[Show abstract][Hide abstract] ABSTRACT: Background:
Congenital cryptorchidism, i.e. failure of the testicular descent to the bottom of the scrotum, is a common birth defect. The evidence from epidemiological, wildlife, and animal studies suggests that exposure to mixtures of endocrine disrupting chemicals during fetal development may play a role in its pathogenesis. We aimed to assess the association between cryptorchidism and prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs).
We conducted a case-control study consisting of 44 cryptorchid cases, and 38 controls operated for inguinal hernia, umbilical hernia, or hydrocele at the Turku University Hospital or Rigshospitalet, Copenhagen in 2002-2006. During the operation a subcutaneous adipose tissue biopsy was taken. Samples were analysed for 37 PCBs, 17 PCDD/Fs and 14 PBDEs by gas chromatography-high-resolution mass spectrometry. Chemical concentrations were adjusted for postnatal variation introduced by differences in duration of breastfeeding, age at the operation, and country of origin with a multiple linear regression. Association between adjusted and unadjusted chemical concentrations and the risk of cryptorchidism were analysed with logistic regression to get an estimate for odds ratio (OR) of cryptorchidism per multiplication of chemical concentrations with ca. 2.71 (Napier's constant).
Total-TEq i.e. the WHO-recommended 2,3,7,8-TCDD equivalent quantity of 17 dioxins and 12 dioxin-like PCBs and sum of PCDD/Fs were positively associated with cryptorchidism [OR 3.21 (95 % CI 1.29-9.09), OR 3.69 (95 % CI 1.45-10.9), respectively], when adjusting for country of origin, the duration the child was breastfed, and age at operation. The association between the sum of PCBs and cryptorchidism was close to significant [OR 1.92 (95 % CI 0.98-4.01)], whereas the association between the sum of PBDEs and cryptorchidism was not [OR 0.86 (95 % CI 0.47-1.54)]. There were no associations between unadjusted chemical concentrations and the risk of cryptorchidism.
Prenatal exposure to PCDD/Fs and PCDD/F-like PCBs may be associated with increased risk for cryptorchidism. Our finding does not exclude the possibility of an association between the exposure to PBDEs and cryptorchidism.
Environmental Health 09/2015; 14(1). DOI:10.1186/s12940-015-0065-0 · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The exact mechanisms by which mechanical loading-unloading affects bone tissue are mostly unknown. Recently, osteocalcin, a direct product of osteoblasts, has been shown to reflect the activity of the mineralization phase of the newly formed bone matrix, and therefore, the in situ detection of osteocalcin could be used for studying the effects of physical activity-inactivity on the osteoblast function or bone formation in the target bone. In this study, the effect of various loading states (immobilization and three forms of subsequent remobilization) on the in situ expression of osteocalcin in the rat patellas and their osteotendinous junctions was studied immunohistochemically using a polyclonal rat antiosteocalcin as the primary antibody. Following immobilization for 3 weeks, the immunoreactivity of osteocalcin was markedly decreased or was completely absent in all the patellar areas which normally show intense reaction as a sign of mineralization of the newly formed bone, that is, in the subperiosteal and subchondral regions, in the osteoid tissue that lies on the surface of the trabecular bone, and around the cortical lacunae. The same was true in the mineralized fibrocartilage zone of the osteotendinous junction of the quadriceps tendon. Free remobilization for 8 weeks (free cage activity) could not improve the situation, but after intensified remobilization of the same duration (low and especially high intensity treadmill running) high osteocalcin expression was observed in the above-mentioned anatomic sites. These findings indicate that formation of new bone tissue is rapidly regulated by the loading states of the bone. Higher than normal activity seems to be needed to restore the bone formation from the disuseinduced depression to normal.
