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Biomedical subjects

J Wallin

Publications and source records attributed to J Wallin.

At least 19 recordsLinked to original sources

Slipped capital femoral epiphysis. The mechanical function of the periosteum: new aspects and theory including bilaterality.

This particular ailment has many designations in the literature but none is quite adequate. Here we use the terminology slipped capital femoral epiphysis (SCFE). The anatomy of the proximal femur in all mammals reflects their growth and function. The main forces acting on the head are perpendicular to the growth plate. The thick tear-proof perichondrium-periosteum on the femoral neck is like a stocking attached to the epiphysis and the trochanter region. Growth in length causes a strong tensile stress in the periosteum, pressing the epiphysis against the metaphysis and thus stabilizing the vulnerable growth plate-the periosteum theory. Several factors may diminish the stability of the growth plate. SCFE begins with fissures, which coalesce to a fracture in the growth plate, invisible on a radiograph. As the slip progresses, an increasing angulation between the epiphysis and the remainder of the femur occurs. Weight and muscular forces displace the epiphysis posteriorly in a flexed hip. A rift in the ventral half of the periosteal stocking occurs at the border to the perichondrium and, after that, a longitudinal rift in the periosteum at the anterior midline of the femoral neck. This rift becomes broader as the epiphysis slips posteriorly, withdrawing the ruptured periosteum. Displacement of the epiphysis is due to a rotational slip and tilt, made possible by a compression fracture in the posterior part of the metaphysis. Parts of the periosteum function as reins steering the slip direction and counteracting the displacement. SCFE may be regarded as a pseudoarthrosis in the growing cartilage of the plate. The periosteum theory extended to a pseudoarthrosis theory has been supported by findings at surgery and on true lateral radiographs of usual and unusual cases of SCFE presented in this opus. On a true lateral view, the displacement can be measured as the slipping angle (SA) based on anatomical and geometrical considerations. SA values from 95 normal hips and from 22 contralateral asymptomatic hips from SCFE patients are presented in a histogram and bar graph. Statistically, SCFE is always bilateral, but in about 1/3 of the asymptomatic, contralateral hips, the physis ossifies and closes with SA below 13 degrees, and surgery is not necessary. It is most important that the position of the femur on the X-ray table is exactly defined in two dimensions: 1) the angle between the femoral shaft and the tabletop (angle of elevation), 2) the degree of rotation of the femur around its axis. A precisely defined positioning of the femur is a prerequisite for an exact reproducible measurement of the SA on a true lateral view and is also valuable for the evaluation of radiographic "signs". An aid, the Youth Hip Triangle (YHT), has been designed to facilitate positioning of the femur and measurement of SA. YHT is recommended for routine use in every X-ray facility. The method is quick, cost effective and makes it possible to diagnose SCFE in the contralateral hip before clinical signs or symptoms have occurred.

Adolescent↗

Reliable X-ray diagnosis of slipped capital femoral epiphysis by combining the conventional and a new simplified geometrical method.

BACKGROUND: The diagnosis of subtle slipped capital femoral epiphysis (SCFE), for example in the contralateral asymptomatic hip, may require use of an exactly defined and reproducible lateral view where the slipping angle can be measured. OBJECTIVE: To test a simplified geometrical method and compare it to the conventional method (AP and frogleg views). MATERIALS AND METHODS: The two methods were compared in 95 normal children 9-14 years old and 100 children 9-20 years old with SCFE. RESULTS: The slipping angle (SA) measurements had very high reproducibility, and the new method was diagnostically superior to the conventional method ( P<0.05). CONCLUSION: An exactly defined and reproducible lateral view is recommended for the X-ray diagnosis of SCFE. Nontraumatic SCFE appears to be bilateral in all cases.

Adolescent↗

Substance P release in the spinal dorsal horn following peripheral nerve injury.

Spinal microdialysis was used to study the potassium induced in vivo release of substance P (SP) in the rat dorsal horn at different time points (3, 14, and 60 days) following partial sciatic nerve ligation (PNL) or sciatic nerve axotomy. The withdrawal threshold to innocuous mechanical stimuli was investigated with von Frey filaments in the PNL rats prior to microdialysis. The release of SP was significantly elevated at 60 days following PNL but not following complete nerve injury. However, the PNL rats in all time groups displayed mechanical hypersensitivity, which implies that this late change in SP release seems to be unrelated to the development of neuropathy. The present results indicate that there is an increase of the releasable pool of SP in the dorsal horn at late post-operative times after PNL. This change in SP release may reflect an altered sensory processing or may instead relate to adaptive responses to promote recovery.

