Illness and disability in Danish Chronic Fatigue Syndrome patients at diagnosis and 5-year follow-up.

OBJECTIVE: Evaluation of the life impact of Chronic Fatigue Syndrome (CFS) over 5 years. METHODS: Thirty-three adult patients meeting 1988 and 1994 CDC case criteria answered identical questionnaires at diagnosis and 5 years later, when a retrospective questionnaire was also completed. RESULTS: Work disability was very high and increased further, social isolation remained high, emotional adjustment improved. There were increased problems with reading and with allergies. Two measures of improvement were used: The relation between these measures was weak. Length of illness, extent of disability and emotional adjustment were poorly related to measures of improvement. Average illness scores were unchanged, but most individuals improved in some ways while worsening or remaining the same in others. Only one participant (3%) neared recovery, one other was substantially better but still severely disabled. CONCLUSION: CFS patients exhibit severe, long-term functional impairment. Substantial improvement is uncommon, less than 6%. Allergies and aspects of cognition may worsen, emotional adjustment often improves.

Importance of the Bcl-2 family in cell death regulation.

Bcl-2 was first identified as a novel transcript associated with the t(14;18) chromosomal breakpoint which occurs in most follicular lymphomas. The deregulated expression of bcl-2 was found to contribute to multistep neoplasia through the suppression of cell death, or apoptosis, in transgenic mouse models. Bcl-2 was subsequently shown to be normally expressed in a variety of tissues and to significantly inhibit the induction of apoptosis in many experimental systems. Bcl-2 is now known to be structurally similar to other proteins, in particular within the domains referred to as BH1 and BH2. This multigene family of cell death regulators includes members which enhance rates of apoptosis, including bcl-xs and bax, and those which inhibit apoptosis, including MCL-1 and bcl-xL. Members of the bcl-2 family physically interact with other proteins, including other family members and these interactions appear to modulate their function. The mechanism(s) by which bcl-2 family members regulate cell death remain in large part unknown, although recent evidence suggests that bcl-2 may interfere with cellular signalling events involved in apoptosis induction.

Group A streptococcal bacteraemias in Denmark 1987-89.

A retrospective study of laboratory-verified cases of Group A Streptococcal bacteraemias in Denmark was conducted for the period 1987-1989 after a sudden increase occurred during the winter 1988-1989. The aim of the study was to describe the epidemiology in the period and to compare cases during the outbreak period with cases in a period with a baseline risk. Based on isolates, a total of 242 cases in 240 patients were included in the study and information on previous health of the patients, source of infection (community-acquired or nosocomial) and outcome were obtained from hospital records. During the epidemic period the total incidence increased three-fold. The frequency of type 1 increased from 1 in 5 to 1 in 2. The number of previously healthy individuals falling ill with type 1 increased 25-fold. The relative increase was higher among patients with community-acquired infection than among patients with nosocomial infection. The lethality rate was 48% during the epidemic in which 38% of the cases occurred. As early diagnosis and treatment are the two most important measures to prevent serious outcome, effectiveness and timeliness of surveillance systems are of extreme importance.

Correlation between leukocyte-associated plasma proteins and white cell differential count.

Prealbumin, albumin, orosomucoid (including the cellular variant orosomucoid2), alpha 1-antitrypsin, haptoglobin and transferrin were quantified in 107 cell samples from acute and chronic myeloid leukaemia, seven polycytaemia, seven normal blood marrow and 56 normal blood leukocytes by crossed immunoelectrophoresis. By statistical multivariate analyses, the individual plasma proteins and their combined protein patterns were correlated with the diagnoses and it was demonstrated that acute leukaemia cell samples contained significantly different protein patterns compared with the other diagnostic groups and normal controls. By comparison with the white blood cell differential count, in 78 samples of acute leukaemia, it was demonstrated that the protein patterns were significantly correlated with the specific cell types in the samples. In all, the differential counts accounted for about 29% of the variation in protein patterns. Alpha 1-antitrypsin was found significantly correlated with the myeloblasts and myelo-band cells. Orosomucoid2 and haptoglobin were significantly correlated with mature granulocytes and albumin was significantly correlated with lymphocytes. In some cell samples, after cytotoxic treatment of acute leukaemia, the granulocytes did not have orosomucoid2 despite normal morphology, suggesting defective maturation of these granulocytes. These results indicate that the mechanisms responsible for uptake of plasma proteins are highly specific for different cell types and in the case of myeloid cells specifically related to cell differentiation.

[Treatment of obesity with energy reducing diet. Results of dietary advice during a period of 17 years]. / Behandling of fedme med energireduceret kost. Resultater fra 17 års kostvejledning.