Journal of Bone and Mineral Research 12/2009; 11(1):79-87. DOI:10.1002/jbmr.5650110112 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Disuse is associated with bone loss, which may not be recoverable. It is not known whether intensified remobilization is beneficial in restoring disuse-related bone loss nor if any such benefit would depend upon continuing mobilization for its maintenance. After an immobilization period of 3 weeks, the effects of free remobilization (11 weeks), and low-and high-intensity treadmill running (11 weeks) with and without subsequent deconditioning (18 weeks) on the bone mineral content (BMC) and density (BMD) of the hindlimb femora of Sprague-Dawley rats (n = 98) were studied using a dual-energy X-ray absorptiometric (DXA) scanner. Our hypothesis was that intensified remobilization is beneficial in restoring the BMC and BMD from disuse to normal while subsequent deconditioning is deleterious to these parameters. Immobilization for 3 weeks produced a significant BMC and BMD loss in the immobilized left femur (range -4.4 to -12.8%; p < 0.05-0.001). In the groups with free remobilization (free cage activity), the body weight-adjusted BMCs and BMDs always remained below those in the controls (range -2.3 to -12.1%; p values ranging from NS to < 0.01). Both low- and high-intensity running restored BMC and BMD in the immobilized limb, the effect being better in the latter group. In both of these groups, the values of the immobilized left limbs and those of the free right limbs exclusively exceeded the corresponding values of the age-matched control rats (left limb values 3.0-21.1% higher with p values ranging from NS to < 0.01; right limb values 7.9-21.4% higher with p < 0.05-0.01). However, after the deconditioning period of 18 weeks, the above described beneficial effects of low- and high-intensity running were lost, the left and right limb BMC and BMD values being lower than those in the age-matched controls (range -3.8 to -8.7%; p values ranging from NS to < 0.05). In conclusion, this study clearly indicates the need for greater than normal activity to restore the BMC and BMD after disuse to normal levels. However, the benefits of intensified remobilization are lost if the activity is terminated, and therefore, after immobilization and disuse, bone loading activities should be continued, perhaps indefinitely.
Journal of Bone and Mineral Research 09/2009; 11(9):1339-46. DOI:10.1002/jbmr.5650110919 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the risk factors and injuries in physical child abuse between November 2003 and February 2007.
The uptake area of the University Hospital of Turku, Finland, consists of about 700 000 inhabitants. Forty-eight cases of physical child abuse were examined. The median age of the abused children was 2.2 years, for children with skull fractures it was 0.5 years. The incidence of child physical abuse increased during the study period; it was 0.6/month in 2004 and 1.7/month in 2006. Mortality in the study group was 2.1 %.
Depression, overactivity, crying and prematurity were risk factors in the physically abused children. Parental risk factors were alcohol and drug abuse. Most often the perpetrator was the father or stepfather; when the perpetrator was unknown, the children were mostly in their mothers' care. The average delay of 3 weeks until starting the investigation into abuse was mostly due to delays by health centers or homes. Radiographs were the cornerstones of the medical examination but magnetic resonance examinations were essential for the examination protocol.
All levels of public health services, day care facilities and schools must be aware of possible physical child abuse and initiate an investigation as soon as possible by contacting the authorities. Physically abused children and their families must be followed up and supported for a sufficiently long period by social pediatric outpatient wards. The general information on child maltreatment provided to the public needs to be increased to prevent abuse. A child welfare report must be made to social workers in every maltreatment case examined in hospital, and in most cases the offence must also be reported to the police. Nevertheless, in certain cases even permanent custody of the child cannot be avoided.
European Journal of Pediatric Surgery 12/2008; 18(6):387-91. DOI:10.1055/s-2008-1038922 · 0.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Complete androgen insensitivity syndrome (CAIS) is a rare disease. However, there is a higher rate of CAIS in girls with inguinal hernia. The aim of this study was to estimate the incidence of CAIS in girls with inguinal hernia and to find a proper screening test for CAIS in these girls.
A total of 109 consecutive girls attending the University Hospitals of Turku and Tampere, Finland, for inguinal hernia repair between January 2003 and December 2007 participated in the study. After induction of anaesthesia, vaginal length was measured with a small, lubricated Hegar dilator. During hernia repair, tension was placed on the round ligament to identify the contents of the hernial sac. The karyotype of all patients was measured, with identification of the Y-chromosome from a buccal mucosa swab sample. Vaginal length measurements were plotted against age and standards for vaginal length in prepuberty were established.
