Studies on Venous Function after Deep Venous Thrombosis

Background The incidence of deep venous thrombosis (DVT) is estimated to be about 1-2/1000 per year of which approximately 4 % are located in the arm veins. Some of the most important late effects of a DVT are chronic venous dysfunction and the development of post-thrombotic syndrome (PTS). Objective diagnosis with detailed information on disease extent and location and global venous function is often important for clinical management of the patient. Color duplex ultrasonography (CDU) and computerized strain-gauge plethysmography (CSGP) are currently available non-invasive methods to study venous function after earlier DVT. Aims The aim of this thesis was to study venous function after earlier deep venous thrombosis assessed by CDU and CSGP; to study how findings with those methods are related to long-term sequelae, and development of postthrombotic diseases after different types of DVT. Study I and II These studies were performed to assess the efficiency of CSGP for evaluation of venous outflow capacity of the upper extremities, to receive reference values and to describe venous function using CSGP and CDU in patients with earlier primary upper extremity deep venous thrombosis (UEDVT). Thirty-four healthy controls and 32 patients with earlier UEDVT were included. The results showed that CSGP is easy to handle and can be used in a reproducible way to study venous function in the upper extremities. CSGP reference values were established for upper extremities. Patients with earlier UEDVT had reduced venous outflow, residual thrombus was a common finding, and one third had a moderate grade of PTS. CSGP and CDU are useful methods that can provide objective information regarding venous function after UEDVT. Study III This study was performed to determine whether asymptomatic deep venous thrombosis (ADVT) following minor surgery affects venous function and contributes to development of PTS. Eighty-three patients operated for Achilles tendon rupture were included; 38 patients with postoperative ADVT and 45 patients without (control group). The follow-up examinations five years after the operation consisted of CSGP, CDU and clinical scoring. More than 50 % of patients with ADVT developed post-thrombotic changes according to CDU, but these changes did not affect global venous function. Eight percent of ADVT patients and 4 % of control group patients developed PTS. Therefore, PTS is not a common sequel to ADVT after minor orthopaedic surgery. Study IV This follow-up study included 83 patients with postoperative DVT examined after a mean of 7 years. There was two series of patients, 45 with symptomatic deep venous thrombosis (SDVT) and 38 with ADVT. The objective was to describe long-term effect of SDVT and ADVT on venous function and subsequent incidence of PTS in patients operated for Achilles tendon rupture. Examinations comprised CSGP, CDU and clinical scoring. The results showed that post-operative DVT after minor surgery consists mainly of distal DVTs and is associated with a low risk for PTS, found in approximately 10 % of the patients. Deep venous reflux was more common in SDVT than in ADVT patients (84 % vs. 55 %). Abnormal plethysmographic results were seen in only a few patients without difference between the two groups. This indicates that DVT provoked by minor orthopaedic surgery represents a transient risk factor with minor long-term sequelae. In summary This thesis concerns studies of venous function and evaluation of clinical sequelae and frequency of PTS in patients with previous primary upper extremity DVT and in patients with postoperative DVT following minor orthopaedic surgery. In general, these studies show that the clinical signs as well as symptoms stated by the patients in these types of DVT are rather non-specific and often consist of pain, paresthesias, cramps, swelling and functional impairment. Therefore, in addition to the clinical examination, objective assessment of venous function and evaluation of the extent of disease are of value. Ultrasonograhy and plethysmograpy are non-invasive tests that can be used for this purpose

Environmental Assessment of Brine Discharge Including Wastewater Collection in the Arabian Gulf