Animals↗

Sequence variation in humans and other primates at six short tandem repeat loci used in forensic identity testing.

A large number of alleles from the six different short tandem repeat (STR) loci FGA, D3S1358, vWA, CSF1PO, TPOX and TH01, used in human identity testing were sequenced to provide support for the robustness of fluorescent STR DNA typing by allele size. Sequence information for some of these loci (FGA, vWA, TH01) is an extension of published work, whereas no extensive sequence information is available with respect to the D3S1358, CSF1PO, and TPOX loci. Sequencing of alleles at each locus has provided quantitative data with respect to the true nucleotide length of common alleles, and of alleles that vary in length from the common alleles. All alleles that were identified as "off-ladder" alleles through fluorescent typing at these STR loci have proven to be true length variant alleles. Sequencing at the D3S1358 and CSF1PO loci allowed for the establishment of a common nomenclature for these loci. A correlation between percent stutter and the length of the core tandem repeat is demonstrated at the FGA locus. Alleles in which the core tandem repeat is interrupted by a repeat unit of different sequence have a reduced percent stutter. DNA samples from three non-human primates (chimpanzee, orangutan, and gorilla) were compared to the human sequences, and shown to differ markedly across loci with respect to their homology. The effects of primer binding site mutations on the amplification efficiency at a particular locus, and methods used to interpret amplification imbalance of heterozygous alleles at a locus is also addressed.

Animals↗

Hyaluronan in serum as an indicator of progressive disease in hyaluronan-producing malignant mesothelioma.

BACKGROUND: Malignant pleural mesothelioma is associated in up to 70% of cases with an elevated content of hyaluronan (HYA) in the pleural fluid. Increased levels of circulating HYA have also been described. The clinical course of the disease can be followed by computed tomography (CT), although there are disadvantages with serial CT scans. An easily analyzed blood test, such as HYA in serum, would be of value for clinical follow-up. The purpose of this study was to relate changes in serum HYA to changes in quantitative estimations of tumor volume in cases of mesothelioma. METHODS: The content of HYA in the pleural fluid was analyzed in 19 men with mesothelioma. CT scans were performed about every third month. The tumor volume was estimated on transilluminated CT scans with a digital planimeter. Blood samples for HYA analyses were drawn every month. The impact of the tumor burden on HYA in serum was indicated in statistical analysis by a straight line for each patient according to the restricted maximum likelihood method. RESULTS: An elevated content of HYA, i.e., >100 mg/L, in the pleural fluid was seen in 13 of 19 patients. There was a positive correlation, although low, between the initial level of HYA in serum and the concentration of HYA in pleural fluid. Increasing levels of circulating HYA were on average accompanied by an increase in tumor volume in the HYA-producing group of mesotheliomas (P = 0.01). This was not seen in the non-HYA-producing mesotheliomas (P = 0.10). CONCLUSIONS: These results provide evidence that it should be possible to follow the clinical course of malignant pleural mesothelioma patients by analysis of circulating HYA in the subgroup of HYA-synthesizing mesotheliomas.

Adult↗

Ifosfamide in malignant mesothelioma: a phase II study.

Malignant mesothelioma is a rare malignancy with a median survival, ranging from 4 to 18 months in untreated patients. In a phase II study of patients with mesothelioma, the efficacy and toxicity of ifosfamide and mesna was evaluated. Twenty-nine previously untreated patients, with histologically proven and unresectable mesothelioma, entered the study. Three patients were later excluded from the study due to revision of the diagnoses. The patients had to have bidimensionally measurable disease by CT scans and a WHO performance status < or = 3. Eligible patients received ifosfamide 3000 mg/m2 per day for 3 days as a 1-h infusion and mesna 1800 mg/m2 per day for 3 days every third week. Dose modifications were made according to the degree of hematologic, neurologic and renal toxicity. Response to treatment was evaluated in accordance with WHO criteria. The median age of patients was 59 years (range 39-68), 18 patients (69%) had a history of asbestos exposure and the median of treatment cycles was four (range 1-10). No complete responses were observed. One patient obtained a partial response after five cycles with a duration of response of 25 months. Nine patients (35%) had stable disease, while 13 (54%) progressed. The median survival for all patients was 10 months. The toxicity of the treatment was considerable. Thirteen patients (50%) had grade 4 leucopenia, ten patients (38%) had grade 3 or 4 reversible neurotoxicity and ten patients (38%) had grade 3 or 4 nausea and vomiting. Eleven patients (42%) went off the study due to the toxicity of the treatment. In conclusion, ifosfamide did not show any substantial activity of relevance in malignant mesothelioma at the dose level investigated, in spite of considerable toxicity.

