Interferons in the treatment of multiple myeloma.
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Biomedical subjects
Publications and source records attributed to J Westin.
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We examined causes and hematological consequences of low serum cobalamin (vitamin B12) concentration in two representative population samples of 70-year-old (N = 293) and 75-year-old subjects (N = 486). Subjects with values below 130 pmol/liter (4.8% and 5.6%, respectively) were investigated with Schilling test, upper gastrointestinal endoscopy, determination of serum gastrin and group I pepsinogens, and bone marrow examination. Gastrointestinal abnormalities of etiologic significance were found in 26 of the 32 examined subjects: atrophy of the gastric body mucosa (N = 16, with pernicious anemia in six), partial gastrectomy (N = 6), and intestinal malabsorption (N = 4). Megaloblastic hematopoiesis was found in 10 individuals, four of whom had macrocytic anemia. Our results indicate that low serum cobalamin concentration in the elderly is usually a consequence of disease rather than of high age per se and that gastric mucosal atrophy is a major etiologic factor.
This study compared plasma levels of dihydrotestosterone, testosterone, corticosterone, luteinizing hormone, growth hormone, and prolactin in migrating juvenile willow tits with those in territorial juveniles. Both categories of birds were caught in late September. Migrating juveniles had higher plasma levels of corticosterone than territorial juveniles. Only corticosterone secretion was affected by "handling stress" in both migrating and territorial juveniles. However, territorial birds showed a much stronger relationship between these two variables. It is suggested that high corticosterone levels are involved in the emigration of juveniles out of the coniferous forest. Only juveniles were found among the migrating willow tits, and these birds were not well adapted for migration. Migrating juvenile males had less fat stored than did territorial ones. Furthermore, migrating juvenile males had higher liver/somatic index and higher plasma levels of growth hormone than did territorial males. These results indicate that migrating males had been, or were, exposed to food restrictions. The same proportion of migrating and territorial juveniles, males as well as females, had high plasma levels of testosterone. We suggest that these high levels were caused by recent aggressive interactions. To test the hypothesis that high plasma levels of testosterone are important for a juvenile to become a member of a territorial winter group, we performed a field experiment in which juveniles were given testosterone implants (controls were given empty silastic tubes) at the beginning of the territorial establishment period. The same proportion of testosterone-implanted birds and control birds succeeded in becoming members of territorial winter groups. Thus, testosterone does not seem to play an essential role in autumn territoriality, and it does not prevent autumn migration.
Annual changes in body weight, fat depots, and plasma levels of thyroxine (T4) and growth hormone (GH) were studied in free-living great tits and willow tits. Birds were collected during six ecologically well-defined periods of the year. Special attention was given to the nonreproductive part of the year. T4 showed simple unimodal cycles in both species and both sexes, with high levels during the warmer part of the year, and low levels during the winter and spring periods. Although increasing levels were temporarily separated between the two species, they were in both cases correlated with the onset of gonadal regression and moult. Plasma levels of GH fluctuated in a much more complex pattern, and no obvious and consistent correlation to any extrinsic or intrinsic factor was found. Body weights and fat depots both showed seasonal variations that varied slightly between the two species. Values, with the exception for breeding females, were generally the highest during the autumn, winter, and spring periods.
Blood haemoglobin (Hb) and related components were determined in a representative sample (n = 973, 449 men and 524 women) of a 70-year-old population, reinvestigated at age 75, 79 and 81. At age 81, 145 men and 259 women remained in the study. Longitudinal analysis demonstrated a significant decline in Hb concentration with advancing age, in the total study groups as well as in subsamples remaining after exclusions due to disease. The mean annual decline from age 70 to 81 in a subsample without definable disorders was in men 0.063 g/dl, in women 0.035 g/dl. There was a similar decline among subjects with high, intermediate or low Hb concentrations during the study. Only part of the observed intraindividual variations could be explained by factors other than age.
A case of primary biliary cirrhosis (PBC) presenting as idiopathic thrombocytopenic purpura is described. The patient, a 59-year-old woman, had, at the time when thrombocytopenia was first observed, an asymptomatic PBC. She responded only temporarily to corticosteroids, and splenectomy had to be performed later. After this operation the platelet count was normalized, but a marked and rapid deterioration of her previously indolent PBC occurred. The time-relationship indicates that the removal of the spleen may be considered the cause of the disease's progression. Possible mechanisms behind this adverse effect of the splenectomy are discussed. After initiation of azathioprine therapy a good response in clinical and laboratory features of the PBC was obtained, although the histological picture has remained unchanged.
