, which are known to participate in intra-alveolar aggregation of organisms and adherence of P. carinii to the lung epithelium.

Acute-Phase Reaction↗
PubMed1993

[Tasks of caregivers in a nursing home. A study of tasks and reactions of caregivers].

This paper describes a study on the task perceptions of enrolled nurses in a nursing home and the relationships between task perceptions and reactions such as burnout, job satisfaction, experienced job significance and absenteeism (Harmsen, 1991). In our study a comparison is made on the one hand between the task perceptions of three different functions in the nursing home, namely the unit heads, the graduated and the student nurses, and on the other hand between the task perceptions of enrolled nurses working on two types of wards, namely somatic and psycho-geriatric wards. Concerning the relationships between task perceptions and reactions, the results of our study show that activities regarding the 'nursing record', the 'nursing report', the 'stimulation of self-care' and 'social contact' usually have a positive relationship with the experienced job significance of enrolled nurses. On the contrary, activities concerning daily care are evaluated negative. Finally, tasks in the area of 'instrumental activities', 'caring for the dying' and 'caring for the privacy of the client' appear to have positive as well as negative effects.

Absenteeism↗
PubMed1989

Acoustic neuroma surgery: results of translabyrinthine tumour removal in 300 patients. Discussion of choice of approach in relation to overall results and possibility of hearing preservation.

The results from the Danish model of acoustic neuroma surgery are presented. In the period from 1976 to 1985, 300 patients with acoustic neuromas were operated upon using the translabyrinthine procedure. Only one small intrameatal tumour was encountered; 96 tumours were medium sized and 203 were larger than 25 mm. Of these 118 measured more than 40 mm. Mortality rate was 2%, CSF leaks occurred in 11%, and had to be closed surgically in 5%. Facial nerve function was postoperatively normal in 66%, slightly reduced in 17%, moderately reduced in 8% and abolished in 9%. Reconstruction, most often as a XII-VII anastomosis, was performed in only 6% of the patients. Cerebellar symptoms, which occurred in 45% preoperatively were present in only 7% after surgery. The preoperative hearing in both the tumour and non-tumour ear was analysed in 72 patients with tumours smaller than 2 cm. In the tumour ear, only four patients had a PTA of 0-20 dB and SDS of 81-100%; eight patients had a PTA of 0-40 dB and SDS of 61-100%; 14 had a PTA of 0-50 dB and SDS of 51-100%. This means that only a maximum of 5% of the patients, using the broadest criteria, could be candidates for hearing-conserving surgery. In all these patients the contralateral ear had hearing within normal limits (PTA 0-20 dB and SDS 95-100%). Since preservation of hearing would be achieved in only half of those subjected to suboccipital removal and since the hearing retained in patients with successful operations generally is poorer than the preoperative level, the number of patients obtaining serviceable hearing is so modest that preservation of hearing cannot be considered a valid argument in favour of suboccipital tumour removal. From a statistical point of view the risk of losing hearing in the opposite ear after tumour removal is negligible. The general morbidity after suboccipital surgery is higher than after translabyrinthine surgery, and hearing loss must be listed low among the other sequelae after tumour removal.

Denmark↗
PubMed1988

Results of translabyrinthine removal of 300 acoustic neuromas related to tumour size.

The results from the Danish model of acoustic neuroma surgery are presented. In the period from 1976 to 1985, 300 patients with acoustic neuromas were operated upon using the translabyrinthine procedure. There were one small intrameatal tumour; 96 medium-sized tumours with an extrameatal diameter up to 25 mm; 85 large tumours, measuring 26-40 mm, and 118 very large tumours with a diameter exceeding 40 mm. The mortality rate was 2%, and CSF leak occurred in 11%, persisting for more than 2 weeks in 5% of the patients in whom the fistula had to be closed operatively. Facial nerve function was completely normal in 66%, slightly reduced in 17%, moderately reduced in 8% and abolished in 9%. The facial nerve was anatomically preserved in 95% of the patients. Reconstruction of the facial nerve, most often an XII-VII anastomosis, was performed in only 6% of the patients. Cerebellar symptoms, occurring in 45% preoperatively, were demonstrated in only 7% postoperatively. We find that a standardization of the measurement of tumor size and of the assessment of sequelae changes is urgently needed.

Adolescent↗
PubMed1988

Is preservation of hearing in acoustic neuroma worthwhile?

In a series of 300 translabyrinthine removals of acoustic neuromas, comprising almost all tumours operated on in Denmark during a period of 10 years, the preoperative hearing in the tumour ear and in the contralateral ear was analysed in 72 patients with tumours smaller than 2 cm in extrameatal diameter. These patients constitute likely candidates for a hearing preserving operation via the suboccipital approach. In the tumour ear in 4 patients there was a pure-tone average (PTA) of 0-20 dB and a discrimination score (DS) of 81-100%. Applying this criterion to the whole series, 1% of the patients would be candidates for a hearing preserving procedure. Changing the criterion to a PTA of 0-40 dB and a DS of 61-100%, the number of candidates would increase to 8 patients (3%), and with a PTA of 0-50 dB and a DS of 51-100% 14 candidates (5%) would have been found. In all of these patients, contralateral hearing was normal (SRT 0-20 dB, DS 95-100%). Since preservation of hearing would be achieved in only half of those subjected to suboccipital removal and since the hearing retained in patients with successful operations is generally poorer than the preoperative level, the number of patients obtaining serviceable hearing is so modest that preservation of hearing cannot be considered an argument in favour of suboccipital tumour removal. It should be borne in mind that contralateral hearing is normal in these patients and that, according to most reports, the mortality rate is higher and paralysis of the facial nerve more frequent with the suboccipital approach than with the translabyrinthine procedure.

