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L M Knudsen

Publications and source records attributed to L M Knudsen.

35 records · Page 2Linked to original sources
PubMed1995

Stimulation tests for the bone marrow neutrophil pool in malignancies.

It has been known for decades that blood neutrophilia occurs after the administration of etiocholanolone, adrenocortical steroids, and endotoxins. Neutrophil leukocytosis in general may be due to several mechanisms such as increased stimulation of the myelopoiesis, increased release from the marrow, a shift from the marginated to the circulating pool (demargination), prolongation in the peripheral half-life, and decreased migration of neutrophils from the blood to the tissue. However, the principal cause of the neutrocytosis for each of the above mentioned agents is increased release of neutrophils from the bone marrow reserves. Since a sufficient reserve capacity is a prerequisite for optimal defenses against infections, the marrow response has been used to estimate the dose of chemotherapy expected to be tolerated without life-threatening neutropenia. However, none of the above "test substances" have gained widespread use due to adverse reactions or undesirable effects on neutrophil function. Recent progress in biotechnology has developed recombinant human (rh) hematopoietic growth factors ready for clinical use. Marrow myelopoiesis is stimulated by granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage CSF (rhGM-CSF). The immediate effect, however, is mobilization of mature neutrophil granulocytes to the blood. Bone marrow cellularity seems to influence the neutrophil number mobilized during 24 hours by one subcutaneous injection of either rhG-CSF or rhGM-CSF. A recent pilot study has suggested such a "24 hour stimulation test" to predict severe neutropenia following cyclic chemotherapy. This concept is illustrated by two case reports. The "stimulation test" suggests that we may devise strategies to define patient subsets which may benefit from prophylactic growth factor administration during cyclic chemotherapy.

Bone Marrow↗
PubMed1994

Renal function in newly diagnosed multiple myeloma--a demographic study of 1353 patients. The Nordic Myeloma Study Group.

This study describes the occurrence of renal failure among 1353 newly diagnosed cases of multiple myeloma. Renal function was evaluated by serum creatinine concentration in 1353 cases, 31% of whom had renal failure at the time of diagnosis. In 1206 cases an estimation of creatinine clearance was made. When renal failure was defined by using creatinine clearance estimation, 49% had renal failure at the time of diagnosis. Renal failure was present in 24% of patients with an M component of IgG-, 31% of IgA- and 100% of IgD-type. 52% of patients with light chain disease had renal failure. The frequency of renal failure was similar in lambda- and kappa-light chain disease. Patients with a high excretion of Bence Jones protein in the urine (> 10 g/24 h) had renal failure significantly more often than patients with lower excretion. Renal failure was related to advanced disease; 41% of patients with stage III (Durie-Salmon) disease had renal failure. Renal failure was found in 45% of patients with hypercalcaemia. When estimated creatinine clearance was used as a predictor of renal function, the same trends were found as mentioned above. In addition, the proportion of patients with renal failure was found to increase with advancing age.

Adult↗
PubMed1994

Biofeedback treatment of children and adults with idiopathic detrusor instability.

In adults and children suffering from urge, urge incontinence, frequent voidings, and nocturia, urodynamic examination often confirms the diagnosis of detrusor instability. We assessed the outcome of biofeedback therapy in 15 children aged 6-12 years and 7 adults aged 20-52 years, all with cystometrically proven detrusor instability. The detrusor pressure was visually conveyed to the patient during repeated bladder fillings. The patient was instructed to interrupt detrusor pressure increments by tensing the pelvic floor musculature. None of the children were found completely cured; however, 9 showed a marked decrease in either the number of the extent of symptoms. Two children showed moderate improvement, while 4 remained unaffected by the treatment. One adult was completely cured, 2 improved moderately, and 4 showed no improvement. None of these patients were converted to stable cystometry. Upon termination of the BF treatment a follow-up study was conducted for patients exhibiting pronounced or moderate improvement. The beneficial effect was maintained except in one case.

Adult↗
PubMed1993

[Renal insufficiency in myelomatosis. Causes and treatment].

Renal failure is a frequent complication in multiple myeloma and it is present in about 50% of patients with newly-diagnosed multiple myeloma. Renal failure at the time of diagnosis has earlier been associated with a bad prognosis, but a better prognostic factor is the response to chemotherapy. In general, it is important to distinguish between 1) renal insufficiency at the time of diagnosis, 2) acute renal insufficiency and 3) chronic renal insufficiency developing during the course of the disease. The patients in the first two groups are treated with intensive therapy which is long-lasting (median four to six weeks). The improved function of the kidney is correlated to an improved survival. Patients developing chronic renal insufficiency late in the course of the disease should receive palliative therapy. The most important factors that provoke acute renal insufficiency are dehydration, hypercalcaemia and/or infection, but renal insufficiency is also provoked by the use of nephrotoxic drugs, hyperuricaemia and/or hyperviscosity. Chronic renal insufficiency is provoked by deposits of light chains, infiltration by plasma cells or deposits of amyloid. The treatment consists of elimination of the provoking factors and start of chemotherapy.

Acute Kidney Injury↗
PubMed1993

[Daily single-dose aminoglycoside administration. Therapeutic and economic benefits].