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A 72-year-old immunocompromised man with myelodysplastic syndrome who developed multiple erythematous, scaly abscesses like lesions on his left foot and lower leg is described. He also had dry scaly lesions on his soles and lesions on several toe nails. A punch biopsy showed abscesses with fungal elements and Trichophyton rubrum was cultured from skin scales and the biopsy. A diagnosis of T. rubrum abscesses should be suspected in all immunocompromised patients with signs of superficial dermatophyte infection.
Dorsal unpaired median (DUM) cells in orthopteran insects are known to contain the neuromodulatory substance octopamine, and DUM cells with peripheral axons augment synaptic activity at neuromuscular junctions. One of the most studied systems in the cockroach is the giant interneuron (GI) system which controls the initial movements of a wind-mediated escape response. Our data demonstrate that DUM cells that are restricted to the central nervous system (DUM interneurons) receive inputs from ventral giant interneurons (vGIs) but not from dorsal giant interneurons (dGIs). In contrast, DUM cells that have peripheral axons consistently fail to be excited by any giant interneurons. The DUM interneurons are excited by vGIs on both sides of the CNS and, when the vGIs are excited in pairs, summation occurs. Wind fields that have been generated for two of the DUM interneurons are omnidirectional. These data, taken along with the known association of DUM cells with the neuromodulatory substance octopamine, suggest that the DUM interneurons may act to modulate central synapses.
The cockroach escape response begins with a turn away from a wind puff such as that generated by an approaching predator. The presence and direction of that wind is detected by hairs on the animal's cerci, and this information is conducted to the thoracic ganglia via two populations of giant interneurons. In the thoracic ganglia, the giant interneurons excite a number of interneurons, at least some of which in turn excite motor neurons that control leg movement. In this paper we examine response properties of various thoracic neurons to wind stimuli originating from different directions. Three sets of thoracic neurons were distinguished on the basis of latency. Type A interneurons had short latencies to wind stimuli (1.3-2.25 ms). Type B interneurons had longer latencies (4-6 ms), and motor neurons had the longest latencies (5.6-17.0 ms). Individual type A interneurons either responded equally to wind from all directions or were biased in their response. Directionality was related to the presence of ventral branches near one or both sides of the midline of the ganglion. Cells with ventral median (VM) branches on either side tended to be omnidirectional or front-rear biased, whereas cells with VM branches on only one side were biased to that side. Although several type B interneurons had strong wind responses and were directionally sensitive, they did not have VM branches. We hypothesize that the presence of VM branches in type A interneurons permits connection with ventral giant interneurons, and this connection accounts for their short latency and directional properties. This hypothesis will be tested in the companion paper.
Seventy splenectomized patients were vaccinated with Pneumovax, a pneumococcal polysaccharide vaccine. Twenty-four of the patients had a malignant and 30 a nonmalignant hematological disorder. The remaining 16 were patients with no known hematological disorder, seven with intra-abdominal carcinomas and nine with non-malignant reasons for splenectomy. About 90% of the patients with non-malignant hematological disorders responded to vaccination with a rise in antibody titres, which was significantly higher than in the other two groups studied. Malignant hematological disorders lowered the response rate to 61-67%. Patients with no known hematological disorder but with intra-abdominal carcinomas also responded less frequently, while those in this group with other surgical reasons for splenectomy had a response rate comparable to healthy individuals. No serious side-effects were reported and we therefore conclude that all splenectomized patients should be vaccinated with a pneumococcal vaccine. However, it must always be born in mind that one third of the patients with malignant disease did not respond to vaccination.
A representative sample (n = 486) of a 75-year-old population was studied, and probands with defined laboratory aberrations were re-investigated. Anaemia was present in 6% of the men and 3% of the women; in 17/22 anaemic subjects a cause was found. The prevalence of plasma cobalamin concentrations less than 130 pmol/l was 6%, of iron deficiency approximately 6%. Divergences in white blood cell and platelet counts were rare. The observed haematological aberrations were almost always caused by disease. Reference intervals for haematological components were calculated in the total study group and two reference sample groups after exclusions based on anamnestic and/or laboratory screening criteria or anamnestic criteria and/or verified disease. The lower reference limits for B-Hb and P-B12 in a group obtained after exclusions based on anamnestic and screening data were considered to be minimum values for healthy subjects. The WHO criteria for anaemia were applicable.
