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Biomedical subjects

C Engström

Publications and source records attributed to C Engström.

At least 19 recordsLinked to original sources

Manometric characteristics of the gastroesophageal junction after anterior versus posterior partial fundoplication.

How best to surgically treat GERD is an unresolved issue. To increase our insights into the fundoplication procedures, functional consequences for the gastroesophageal junction of an anterior or a posterior partial fundoplication were studied by manometry. Patients were randomly selected from a larger study in a randomised comparison between posterior and anterior partial fundoplications. The manometric studies were done 12 months after respective procedures in 24 patients. The motor characteristics of the esophagus and lower esophageal sphincter (LES) function were determined by use of sleeve catheter manometry. The manometric characteristics of the esophageal body were similar in the study groups except for the ramp pressure. This was significantly higher in patients with posterior partial fundoplications. The posterior group had significantly longer total length (P < 0.02) as well as longer intra-abdominal portions (P = 0.07) of the LES while the basal tone, albeit numerically higher, did not reach statistical significance. Water-swallow induced LES relaxations reached lower nadir values in the anterior group (1.7 vs 2.7 mmHg). Gas distension triggered few transient LES relaxations in both study groups while common cavities were more frequently observed in those having an anterior partial wrap (P < 0.01). A posterior partial fundoplication is followed by manometric characteristics suggesting a well functioning antireflux barrier with some obstruction to bolus passage as well as restricted venting of air from the stomach. The manometric mechanisms behind the inferior reflux control achieved by a Watson type of anterior partial wrap has now been further elucidated.

Adult↗

Effects of wood-related sterols on the offspring of the viviparous blenny, Zoarces viviparus L.

The parent generation of the viviparous blenny, Zoarces viviparus L., were exposed to phytosterols (a) from oogenesis to parturition and (b) from breeding to parturition. The experiments were performed under laboratory conditions in a test unit supplied with continuous renewal of brackish water. After parturition the offspring were further reared either in clean or in phytosterol-contaminated brackish water. The objective was to study the significance of preexposure of the parent on the effects of phytosterols on the offspring in comparison with effects occurring directly on previously unexposed offspring. The phytosterol concentrations used were (a) 0, 10, 20, and 30 microg/L and (b) 0, 10, and 20 microg/L. Offspring exposed in (a) was further reared in clean water and in (b) offspring from parents exposed to 10 microg/L was either exposed further in the same concentration or left in clean water. Offspring from parents exposed to 20 microg/L was further exposed in the same concentration. Finally one group from unexposed parents was exposed to 10 microg/L after birth. The offspring was studied for 6 months after birth. The results showed that blenny offspring are affected by phytosterols at exposure through the parental generation. The results imply that phyto- sterols affect embryological development of the larvae before hatching as well as the levels of circulating hormones of the parent fish. The larvae contained higher levels of phytosterols as did controls and the bile of exposed female fish contained lower levels of phytosterols implying a link between the higher levels in larvae and lower excretion of the females. The growth of the larvae at 10 microg/L was stimulated regardless of whether the larvae were further exposed, indicating that newborn larvae carried within the female are sensitive to exposure to phytosterols.

Abnormalities, Drug-Induced↗

Effects of pulp mill effluents and restricted diet on growth and physiology of rainbow trout (Oncorhynchus mykiss).

Juvenile female rainbow trout was exposed for 4.5 months (June to October) to two dilutions of untreated and activated sludge treated whole mill effluent from a pulp mill producing bleached ECF pulp. Two controls were used, on fed ad libitum and a second receiving 0.5% feed of the body weight. All effluent exposed groups were fed ad libitum. Mean weight of the fish was measured monthly. At the end of the experiment a number of physiological and biochemical parameters were analyzed in order to establish the physiological status of the exposed fish in comparison with unexposed fish that obtained ad libitum or restricted amount of feed. The fish exposed to treated effluent grew significantly more than ad libitum control fish until August, whereupon growth retarded in fish exposed to the lower effluent dilution (400 v/v). The growth of fish exposed to untreated effluent did not deviate significantly from the control fed ad libitum. The results from the hematological analysis clearly showed that fish fed restricted amount of feed deviated significantly in most parameters compared with the control fed ad libitum. Fish exposed to treated effluent showed a response pattern similar to that of the control fed restricted amount of feed, whereas the fish exposed to untreated effluent showed a response pattern that did not deviate from that of the ad libitum control. The metabolic parameters suggested that fish exposed to treated effluent had a higher metabolic demand than ad libitum control and that the energy allocation at the end of the experiment was directed to processes other than growth. The responses on hematology were mainly a consequence of the increased energy demand and were not primary effects. The implications of using feed related parameters at field studies are discussed.