Adult↗

[Pulmonary embolism remains an overlooked diagnosis. Proposed strategy in suspected cases].

The problem of misdiagnosed pulmonary embolism (PE) is reviewed in the light of the introduction of new diagnostic methods such as spiral tomography (helical scanning). Despite new diagnostic methods, the frequency of misdiagnosed PE will not be reduced unless PE is suspected at the right juncture. PE should always be suspected in the presence of 'pulmonary syndromes' and venous thromboembolic risk factors. A strategy for the management of cases of suspected PE is proposed in the article: 1, recognition of the presence of cardiopulmonary disease, 2, determination of the clinical probability of PE; 3, confirmation (or exclusion) of PE; 4, determination of its severity and prognosis; and 5, choice of treatment. A two-part algorithm for use in patients with stable or unstable haemodynamics is also presented.

Diagnosis, Differential↗

Genotyping of forensic short tandem repeat (STR) systems based on sizing precision in a capillary electrophoresis instrument.

Automated fluorescence analysis of polymerase chain reaction (PCR)-amplified short tandem repeat (STR) systems by capillary electrophoresis (CE) is becoming an established tool both in forensic casework and in the implementation of both state and national convicted offender DNA databases. A new capillary electrophoresis instrument, the ABI Prism 310 Genetic Analyzer, along with the Performance Optimized Polymer 4 (POP-4) provides an automated and precise method for simultaneously analyzing ten fluorescently labeled STR loci from a single PCR amplification kit, which provides a power of discrimination of approximately one in five billion from a single PCR amplification. Data are presented on sizing precision, sizing accuracy, and resolution for the STR loci in the AmpFlSTR Profiler kit. Sizing accuracy is highly dependent on the electrophoresis system, and therefore the reporting of alleles based on the nucleotide size obtained from an electrophoresis system is not recommended for forensic work. The precision of the 310 capillary electrophoresis system, coupled with software developed for automated genotyping of alleles based on the use of an allelic ladder, allows for accurate genotyping of STR loci. Sizing precision of < or = 0.16 nucleotide standard deviation was obtained with this system, thus allowing for accurate genotyping of length variants that differ in length by a single nucleotide.

Alleles↗

Long-term results after nailing in situ of slipped upper femoral epiphysis. A 30-year follow-up of 59 hips.

We reviewed the radiological and clinical long-term results after the nailing in situ of slipped upper femoral epiphysis in 59 hips in 43 patients. The displacement of the epiphysis had been measured as the 'slipping angle' before operation and related to the results at follow-up at a mean of 30.9 years (27 to 34). The mean age at follow-up was 44.2 years (39 to 50). Radiographic re-examination of 41 hips with slipping angles of < or =30 degrees at the time of operation showed that eight (20%) had developed mild osteoarthritis and one had severe changes. For 18 hips with slipping angles ranging from 31 to 50 degrees at surgery six (33%) had mild osteoarthritis and three had severe changes. The differences did not quite achieve statistical significance (p = 0.09). Clinical re-examination of the 41 hips with slipping angles of < or =30 degrees showed fair or poor results (Harris hip score <90) in three (7%). In the 18 hips with slipping of 31 to 50 degrees, four had fair or poor results (22%) (p = 0.13). We conclude that nailing in situ for slipping of < or =30 degrees, using one thin nail, can give excellent long-term results. At present we recommend that hips with slips ranging from 31 to 50 degrees should also be nailed in situ, but further long-term studies are required, especially on the choice between nailing in situ and corrective osteotomy for slips in excess of 50 degrees.