The results of treatment of obesity by means of conventional dietary advice in the nutritional physiological laboratory. The Municipal Hospital, Copenhagen, during a period of 17 years are reviewed. This review involves 1,640 patients, 973 women and 667 men. 31% had a body mass index (BMI) of 25-29 kg/m2, 59% had BMI of 30-39 kg/m2 and 10% had BMI greater than or equal to 40 kg/m2. After 12 weeks, a total of 56.4% and after 16 weeks 50% of the patients were still receiving treatment. The weight-loss by the 12th week averaged 6.7 kg for women and 7.8 kg and 9.2 kg, respectively. The percentage of defaulters by the 12th week was independent of sex, initial BMI and the presence of other possible diagnoses but was significantly higher for the younger patients (less than 40 years) as compared with the older patients (greater than or equal to 40 years). The weight-loss at the 12th week was independent of age but was significantly positively correlated to high initial BMI and presumably high energy intake in the dietary history. The number of control weighings (frequency of attendance) was the parameter which best correlated to the weight-loss with an average weight-loss of 0.14 kg per attendance.

[Dietary advice in hypercholesterolemia. Relation of selected dietary factors to total serum cholesterol and high density lipoprotein cholesterol]. / Kostvejledning ved hyperkolesterolaemi. Udvalgte kostfaktorers relation til total serum-kolesterol og high density lipoprotein kolesterol.

Forty patients (14 women and 26 men) with slight to moderate hypercholesterolaemia received dietary advice and were followed-up for 12 weeks, the majority for 26 weeks. After 12 weeks, the total cholesterol had decreased by an average of 12% (from 7.92 to 6.97 mmol/l), the high density lipoprotein (HDL) cholesterol had increased by 5.3% (from 1.14 to 1.20 mmol/l) and thus the ratio of total cholesterol/HDL cholesterol had decreased by 17% (from 7.42 to 6.15). In the 35 patients who were followed-up for 26 weeks, the total cholesterol/HDL cholesterol decreased further (to 22% below the original value). HDL cholesterol was found by univariate regression analysis to be correlated significantly with the dietary content of the patients of fats (negative), polyunsaturated fatty acids (positive), sugar (negative), fibre (positive) and the total value (positive). Employing multivariate analysis with stepwise reduction, fats and fish sandwich spreads were found to be significantly correlated. The ratio of total cholesterol/HDL cholesterol by means of univariate analysis was found to be inversely correlated with the same dietary factors as HDL cholesterol while multivariate analysis revealed the content of polyunsaturated fatty acids, sugar and alcohol intake to be significantly correlated.

Tumor markers identified by line immunoelectrophoresis.

Line immunoelectrophoresis was used as a screening procedure for the recognition of tumor markers using the human promyelocytic leukemia cell line HL-60 as a model system. The polyspecific antiserum used was raised by immunization with tumor cells grown in RPMI medium enriched with serum from the species used for immunization in order to avoid interference from serum proteins in the immune response. Among the HL-60 antigens recognized, 4 were tumor-associated in as much as they were present only or in relatively high concentrations in the HL-60 cells. One of the antigens was identified as ferritin. Evidence is presented that the remaining potential HL-60 tumor markers are unrelated to known oncofetal antigens. It is suggested that for the recognition of tumor associated antigens the present approach may be useful as a supplement to hybridoma techniques.

Leucocyte-associated plasma proteins in leucocytes during disease states, and in leukaemic cells.

The concentrations and molecular forms of prealbumin, orosomucoid, albumin, alpha 1-antitrypsin and haptoglobin in leucocytes were studied in patients with alpha 1-antitrypsin deficiency, in acute phase and with leukaemia, by rocket and crossed immunoelectrophoresis. Alpha 1-antitrypsin was the only protein being synthesized by bone marrow cells, blast cells and leucocytes present in the blood during cytotoxic treatment. The other proteins are taken up by the cells. The concentration of alpha 1-antitrypsin in serum and cells was correlated in alpha 1-antitrypsin deficiency and the acute phase, suggesting either that the same signal for synthesis is used in the liver and leucocytes, or that a balance is kept by means of leucocyte uptake. Chronic lymphocytic leukaemia lymphocytes contained only traces of albumin, which may be related to the decreased membrane mobility of these cells. Polycythemia leucocytes, however, contained increased concentrations of all plasma proteins, especially orosomucoid and haptoglobin2 . These two protein forms were found to be markers of mature granulocytes. The cellular concentrations of prealbumin, albumin and transferrin were about 35% of normal in acute myeloid leukaemia cells and no orosomucoid2 and haptoglobin2 was present. Alpha 1-antichymotrypsin was present in a heterogeneous form and the molecular form of alpha 1-antitrypsin (alpha 1 AT4 ) was the same as in monocytes. These findings suggest the existence of a distinct 'AML'-type protein pattern which could be of functional and diagnostic importance.

