| 11. |
- Hensing, Gunnel
(författare)
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Sickness absence and psychiatric disorder : epidemiological findings and methodological considerations
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psychiatric disorder is an important health problem among people of working age, with consequences for work capacity and sickness absence. Increased knowledge of sickness absence and psychiatric disorder is important for early detection of psychiatric disorders and appropriate rehabilitation measures.The occurrence of psychiatric sick-leave (sick-leave spells >7 days) during the years 1985, 1986 and 1987 was analysed in the county of Östergotland (400 000 inhabitants). Women working in male-dominated occupational groups, such as industrial work and as craftsmen, had the highest incidence. Men working in extremely female-dominated occupational groups, social workers and secretaries, had the highest incidence among all men. Occupational groups with an equal sex distribution had the lowest psychiatric sick-leave. More women were sick-listed, but men had more sick-leave days. There were small sex differences in the pattern of sickleave diagnosis.The role of psychiatric disorder for sick-leave in all diagnoses (not only psychiatric) was analysed in a stratified sample of 292 women selected from a population-based study of the female general population ofGoteborg (425 000 inhabitants). Women with psychiatric disorders according to a research interview had higher general sickness absence over ten years (1981-1990) both regarding spells and length, also when stratified for age, functional capacity, physical health, marital status, motherhood and socio-economic group. Single women with children did not have any increased sick-leave unless they had a psychiatric disorder. Women with psychiatric disorders also had an increased number of sick-leave days in diseases of the locomotor system, the digestive system and in mental illness. Women with alcohol problems had high sick-leave due to· diseases of the locomotor system. Eighty-nine per cent of the women with psychiatric disorders were sick-listed at least once 1989-1990 but only 16% were sick-listed with mental illness. Unrecognised psychiatric disorder is suggested as an explanation.In the methodological studies, critical evaluations of population at risk, sick-leave measures and estimation of person-time were made. Five sick-leave measures; frequency, length, duration, cumulative incidence and incidence rate, were defined and tested in a pilot study. Results from the pilot study showed that women with 1-7 sick-leave days over a year had a better self-reported health than women without any sick-leave and those with more than 8 days. Methods for assessing recurrency, duration and intensity within an epidemiological framework need to be developed.In conclusion, psychiatric disorder is an important factor in sickness absence, especially in the number of sick-leave days. The relation between psychiatric morbidity, environmental factors and individual coping behaviour for sickness absence is not clear, and further research is needed. Epidemiological and clinical research from a gender perspective is needed, with a focus on the health care and the social insurance systems. Prevention and rehabilitation programs should focus on the interplay between somatic illness, mental health and the use of health services and the sickness insurance.
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| 12. |
- Hermanson, Ola
(författare)
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Molecular mechanisms of nociception in the rat brain : anatomical connections and trans-synaptic regulation of gene expression of neurons in the pontine parabrachial nucleus
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pontine parabrachial nucleus (PB) is a major recipient of fibers fromnociceptive (pain-responsive) spinal and trigeminal dorsal horn neurons. With the use of combinations of molecular and morphological techniques, the anatomical connections of PB neurons and their expression of neuropeptide genes and transcription factors were studied, both in naive rats and in rats that had been subjected to nociceptive stimulation.A large number of neurons in PB expressed preproenkephalin mRNA(ppENK), which implies that these neurons synthesize the opioid enkephalin. One region of PB, the internal lateral subnucleus, contained many ppENKexpressing neurons that projected to the thalamic intralaminar nuclei, suggesting a role for these neurons in attentional mechanisms. Another region, the Kölliker-Fuse subnucleus (K-F), contained many ppENK-expressing