The environmental effects of brine discharge in the Arabian/Persian Gulf have been assessed. The Arabic Gulf is a wide and shallow system having a horizontal shear dominance. The management choice of mixing brine with wastewater to reduce the salt content in the discharge has also been considered. Approximately 90% of the area around the Arabian Gulf has been compared with the world data for desalination and population growth rate. The Arabian Gulf region is occupying about 3.3% of the world area and 1.0, 2.0 and 2.2% of the total world population in the years 1950, 2008 and 2050 respectively. The annual population growth rate during the whole period is approximately 1.30 in the world and 2.07 in the area studied. The results for the study area were obtained from desalination capacities that are about 50, 40 and 45% of total world capacity for the end of 1996, 2008 and 2050 respectively.The increased recovery ratio in desalination plants over the years was considered as one important environmental factor. At the end of 1996 it was about 30 to 35% and 2008 about 40 to 45%. In some countries it can reach 50%. This development will significantly increase the brine salt concentration from 1.5 to more than 2 times seawater and negatively affect the receiving water. Water and salt mass balance were used to calculate residual flow, exchange flow and exchange time of the Arabian Gulf. For example at zero wastewater discharge and from 1996 to 2008, the net volume has decreased by the amount of 7.4 millions m3/day, exchange volume increased by 69 millions m3/day and the mixing time decreased with 22.5 days. For the next 42 years from 2008 until the year 2050 the calculation shows a decrease in the net volume by 48.7 millions m3/day, an exchange volume increase by 424 millions m3/day and a mixing time decrease of about 126 days. The more desalted water that is collected from the Gulf, the higher remaining salinity is found in the Gulf.With higher salinity in the Gulf, the exchange between the Gulf and the Indian Ocean will increase. Mixing brine with wastewater dampens the water and salt exchange between the Gulf and the Indian Ocean. This method will however also minimize the water that is coming from ocean to the Gulf. The content of nutrients in wastewater is positive for irrigation but with only secondary treatment problems like eutrophication in the Gulf may be increased if the exchange of water is low

Hemodynamic and morphologic evaluation of sequelae of primary upper extremity deep venous thromboses treated with anticoagulation

ObjectivesThis study was performed to describe venous function, residual morphologic abnormalities, and the occurrence of post-thrombotic syndrome in patients with conservatively treated primary upper-extremity deep venous thromboses (UEDVT).MethodThis was a retrospective follow-up study of 31 patients with previous primary UEDVT treated with anticoagulation only, identified by a search of medical records. The mean follow-up time was 5 years. The patients were evaluated by interview, clinical examination, computerized strain-gauge plethysmography, and color duplex ultrasound imaging. The grade of post-thrombotic syndrome was rated according to the Villalta score (0 to 3 on each of four subjective and five clinically assessed features).ResultsThe rate of venous emptying was significantly lower in the arms with DVTs than in the contralateral arms (P < .001). Eleven of the patients (35%) had a remaining outflow obstruction in the affected arm (venous emptying <68 mL/100 mL per min). Eighteen (58%) had a residual thrombus according to color duplex ultrasound scans, with four remaining occluded subclavian veins. None of the patients had deep or superficial venous reflux. There was no statistically significant relationship between plethysmographic and duplex findings. Most (77%) of the patients reported remaining symptoms in the affected arm, and there was a significant side difference in upper arm circumference (P < .001). Approximately one third had developed a moderate grade of post-thrombotic syndrome according to the Villalta score (total, 5 to 9). No significant relation was evident between the post-thrombotic syndrome score and duplex findings. Patients with post-thrombotic syndrome had a lower venous emptying value than those without (69 vs 84 mL/100 mL per min), but this difference was not statistically significant.ConclusionsPatients with conservatively treated previous primary UEDVT had significantly reduced venous outflow capacity and a residual thrombus was common. Swelling of the arm was the most common symptom, and one third had a moderate grade of post-thrombotic syndrome. However, there was no clear relation between hemodynamic and morphologic factors and the development of post-thrombotic syndrome in these 31 patients, examined at a mean of 5 years after an acute DVT episode

A follow-up study of the fate of small asymptomatic deep venous thromboses

<p>Abstract</p> <p>Background</p> <p>Postoperative asymptomatic deep venous thromboses (ADVT) can give rise to posttthrombotic syndrome (PTS), but there are still many unresolved issues in this context. For example, there is a lack of knowledge regarding the fate of small ADVT following minor orthopedic surgery. This follow-up study evaluates postthrombotic changes and clinical manifestations of PTS in a group of patients with asymptomatic calf vein DVT after surgery for Achilles tendon rupture.</p> <p>Methods</p> <p>Forty-six consecutive patients with distal ADVT were contacted and enrolled in a follow-up consisting of a single visit at the hospital at a mean time of 5 years postoperatively, including clinical examination and scoring, ultrasonography and venous plethysmography. All patients had participated in DVT-screening with colour duplex ultrasound (CDU) 3 and 6 weeks postoperatively and 80% of them were treated with anticoagulation.</p> <p>Results</p> <p>With CDU postthrombotic changes and deep venous reflux were detected at follow-up in more than 50% of the patients, more commonly in somewhat larger calf DVT:s initially affecting more than one vessel. However, only about 10% of the patients had significant venous reflux according to venous plethysmography. No patient had plethysmographic evidence of remaining outflow obstruction, but presence of postthrombotic changes shown with CDU negatively influenced venous outflow capacity measured with plethysmography. A clinical entity of PTS was rarely found and occurred only in two patients (4%) and then classified by Villalta scoring as of mild degree with few clinical signs of disease. Distal ADVT:s detected in the early postoperative period (3 weeks) showed DVT-progression in 75% of the limbs that were still immobilized and without anticoagulation.</p> <p>Conclusions</p> <p>Asymptomatic postoperative distal DVT:s following surgery for Achilles tendon rupture have a good prognosis and a favourable clinical outcome. In our material of 46 patients the general appearance of the clinical entity of PTS at 5 years follow-up was low (<5%). Morphological and functional abnormalities were mainly seen in those patients that initially had somewhat larger distal DVT:s involving more than one deep calf vein segment.</p

