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Biomedical subjects

L Brandt

Publications and source records attributed to L Brandt.

At least 109 records · Page 6Linked to original sources

Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation.

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.

Adult↗

Immunity to experimental Salmonella typhimurium infections in rats. Transfer of immunity with primed CD4+CD25high and CD4+CD25low T lymphocytes.

The protective effect of primed CD4+ T lymphocytes against a lethal dose of 10(8) viable Salmonella typhimurium was studied in Lewis rats. Primed CD4+ T lymphocytes were obtained by inoculating Lewis rats with a non-lethal dose of 10(6) viable S. typhimurium. Four weeks after the infection, spleen CD4+ T lymphocytes were separated using magnetic microspheres coated with an antibody against the CD4 molecule (W3/25). Subsequent sorting into activated and non-activated subpopulations using the p55 alpha-chain of the interleukin-2 receptor (CD25) as an activation marker was performed by a fluorescence-activated cell sorter. Untreated Lewis rats were injected with 10(4) different primed CD4+ T-cell populations 24 h prior to the lethal dose of 10(8) viable S. typhimurium. Blood samples were drawn from the orbital plexus 1, 2, 3, and 4 weeks after the infection, and analysed for specific IgM and IgG antibodies. Cell sorting revealed that 2/3 of the primed CD4+ T lymphocytes expressed high levels of CD25. Cell transfer revealed that both CD25high and CD25low expression populations could induce immunity against a lethal dose of S. typhimurium, whilst antibody analysis revealed that antibody levels were not correlated with protection against S. typhimurium infections, although it showed that a higher and more persistent level of specific IgG antibodies was produced in animals receiving the CD4+CD25high fraction. It is concluded that 10(4) primed CD4+ T lymphocytes can induce immunity in animals challenged with a lethal dose of S. typhimurium and that antibodies do not seem to be correlated with the immunity induced. The CD4+CD25high fraction was, however, associated with a higher and more persistent level of specific IgG antibodies.

Animals↗

Electroneurography index: a standardized neurophysiological method to assess peripheral nerve function in patients with polyneuropathy.

An index based on 12 electrophysiological parameters (conduction velocities, F-latencies, and amplitudes) was constructed to obtain an overall estimation of peripheral nerve conduction. The index was expressed as the mean deviation (in SD) compared to controls standardized for age or height. The stability of the index was tested by repeated examinations during intervals of several months in healthy subjects. The use of a compound index enabled detection of slight impairments of nerve conduction. The relatively low interrecording variability of the index makes it suitable to follow the progression of a polyneuropathy.

Adolescent↗

Effects of pinacidil on cerebral and mesenteric arteries--influence of the endothelium.

The effect of pinacidil on the contractile response to stepwise increases of the extracellular K+ concentration ([K+]o) was investigated in isolated segments of human pial and mesenteric arteries and rabbit basilar and mesenteric arteries. The [K+]o eliciting half maximum contraction (EC50) was lower in human pial (18 mM) and rabbit basilar (27 mM) arteries than in human (33 mM) and rabbit (32 mM) mesenteric arteries, respectively. The alpha-adrenoceptor blocker, prazosin, increased the EC50 value for K+ from 27 to 40 mM and reduced the maximum response in rabbit mesenteric arteries, but had no effect on the K(+)-induced contraction in rabbit basilar arteries, indicating a substantial noradrenergic component of the K+ response in the former arteries. Removal of the endothelium decreased the EC50 value for K+ from 27 to 15 mM in rabbit basilar arteries, whereas the K+ sensitivity was unaffected in rabbit mesenteric arteries. Pinacidil shifted the K+ concentration-response curve to the right in human and rabbit cerebral and mesenteric arteries. In rabbit basilar arteries, but not in mesenteric arteries, the shift was larger in the absence than in the presence of an intact endothelium. When endothelium-denuded rabbit arteries were compared, the inhibitory effect of pinacidil was larger in basilar than in mesenteric arteries. Thus, pinacidil inhibits K(+)-induced contractions in both cerebral and mesenteric arteries, but appears to act preferentially on endothelium-denuded rabbit basilar arteries. Provided that endothelial damage and depolarization-induced vasoconstriction are of pathophysiological importance in cerebrovascular disorders such as stroke and cerebral ischemia secondary to vasospasm after subarachnoid hemorrhage, pinacidil may have a therapeutic potential.

Adrenergic alpha-Antagonists↗

Myelography in the late postoperative period in patients subjected to anterior cervical decompression and fusion.