neurons with descending projections to regions in the ventral medulla and spinal cord involved in pain control and autonomic modulation. The ppENKexpression in K-F increased after nociceptive stimulation of the neck or tail, suggesting that supraspinal opioidergic neurons with descending projections are activated by pain stimuli.Stimulation of the K-F region has been shown to elicit analgesia inanimals and humans. This analgesia has previously been ascribed to theactivation of noradrenergic neurons located in and close to K-F (the A7 cell group). Double-labeling procedures demonstrated that the ppENK-expressing neurons constituted a separate, much larger population, interspersed with the noradrenergic neurons. Thus, analgesia elicited by stimulation of K-F must involve the activation of opioidergic neurons.In search for the intracellular proteins that mediate the noxious-inducedup-regulation of ppENK, the expression of FOS in PB was studied after various types of nociceptive stimulation. FOS expression is low in PB of the naive animal, but FOS is rapidly produced after trans-synaptic activation, and it can bind to the DNA site that regulates ppENK transcription. However, noxiousevoked FOS was predominantly expressed in ppENK-negative neurons in PB. Another protein, CREB, can also regulate ppENK transcription. Therefore, the expression of active, phosphorylated, CREB was investigated in PB after nociceptive stimulation and was found to be present in the majority of theppENK-expressing neurons in K-F and the internal lateral subnucleus. These findings suggest that phosphorylation of CREB can mediate noxious-induced up-regulation of ppENK transcription in PB.Following nociceptive stimulation of the neck, tail, and hindlimb, most ofthe FOS was found in the dorsal and the superior lateral subnuclei of PB. The results suggest that neurons in these subnuclei are activated trans-synaptically by a direct spinal nociceptive input. The expression of FOS in PB after nociceptive stimulation of the face was found to be different from that seen after nociceptive stimulation of other parts of the body. Most of the FOSexpressing neurons were now detected in K-F, the external lateral, and the external medial subnuclei. This result is coherent with the termination pattern of fibers from the trigeminal dorsal horn, and suggests that neurons that are activated by nociceptive stimulation of the face have other functions than those activated by stimulation of other regions.Since FOS can bind to the ppCCK gene and regulate cholecystokininproduction, the parabrachial expression of preprocholecystokinin mRNA(ppCCK), which encodes the neuropeptide cholecystokinin, was investigated. Many ppCCK-expressing neurons were present in the superior lateral subnucleus, and these neurons displayed FOS after noxious stimulation. In addition, many ppCCK-expressing neurons in PBsl displayed the second messenger Ca2+/calmodulin-dependent kinase Il (CaMKII) and, after noxious stimulation, phosphorylated CREB. These findings point to a putative intracellular route for noxious-induced calcium-mediated regulation of ppCCK transcription through FOS induction via CaMKII and CREB. The ppCCKexpressing neurons in the superior lateral subnucleus were shown to project to the ventromedial hypothalamic nucleus, suggesting that they influence blood glucose homeostasis as a response to tissue damage.In search for a neuropeptide that is expressed by noxious-activated(FOS-1abeled) neurons in the dorsal lateral subnucleus, the preprodynorphin mRNA (ppDYN) expression was investigated. ppDYN encodes the opioid dynorphin, and the transcription of ppDYN can similar to other neuropeptide genes be regulated by the FOS protein. The dorsal lateral subnucleus was rich in ppDYN-expressing neurons, and many of the ppDYN-expressing neurons contained FOS, which implies that they are activated by nociceptive stimulation. The ppDYN-expressing neurons were found to project to the hypothalamic median preoptic nucleus, suggesting an involvel)lent of these neurons in cardiovascular regulation.In summary, the present study demonstrates that both opioidergic andnon-opioidergic neurons in a brainstem region, PB, are trans-synapticallyactivated by nociceptive stimulation in the awake rat. It is shown thatnociresponsive neurons in PB are organized in distinct cell groups that display different anatomical connections, intracellular signaling mechanisms, and gene expressions, suggesting different functions for these cell groups. It is suggested that nociresponsive parabrachial neurons influence the tuning and excitability of autonomic reflex circuits as part of an integrated response to tissue damage.