Adolescent↗

Does a single device prevent further slipping of the epiphysis in children with slipped capital femoral epiphysis?

All 170 patients (212 hips) treated between 1946 and 1992 for slipped capital femoral epiphysis (SCFE) with fixation in situ with a single device were reviewed to evaluate the incidence of further slipping of the epiphysis after primary treatment. In 154 hips, a smooth device without anchorage in the epiphysis was used and in 58, a device anchored in the epiphysis. In 3 hips, further slipping of the epiphysis occurred after primary treatment with no obvious cause. In 10 hips, an obvious cause for further slipping of the epiphysis was found. These 10 hips were re-operated due to the loss of epiphyseal grip in 6 hips, unsatisfactory placement of the device in 1, while in the remaining 3 hips, the device was removed before physeal closure. Twenty-six hips (12.3%) were re-operated because the device had lost its epiphyseal grip before physeal closure, and in 25 of these hips the device was smooth and had no anchorage in the epiphysis. The conclusion of this study is that a single device with anchorage in the epiphysis is stable enough to prevent further slipping of the epiphysis in hips with SCFE.

Adolescent↗

External rotational positioning of the leg after intertrochanteric combined varus-derotational osteotomy in Perthes' disease.

A 13-year-old boy underwent an intertrochanteric combined varus derotational osteotomy (VDO) for Perthes' disease of his right hip. After surgery he walked with his right leg externally rotated. Computed tomography scans of both knees and hips were obtained with the legs in their spontaneous position to evaluate rotation and anteversion. The femoral condyles were in 28 degrees of external rotation on the operated side compared with 2 degrees on the non-operated side. The angle between the femoral neck and the horizontal plane was 32 degrees on both sides. We conclude that there may be a risk that a derotational osteotomy may produce an external rotational position of the leg instead of altering the angle between the femoral neck and the horizontal plane.

Adolescent↗

Bilaterality in slipped capital femoral epiphysis: importance of a reliable radiographic method.

One hundred patients treated for slipped capital femoral epiphysis (SCFE) were reviewed to evaluate the incidence of bilateral slipping of the epiphysis at an average follow-up time of 32 years. When the patients were examined during adolescence, repeat lateral radiographs of the hips had been obtained by the frog lateral view in 33 patients and by the standardized lateral view according to the method of Billing in 67 patients. At re-examination, 59 patients (59%) were judged to have had a previous bilateral SCFE; in 42 of these 59 patients (71%), slipping of the contralateral hip was asymptomatic. In 23 patients (23%), the diagnosis of bilateral slipping was established at primary admission, in 18 (18%) later during adolescence, and in 18 (18%) not until the patients were reexamined as adults and the primary radiographs were reviewed. The incidence of bilateral slipping was higher in patients in whom the Billing standardized lateral view was used (63%) than in patients in whom the frog lateral view was used (52%). We conclude that the incidence of bilateral slipping of the epiphysis in patients with SCFE is approximately 60% in Sweden. If repeat radiographs of the contralateral hip are obtained with the Billing standardized lateral view until physeal closure occurs, even minor slipping of the epiphysis, which is often advisable to treat, will be apparent.

Adolescent↗

Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation.

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels.

Animals↗

Long-term results after realignment operations for slipped upper femoral epiphysis.

We reviewed the long-term results of the treatment of slipped upper femoral epiphysis (SUFE) using realignment procedures in 36 patients (37 hips) at an average follow-up of 33.8 years (26 to 42). There were serious short-term complications in seven of the 22 hips treated by subcapital osteotomy, three of the 11 hips treated by intertrochanteric osteotomy and three of the four hips treated by manipulative reduction. At re-examination, the clinical and radiological results were excellent or good in 41% of the hips treated by subcapital osteotomy, in 36% treated by intertrochanteric osteotomy and in none treated by manipulative reduction. In all, seven hips (19%) had had arthrodesis or total hip replacement. The natural history of SUFE was probably not improved by any of the treatments used in our study. We therefore discourage the use of subcapital and intertrochanteric osteotomy as well as manipulative reduction in the primary treatment of chronic SUFE.

Adolescent↗

Pax-1 in the development of the cervico-occipital transitional zone.