During a 13 year period, 286 patients with cervical disc herniation and/or spondylotic spurs, were subjected to anterior decompression and vertebral interbody fusion with autologous bone. Twenty patients were re-admitted in the late postoperative period due to recurrent radicular symptoms and/or signs of myelopathy. In these patients myelography was performed again. In 14 patients spinal cord compression and/or nerve root involvement at a new level was visualized. At the operated level, however, the myelograms demonstrated a smooth anterior wall in the spinal canal. The series confirms the safety, effectiveness and reliability of the Cloward procedure in achieving long term spinal cord and nerve root decompression, and a solid vertebral interbody fusion.

Cervical Vertebrae↗

Cytomegalovirus viraemia and specific T-helper cell responses as predictors of disease after allogeneic marrow transplantation.

Risk factors for cytomegalovirus viraemia and disease, the relation between viraemia and disease, effect of antiviral treatment, and T-helper cell response to cytomegalovirus antigen were analysed retrospectively among 279 patients who underwent bone marrow transplantation at Huddinge Hospital. Ninety-one of 279 (32.6%) patients developed viraemia. Donor and recipient pre-transplant serologic status and degree of acute graft-versus-host disease were independent risk factors for viraemia. Forty-nine patients (17.6%) developed cytomegalovirus disease and 44 of these patients had viraemia. Seventeen patients (6%) developed cytomegalovirus pneumonia and 14 of these patients had preceding viraemia. Among patients with viraemia, acute graft-versus-host disease and total body irradiation were risk factors for pneumonia. Antiviral treatment initiated within 7 d of development of viraemia was associated with lower risk for development of pneumonia (P < 0.05). Sixty-seven patients with viraemia were repeatedly tested by lymphocyte stimulation with cytomegalovirus antigen. No patient who developed cytomegalovirus pneumonia had measurable specific helper T-cell response at the time of viraemia detection compared to 42% of patients with other concurrent or subsequent cytomegalovirus disease, and 75% of patients without subsequent disease. We conclude that viraemia is a major risk factor for development of cytomegalovirus disease. Furthermore, early antiviral treatment based on detection of viraemia can be effective in preventing cytomegalovirus disease. The length of antiviral treatment might be decided through measurements of the helper T-cell response to cytomegalovirus antigen.

Adolescent↗

Causes of morbidity and mortality, with special reference to surgical complications, after early aneurysm operation: a prospective, one-year study from neurosurgical units in Sweden.

In the present prospective study, 6.93 of Sweden's 8.59 million inhabitants (81%) were covered by the five participating centres. All patients with verified aneurysmal SAH admitted between June 1, 1989 and May 31, 1990, were enrolled. Basically, all participating centres have the same management protocol for SAH victims, including ultra-early referral to a neurosurgical unit, followed by pan-angiography and surgery as early as logistically possible. In this presentation, 145 patients who preoperatively were in Hunt & Hess Grades I-III and who underwent surgery for a supratentorial aneurysm within 72 h after the bleed, are evaluated. Eighty-one % (117 patients) made a good recovery. The morbidity was 12% (17 patients) and the mortality 7% (11 patients). The most common cause of unfavorable outcome was surgical complications, which accounted for 8% of the total series (12 patients). A subanalysis of these cases did reveal a positive correlation to higher age and more severe SAH on CAT scan.

Adult↗

Predictors of alcoholism in young Swedish men.

OBJECTIVES: The purpose of the study was to assess risk indicators for admission for alcoholism in young men. METHODS: Level of alcohol consumption and background variables were analyzed in a survey of 49,464 Swedish conscripts. Admissions to psychiatric care were registered during a 15-year follow-up. RESULTS: A strong association was found between level of alcohol consumption at conscription and future admission for alcoholism. The strongest risk indicator for admission for alcoholism, however, was "Contacts with police or child care authorities," with an odds ratio of 4.9. CONCLUSIONS: For conscripts reporting moderate alcohol consumption at conscription there was a clear association between an increasing burden of risk indicators and future alcoholism. Among men who already had a high level of alcohol consumption at conscription, additional risk indicators, with the exception of psychological factors, had relatively little impact on future admission for alcoholism. Poor emotional control and early symptoms of mental disorder, however, were instrumental not only in enhancing the risk for high consumption at conscription, but also in enhancing the risk for high consumers to become abusers or addicted.

Adolescent↗

[The behavior of arterial and mixed venous oxygen and carbon dioxide partial pressure and the pH value during and following intubation apnoea. Studies on the occurrence of the Christiansen-Douglas-Haldane effect].