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| 13. |
- Hildén, Jan-Olof
(författare)
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Anti-D antibodies : In vitro tests to predict the severity of hemolytic disease of the newborn
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ability of different in vitro tests to predict the severity of hemolytic disease of the newborn (HDN) has been studied. When properly performed the traditional indirect antiglobulin titers (IAT) on maternal serum can be used to identify a low !iter group ~32 in which the fetus will not suffer from severe hemolytic disease and a high titer group ~1000 where all newboms will be affected. However, in the titer interval64-512, the prediction by IAT titers is poor and additional tests are needed. Widely used are determination of the anti-D concentration in maternal serum and measurement of the bilirubin concentration inamniotic fluid, the latter requiring amniocentesis (AMC). The negative predictive value using bilirubin measurements was 0.53 and using anti-D concentration determination 0.73. This shows that no further information is gained by adding amnion fluid examination if anti-D concentration determination is carried out. Moreover, as invasive procedures such as AMC may be dangerous to the fetus, it is preferable to use measurements of anti-D concentration, requiring only a venous blood sample from the mother. AutoAnalyzers have been used for 25 years and are still the main instrument for determining anti-D concentration. As this test is important in the prediction of HDN, there is an obvious need for a modern and reliable method of anti-D quantitation. A new method using flow cytometry was developed and found to give exactly the same classification as the AutoAnalyzer in 89% of cases. In the !I% that differed, the flow cytometer found more relevant cases than the AutoAnalyzer. The IgG subclass of the maternal anti-D can be of importance for the outcome in the newborn. To perform IgG subclassing of anti-D, a method using the gel technique was elaborated. Among severely affected cases, two or more subclasses were detected in 77%, compared to 20% in moderately or unaffected cases. When used as a complementary test in borderline cases having anti-D concentrations 0.6-1.4 jlg/mL_, no cases at risk of HDN would be missed and cases where additional invasive procedures must be performed would bereduced by about 60% (in the present series from 22to 9). HLA typing revealed the HLA DQB 1 a!lel *020 I to be four times more common in women with severe immunizations than in those with low levels of anti-D. Typing for this allel may be a means of identifying women with a high risk of developing severe immunizations.
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| 14. |
- Johansson, Uno
(författare)
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Heavy metal-induced activation of the murine immune system and autoimmunity : a comparative study of mercury and silver
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The activation and proliferation ofT- and B-cells induced by treatment with mercuric chloride (HgC12) or silver·nitrate (AgN03) was studied in mouse strains genetically susceptible (SJL, A. SW, A.TH, BALE/C) or resistant (A.TL, BALB.B) to induction of antinucleolar antibodies (ANoA) and systemic immune-complex (I C) deposits. SJL mice homozygous for the nude (nu) mutation were severely T-cell deficient. Neither these athymic SJL mice, nor euthymic SJL mice in which T-helper (CD4+) cells were eliminated by antiCD4 MAb treatment, developed ANoA or systemic IC-deposits in response to HgCI2 . Once induced, serum ANoA were not suppressed by 7 weeks high-dose anti-CD4 MAb therapy. This shows that chronic autoantibody (ANoA) production is relatively independent of CD4+ cells, and indicates that anti-CD4 MAb therapy should be given early in the course of autoimmune conditions in order to be efficient. A single subcutaneous injections ofHgCl2 induced after 4-5 days in the susceptible strains a shortlived increase in cells producing IL-2, TNF-a., IFN-y and ll.,-4, but resulted in neither immune activation nor ANoA. Subcutaneous injections ofHgC12 every third day induced on day 4-5 in the A. SW strain an activation ofT-cells with upregulation of the IL-2 receptor, an increase in IL-2- producing cells (IL-2'), and proliferation of CD4' and CD8' cells. While TNF-a' and IFN-"( cells were modestly increased on day 4 -6, IL- 4' cells dominated on day 8-10. In the susceptible SJL