The Pax-1 gene has been found to play an important role in the development of the vertebral column. The cervico-occipital transitional zone is a specialized region of the vertebral column, and malformations of this region have frequently been described in humans. The exact embryonic border between head and trunk is a matter of controversy. In order to determine a possible role of Pax-1 in the development of the cervico-occipital transitional zone we studied the expression of this gene in a series of quail embryos and murine fetuses with in situ hybridization and immunohistochemistry. Pax-1 is expressed in all somites of the embryo, including the first five occipital ones. During embryonic days 3-5 the gene is down-regulated in the caudal direction within the first five somites, whereas more caudally Pax-1 is strongly expressed in the cells of the perinotochordal tube. In 5-day-old quail embryos, the cartilaginous anlage of the basioccipital bone has developed and ther is no more expression of Pax-1 in this region. The fusion of the dens axis with the body of the axis also coincides with switching off of the Pax-1 gene. More caudally, the gene is continuously expressed in the intervertebral discs of murine embryos and therefore seems to be important for the process of resegmentation. Quail embryos do not possess permanent intervertebral discs. ¿Hyper-¿ or ¿hyposegmentation¿ defects may be explained by an over- or under-expression of Pax-1 during development. We also reinvestigated the border between the head and trunk in chick embryos by performing homotopical grafting experiments of the 5th somite between chick and quail embryos.

Animals↗

Expression and function of Pax 1 during development of the pectoral girdle.

Pax 1 is a member of the paired-box containing gene family. Expression has previously been observed in the developing sclerotomes and later in the anlagen of the intervertebral discs. Analysis of Pax 1-deficient undulated mice revealed an important role for this gene in the development of the axial skeleton, in which Pax 1 apparently functions as a mediator of notochordal signals during sclerotome differentiation. Here we demonstrate that Pax 1 is also transiently expressed in the developing limb buds. A comparative phenotypic analysis of different undulated alleles shows that this expression is of functional significance. In mice that are mutant for the Pax 1 gene severe developmental abnormalities are found in the pectoral girdle. These include fusions of skeletal elements which would normally remain separate, and failures in the differentiation of blastemas into cartilaginous structures. Although Pax 1 is also expressed in the developing hindlimb buds and Wolffian ridge, no malformations could be detected in the corresponding regions of Pax 1 mutant mice. These findings show that, in addition to its role in the developing vertebral column, Pax 1 has an important function in the development of parts of the appendicular skeleton.

Animals↗

The role of Pax-1 in axial skeleton development.

Previous studies have identified a single amino-acid substitution in the transcriptional regulator Pax-1 as the cause of the mouse skeletal mutant undulated (un). To evaluate the role of Pax-1 in the formation of the axial skeleton we have studied Pax-1 protein expression in early sclerotome cells and during subsequent embryonic development, and we have characterized the phenotype of three different Pax-1 mouse mutants, un, undulated-extensive (unex) and Undulated short-tail (Uns). In the Uns mutation the whole Pax-1 locus is deleted, resulting in the complete absence of Pax-1 protein in these mice. The other two genotypes are interpreted as hypomorphs. We conclude that Pax-1 is necessary for normal vertebral column formation along the entire axis, although the severity of the phenotype is strongest in the lumbar region and the tail. Pax-1-deficient mice lack vertebral bodies and intervertebral discs. The proximal part of the ribs and the rib homologues are also missing or severely malformed, whereas neural arches are nearly normal. Pax-1 is thus required for the development of the ventral parts of vertebrae. Embryonic analyses reveal that although sclerotomes are formed in mutant embryos, abnormalities can be detected from day 10.5 p.c. onwards. The phenotypic analyses also suggest that the notochord still influences vertebral body formation some days after the sclerotomes are formed. Furthermore, the notochord diameter is larger in mutant embryos from day 12 p.c., due to increased cell proliferation. In the strongly affected genotypes the notochord persists as a rod-like structure and the nucleus pulposus is never properly formed. Since the notochord is Pax-1-negative these findings suggest a bidirectional interaction between notochord and paraxial mesoderm. The availability of these Pax-1 mutant alleles permitted us to define an early role for Pax-1 in sclerotome patterning as well as a late role in intervertebral disc development. Our observations suggest that Pax-1 function is required for essential steps in ventral sclerotome differentiation, i.e. for the transition from the mesenchymal stage to the onset of chondrogenesis.

Animals↗