Four patients were found to have very short vaginas, with one CAIS patient confirmed as having a 46XY karyotype from the verification of the Y-chromosome from buccal mucosa. The other three patients with abnormal vaginal length were karyotypically normal XX girls and had visible ovaries, fallopian tubes or round ligament, which suggests an error in the measurements. Unlike all the other operated girls, the CAIS patient lacked a round ligament.
The incidence of CAIS in girls undergoing hernia repair was 1%. The CAIS patient had a significantly shorter vagina than girls with normal karyotype. Vaginal length is a useful additional clinical tool in screening girls for karyotyping CAIS, especially if abnormalities in the round ligament and contents of the hernial sac are suspected. It is recommended that ovaries and fallopian tubes are searched for if the round ligament is not found to be normal during the hernia operation. If no ovaries or fallopian tubes are found, consent for karyotyping should be sought in cases where the vaginal length is <4 cm in girls older than 4 years and <3 cm in younger girls.
Scandinavian Journal of Urology and Nephrology 09/2008; 43(1):42-6. DOI:10.1080/00365590802299247 · 1.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Minimally invasive repair of pectus excavatum (MIRPE) is the preferred technique for repair of funnel chest deformity. The aim of this study is to evaluate our initial postoperative results, to identify factors related to postoperative complications and to examine the acceptability of MIRPE by the patients.
25 MIRPE patients (20 male and 5 female) were operated on between November 2002 and February 2007 at the Department of Pediatric Surgery, Turku University Central Hospital. The median age of the patients was 14 years (range from 5 to 23 years). One patient had undergone previously open Sulamaa reconstruction and one had a history of intrathoracic lymphoma. The remaining 23 patients had primary pectus excavatum. A right thoracoscopy was performed to every patient.
Operative mortality was zero and there were no clinically significant bleeding complications. Epidural analgesia was necessary for adequate pain control. Small symptomless residual pneumothoraxes and pleural effusions were common after the operation but neither required intervention. One patient had a hemothorax 7 months postoperatively, which was cured with a single puncture. Bar displacement took place in 2 patients but required correction in only one of these patients. There were 2 wound infections, one superficial and one which led to removal of the bar was 6 months after the operation. This may have been unnecessary. Two patients had pneumonia, one probably unrelated to the operation. One patient required psychiatric ward treatment, and 3 patients had mild psychological symptoms not requiring specific therapy. The preliminary cosmetic results were good or excellent in 90% of the cases, but a longer follow-up is needed for information on the final outcome.
MIRPE is a safe operation and gives a cosmetically good result. Thoracoscopy is needed during the operation. The early postoperative period in hospital is painful and there the patients need intensive care. We found the high epidural analgesia beneficial and safe during early period of pain treatment. The bar is removed not earlier than 3 years after the operation as a day care surgical procedure.
Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 02/2008; 97(1):63-70. · 1.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of early cryotherapy on healing of rat gastrocnemius muscle injury were investigated in schedules similar to those in clinical use. After the treatment: (1) hematoma between ruptured myofiber stumps was smaller and (2) extravasation of inflammatory cells to the injury site and (3) activation of satellite cells to myotubes and mature myofibers were delayed. Early proliferation of granulation tissue was not altered. Thus, cryotherapy affected the time-table of the healing process rather than causing qualitative differences. No negative side effects of cryotherapy were found. Positive effects of cryotherapy in clinical practice most likely depend on factors other than those involved with actual regeneration of the muscle lesion, such as reducing muscle spasms, which can cause reruptures, and analgesia allowing early mobilization. The results support the current clinical practice of treating acute muscle fiber ruptures with initial cold application followed by active early mobilization.
Scandinavian Journal of Medicine and Science in Sports 01/2007; 3(1):46 - 51. DOI:10.1111/j.1600-0838.1993.tb00360.x · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Magnetic resonance imaging (MRI) evaluation of pediatric elbow trauma with or without a visible fracture on radiography.
MRI was performed in the acute phase in 25 children with an elbow injury. Nine patients with an elbow effusion only on radiographs and 16 with a fracture or luxation seen on radiographs underwent subsequent MRI. No sedation was used.