strain, constitutionally deficient in early IL-4-producing, Th2-promoting CD4' NKl.l' cells, IFN-y cells dominated on day 8-10. TheA.SW strain showed a doubling ofB-cells on day 14, whereas theincrease in B-cells was smaller and did not appear until day 28 in the SJL strain. Serum levels of both Th1- and Th2-dependent Ig isotypes were significantly increased after 2-4 weeks HgC12 treatment. Serum anti-ssDNA and anti-DNP antibodies of the IgM and IgG class, which are indicators of a polyclonal B-cell activation, reached a maximum in A.SW and SJL mice after 2-4 weeks treatment and then decreased. Serum ANoA, exclusively of the IgG class, first appeared after 2 weeks HgCl2 treatment in these mice, reached a maximum titre after 4 weeks, but remained increased for the next 16 weeks in both A. SW and SJL mice. Since ANoA and systemic IC-deposits developed in response to HgC12 irrespectively if a strain showed a dominance of Th2/IL-4 or Thl/ IFN-y, we found no support for the hypothesis that murine mercury-induced autoimmunity is linked to a Th2-dorninant response. However, mice with a Th2-donrinant response showed a stronger and more rapid B-cell activation than mice with a Thl -dominated response. TheA.TL and BALB.B strains showed neither activation of the immune system, nor signs of systemic autoimmunity after treatment with HgCl2. AgN03 caused in the susceptible strains less activation and proliferation of T and B cells than HgC12, and no polyclonal B-cell activation. However, the ANoA titre was not significantly different from that in HgClrtreated mice. This shows that a strong activation of the immune system with a polyclonal B-cell response, as seen in mercury treatment, is no prerequisite for development of ANoA, lending support for the importance of autoantigen-specific mechanisms in mercury- and silver-induced autoimmunity. Implantation of silver amalgam fillings, dominated by silver and mercury, in the peritoneal cavity of SJL mice caused an accumulation of mercury and silver in the internal organs, chronic stimulation of the immune system, ANoA and systemic IC-deposits in a dose- and time-dependent manner.
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| 15. |
- Juthberg, Sonya K. A.
(författare)
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Ion Transport in Glial and Neuroblastoma Cells
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis has been to increase our understanding of the ion channel function and the ion transport mechanisms in glial cells. The analysis has also covered Na channel function in human neuroblastoma cells in order to get a basis for similar studies of glial cells In paper I isotopes 42K and 201 Tl were used to compare the K+ transport properties in cell lines from human malignant gliomas (U-251MG and Tp-378MG), carcinomas, and brain metastasis. In papers II and Ill the patch-clamp technique has been used in studies of the membrane potential and K+ conductance in human glioma cells (U-251MG) and in astrocytes of primary cultures from newborn rats. Paper IV is a patch clamp analysis of the Na+ channel voltage dependence in a human neuroblastoma (SK-N-SH) and esthcsioneuroblastoma (Tp-410) cell line.From these studies it was concluded that:(1) Cultured human glioma cells have a high specific K+ and Tl+ uptake of which approximately 90% is carried by Na,K-ATPase-dependent transport and Na-K-Cl cotransport. Inwardly rectifying K+ channels seem to have little importance for the K+ -uptake, at least in isolated cells.(2) The membrane potential in rat astrocytes hyperpolarizes while human glioma cells depolarize in low concentrations of K+. This difference may be related to the effect of K+ on inwardly rectifying K+ channels which were present in higher density in human glioma cells.(3) ca2+ free solutions depolarize the cells which seem to involve a transformation of K+ channels to unspecific leakage channels in rat astrocytes. The depolarization caused by Ba2+ was explained by a block of K+ channels.(4) Metabolic inhibition with protonophores (DNP and FCCP) is associated with specific effects on the plasmalemma in rat astrocytes in addition to the inhibition of the cellular ATP production. These agents should therefore be used with caution in studies of energy dependent mechanisms at the cellular level.(6) Neuroblastoma SK-N-SH cells and esthesioneuroblastoma Tp-410 cells have prominent Na+ currents. Both activation .and inactivation of the Na+ channels differed in their time and voltage dependence between these two types of neuroblastoma ce11s.