Acquisition of complement fixing antibodies targeting Plasmodium falciparum merozoites in infants and their mothers in Uganda

BackgroundAntibody-mediated complement fixation has previously been associated with protection against malaria in naturally acquired immunity. However, the process of early-life development of complement-fixing antibodies in infants, both in comparison to their respective mothers and to other immune parameters, remains less clear.ResultsWe measured complement-fixing antibodies in newborns and their mothers in a malaria endemic area over 5 years follow-up and found that infants’ complement-fixing antibody levels were highest at birth, decreased until six months, then increased progressively until they were similar to birth at five years. Infants with high levels at birth experienced a faster decay of complement-fixing antibodies but showed similar levels to the low response group of newborns thereafter. No difference was observed in antibody levels between infant cord blood and mothers at delivery. The same result was found when categorized into high and low response groups, indicating placental transfer of antibodies. Complement-fixing antibodies were positively correlated with total schizont-specific IgG and IgM levels in mothers and infants at several time points. At nine months, complement-fixing antibodies were negatively correlated with total B cell frequency and osteopontin concentrations in the infants, while positively correlated with atypical memory B cells and P. falciparum-positive atypical memory B cells.ConclusionThis study indicates that complement-fixing antibodies against P. falciparum merozoites are produced in the mothers and placentally-transferred, and they are acquired in infants over time during the first years of life. Understanding early life immune responses is crucial for developing a functional, long lasting malaria vaccine

Development of lower limb range of motion from early childhood to adolescence in cerebral palsy: a population-based study

<p>Abstract</p> <p>Background</p> <p>The decreasing range of joint motion caused by insufficient muscle length is a common problem in children with cerebral palsy (CP), often worsening with age. In 1994 a CP register and health care programme for children with CP was initiated in southern Sweden. The aim of this study was to analyse the development of the passive range of motion (ROM) in the lower limbs during all the growth periods in relation to gross motor function and CP subtype in the total population of children with CP.</p> <p>Methods</p> <p>In total, 359 children with CP born during 1990-1999, living in the southernmost part of Sweden in the year during which they reached their third birthday and still living in the area in the year of their seventh birthday were analysed. The programme includes a continuous standardized follow-up with goniometric measurements of ROM in the lower limbs. The assessments are made by each child's local physiotherapist twice a year until 6 years of age, then once a year. In total, 5075 assessments from the CPUP database from 1994 to 1 January 2007 were analysed.</p> <p>Results</p> <p>The study showed a decreasing mean range of motion over the period 2-14 years of age in all joints or muscles measured. The development of ROM varied according to GMFCS level and CP subtype.</p> <p>Conclusion</p> <p>We found a decreasing ROM in children with CP from 2-14 years of age. This information is important for both the treatment and follow-up planning of the individual child as well as for the planning of health care programmes for all children with CP.</p

Cerebral palsy in a total population of 4–11 year olds in southern Sweden. Prevalence and distribution according to different CP classification systems

