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Biomedical subjects

L Dragsted

Publications and source records attributed to L Dragsted.

At least 19 recordsLinked to original sources

Myoclonic spasms during treatment with high doses of intravenous morphine in renal failure.

Myoclonic spasms occurred in a patient suffering from renal failure after high doses of continuous intravenous morphine (100 mg/h). The concentrations of morphine, morphine-6-glucuronide and morphine-3-glucuronide (mumol/l) in plasma were: 1.93, 52.06 and 381.8, and in cerebrospinal fluid were: 1.02, 5.86 and 61.82, respectively. The role of morphine and morphine glucuronides in myoclonic spasms is discussed.

Acute Kidney Injury↗

Epidemiology of intensive care.

It is difficult to study the epidemiology of ICUs, as they lack a uniform nomenclature and/or classification. The organization and distribution of intensive care medicine depend on the size and function of the hospital. The patients in ICUs are predominantly men, with a high proportion of elderly patients (greater than or equal to 70 years) constituting 25-30% of the total. Case-mix, severity of illness and outcome differ from one unit to another, and can be compared only if the patients are classified with a common classification system. Most survivors of intensive care seem to return to normal or near normal functional level within one year. Compared to Western Europe, the United States has more ICU beds and a nearly ten times higher admission rate to intensive care. These variations can be seen as a result of a fundamental difference in the attitudes toward withdrawing or withholding life support.

Aged↗

Reaction of the N2-acetoxy derivative of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) with 2'-deoxyguanosine and DNA. Synthesis and identification of N2-(2'-deoxyguanosin-8-yl)-PhIP.

The direct acting mutagenic N2-hydroxylated metabolite of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) does not react with DNA. Upon acetylation of the N2-hydroxy-PhIP with acetic anhydride two products could be detected. Mass spectrometric analysis showed that both products were monoacetyl derivatives of N2-hydroxy-PhIP. One of the products did not show any reactivity towards DNA and is probably the N-acetyl derivative of N2-hydroxy-PhIP. The other product which is most likely to be N2-acetoxy-PhIP reacted with DNA and 2'-deoxyguanosine but not with 2'-deoxycytidine, 2'-deoxyadenosine or 2'-deoxythymidine. The PhIP-2'-deoxyguanosine adduct was purified and characterized by mass spectral, 1H and [13C]NMR analysis, showing that PhIP like the other cooked food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline, had reacted with C-8 of guanine forming N2-(2'-deoxyguanosin-8-yl)-PhIP. HPLC analysis of enzymatically hydrolyzed calf thymus DNA which had been reacted with N2-acetoxy-PhIP showed one adduct which was chromatographically and spectroscopically identical to N2-(2'-deoxyguanosin-8-yl)-PhIP. HPLC separation followed by liquid scintillation counting of hydrolyzed liver DNA from a rat dosed with [3H]PhIP showed that radioactivity coeluted with the hydrolysis product of the synthetic PhIP-2-deoxyguanosine adduct, indicating that PhIP in vivo also forms an N2-(2'-deoxyguanosin-8-yl)-PhIP adduct.

Animals↗

The nursing care recording system. A preliminary study of a system for assessment of nursing care demands in the ICU.

A new system, Nursing Care Recording (NCR), for the recording of nursing care in a general ICU is presented. NCR classifies ICU patients according to their need for intensive nursing care. Comparing the NCR with the Therapeutic Intervention Scoring System (TISS), a correlation coefficient of 0.60 was found. The main difference between the two systems was related to recording procedures allowing changes in nursing intensity within a 24-h period, reflecting patient improvement due to therapy, which was detected by NCR but not by TISS. NCR can be used to estimate nursing capacity during different shifts and may be useful in the assessment of the total nursing staff necessary for a given ICU. It is suggested that NCR will allow detection of changes in the nursing care work load, whether this change is due to new activities in the unit or to alterations in the individual patient care.

Adult↗

Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine (PhIP).

Hepatic microsomes from rats pretreated with PCB were found to metabolize the food mutagen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) to two major metabolites, one of which was identified as the N-hydroxy derivative, 2-hydroxy-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (N-OH-PhIP). This identification was based on mass spectral (MS), UV and HPLC data by comparison with N-OH-PhIP prepared by chemical synthesis, as well as the specific activity of the compound in the Ames Salmonella test. Synthetic N-OH-PhIP was prepared by catalytic reduction of the nitro derivative of PhIP, which was synthesized from PhIP by diazotization and reaction with sodium nitrite. N-OH-PhIP was mutagenic to Salmonella typhimurium TA98 without metabolic activation and had a specific mutagenic activity of 2700 revertants/nmol. N-OH-PhIP thus seems to be a proximate mutagenic metabolite of PhIP. Other direct acting mutagens were not detected in the microsomal incubation mixture after HPLC separation. N-OH-PhIP also induced sister chromatid exchange (SCE) in Chinese hamster ovary cells (CHO cells) without metabolic activation. The specific activity of N-OH-PhIP in this assay was approximately 3 times higher than the activity of PhIP with microsomal activation.