MRI revealed eight occult fractures (89%) in seven out of nine patients who had only an effusion on radiographs. Based on MRI findings, septic arthritis was suspected in one patient. Two patients out of five with a supracondylar fracture on the radiograph had a cartilage lesion in the humerus. MRI depicted a 3-mm gap on the articular surface in two patients with a lateral condyle fracture, a more accurate fracture location in two patients than the radiographs, and an additional occult fracture in two patients. MRI showed a fracture not seen on radiographs in two of three patients with prior luxation.
MRI is a sensitive and accurate method in the diagnosis of pediatric elbow injuries, especially when only an effusion is present on radiographs. Occult fractures are more common in pediatric patients with elbow injury than reported earlier.
[Show abstract][Hide abstract] ABSTRACT: Tenascin-C is a hexabrachion-shaped matricellular protein with a very restricted expression in normal musculoskeletal tissues, but it is expressed abundantly during regenerative processes of these tissues and embryogenesis. To examine the importance of mechanical stress for the regulation of tenascin-C expression in the muscle-tendon unit, the effects of various states of mechanical loading (inactivity by cast-immobilization and three-varying intensities of subsequent re-activity by treadmill running) on the expression of tenascin-C were studied using immunohistochemistry and mRNA in situ hybridization at the different locations of the muscle-tendon unit of the rat gastrocnemius muscle, the Achilles tendon complex. This muscle-tendon unit was selected as the study site, because the contracting activity of the gastrocnemius-soleus muscle complex, and thus the mechanical loading-induced stimulation, is easy to block by cast immobilization. Tenascin-C was expressed abundantly in the normal myotendinous and myofascial junctions, as well as around the cells and the collagen fibers of the Achilles tendon. Tenascin-C expression was not found in the normal skeletal muscle, although it was found in blood vessels within the muscle tissue. Following the removal of the mechanical loading-induced stimulation on the muscle-tendon unit by cast immobilization for 3 weeks, the immonoreactivity of tenascin-C substantially decreased or was completely absent in the regions expressing tenascin-C normally. Restitution of the mechanical loading by removing the cast and allowing free cage activity for 8 weeks resulted in an increase in tenascin-C expression, but it could not restore the expression of tenascin-C to the normal level (in healthy contralateral leg). In response to the application of a more strenuous mechanical loading stimulus after the removal of the cast (after 8 weeks of low- and high-intensity treadmill running), the expression of tenascin-C was markedly increased and reached the level seen in the healthy contralateral limb. Tenascin-C was abundantly expressed in myotendinous and myofascial junctions and in the Achilles tendon, but even the most strenuous mechanical loading (high-intensity treadmill running) could not induce the expression of tenascin-C in the skeletal muscle. This was in spite of the marked immobilization-induced atrophy of the previously immobilized skeletal muscle, which had been subjected to intensive stress during remobilization. mRNA in situ hybridization analysis confirmed the immunohistochemical results for the expression of tenascin-C in the study groups. In summary, this study shows that mechanical loading regulates the expression of tenascin-C in an apparently dose-dependent fashion at sites of the muscle-tendon unit normally expressing tenascin-C but can not induce de novo synthesis of tenascin-C in the skeletal muscle without accompanying injury to the tissue. Our results suggest that tenascin-C provides elasticity in mesenchymal tissues subjected to heavy tensile loading.
[Show abstract][Hide abstract] ABSTRACT: During regeneration of transected myofibres a scar is formed between their stumps. Myofibres restore their tendon-muscle-tendon continuity and contractile function by attaching to the scar with new myotendinous junctions. The scar contracts with time, and thereby the stumps are pulled close to each other. During early regeneration, myoblasts and myotubes can fuse with the surviving parts of the transected myofibres. However, it is not known whether it is possible that the opposite stumps could eventually fuse to reunite the divided parts of the transected fibres. In this study, we show in rat that even after 12 months the stumps remain attached to the separating scar by myotendinous junctions without showing definite fusion of the stumps. We conclude that transected myofibres probably remain permanently divided in two consecutive tendon-muscle-tendon units.