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| 16. |
- Kald, Anders
(författare)
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Audit of groin hernia repair
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inguinal hernia repair is the most frequent procedure in general surgery. In the USA approximately 700,000 groin hernioplasties are carried out annually and accounts for almost US$ 3 billion in annual health care revenue. In Sweden approximately 20,000 hernia operations are performed annually and more than 3,000 of them are recurrent hernias. The renewed interest in cost-effectiveness and the introduction of new techniques, among them laparoscopic surgery, underlines the importance of quality assurance in hernia surgery. The aim of this thesis was to establish an audit of hernia surgery in a defined population allowing evaluation of management, riskfactors, outcome and economy. The method of control and definition of recurrence was studied. When recurrence was classified as "a weakness in the operated area necessitating a further operation or provision of a truss", the predictive value for postitive (recurrence) and negative (no recurrence) answers in the questionnaire was 38 and 99%, respectively. Thus, by using a questionnaire to identify symptomatic recurrences only a minority of the patients (10%) had to be examined at a follow-up . A study of eight Swedish hospitals showed that it is possible to include more than 99% in a medical audit of hernia operations within the frame-work of routine registration. In a three-year follow-up study of these hospitals, the total recurrence rate was 9.6% with an interhospital variation between 3.1 and 20.5%. Postoperative complications, direct hernia and recurrent hernia were factors associated with an increased risk for recurrence. The re-operation rate for recurrence may be an appropriate surrogate endpoint, although this underestimates the real recurrence rate by approximately 40%. An audit scheme based on prospective registration, annual analysis of outcome, regular use of questionnaire and selective follow-up, can identify significant inter hospital differences in outcome as well as variables associated with increased risk for recurrence, thereby raising quality awareness and facilitating the process of improvement. The introduction of a new technique, laparoscopic hernia repair, was studied in one of the units participating in the overall prospective registration. Two surgeons performed over 90% of the operations. After an initial period with 6 recurrences in the first 31 patients (recurrence rate 22.6%), the results improved and only one recurrence was diagnosed in the following 395 patients who underwent 360 transabdominal and 98 totally extraperitoneal repairs (recurrence rate 0.2%) with a mean (SD) follow-up of 19 (10) months. In the treatment of recurrent hernias a tenfold difference in recurrence rate was obtained by one unit using the laparoscopic approach with a preperitoneal mesh, compared to the three-year follow-up results from the eight hospitals studied. Laparoscopic hernia repair was cost-effective compared to the Shouldice operation among employed patients, due to faster recovery, provided that hoth direct and indirect costs were included. If laparoscopic herniarepair is considered the totally extraperitoneal operation should be used because of the risk for serious intraabdominal complications with the transabdominal technique.
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| 17. |
- Källman, Jan, 1958-
(författare)
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Group B streptococcal infections in neonates : Clinical and pathogenic aspects
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Clinical and pathogenic aspects of Group B streptococci (GBS), as a major pathogen responsible of invasive disease in newborn infants, were investigated.Cases of neonatal septicaemia during 1981-1994 were studied at Orebro Medical Centre Hospital. 132 children ful1filled laboratory and clinical criteria for neonatal septicaemia. The annual incidence increased significantly, from 2.3 cases during the first 7-year period to 3.3 per 1000 live births during the second 7-year period. The increase in incidence between the two 7- year periods was almost entirely due to an increase in Staphylococcus aureus ( from 9 to 32, pTo study the ability of GBS to adhere to the target cell, a cell-culture model with human umbilical vein endothelial cells (HUVEC) was used. Clinical isolates of serotype Ill adhered significantly (p=O.OOOl) better than other serotypes. Isogenic variants of serotype Ill with low amounts of capsule substance adhered significantly (p=O.OOl) better to the HUVEC than variants expressing high amount of capsule substance. The role of GBS capsular substance as a major virulence factor is further underlined by the fact that it impair the phagocytic capacity by polymorphonuclear leukocytes (PMNL). Growth conditions for GBS, simulating different in vivo environments, greatly affect capsule expression.The extent of and the penetration route of GBS over epithelial linings was examined with a model using Madin Darby Canine Kidney cells (MDCK). It was demonstrated that GBS can penetrate intact polarized MDCK cells by transcytosis in a selective apical-to-basolateral direction and the mechanism for this is metabolically dependent.In a chemiluminescence assay (CL), PlviNL function and opsonic capacity were shown to be significantly impaired in neonates and correlate to maturation of the newborn child. This combined defect in cellular and humoral defences may contribute to the increased susceptibility to GBS infection in preterm infants.In a prospective study in newborn having suspected sepsis, IL-6 and C-reactive protein (CRP) were measured early. Early-sampled IL-6 levels were significantly better than early-sampled CRP levels in distinguishing between mild respiratory disorders and septicaemia in the newbom child.