Animal Feed↗

Effects of wood-related sterols on the reproduction, egg survival, and offspring of brown trout (Salmo trutta lacustris L.).

Maturing lake trout (Salmo trutta lacustris) of both sexes were exposed to 10 and 20 microg/liter phytosterols, mainly ss-sitosterol, for 4.5 months prior to spawning. Eggs from preexposed females were artificially fertilized with milt from preexposed males in clean water, whereupon the eggs were incubated in clean water until hatching. Yolk sac fry were followed until swim-up, and mortality as well as deformities was recorded. The physiological status of the parent fish was documented, as was the occurrence of phytosterols in bile liquid and gonads. In addition, eggs from preexposed females were fertilized with milt from unexposed males to evaluate the existence of possible sex-linked differences. The results indicate a markedly increased dose-dependent egg mortality, smaller egg size, and lower mean weight of the the yolk sac stage larvae. There was a higher prevalence of deformed or otherwise diseased larvae, especially at the higher dose, but also in the groups where unexposed males were used for fertilization, indicating a female-linked effect mechanism. A causal link between effects on eggs and brood was obtained through a dose-dependent increase in phytosterols in the roe. Several physiological parameters (higher plasma estradiol, higher 7-ethoxyresorufin O-deethylase activity) implied slower maturation of the exposed female fish, whereas indications of accelerated maturation were obtained for the male fish from the same groups. The results indicate that naturally occurring wood-derived compounds in pulp mill effluents may be responsible for reproductive impacts previously observed in fish both in the laboratory and in the receiving waters of pulp mill effluents. The results also suggest that more attention should be paid to process streams emanating from the unbleached part of the mill.

Animals↗

Linkage analysis of candidate loci in families with recurrent major depression.

Recurrent major depression, RMD, is characterized by the occurrence of depressive episodes in the absence of mania and/or hypomania. In linkage studies, RMD (or, in general, unipolar depression) are frequently grouped together with bipolar illnesses into a broad definition of affective disorders. However, twin studies suggest that RMD and bipolar disorders might have different genetic determinants. The objective of this study was to test a set of families with RMD for linkage to chromosomes that have been recently proposed to contain susceptibility loci for bipolar disorders: chromosomes 16, 18, 21 and the short arm of chromosome 4. We analysed five large families from the northern part of Sweden ascertained through a proband with RMD and containing several patients with RMD. For the genetic analysis, we included only severely affected individuals (those who had at least three episodes that required medical treatment) to increase the chances of finding a larger degree of genetic determination. The genetic model led to a total disease prevalence of 5% in females and 3% in males. We did not find significant evidence for linkage to any of the candidate chromosomes in the combined family set. Only one of the families showed a slight indication for linkage with markers from the pericentromeric region of chromosome 18. A genome scan analysis on an extended collaborative family material with severely affected individuals with RMD should be performed to evaluate whether RMD and bipolar disorders have a different genetic etiology.

Adult↗

Two commonly expanded CAG/CTG repeat loci: involvement in affective disorders?