[Show abstract][Hide abstract] ABSTRACT: Intermediate filament (IF) proteins show specific spatial and temporal expression during development of skeletal muscle. Nestin, the least known muscle IF, has an important role in neuronal regeneration. Therefore, we analyzed the expression pattern of nestin as related to that of vimentin and desmin during skeletal muscle regeneration. Nestin and vimentin appear at 6 h post-injury in myoblasts, with maximum expression around day 3–5 post-injury. Thereafter, vimentin expression ceases completely, whereas that of nestin is downregulated to remain only in the sarcoplasm next to neuromuscular and myotendinous junctions. Desmin appears at 6–12 h post-injury and becomes the predominant IF in myofibers simultaneously with the appearance of cross-striations. The expression pattern and colocalization of nestin and vimentin, known to form heteropolymers, suggests that they are essential during the early dynamic phase of the myofiber regeneration when migration, fusion, and structural modeling of myogenic cells occurs, whereas desmin is responsible for keeping myofibrils in register in mature myofibers. In conclusion, the expression of nestin is dynamically orchestrated with that of vimentin and desmin during skeletal muscle regeneration and recapitulates that seen during myogenesis, i.e. these IFs have key functional roles in the construction and restoration of skeletal myofibers.
Journal of Neuropathology and Experimental Neurology 05/2001; 60(6):588–597. · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The long-term behaviour of cellulose sponge implants, 10 x 10 x 5 mm in size, and tissue reactions in and around them were examined in the subcutaneous tissue of the rat from 1 to 60 weeks after implantation. The cellulose sponge used was filled up with connective tissue 4 to 8 weeks after implantation. Histologically, moderate foreign body tissue reaction inside the implant, the appearance of cracks and fissures, spotty colouration, and softening of the pore walls were observed up to 16 weeks after implantation. Later, the foreign body reaction inside the sponge became milder, the spotty colouration disappeared and micropores enlarged in the viscose cellulose matrix. Histomorphometrically, the cross-sectional area of the implants and the size of the pore wall fragments decreased, and the number of pore wall fragments increased significantly. The cellulose sponge used can be regarded as a slowly degradable implantation material. However, the time needed for the total disappearance of the cellulose sponge from subcutaneous tissue is longer than the 60 weeks.
[Show abstract][Hide abstract] ABSTRACT: Elastic extracellular matrix protein tenascin-C (TN) has very restricted expression in normal tissues, but is expressed in large quantities during embryogenesis and hyperplastic processes. To examine the importance of mechanical stress on the regulation of TN expression in vivo, the effects of various mechanical loading states (immobilization and three forms of subsequent remobilization) on the expression of TN were studied immunohistochemically at the bone-tendon attachment of the rat quadriceps muscle. This osteotendinous junction (OTJ) was selected as study site, since it receives its mechanical stimuli only from muscle contracting activity, which is easy to block by cast immobilization. TN was expressed abundantly in the normal OTJ. Following the removal of the mechanical stress from the junction by cast-immobilization of three weeks, the immunoreactivity of TN was almost completely absent. Normal mechanical stress in the form of free remobilization of eight weeks (free cage activity) resulted in a slight increase in TN expression, but could not restore the expression of TN to the level of the healthy contralateral leg. After the application of the increased mechanical stress (intensified remobilization of the eight weeks by low- or high-intensity treadmill running), the distribution and immunoreactivity of TN reached the level of the healthy contralateral limb in the low-intensity running group or even exceeded that in the high-intensity running group. High TN expression was seen around the chondrocytes and fibroblasts of the OTJ as well as around the collagen fibers of the tendon belly. We conclusively show that mechanical strain regulates the expression of TN in vivo, and propose that mechanical stress is a major regulator of TN expression in fibroblasts and chondrocytes. This may be an important aspect of the regulation of TN expression during embryogenesis, tendon degeneration, wound healing, bone formation, and in the other normal or regenerative morphogenetic processes TN is postulated to take part in.