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| 18. |
- Leckström, Arnold
(författare)
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Islet amyloid polypeptide : Perspectives on the storage and plasma concentration of islet amyloid polypeptide (IAPP) in rodent models of obesity and non-insulin-dependent diabetes mellitus and aspects of amyloidogenesis andelimination of IAPP
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present study was aimed to investigate plasma concentrations and pancreatic storage of IAPP in relation to that of insulin in four different animal models with hyperglycemia, hyperinsulinemia, obesity and/or NIDDM. The NMRI mice fed a high-fat diet for six months, the Psammomys on high-energy (HE) diet and the genetically obese (ob/ob) mice studied for one year all revealed significantly elevated plasma IAPP concentrations, while the IAPP levels were unchanged in the spontaneously diabetic GK rats during a glucose tolerance test.In the NMRI mice the fasting plasma glucose and insulin concentrations had also increased, suggesting a possible development of insulin resistance. The increase in plasma IAPP concentrations was even greater than that of insulin, which was reflected in an increased plasma IAPP/insulin molar ratio.The Psammomys developed obesity, hyperinsulinemia and hyperglycemia in response to the HE diet. The plasma IAPP concentration was also elevated, but changed in parallel with that of insulin. After vanadyl sulphate treatment the glucose and insulin concentrations were normalized, while IAPP remained elevated.The OK rats showed significantly decreased plasma concentrations of IAPP and insulin during the glucose tolerance test. The insulin response to the glucose load was even lower than that of IAPP, resulting in a modest elevation of the plasma IAPP/insulin ratio. The elevated IAPP/insulin ratios in these three animal models might reflect a negative feedback effect of IAPP on insulin release.In the ob/ob mice the plasma glucose concentration was initially greatly elevated, but had by the end of study returned to almost normal, presumbly due to the tremendous increase in hyperinsulinemia. The plasma IAPP concentration reached extremely high levels, which however was relatively low to that of insulin, resulting in a sudden significant decrease in the plasma IAPP/insulin ratio at 21 weeks of age, possibly indicating a deficiency in the negative feedback effect of IAPP on insulin secretion.IAPP-immunoreactivity was detected in the morning urine of healthy human volunteers and was by reverse phase HPLC-analysis confirmed to be identical to full-length IAPP. This finding gives strong support to the previous suggestions that IAPP is eliminated by the kidneys, why slight disturbances in plasma TAPP/insulin ratios in dynamic situations (as e.g. in the GK rat) should be carefully interpreted.
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| 19. |
- Lönn, Urban
(författare)
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A minimally invasive axial blood flow pump : an experimental and clinical study
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first aim of this thesis was to evaluate a new minimally invasive axial blood flow pump for treatment of patients needing circulatory support after open heart surgery. This system, the Hemopump temporary cardiac assist device, is a very small catheter mounted intracorporeal pump, which is introduced transvalvularly into the left ventricle. The pump can be inserted either through the femoral artery or directly through a graft sutured to the ascending aorta. In an experimental model, the flow capacity of three different designs of the system was investigated. Flow capacity varied between 2.0 and 4.5 liters per minute, depending on the working conditions for the different pump models. Twenty,four patients were treated for post,cardiotomy heart failure. Fourteen patients (58 %) were weaned from the device and later discharged from the hospital. In a subgroup of these patients (54%) where early intervention was instituted, the survival rate was 85%. The pump proved to be an effective tool for unloading a failing left ventricle with preservation of multi-organ perfusion. A clinical protocol was established for postoperative management. The Hemopump was easy to adapt to the clinical setting, and device~ related complications were few.The second aim was to develop a new less invasive procedure for CABG, avoiding the need for cardio~pulmonary bypass during these procedures. First an animal trial was performed as a feasibility study. In combination with the administration of a short~acting ~~blocker, esmolol, this method enabled precise coronary bypass surgery. When results became consistent a small pilot study was done on five patients showing that this was a reproducible technique. Finally a prospective randomized trial comparing this technique with conventional bypass surgery was carried out. The Hemopump supported bypass surgery did not prolong the procedure, did not require a longer time on circulatory support and bleeding was less. Postoperative enzyme levels indicated that ischemic insult to the myocardium was less than with conventional surgery.In summary, this minimally invasive axial blood flow pump proved to be a powerful left ventricular assist system enabling a less invasive approach during conditions where circulatory support is needed.