We compared three representative population samples aged 70 (n = 312), 75 (n = 486) and 81 (n = 404) years. Anaemia defined either as blood haemoglobin concentration below the corresponding health-related lower reference limits or according to WHO was, in the total study groups, more common at age 81. Anaemia of unknown cause was rare, but somewhat more common at age 81. Mean blood haemoglobin concentrations in subsamples without definable disorders were significantly lower at age 81 than at ages 70 and 75, whereas the lower health-related reference limits did not differ significantly. White blood cell counts tended to be lower and iron deficiency was somewhat more common at age 81. No significant differences were found in platelet counts or in the prevalence of low plasma cobalamin concentrations. These results indicate a fall in blood haemoglobin with advancing age. The arbitrary WHO criteria for anaemia are clinically applicable at age 70-81.
This paper reports the results of cytogenetic studies in a consecutive series of 64 patients with polycythemia vera, 57 of whom could be followed prospectively. The median length of the cytogenetic observation time was 93 months (range, 24 to 224 months) after diagnosis. Clonal chromosome abnormalities were observed initially in 11 patients (17%) and later during the course of the disease in another 20 patients. An abnormal karyotype was found in 71% to 80% of the patients who were examined after the development of myeloid metaplasia, myelofibrosis, or leukemia. Patients treated with myelosuppressive agents showed a significantly greater risk of chromosome abnormalities developing than did patients who had been phlebotomized. Acute leukemia developed in eight patients, all of whom had been treated with myelosuppressive agents. A chromosome abnormality preceded the leukemia in only two of the patients. The initial presence of an abnormal karyotype did not predict a greater risk of development of leukemia. No consistent relationship was demonstrated between the occurrence of chromosome abnormalities and the development of myeloid metaplasia and/or myelofibrosis, which was observed in 42% of the patients. The chromosome abnormalities followed a nonrandom pattern, and those most frequently observed were trisomies for 1 q, 8, 9, or 9p and deletion of 20q. Deletions seem to be common and were found in 14 patients.
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Fifty-two immunocompromised patients with suspected septicaemia were randomized on 61 occasions to treatment with ceftazidime or with tobramycin and cefuroxime. Most (90%) of the patients had haematological malignancies and were neutropenic (granulocytes less than 1 X 10(9)/1 in 40 of the 61 episodes). Blood cultures were positive in 22 (39%) febrile episodes and in four other instances positive cultures were obtained from other sources. Clinical cure or improvement was noted in 10 of 12 culture verified infections in the tobramycin and cefuroxime group and 11 of 14 episodes in the ceftazidime-group. The effect on the kidney of the two antibiotic regimens was studied by following the serum levels of creatinine, urea and beta 2-microglobulin and the urinary excretion of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase (beta-NAG) and beta 2-microglobulin. No clinically important renal side effects were observed. However, an increase in the urinary excretion of AAP was seen in both groups with significantly greater elevation in the tobramycin and cefuroxime group. Urinary beta-NAG increased only in the tobramycin and cefuroxime group.
At our hospital, 47 out of 184 consecutive splenectomies performed over 7 recent years were carried out on patients afflicted with various hematologic diseases. The results of these 47 splenectomies were the subject of a careful retrospective analysis. The majority of the splenectomies (81%) were therapeutic. Cytopenia, particularly thrombocytopenia, was the most common indication for surgery. As a whole, good therapeutic responses with rapid improvements in peripheral blood picture and/or diminished symptoms of pressure discomfort from an enlarged spleen were obtained. There was no peri- or postoperative mortality; 23% major and 26% minor postoperative complications were recorded. In patients with perioperative bleeding and various postoperative complications, the spleens were larger than in subjects who run an uneventful peri- and postoperative course. During the follow-up period, 4 septicemias occurred in 3 patients. In 2 of these patients, the septicemias coincided with a cholecystitis and a pneumonia, respectively. None of the infections was lethal. It is concluded that elective splenectomy for hematologic disease in well selected and carefully prepared patients is beneficial and can be performed without mortality or major hazards.
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