[Show abstract][Hide abstract] ABSTRACT: The intermediate filament proteins nestin, vimentin, and desmin show a specific temporal expression pattern during the development of myofibers from myogenic precursor cells. Nestin and vimentin are actively expressed during early developmental stages to be later down-regulated, vimentin completely and nestin to minimal levels, whereas desmin expression begins later and is maintained in mature myofibers, in which desmin participates in maintaining structural integrity. In this study we have analyzed the expression levels and distribution pattern of nestin in intact and denervated muscle in rat and in human. Nestin immunoreactivity was specifically and focally localized in the sarcoplasm underneath neuromuscular junctions (NMJs) and in the vicinity of the myotendinous junctions (MTJs), ie, in regions associated with acetylcholine receptors (AChRs). This association prompted us to analyze nestin in neurogenically and myogenically denervated muscle. Immunoblot analysis disclosed a marked overall increase of accumulated nestin protein. Similar to the extrajunctional redistribution of AChRs in denervated myofibers, nestin immunoreactivity extended widely beyond the NMJ region. Re-innervation caused complete reversion of these changes. Our study demonstrates that the expression levels and distribution pattern of nestin are regulated by innervation, ie, signal transduction into myofibers.
American Journal Of Pathology 03/1999; 154(2). DOI:10.1016/S0002-9440(10)65304-7 · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We used a rat model to study the effects of immobilization of the calf muscle-tendon complex after an experimental Achilles tendon repair. Immobilizations of the complex in either a relaxed or tensioned position were compared by histochemical and morphometric analyses at the site of the tendon injury as well as in the gastrocnemius and soleus muscle bellies. The type of immobilization did not affect the healing of the tendon injury because no reruptures occurred in either of the treatment groups and the average tendon end-to-end distance did not differ between the groups. However, immobilization in a relaxed position led to a significantly more extensive fiber atrophy in the calf muscles. In clinical practice, these results suggest that rehabilitation after Achilles tendon surgery can be early and gradually tension- and load-increasing without a significant increase in the risk of rerupture of the tendon.
Scandinavian Journal of Medicine and Science in Sports 03/1999; 9(1):57-61. · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Therapeutic ultrasound is used by many in the treatment of muscle injuries, but no previous attempts to objectively assess its effects on regenerating skeletal myofibers have been published. In this descriptive study, we followed the regeneration of contusion injury to the rat gastrocnemius muscle during treatment with pulsed ultrasound. The speed of myoregeneration in ultrasound-treated animals was compared with that in control animals by immunohistochemical, morphometric, and scintigraphic analyses. Although satellite cell proliferation was enhanced significantly (up to 96%) by the ultrasound treatment during the early stages of regeneration, there was no such effect on myotube production. The period of rapid fibroblast proliferation was extended from 3 to 4 days in the control group to 7 to 10 days in the ultrasound therapy groups, whereas recapillarization was virtually unaffected. We conclude that although treatment with pulsed ultrasound can promote the satellite cell proliferation phase of the myoregeneration, it does not seem to have significant effects on the overall morphological manifestations of muscle regeneration.
The American Journal of Sports Medicine 01/1999; 27(1):54-9. DOI:10.1177/03635465990270011701 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous experimental studies have indicated delayed muscle regeneration after nonsteroidal antiinflammatory drug therapy. Successful regeneration of muscle after injury requires activation of normally dormant satellite cells that share the basal laminae with adjacent muscle cells. In the presence of adequate capillary ingrowth, satellite cells proliferate into myotubes and eventually form new muscle cells. In this study, the onset and extent of satellite cell and fibroblast proliferation as well as the production of myotubes and capillaries were analyzed with immunohistochemical methods after contusion injuries to rats' gastrocnemius muscles. Two groups of animals received daily doses of an intramuscular nonsteroidal antiinflammatory drug (naproxen) starting 6 hours and 3 days after injury, respectively. Treated animals were compared with similarly injured untreated animals. Satellite cell and fibroblast proliferation were unaffected by the treatment, and there were no significant differences in myotube or capillary production between treated and control animals. We conclude that naproxen treatment does not compromise the basic process of myofiber regeneration after injury.
The American Journal of Sports Medicine 03/1998; 26(2):172-6. · 4.36 Impact Factor