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| 20. |
- Mølgaard, Jørgen
(författare)
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Intermittent Claudication : Prevalence and metabolic risk factors
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of intermittent claudication (IC) in middle-aged men (45-69 years old) and metabolic risk factors for this disease was studied in a Swedish community. All 15 253 middle-aged male residents in Linköping community, were screened for symptoms of IC using a postal questionnaire, which included detailed questions about smoking habits and presence of hypertension and diabetes mellitus.The overall response rate was 86.6% (n=l3 209). The prevalence of walking-related pain was 9.3% (n=l232), and 4.2%(n=552) had symptoms consistent with peripheral atherosclerotic disease (PAD). All men with leg symptoms according to the classical Rose criteria for IC (1.2%, n=156), and a sample of subjects (0.6%, n=84) with symptoms indicating PAD, but not fully complying with the Rose c.riteria, were invited for further examination.Subjects with IC were compared with randomly selected sex- and age-matched controls from the same population. One control group was matched for smoking habits (n=157), and one control group consisted of never-smokers (n=143). Both claudicants and healthy controls underwent objective examination of the peripheral circulation with segmental blood pressure measurements and a short treadmill exercise test.IC could objectively be verified in 1.7% (n=219) of all middle-aged men. The prevalence of IC was highly age-dependent and objectively verified IC increased from 0.2% in males 45-49 years old to 3.4% in those 65-69 years old. The prevalence of Rose IC was 0.5% for 45-49 year-old males and 2.0% for 65-69 year-old males. Thus the Rose criteria underestimated the prevalence ofiC in the older age group and overestimated it in the youngest age group. The estimated true average prevalence ofiC was at least 2.8%.More than half (57%) of all claudicants had ischaemic heart disease, and 21% had experienced a TIA or stroke.The metabolic studies investigated the role of dyslipidaemia and various metabolic abnormalities as risk factors for IC. Claudicants had multiple minor and moderate lipid and lipoprotein abnormalities, the strongest association being with elevated plasma levels of low-density lipoproteins (LDL) cholesterol and low levels of high-density lipoproteins (HDL) cholesterol, after multivariate adjustment for other major risk factors, i.e. hypertension, diabetes mellitus and smoking, and other factors that influence lipid levels. Ve1y-low-density lipoproteins (VLDL) triglycerides had a high univariate association, but did not contribute to risk for IC after multivariate adjustment for the above factors.Plasma lipoprotein (a) [Lp(a)] showed a strong association with risk for IC, which in part could be explained by a significant overrepresentation of small apo(a) isoforms, genetically associated with higher Lp(a) concentrations.Plasma a- and ~-carotene, Iycopene and retinol, but not a- or y-tocophcrol (vitamin E), showed a multivariate significant association with risk for IC in men. However, when dietary data had been accounted for, only the significance of plasma retinol remained. Lower plasma levels of lipid-soluble antioxidants after adjustment for lipid concentrations may be secondary to the atherosclerotic disease. Moderately elevated levels of plasma homocyst(e)ine, a su\fbydryl-containing amino acid with a known atherogenic potential, were significantly associated with risk of IC after adjustment for other risk factors in multivariate analyses.In conclusion, the risk for IC amongst middle-aged males was significantly associated with presence of both major traditional risk factors such as smoking (96%), hypertension (49%), diabetes mellitus (18%) and additional metabol~c risk factors such as dyslipidaemia, hypcrhomocyst(e)inaemia and elevated Lp(a) levels. Plasma levels of tocophero!s (vitamin E) were not associated with risk for IC. Carotenoids do not seem to contribute, whereas the role of plasma retinol remains unclear.
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