The Christiansen-Douglas-Haldane effect describes the reduced CO2 binding capacity of oxygenated compared to deoxygenated haemoglobin. Under the condition of a "closed system", for example hyperoxic apnoea after adequate preoxygenation (continuous O2 uptake with lack of CO2 delivery), specific effects on the arterial and mixed venous blood gas status, due to the Haldane effect, are seen: within 30 s after onset of apnoea, "paradoxical pCO2" (paCO2 exceeds pvCO2) and "pH reversal" (pHa falls under pHv) can be observed. It was the aim of this study to demonstrate how fast arterial and mixed venous pCO2 and pH normalize when a change from apnoea ("closed system") to controlled ventilation ("open system") takes place. METHODS. 12 patients (ASA II-IV, NYHA II-III) scheduled for coronary artery bypass grafting were studied. Premedication consisted of flunitrazepam 2.0 mg p.o. given the evening before operation and another 2.0 mg p.o. given 90-120 min before induction of anaesthesia. Routine preparation for induction consisted of venous and arterial cannulas, pulmonary artery catheter and continuous pulse oximetry. Following standardized preoxygenation, induction of anaesthesia was performed with fentanyl, pancuronium and etomidate. After cessation of spontaneous respiration, controlled ventilation was continued with 100% O2 until intubation. Intubation and insertion of stomach tube and oesophageal temperature probe were undertaken after exactly 2 min. After reconnection to the semi-closed circle breathing system, controlled ventilation was continued with 100% O2. Eighteen arterial (a) and 18 mixed-venous (v) blood samples were drawn simultaneously in a sequential manner immediately before and during the last 20 s of apnoea, as well as within 4 min after onset of controlled ventilation (Table 1). The pO2 (mmHg), pCO2 (mmHg) and pH were determined using a Stat Profile 5 blood gas analyser. RESULTS. During apnoea and within the first 35 s of controlled ventilation the paO2 showed a total decrease of 131.5 mmHg that was followed by an almost linear increase of 29.7 mmHg/min (Fig. 1a). In the course of apnoea and controlled ventilation the pvO2 remained relatively stable, with values ranging from 42 to 43 mmHg (Fig. 1b). During apnoea the paCO2 showed an increase of 12.5 mmHg that was followed by a biphasic decrease (first 13.8 mmHg/min and then 0.75 mmHg/min) beginning 15 s after the onset of controlled ventilation (Fig. 2a). With an increase of 4.2 mmHg, the pvCO2 showed about a third of the increase of the paCO2 during apnoea, reaching a maximum 45 s after the onset of controlled ventilation and then being followed by a linear decrease of 0.86 mmHg/min (Fig.2b). Comparing the course of paCO2 and pvCO2 during apnoea as well as during the period of controlled ventilation, pHa and pHv changed in a reciprocal manner (Fig. 3a/b). The so-called normalization of pCO2 (paCO2 falls under pvCO2) and pH (pHa exceeds pHv) began 18.2 s and 23.2 s respectively after the onset of controlled ventilation (Fig. 4a, b). CONCLUSION. Considering the expected decrease of paO2 during hyperoxic apnoea, insufficient pulmonary N2 elimination prior to the onset of apnoea, as well as direct N2 delivery into the alveoli, due to the so-called a ventilatory mass flow, will limit unrestricted pulmonary O2 uptake. The continuing decrease of the paCO2 after the onset of controlled ventilation can be regarded as indirect proof of a ventilatory mass flow. The course of pCO2 and pH after the onset of controlled ventilation shows that normalization in arterial and mixed-venous blood gas status takes place in about 18.2 s after the cessation of apnoea.

Aged↗

[The effect of hyperbilirubinemia on the measurement of oxygenated hemoglobin (O2Hb), carboxyhemoglobin (COHb) and methemoglobin (MetHb) using multiwavelength oximeters in mixed venous blood].