An association between bipolar affective disorder and CAG/CTG trinucleotide repeat expansions (TRE) has previously been detected using the repeat expansion detection (RED) method. Here we report that 89% of RED products (CAG/CTG repeats) > 120 nt (n = 202) detected in affective disorder patients as well as unaffected family members and controls correlate with expansions at two repeat loci, ERDA1 on chromosome 17q21.3 and CTG18.1 on 18q21.1. In a set of patients and controls in which we had previously found a significant difference in RED size distribution, the frequency of expansions at the CTG18.1 locus was 13% in bipolar patients (n = 60) and 5% in controls (n = 114) (P < 0.07) with a significantly different size distribution (P < 0.03). A second set of patients were ascertained from 14 affective disorder families showing anticipation. Twelve of the families had members with RED products > 120 nt. The RED product distribution was significantly different (P < 0.0007) between affected (n = 53) and unaffected (n = 123) offspring. Using PCR, a higher frequency (P < 0.04) of CTG18.1 expansions as well as a different (P < 0.02) repeat size distribution was seen between affected and unaffected offspring. In addition, a negative correlation between RED product size and the age-of-onset could be seen in affected offspring (rs = -0.3, P = 0.05, n = 43). This effect was due to an earlier onset in individuals with long CTG18.1 expansions. No difference in ERDA1 expansion frequency was seen either between bipolar patients (35%, n = 60) and matched controls (29%, n = 114), or between affected and unaffected offspring in the families. We conclude that expanded alleles at the CTG18.1 locus confers an odds ratio of 2.6-2.8 and may thus act as a vulnerability factor for affective disorder, while the ERDA1 locus seems unrelated to disease.

Bipolar Disorder↗

Expanded trinucleotide CAG repeats in families with bipolar affective disorder.

Clinical anticipation has been reported in bipolar affective disorder (BPAD). The hypothesis that expanded trinucleotide repeats are related to anticipation and transmission pattern in families with bipolar affective disorder is tested in this study. Eighty-seven two-generation pairs of patients recruited from 29 bipolar families were analyzed. The repeat expansion detection method was used to detect CAG repeat expansions between successive generations. Significant changes in age at onset and episode frequency in successive generations were observed. Mean trinucleotide CAG repeat length between parental and offspring generation significantly increased when the phenotype increased in severity, i.e., changed from major depression, single episode or unipolar recurrent depression to BPAD. A parent-of-origin effect was also observed with a significant increase in median length CAG between G1 and G2 with maternal inheritance. This increase was observed notably in female offspring. Our findings indicate for the first time that expansion of CAG repeat length could explain the clinical observation of anticipation in families with BPAD. These results provide further support for expanded trinucleotide repeat sequences as risk factors in major affective disorders.

Adult↗

Relationship between prophylactic effect of lithium therapy and family history of affective disorders.

Lithium therapy response and age of onset (AOO) were studied in 98 patients with bipolar affective disorder (BPAD) who were divided into subgroups depending on type of family history of affective disorders. The highest (33.0 years) and lowest (25.5 years) age of onset were found in nonfamilial patients and in familial patients with a first-degree relative of BPAD, respectively. Nonfamilial patients showed the best response to lithium. There were 0.9 episodes/year off lithium compared to 0.3 episodes/year on lithium (an 88% decrease). A poorer response (a 71% decrease; a reduction from 1.39 episodes per year off lithium to 0.65 on lithium) was found in familial patients with a first-degree relative of BPAD. Differences in serum lithium values between the groups could not explain the observed differences. Thus, familial patients showed a more severe manifestation of the disease with an earlier AOO and a lower prophylactic effect of lithium.

Age of Onset↗

Craniofacial bone remodeling in growing rats fed a low-calcium and vitamin-D-deficient diet and the influence of masticatory muscle function.

Fifty-two male growing rats were randomly divided into three groups. The first group (n = 18) received a hard deficient diet, and the second (n = 18) a soft deficient diet. The control group (n = 16) was fed the normal hard diet. At the beginning and in the middle of the 28-day experimental period oxytetracycline was injected. Two representative coronal sections of the snout and the corresponding contact microradiographs were analyzed. The bone mass of the premaxillary and nasal bones seemed to be less in the two deficient diet groups than in the normal one, due to an increased endosteal bone resorption and decreased bone formation. No difference in the bone apposition rate and pattern could be seen between the deficient hard and soft diet groups, except in the dorsal part of the premaxilla, where the bone formed in the first half of the experiment was markedly more resorbed in the deficient soft diet group during the remaining period than in the deficient hard diet group. The morphology of the sutures was influenced by the altered function, since the sutural space became narrower, and premature obliterations of the internasal suture were observed in the deficient soft diet group. In conclusion, poor bone quality was observed in the skull of rats fed a low-calcium and vitamin-D-deficient diet, with less bone mass than in normal conditions. Masticatory function was a significant factor influencing bone remodeling and sutural growth even in situations in which a metabolic bone disturbance exists.