Adolescent↗
PubMed1987

Resistance to cerebrospinal fluid outflow and intracranial pressure in patients with hydrocephalus after subarachnoid haemorrhage.

Resistance to CSF-outflow (Rout) and intracranial pressure (ICP) were measured in 33 patients with hydrocephalus after subarachnoid haemorrhage (SAH). Eleven patients examined between 10 to 30 days after SAH had high pressure hydrocephalus (HPH). Twenty-two patients had normal pressure hydrocephalus (NPH). All HPH-patients had ICP above 15 mmHg, plateau waves and B-waves, a median Rout of 59 mmHg x ml-1 x min-1 (range 29-100). All NPH-patients had a normal ICP level, no plateau waves, but long periods of B-waves and a median Rout of 22 mmHg x ml-1 x min-1 (range 6-47). Of the 11 patients with HPH six were shunted and five had temporary ventricular drainage. Five patients improved and six died. Of the five survivors only one went back to work. Of the 22 NPH-patients 18 were treated with a shunt, one refused shunt operation and three had normal Rout. Seventeen improved after shunting. At follow-up 12 had a normal social life, 5 lived in a nursing home and 1 was dead. Thus, early development of hydrocephalus after subarachnoid haemorrhage is associated with a high Rout and a high ICP, whereas late (more than one month) hydrocephalus may be associated with normal ICP and high Rout. Patients with NPH and a high Rout have frequent B-waves and should be shunted. Patients with a long interval from subarachnoid haemorrhage to the diagnosis of hydrocephalus often have a normal ICP, low frequency of B-waves, normal CSF-dynamics and need no shunting.

Adult↗
PubMed1987

Clinical features and outcome in 1076 patients with ruptured intracranial saccular aneurysms: a prospective consecutive study.

In a well-defined area, The Kingdom of Denmark, 1076 patients with ruptured intracranial aneurysms were admitted to the six Danish neurosurgical departments in a prospective consecutive study in the 5-year period 1978-1983. Follow-up examinations were accomplished 3 months and 2 years after the admission. A total of 674 women and 402 men with a median age of 49 years were included in the study. The localisation of the ruptured aneurysms were: internal carotid artery 285, anterior communicating artery and horizontal part of anterior cerebral artery 383, middle cerebral artery 291, basilar and vertebral arteries 83 and peripheral or other localisation 34. A significantly better outcome was seen in cases with internal carotid aneurysms compared to other localisations. 670 patients underwent operation. A highly significantly better outcome was found in operated versus non-operated patients in comparable clinical conditions. The advantage of microneurosurgery was well documented. Patients with vasospasm had a significantly worse outcome. Within the first 2 weeks a daily rebleeding rate from 0.2% to 2.1% was observed, and patients who rebled had a significantly worse outcome compared to patients, who did not rebleed. The overall outcome at 2-year follow-up was: normal 27.5%, mild dementia 15.8%, severe dementia 9.9%, vegetative 1.3% and mortality 45.5%.

Denmark↗
PubMed1987

Clinical features and outcome in 48 patients with unruptured intracranial saccular aneurysms: a prospective consecutive study.

During a 5-year period (1978-1983) the clinical features and operative morbidity/mortality were registered prospectively for all patients in Denmark with an unruptured symptomatic (27 patients) or incidental (21 patients) intracranial saccular aneurysm. A follow-up examination was performed 2 years after diagnosis of the aneurysm. Thirty symptomatic aneurysms in 27 patients most frequently involved the visual pathways or ocular motility (66%). The median diagnostic delay for patients with impaired visual acuity was 7 months but only 14 days for patients with impaired ocular motility. The localisation of the 30 symptomatic and 23 incidental aneurysms were: internal carotid artery (73% approximately 35%), anterior communicating artery (3% approximately 26%) and middle cerebral artery (7% approximately 35%). The diameters of 73% of the symptomatic aneurysms were greater than 10 mm, while the diameter of 74% of the incidental aneurysms were below 10 mm. The total operative morbidity and mortality were 15% and 4%, respectively. The mortality rate in the follow-up period was 10-11% mainly due to fatal bleeding from unoccluded aneurysms. In 21 survivors, a normal mental status was found in 43% and mild dementia was found in another 43%. The impaired visual acuity was unchanged in 67% of patients, while the ocular motility had normalised in 75%. A normal daily functional capacity was enjoyed by 57% while 43% had a moderate reduction, mostly due to visual disturbances.

Denmark↗
PubMed1985

Severe headache as the only symptom of long-standing shunt dysfunction in hydrocephalic children with normal or slit ventricles revealed by computed tomography.

Four patients aged 11, 11, 8 and 18 years, shunted in early childhood for hydrocephalus, were followed in the outpatient clinic for severe headache from 3 months to 2 years. The headache lasted for days and up to a week, was usually severe, and was often followed by screaming attacks or aggressive behavior. In all patients repeated computed tomography disclosed a normal ventricular system or slit ventricles. The intracranial pressure (ICP) was measured in all four patients and showed an increased intracranial steady-state pressure between 20-50 mmHg, plateau waves and, in two of the patients, a very high intracranial pulse-pressure amplitude. At operation all patients had dysfunction of the shunt (most often of the distal end). In three patients ICP monitoring post-operatively showed normal intracranial pressure without any abnormal increments from the normal steady-state pressure. Thus, severe headache can be the only symptom of long-standing shunt dysfunction, even without ventricular dilation. In shunted hydrocephalic children complaining of headaches, ICP measurement is highly recommended.

Adolescent↗