Aminoglycosides are among the most active antimicrobial agents against Gram-negative infections, but they also share the potential for oto- and nephrotoxicity. Animal studies have shown that dosing aminoglycosides once daily is more efficient and less nephrotoxic than the conventional multiple daily dosing regimens. Pharmacokinetic and microbiological data support this finding. Clinical trials confirm that once-daily dosing is more efficient and less toxic than multiple daily dosing. The two most important risk factors for nephrotoxicity seem to be the duration of aminoglycoside treatment and high trough levels of aminoglycoside. Netilmicin and amikacin are the drugs most often used in clinical trials of once-daily dosing regimens. Recommendations for once-daily dosing of netilmicin are given.

Aminoglycosides↗
PubMed1993

Urodynamic biofeedback training for children with bladder-sphincter dyscoordination during voiding.

Neurologically normal children with recurrent urinary tract infections (UTIs), night- and daytime wetting, and urge and painful voiding may have staccato voiding due to pelvic floor contractions. The immediate effect of non-invasive urodynamic biofeedback (BF) therapy was assessed using a historical follow-up study in 31 children aged 5-15 years suffering from urodynamically proven overactive urethra during voiding. A long-term follow-up study was performed to investigate whether improvement was maintained. Twenty-four children (77.5%) benefited from the treatment. Of these 16 (51.5%) were cured, while 8 (26%) had a pronounced reduction in their symptoms. Although the flow was normalized in 17 (55%) and nearly normalized in 7 (22.5%), there was no significant correlation between subjective and objective criteria of improvement. Similarly, no relationship was found between the initial urodynamic characteristics and the treatment outcome. During a mean follow-up time of 4 years (range: 1-7.5 years) two of the initially cured patients relapsed. They were recurred with a refresher course. Three had had a single or a few episodes of cystitis in the course of several years. Of the patients with pronounced reduction in their symptoms, three relapsed. A refresher course was attempted in two patients; one was successful. It can thus be concluded that BF is an effective way of treating this disturbance and the beneficial effect is to a wide degree maintained.

Adolescent↗
PubMed1992

[Duplication in a medical department of tests previously performed in a primary sector].

The aim of this study was to evaluate whether an insufficient flow of information from the primary to the secondary sector was the cause of unnecessary duplications of investigations. From practitioners of 202 patients admitted to a medical department information about paraclinical examinations during the previous year was obtained. In all 111 general practitioners participated. An average of 3.0 blood analyses and 0.9 other investigations were carried out on each patient. 44% of the patients were not investigated at all. An average of 1.9 blood analyses and 0.2 other investigations on each patient were repeated. 22% of the repetitions in both cases were due to insufficient communication between the practitioner and the hospital. These figures seem low and insufficient communication between the primary and the secondary sector appears to be a minor problem.

Blood Chemical Analysis↗
PubMed1987

Urethral pressure variations in healthy females during rest and sleep.

Recent studies have shown the occurrence of rhythmic urethral pressure variations (UPV) in the normal female urethra in the awake state. The nature of these variations still needs further elucidation. In this study we investigated the changes in urethral pressure (UP) and in UPV as they occur in healthy females awake and asleep. UPV, intravesical-(IVP) and rectal pressure (RP), together with anal electromyography (EMG) and electroencephalography (EEG) were measured in 10 healthy fertile female volunteers. The registration was done in the awake state, during falling asleep and during sleep. During falling asleep the average urethral pressure as well as the UPV amplitude and frequencies decreased and remained at a lower stable level during sleep. Urethral pressure and its variations seemed to be interrelated since the UPV frequency and amplitude decreased when the average UP decreased. From this study it appears that urethral pressure is influenced by extrinsic factors such as the waking, resting and sleeping states. Although some extrinsic modulation of urethral pressure variations occurs, their persistance in sleep suggests their local nature.

Adult↗
PubMed1986

The preservation and loss of various non-haematopoietic antigens in human post-mortem tissues as demonstrated by monoclonal antibody immunohistological staining.

Immunohistological methods using monoclonal antibodies have proved to be valuable in the differentiation between cells of various origins. We have previously shown most leucocyte differentiation antigens to be very resistant to post-mortem disintegration (Pallesen & Knudsen 1985). In the present study we have examined the preservation of several non-haematopoietic antigens in tissue samples of human skin, kidney, liver, pancreas, lung, thyroid gland, uterine tissue, female breast and brain from 30 autopsies performed at specific intervals after death. Frozen tissue sections were stained using monoclonal antibodies and an immunoperoxidase method. A total of 17 monoclonal antibodies against various intermediate filament proteins, epithelial antigens, various hormones and factor VIII related antigen were tested. We found surprisingly good preservation and staining of tissue antigens--even 3 d after death--in all organs except pancreas. It is concluded that many tissue antigens are fairly resistant to post-mortem disintegration and that immunohistology may be applied to diagnostic problems in human autopsy material.

Antibodies, Monoclonal↗
PubMed1985

Leucocyte antigens in human post mortem tissues: their preservation and loss as demonstrated by monoclonal antibody immunohistological staining.