Animals↗

Occurrence of adenylate kinase in cerebrospinal fluid after isoflurane anaesthesia and orthognathic surgery.

UNLABELLED: The study objective was, firstly, to investigate whether anaesthesia with induced arterial hypotension would cause leakage of a biochemical marker of neuronal injury, adenylate kinase (AK), into the cerebrospinal fluid (CSF). ( DEFINITION: arterial hypotension = mean arterial pressure (MAP) 50-65 mmHg during > or = 10 min). Secondly, a subgroup of patients was examined with a limited battery of psychometric tests. Patients, scheduled for orthognathic surgery, were allocated to either hypotension (n = 20) or normotension (n = 20). Seventeen patients were subjected to psychometry. Arterial blood pressure was recorded continuously and controlled by adjustments of the administered concentration of the inhalational anaesthetic isoflurane. Fentanyl, an opioid, was given equally in both groups. A lumbar puncture was performed approximately 20 h post-operatively for a CSF sample, later analysed for AK activity. Neuropsychological tests were performed the day before surgery and the fourteenth day postoperatively. The CSF-AK value was pathologically increased ( > 0.040 U/L) in 24 patients (65%), of whom 9 were normotensive. There was no significant difference between the CSF-AK values in the hypotensive and normotensive groups, mean values were 0.082 (s.d. 0.051) and 0.066 (s.d. 0.059) U/L, respectively. The overall correlation between the 10 min MAP levels and the CSF-AK values was close to zero. In the pilot neuropsychological investigation some abnormalities were observed, indicating clinically significant adverse effects in four hypotensive patients, of whom two displayed pathologically increased CSF-AK values. At the group level, the correlation between the changes in psychometry and the measured CSF-AK values was poor. Increases in CSF-AK activities may be a non-specific occurrence in the perioperative interval, possibly indicating an adverse effect on the brain. Arterial hypotension could not be proven to explain the CSF-AK outcome.

Adenylate Kinase↗

Anticipation in unipolar affective disorder.

Anticipation describes an inheritance pattern within a pedigree with an increase in disease severity and/or decrease in age at onset in successive generations. The phenomenon of anticipation has recently been shown to be correlated with the expansion of trinucleotide repeat sequences in a neuromuscular disease, various neurodegenerative disorders and mental retardation. We have studied parent-offspring differences in age at onset and disease severity in 31 pairs with unilineal inheritance of unipolar affective disorder (UPAD). Life-table analyses showed a significant decrease in survival to 1st episode of major depression in the offspring generation compared with the parental generation (P = 0.0007). There was also a significant difference in age at onset (P < 0.001) between parents and offsprings. The offspring generation experienced onset 15.6 years earlier and illness 1.5 x more severe than did the parent generation. Furthermore, there was a significant correlation (P < 0.05) in age at onset between parent and offspring generations. When we excluded pairs where the affected parent has an age of onset greater than the age of the child at the time of ascertainment (i.e., 23 pairs left), there was still a significant (P = 0.02) decrease in age at onset (8.4 years) and 1.5 x more severe disease in the offspring generation. No evidence for specific maternal or paternal inheritance was found. We found evidence of anticipation in 75-80% of this sample of unilineal family pairs of UPAD. Anticipation is, thus, an inheritance pattern in a large group of UPAD which suggests that the expansion of trinucleotide repeat sequences is a possible mode of inheritance in this group of UPAD. The findings of anticipation in this study of families with UPAD and previous findings in families with BPAD suggest that the variable expression of unstable expansions of trinucleotide repeats may turn out to be the basis of the continuum of liability in affective disorders.

Adolescent↗

Detection of expanded CAG repeats in bipolar affective disorder using the repeat expansion detection (RED) method.