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the prevalence of cerebral palsy (CP) as well as to characterize the CP population, its participation in a secondary prevention programme (CPUP) and to validate the CPUP database.</p> <p>Methods</p> <p>The study population was born 1990–1997 and resident in Skåne/Blekinge on Jan 1^st2002. Multiple sources were used. Irrespective of earlier diagnoses, neuropaediatrician and other professional medical records were evaluated for all children at the child habilitation units. The CPUP database and diagnosis registers at hospital departments were searched for children with CP or psychomotor retardation, whose records were then evaluated. To enhance early prevention, CP/probable CP was searched for also in children below four years of age born 1998–2001.</p> <p>Results</p> <p>The prevalence of CP was 2.4/1,000 (95% CI 2.1–2.6) in children 4–11 years of age born in Sweden, excluding post-neonatally acquired CP. Children born abroad had a higher prevalence of CP with more severe functional limitations. In the total population, the prevalence of CP was 2.7/1,000 (95% CI 2.4–3.0) and 48% were GMFCS-level I (the mildest limitation of gross motor function).</p> <p>One third of the children with CP, who were born or had moved into the area after a previous study in 1998, were not in the CPUP database. The subtype classification in the CPUP database was adjusted in the case of every fifth child aged 4–7 years not previously reviewed.</p> <p>Conclusion</p> <p>The prevalence of CP and the subtype distribution did not differ from that reported in other studies, although the proportion of mild CP tended to be higher.</p> <p>The availability of a second opinion about the classification of CP/CP subtypes is necessary in order to keep a CP register valid, as well as an active search for undiagnosed CP among children with other impairments.</p

Insulin-like growth factor-I (IGF-I) and thioredoxin are differentially expressed along the reproductive tract of the ewe during the oestrous cycle and after ovariectomy

Insulin-like growth factor-I (IGF-I) and thioredoxin are regulated by gonadal steroids in the female reproductive tract of many species. Oestradiol regulates IGF-I and thioredoxin mRNA levels in the reproductive tract of prepubertal lambs. The physiological status (different endocrine environment) may affect the sensitivity of the reproductive tract to oestradiol and progesterone. We studied the effects of different endocrine milieus (late-follicular and luteal phases of the oestrous cycle, and ovariectomy before or after puberty) on the expression of IGF-I, thioredoxin, oestrogen receptor α (ERα) and progesterone receptor (PR) in sheep. The mRNA levels were determined by a solution hybridisation technique. In the uterus the levels of ERα, PR and thioredoxin mRNA were higher in the late-follicular phase group than in the other three groups, and IGF-I mRNA was high during both the late-follicular and the luteal phases. In the cervix only PR mRNA was significantly higher in the ewes in the late-follicular phase than in the other groups. In the oviducts the levels of thioredoxin and ERα mRNA were highest in the ovariectomised adult ewes, and thioredoxin mRNA was higher than the levels found in the ewes in the late-follicular phase. The IGF-I mRNA levels in the oviduct did not differ between any of the groups. The transcripts of IGF-I, thioredoxin, ERα and PR, varied according to the physiological status and also along the female reproductive tract, suggesting that the regulation of the mRNA levels of these factors by the steroid environment is tissue specific. Koncentrationen av insulin-like growth factor-I (IGF-I) och thioredoxin regleras hos många arter i honors reproduktionsorgan av könssteroider. Sålunda reglerar östradiol IGF-I och thioredoxin mRNA i reproduktionsorganen hos prepubertala lamm. Djurets fysiologiska status (dvs den endokrina miljön) kan påverka känsligheten hos reproduktionsorganen för östradiol och progesteron. Vi studerade effekterna av olika endokrina miljöer (sen follikelfas och lutealfas i östruscykeln, samt ovariektomi före och efter puberteten) på uttrycket av IGF-I, thioredoxin, östrogenreceptor α (ERα) och progesteronreceptorn (PR) hos får. Lösningshybridisering användes för att bestämma mRNA nivåerna. I livmodern var mRNA koncentrationen för ERα, PR och thioredoxin högre i sen follikelfas än i de andra tre grupperna och IGF-I mRNA nivån var hög både under sen follikelfas och i lutealfas. PR mRNA i cervix var signifikant högre hos tackorna under sen follikelfas än i de andra grupperna. I äggledarna var mRNA nivåerna av thioredoxin och ERα högst i de djur som ovariektomerats som vuxna, och thioredoxin mRNA var högre än hos tackorna under sen follikelfas. Det förelåg ingen skillnad vad gäller IGF-I mRNA nivåerna i äggledaren mellan någon av grupperna. IGF-I, thioredoxin, ERα och PR mRNA nivåerna varierade beroende på fysiologisk status och morfologisk lokalisation i reproduktionsorganen. Detta tyder på att steroidhormonernas reglering av dessa faktorers mRNA uttryck också är vävnadsspecifik