Leucocyte-associated plasma proteins. Association of prealbumin, albumin, orosomucoid, alpha 1-antitrypsin, transferrin and haptoglobin with human lymphocytes, monocytes, granulocytes and a promyelocytic leukaemic cell line (HL-60).

The distribution of prealbumin, albumin, orosomucoid, alpha 1-antitrypsin, haptoglobin and transferrin, including their electrophoretic heterogeneous variants, was studied in isolated lymphocytes, monocytes and granulocytes and in a human promyelocytic cell line (HL-60) by crossed immunoelectrophoresis. Prealbumin, albumin and transferrin were present in lymphocytes, monocytes and granulocytes, whereas the cellular variants of orosomucoid and haptoglobin were present only in granulocytes. alpha 1-Antitrypsin was present in four electrophoretic variants which were differently distributed among the various cell types. Synthesis of alpha 1-antitrypsin by monocytes, granulocytes and HL-60 cells was demonstrated by 14C-leucine incorporation. The six plasma proteins could not be removed from intact cells by incubation with the respective antibodies at 0 degrees C, or iodinated by lactoperoxidase catalysed iodination at 23 degrees C. They were, however, readily solubilized by freeze-lysis of the cells, suggesting an intracellular localization. Compared to their plasma counterparts none of the proteins differed in their hydrophobic properties but the carbohydrate residues of orosomucoid, alpha 1-antitrypsin and haptoglobin were different. The pattern of disappearance of the proteins from the cells during incubation suggested that the localization of albumin and transferrin in relation to the cells differed from that of the other proteins.

Leucocyte-associated plasma proteins. I. Plasma proteins in supernatants and cell pellets during successive washings of human blood cells.

Sixteen plasma proteins were studied in the supernatants from 20 successive washings of human leucocytes by a new sensitive immunoelectrophoretic method. In the first few supernatants a fast and parallel decrease in concentration of all proteins took place, but for 11 proteins this was followed by a phase of slow decrease due to cellular release. Eight proteins could be quantitated throughout the 20 washings: prealbumin, albumin, orosomucoid, alpha 1-antitrypsin, transferrin, C3, haptoglobin, and IgG. These proteins and trace amounts of eight other plasma proteins were present in the cell lysate after the washings. In comparison with plasma, the leucocytes contained relatively higher concentrations of prealbumin, orosomucoid, alpha 1-antitrypsin, and haptoglobin than of albumin. In crossed immunoelectrophoresis these same four proteins were present as molecular variants differing from their plasma counterpart in electrophoretic mobility and morphology of the precipitate.

Protein composition in the fluid of individual bovine follicles.

The proteins in follicular fluid from individual and pooled bovine follicles were studied by gel chromatography and quantitative immunoelectrophoresis. The mean protein concentration was 86-4% of serum; very large proteins were present in only low concentrations. A minimum of 40 individual proteins was distinguished in follicular fluid, and 15 of these proteins were quantitated. A correlation between molecular weight and follicular fluid: serum concentration ratio was found. Fluid from individual follicles differed only in the relative concentrations of small and large proteins. An exception to this was IgG which was occasionally, but never in healthy growing follicles, present in concetrations above 150% of serum. Healthy growing, preovulatory and atretic follicles had higher, and cystic follicles mostly lower, concentrations of small proteins than serum. The concentration of alpha2-macroglobulin in healthy growing follicles never exceeded 16% of serum. The concentration of large proteins in follicular fluid increased with increasing follicle size. Attempts to detect proteins specific to follicular fluid by immunizing rabbits with pooled follicular samples and the follicular fluid proteins not bound by anti-bovine antiserum resulted in production of antibodies against fibrinogen and its split products D+E only.

Specific antisera produced by immunization with precipitin lines.

Individual plasma proteins were precipitated, identified and isolated on the basis of line immunoelectrophoresis. A monospecific antibody response was induced by immunization of rabbits with less than 50 ng of precipitated antigen. Preservation of monospecificity was obtained by reimmunization with precipitates developed against the specific antisera.

Identification of immunoprecipitates in line immunoelectrophoresis.

A technique has been developed for the identification of immunoprecipitates in complex line-immunoelectrophoretic patterns. It is based on localized adsorption of individual antigens by monospecific antisera. The technique is suited for the following purposes as well: (1) testing the specificity and titer of uncharacterized antisera and (2) evaluation of binding properties of chromatographic media.