Oximetric measurements are influenced by several mechanisms. Severe jaundice is one of these mechanisms with some clinical interest. In the literature it is pointed out that a high bilirubin concentration may falsify oximetric measurements and is often accompanied by elevated COHb levels. The reason for this phenomenon is thought to be an interference in the absorption spectra of haemoglobin derivatives and bilirubin [2, 3, 4, 10]. In our investigation we attempted to answer the following questions: 1. How do multiwavelength oximeters measure haemoglobin derivatives in different bilirubin concentrations? 2. Do different multiwavelength oximeters give different concentrations of haemoglobin derivatives? METHODS. In 13 patients who developed postoperative jaundice on the intensive care unit, O2Hb, COHb and MetHb were measured in mixed venous blood with two multiwavelength oximeters (OSM3, Radiometer; CO 2500, Ciba-Corning). Bilirubin concentration was measured by the DPD (dichlorphenyldiazonium) method in the central laboratory of our hospital. RESULTS. With increasing bilirubin concentrations, both oximeters measured increasing O2Hb values; the OSM3 consistently showed higher O2Hb concentrations than the CO 2500, with a maximal difference of 2.8% (Fig. 3). Regarding COHb, we saw clear increases in the values with increasing bilirubin concentrations (Fig. 4). The CO 2500 showed higher COHb values than the OSM3 (average 1.54 +/- 0.3%). The findings regarding MetHb differed. The CO 2500 showed increasing MetHb values as the bilirubin concentration increased (Fig. 5). All measurements exceeded normal values above a bilirubin concentration of 17 mg/dl. The OSM3, however, measured constant MetHb values which did not depend on jaundice. CONCLUSIONS. 1. The in vitro measurement of haemoglobin derivates by multiwavelength oximeters is influenced by hyperbilirubinaemia. This is caused by an interference between the light absorption spectra of the haemoglobin derivates and of bilirubin and by the increasing development of endogenous CO in the haem metabolism during severe jaundice (Fig. 7). 2. With increasing bilirubin levels, a lower O2Hb is measured with the CO 2500 than with the OSM3. 3. We also see increasing COHb values with rising bilirubin concentrations. 4. With increasing bilirubin levels the MetHb concentration measured with the CO 2500 rises, while the OSM3 gives constant MetHb values. 5. In severe jaundice the O2Hb values measured with multiwavelength oximeters are not identical with the real blood concentration of this haemoglobin derivative. In this situation multiwavelength oximeters cannot be used as a reference method for in vivo oximetric systems such as pulse oximeters or fibreoptic pulmonary artery catheters.

Adult↗

[Anesthesia and intensive therapy for a patient with mitochondrial myopathy].

Since 1983 we have been involved in the diagnostic work-up and emergency treatment of a female patient now 48 years old who has a mitochondrial myopathy resembling Luft's disease. The syndrome was first described in 1959, and in more detail in 1962, by Luft and et al., who reported a picture of hypermetabolism with high temperature, extreme sweating, tachycardia, dyspnoea at rest, polydipsia, polyphagia and irritability but normal thyroid function. In 1971 and 1976 Haydar and Di Mauro presented a second case and proposed treatment with chloramphenicol. Our patient has the third case of the syndrome reported so far: her case was initially published in 1987. CASE REPORT. Since her 17th year of life the patient had suffered from episodes of fever, tachycardia and sweating. At the age of 32 these attacks worsened, leading to unconsciousness and apnoea. The patient then had to be intubated, ventilated and sometimes resuscitated. The diagnosis of MH susceptibility and Luft's disease was made on biochemical grounds after the first muscle biopsy in 1983. Therapy with chloramphenicol failed. Therapy with beta blockers, vitamin C and K or E, coenzyme Q10 and a high-caloric diet was started in 1985. The patient was registered with an emergency service, which flew her to our ICU whenever she had a severe crisis. For milder episodes she was supplied with an oxygen breathing mask at home. Myalgia increased with the episodes starting in 1988, and the patient needed dantrolene infusions and analgesics at home. To facilitate venepuncture a Port-A-Cath system was implanted in 1987, which had to be removed four times due to infection and sepsis. A muscle biopsy was taken in Rotterdam, which revealed differences in mitochondrial function from the biochemical findings recorded in 1983 and not in keeping with Luft's disease. Unfortunately, the patient was not able to undergo further metabolic investigations or therapeutic trials. ANAESTHESIA. The patient received three local and six general anaesthetics in our clinic. The muscle biopsies, two in 1983 and one in 1985, were performed under local infiltration with procaine and were uneventful. The general anaesthetics were carried out without MH trigger substances following pretreatment with dantrolene for the following surgical procedures: the repair of an extensive arterio-venous fistula between the brachiocephalicus trunk and the right jugular and subclavian vein, revision of the sternum cerclage, implantations and explanations of infectious Port-A-Cath systems. We used etomidate, propofol and fentanyl or alfentanil with nitrous oxide and oxygen for induction and maintenance of anaesthesia. Muscle relaxation was induced with vecuronium or atracurium. All cardiovascular, respiratory, metabolic and temperature measurements stayed in normal ranges. After the extensive vascular repair (av fistula) the patient had to be mechanically ventilated for some hours until normal body temperature was restored. At the end of all other periods of anaesthesia she was extubated in the operating theatre. In five cases the postoperative period was uneventful. Only once she developed a crisis with hyperthermia, tachycardia, sweating and dyspnoea. INTENSIVE CARE. From 1985 to 1992 the patient was treated in our ICU 21 times. On 11 occasions she was already intubated and being ventilated by the emergency service on arrival. Extubation was usually possible within 2-20 h. During the crisis, heart rate was about 160-190 per minute and temperature above 40 degrees C. Serum values of CK, glucose, BUN, electrolytes, lactate and thyroid hormones were always in the normal ranges. Blood gas controls showed a constant respiratory alkalosis, arterial pCO2 values decreasing to 20 mm Hg or less. In addition to mechanical ventilation, treatment consisted in dantrolene infusions and droperidol injections, supplemented from 1989 onward with piritramide injections because of the increased severity of myalgia. In 1991 we gave propofol by