Animals↗

Interhospital comparisons of patient outcome from intensive care: importance of lead-time bias.

We studied 432 admissions to two Danish ICUs by using a standard severity of illness classification system to assess utilization and outcome. Substantial differences in utilization were found. The patients in Hospital 2 were younger, had better previous health records, and were admitted significantly more often for active treatment as opposed to monitoring than the patients in Hospital 1. Although their measured severity of illness was similar, patients at Hospital 2 received significantly more therapy and their mortality exceeded that of the patients at Hospital 1. The mortality rate of Hospital 2 also exceeded that predicted from a recent survey of U.S. hospitals. We found, however, that 35% of the patients at Hospital 2 had been transferred to the ICU from other ICUs. This created the possibility of an adverse selection and lead-time bias for the patients at Hospital 2. These findings indicate that although national and international comparisons of intensive care are now possible using common classification systems, this progress has created a new need for more precise measurement of potential confounding biases, such as the duration of intensive care services received before formal ICU admission.

Adult↗

Outcome from intensive care. I. A 5-year study of 1308 patients: methodology and patient population.

During a 5-year period, from 1979 to 1983, demographic and disease-related data were collected prospectively on 1308 adult patients from 1555 admissions to a multidisciplinary intensive care unit (ICU) in a Danish university hospital. The patients were followed during the stay in ICU, the ensuing hospital stay, and up to 8 years after discharge from hospital. The male: female ratio was 1:1. One-third of the patients were admitted from medical wards, two-thirds were surgical patients (including gynaecological and obstetric patients). Median age was 60 years, and 25% of the patients were aged 70 years and older. Median length of stay in ICU was 2 days, and the median length of the ensuing hospital stay was 10 days. Respiratory diseases (43%) and cardiovascular diseases (16%) were the most common primary indications for ICU admission; increasing age was associated with more frequent cardiovascular diseases. Six-hundred and twenty-three (48%) patients needed mechanical ventilation; of these 373 were on mechanical ventilation for more than 24 h. Increasing age was associated with a more frequent need for mechanical support. Cancer was diagnosed in 290 patients prior to ICU admission. In 41% the cancer originated from the digestive tract. Cancer was more frequent in surgical patients than in medical patients. The APACHE- and TISS-systems were simultaneously applied to a representative sample of 216 consecutive admissions. The average APACHE score was 14.9 +/- 8.2 and the average TISS score 28.3 +/- 11.1 points. The ICU patients presented in this paper do not differ much from ICU patients in other outcome studies.

Adult↗

Outcome from intensive care. II. A 5-year study of 1308 patients: short-term outcome.

All patients (n = 1308) admitted to a multidisciplinary intensive care unit (ICU) during a 5-year period (1979-83) were followed prospectively. The in-unit mortality was 18% and the in-hospital mortality (mortality during ICU-stay plus mortality during the ensuing hospital stay) was 29%. Increasing age was associated with increasing in-hospital mortality, up to 40% mortality rate in patients aged 80 years and older. Using multiple logistic regression analyses, prognostic factors for mortality were identified. Risk factors for death in the ICU included age, cardiovascular diseases, sepsis, adult respiratory distress syndrome and acute renal failure. Cancer did not appear as a risk factor. The mortality during the ensuing hospital stay, however, was significantly influenced by cancer as well as the aforementioned risk factors. When controlled for severity of illness, expressed by the level of organ system failure after 48 h of ICU treatment, only sex, sepsis and severity of illness showed significant influence on the mortality in the ICU, and only sex and severity of illness significantly influenced mortality during the ensuing hospital stay after discharge from the ICU.

Adult↗

Outcome from intensive care. III. A 5-year study of 1308 patients: activity levels.