Genetic factors are of major aetiological importance in Bipolar Affective Disorder (BPAD type I and II). The exact mode of inheritance of BPAD is unknown, but the recent demonstration of anticipation suggests that dynamic mutations could be involved in the clinical expression of the disease. We have used the repeat expansion detection (RED) method to test whether the anticipation in BPAD could be explained by the presence of expanded trinucleotide repeat sequences. Using a (CTG)10 oligonucleotide a significantly higher number of expanded CAG repeats were found in the genomic DNA of two independent samples of unrelated BPAD patients of Swedish and Belgian ancestry as compared with normal controls. The difference in repeat number was more consistent if data of the two samples of patients was pooled. In this study a CAG trinucleotide repeat expansion was associated for the first time with a major psychiatric disorder. It is possible that the CAG trinucleotide repeat expansion is involved in the clinical expression of BPAD and that it is the molecular basis explaining the phenomenon of anticipation observed in this disorder.

Aged↗

Anticipation in Swedish families with schizophrenia.

Nineteen parent-offspring pairs obtained from 14 two-generation families with available medical records and diagnosis of schizophrenia were studied to compare the ages of onset of the parent generation with those of the offspring generation. The mean age of onset for the parent generation was 37.3 +/- 6.0 years and for the offspring generation was 20.8 +/- 4.4. The mean difference was thus 16.5 +/- 6.2, suggesting the occurrence of anticipation in schizophrenia (p < 0.001). Although some ascertainment biases (like reduced fertility in early-onset parents or early detection of symptoms in offsprings of affected parents) may partially contribute to the occurrence of anticipation, this study replicates recent reports of anticipation in several neuropsychiatric disorders, some of which have been shown to be associated with unstable expansions of trinucleotide repeats in the genomic DNA.

Adolescent↗

Growth effects of instantaneous change in mandibular position: experimental study.

PURPOSE: To investigate the mandibular growth pattern in rats during adolescence after altering the position of the mandible in the frontal plane instanteously by two surgical procedures. METHODS: Mandibular morphology during growth was recorded by cephalometric methods during the 3-week experimental period. RESULTS: All procedures tested caused an altered mandibular morphology. An overall change was found in the shape of the mandible in the experimental groups, with the jaw being more square compared with the rectangular form found for the mandible in the control group. Condylar growth was abnormal and the cartilage of the experimental groups showed a reduced thickness and distorted morphology, indicating disturbed cellular activity. CONCLUSION: In view of the findings, it was concluded that considerations to instantaneously alter the mandibular position during adolescence may not be advisable.

Age Factors↗

Thyroid function and root resorption.

The regulation of degradative activity such as phagocytosis and bone resorption in the periodontal region is greatly influenced by factors controlling general bone modeling. The purpose of this study was to determine if thyroxine has any influence on the occurrence of force-induced root resorption. Young male rats were divided into three groups: a group of normal rats, a control group in which appliances were placed, and an experimental group in which appliances were placed and I-thyroxine was administered (5 micrograms/kg bw for 12 days). Root resorptions were induced by orthodontic force on the maxillary incisors. Fewer force-induced root resorption lesions occurred in the thyroxine group than in the control group. Alkaline phosphatase activity in the thyroxine group was significantly different from the normal and control groups. Thus, the decrease of resorptive lesions in the thyroxine group seemed correlated to a change in the bone modeling process, especially as related to the resorption activity.

Alkaline Phosphatase↗

Anticipation in Swedish families with bipolar affective disorder.

Anticipation describes an inheritance pattern within a pedigree with an increase in disease severity or decrease in age at onset or both in successive generations. The phenomenon of anticipation has recently been shown to be correlated with the expansion of trinucleotide repeat sequences in different disorders. We have studied differences of age at onset and disease severity between two generations in 14 families with unilinear inheritance of bipolar affective disorder (BPAD). There was a significant difference in age at onset (p < 0.008), in episodes per year with (p < 0.006) and without (p < 0.03) lithium treatment, and in total episodes per year (p < 0.002) between generations I and II. Furthermore, there was a highly significant correlation (p < 0.001) in age at onset between generations I and II. No evidence for specific paternal or maternal inheritance was found. We found evidence of anticipation and could rule out ascertainment bias or some other artefact. Anticipation is thus an inheritance pattern in BPAD which suggests that the expansion of trinucleotide repeat sequences is a possible mode of inheritance in BPAD.

Adolescent↗