The development of monoclonal antibodies and of techniques for demonstrating antigens in situ in frozen tissue sections has been responsible for remarkable progress in diagnostic histopathology. We explored the potential of these techniques when applied to post mortem tissues that were frozen at various intervals after death and stained by monoclonal antibodies using immunoperoxidase technique. The monoclonal antibodies were selected according to their reactivity with essential markers of the lymphatic system and also to their availability. Lymph nodes and splenic tissue from 30 autopsy cases were stained in addition to thymic tissue from eight deceased infants. The antigens proved to be surprisingly well preserved. Staining could be precisely evaluated with UCHT1, OKT6 and anti-Leu-7 antibodies at least 72 h after death; staining with DAKO-pan-B, DAKO-LC and anti-Leu-3a was also very reliable. Antigens expressed by T-suppressor lymphocytes and dendritic reticulum cells were less well preserved. The T8-antigen of suppressor lymphocytes was usually demonstrable in the lymph nodes but less frequently in the splenic tissues. It is concluded that most leucocyte antigens are very resistant to post mortem disintegration, and that they can be reliably interpreted by immunohistological staining using monoclonal antibodies. We therefore recommend this in autopsy specimens in cases where in-vivo examination was not feasible.

Adult↗
PubMed1984

Changes in bladder volumes with repetition of water cystometry.

Fifty-six patients were investigated by repetitive cystometry in the supine or sitting position. The incidence of detrusor hyperreflexia and the circumstances under which it was found did not differ from previous studies. The cystometry data concerning volumes showed a remarkable degree of variability. Values for first sensation and maximal capacity could vary more than 500%. An increment from the first cystometry to the fourth was consistently found. The increments were most pronounced when cystometry with fast filling followed cystometry with medium filling regardless of the patient's position. The major factor in the changes is considered to be the patient's adaptation to the investigational situation. This finding might have major significance in the evaluation of drug studies where repeated cystometries with different time intervals are used.

Adaptation, Physiological↗
PubMedDate not supplied

Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myeloma.

BACKGROUND: Cells belonging to the malignant clone are found in the peripheral blood in myeloma patients. In order to minimise the content of tumour cells in the stem cell product it is crucial to perform stem cell harvest at a time when tumour cells in the peripheral blood are at a minimum. OBJECTIVE: The aim of the study was to compare the mobilisation kinetics of normal CD34+ cells and myeloma plasma cells during mobilisation with either G-CSF alone or high-dose cyclophosphamide (HDCy) plus G-CSF. DESIGN AND METHODS: Morning blood samples were drawn each day during mobilisation from start of G-CSF or HDCy and to the end of leukapheresis, and were analysed by flow cytometry for content of CD34+ cells and myeloma plasma cells (CD38+ + CD45-). Tumour cells were also estimated by a patient-specific real-time polymerase chain reaction (PCR) method based on the 5' nuclease TaqMan technology. RESULTS: Flow cytometry data from 16 patients showed concomitant mobilisation of CD34+ cells and myeloma plasma cells. Seven patients were mobilised twice; first with G-CSF alone and then with HDCy plus G-CSF. There was no difference between the two mobilisation regimens regarding tumour cell mobilisation kinetics. Real-time PCR was performed in one patient and confirmed the mobilisation of tumour cells at the time when CD34+ blood cells were at a maximum. CONCLUSIONS: Tumour cells are mobilised to the peripheral blood at the same time as CD34+ cells in multiple myeloma patients after priming with both G-CSF alone and HDCy in combination with G-CSF.

Adult↗
PubMedDate not supplied

Frequency and prognostic relevance of cyclin D1 dysregulation in multiple myeloma.

OBJECTIVE: Cyclin D1 dysregulation has been found with varying frequencies in multiple myeloma (MM) and has been suggested to be associated with a poor prognosis. The aim of this study was to investigate the frequency of cyclin D1 dysregulation in patients being treated for MM and to test whether cyclin D1 dysregulation is a prognostic factor for MM patients. METHODS: To achieve the above aims we designed a highly sensitive and reproducible real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for quantitation of cyclin D1 mRNA. Using this assay, 110 diagnostic bone marrow (BM) samples from patients with MM were screened for cyclin D1 dysfunction. RESULTS: The real-time assay was able to detect the presence of 0.01% cyclin D1 positive cells allowing a safe detection in MM BM samples. In 42% (46/110) of MM BM samples a greater-than-or-equals 3-fold increase in cyclin D1 mRNA was observed compared to the cyclin D1 level in normal BM. In the remaining group of MM patients the cyclin D1 mRNA levels were comparable to normal donors. Follow-up of 76 MM patients showed no significant (P = 0.35) difference in survival between cyclin D1 positive and negative MM patients. In addition, cyclin D1 dysregulation did not correlate with known prognostic factors. CONCLUSION: The developed real-time RT-PCR assay for detection of cyclin D1 mRNA levels offers a fast and safe screening for cyclin D1 dysfunction. When a large cohort of MM patients was screened, the cyclin D1 gene was found to be frequently dysregulated, but there was no significant correlation to survival or known prognostic parameters.

Adult↗