In a prospective study of 1308 intensive care unit (ICU) patients, we studied the patients' activity levels, using a brief questionnaire posted to the patients every third month, for up to 1 year after the day of ICU admission. Patients were asked to indicate their present activity level compared with their perceived pre-hospital activity level. The response rate was 91%. One year after ICU admission 42% of the patients were dead; 44% of the survivors were recorded to have normal and 26% limited activity. Age influenced both the 1-year mortality and the activity level, the mortality increased from 25% among the youngest to 56% in the oldest patients. In the youngest age group 60% of the survivors reported having normal activity while almost 30% of the oldest survivors had returned to normal activity level within 1 year. Medical patients had a higher mortality and fewer of the survivors returned to their normal activity level compared with surgical patients. Having survived critical illness, a realistic hope of regaining a normal or near-normal activity level exists for many patients.

Activities of Daily Living↗

Severity of illness and outcome of treatment in alcoholic patients in the intensive care unit.

To study whether critically ill alcoholics were more sick and had a worse outcome than other patients treated in the intensive care unit, data were collected during the initial 24 h on 216 consecutive patients admitted to an intensive care unit. Twentysix patients (12%) met the criteria for alcohol abuse. The patients' chronic health 6 months prior to admission and the extent of physiological derangement (Acute Physiology Score and Chronic Health Evaluation (APACHE] were recorded just as the type and amount of treatment (Therapeutic Intervention Scoring System (TISS]. Alcoholics were found to be significantly more sick and had a higher mortality (50% compared to 26%) than other critically ill patients. However, when analyzing the TISS points, no difference was found between the two groups. All survivors were, every third month up to 1 year after admission, asked to fill in a questionnaire indicating their level of activity. No differences were found between the two groups 1 year after admission, but the alcoholics had lost more time due to death. It is concluded that studies with larger number of patients will reveal whether alcoholics constitute a special category of patients with a different prognosis than other ICU patients.

Alcoholism↗

Cancer risk and occupational exposure to aflatoxins in Denmark.

A study of cancer risk among male employees at 241 livestock feed processing companies in Denmark was conducted on the basis of a data linkage system for detailed investigation of occupational cancer providing employment histories back until 1964, established at the Danish Cancer Registry. Crops imported for feed production have often been contaminated with highly variable concentrations of aflatoxins; an estimated average concentration of at least 140 micrograms aflatoxin B1 kg-1 prepared mixed cattle feed prevailed in the past, yielding a daily intake for workers via the respiratory route of approximately 170 ng. Risk was established on the basis of cancer cases among male workers, whose employment in one of the companies was the job they had held for the longest time since 1964. Elevated risks for liver cancer and for cancers of the biliary tract were observed, which increased by two- to three-fold significance after a 10-year latency. Exposure to aflatoxins in the imported crops was judged to be the most probable explanation for these findings, although the influence of lifestyle factors, e.g. alcohol consumption on the results cannot be fully disregarded. Increased risks for salivary gland tumours and multiple myeloma were also detected. However, due to multiple comparisons carried out in this study these new associations must await further confirmation. A decreased risk for lung cancer was observed; despite possible negative confounding due to the smoking habits of the employees, the lung does not seem to be a target organ for the carcinogenic effect of inhaled aflatoxins in humans.

Adult↗

Metabolism of benzo[a]pyrene by cultured rat and human buccal mucosa cells.

Primary cultures of epithelial and fibroblast cells derived from human oral mucosa were studied for the ability to activate a tobacco smoke carcinogen, benzo[a]pyrene (BP). The cells were exposed to benzo[a]pyrene for 18 h. The cell-free medium was extracted with ethylacetate/acetone, and high-pressure liquid chromatography analysis of this fraction revealed that BP tetrols and diols were the major metabolites formed by both epithelial and fibroblast cells. However, the epithelial cells had a much higher rate of biotransformation of BP as measured by binding to cellular DNA. The mean binding level to human buccal mucosal DNA was among the highest observed in stratified human epithelia. The major BP-DNA adduct was formed by the reaction of the 'bay-region' BP diolepoxide with the exocyclic 2-amino group in guanine. In contrast to human cells, BP phenols and BP 9,10-diol were the major metabolites produced by primary epithelial and fibroblast cells derived from rat buccal mucosa. The DNA binding levels of BP in the two rat cell types were identical, and the binding level was several-fold lower than in the human epithelial cells. When an established rat tongue epithelial cell line (RTE 2) was treated with polycyclic aromatic hydrocarbons--BP and 7,12-dimethylbenz[a]-anthracene--a slight toxic effect was observed. Our results indicate that primary cultures of oral mucosa are able to metabolize BP into its ultimate carcinogenic form at a rate similar to or higher than other potential target tissues for BP-induced carcinogenesis.

Animals↗