Anesthesia↗

Exposure to organic solvents and risk of haematological malignancies.

Epidemiological studies indicating that exposure to organic solvents is a risk factor for haematological malignancies are reviewed. Exposure to benzene is a risk factor for ANLL. A preleukaemic phase with pancytopenia is common and may be associated with a normo- or hypercellular marrow with morphological characteristics suggesting MDS. There are indications that other organic solvents than benzene may be leukaemogenic. Certain chromosome aberrations are characteristic in leukaemic cells from solvent exposed ANLL patients. The average latency time from start of occupational exposure until diagnosis is about 10-11 years. There is epidemiological evidence that exposure to organic solvents may also increase the risk of lymphoproliferative malignancies, i.e. ALL, NHL, HD and myeloma.

Hematologic Diseases↗

Detection of DNA damage in stimulated human lymphocytes after enflurane exposure in vitro.

DNA damage was detected by nucleoid sedimentation in human lymphocytes stimulated with pokeweed mitogen after exposure to enflurane. Enflurane induces DNA damage at an exposure concentration of 0.2 vol%. Higher enflurane concentrations increase the rate of DNA damage. The DNA damage seen after exposure to enflurane concentrations of 0.2 and 3.0% vol is comparable to damage after X-radiation of 0.1 and 0.7 Gy. DNA single-strand breaks can be demonstrated by nucleoid sedimentation and can indicate damage before DNA repair begins. Therefore, detected DNA single-strand breaks may be reversible. However, DNA repair is not always successful and an increased number of DNA single-strand breaks could lead to irreversible DNA damage. The method of nucleoid sedimentation helps to show DNA damage in proliferating cells after exposure to volatile anesthetics or therapeutic gases.

Cells, Cultured↗

Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group.

Data on 49 allogeneic bone marrow transplant (BMT) recipients who developed interstitial pneumonia due to cytomegalovirus (CMV) were collected retrospectively. All patients were treated with ganciclovir and high doses of intravenous immune globulin, although types of immune globulins and schedules of treatment varied. Seventeen (35%) of 49 patients responded to treatment. Thirty days after the diagnosis of interstitial pneumonia, the survival rate among patients was 31%. CMV was detected in 81% of patients on whom autopsies were performed. The survival rate among patients who received total body irradiation (TBI) was significantly lower (11 [27%] of 41) than that among patients who did not receive TBI (six [75%] of eight; odds ratio = 12.3; P = .009). No other factor, including age, grade of graft-versus-host disease, types and dose of immune globulin used, or dose of ganciclovir, was correlated to survival. These results show that although survival of allogeneic BMT recipients with CMV interstitial pneumonia has improved, more than one-half of the patients still died of pneumonia. Thus, both prophylaxis for and treatment of CMV infection must be improved.

Adolescent↗

Antecedents and covariates of high alcohol consumption in young men.

The role of social, behavioral, and psychological characteristics and other risk indicators for high alcohol consumption in young men was analyzed using a survey of 49,464 Swedish conscripts. A strong association between an increasing weight of adverse social and behavioral risk indicators on the one hand and high alcohol consumption on the other was found. Yet many high consumers had no or few risk indicators. In multivariate analysis, substance use and indicators of deviant behavior came out as the strongest risk indicators for high alcohol consumption. Indicators of poor social background generally had relatively low odds ratios. Poor home wellbeing, for instance, had an odds ratio of 0.9. Social group of father was nonsignificant. Very good family economy had a higher odds ratio, 1.7, than average or poor family economy. Psychosomatic symptoms had relatively low odds ratios. Among psychological variables, low emotional control had a significantly elevated odds ratio of 1.8. Increased odds ratios were found for conscripts who were never anxious or never felt insecure. In conclusion, although many high consumers of alcohol had no or few risk indicators, we identified a high-risk group characterized by high levels of alcohol consumption and several indicators of personality disturbances, early deviant behavior, and social maladjustment.

Adult↗