The outcome of angiography in patients with Raynaud's phenomenon: an unexpected role for atherosclerosis and hypercholesterolemia.

OBJECTIVE: Upper extremity angiography can make an important contribution to the diagnosis in vasculopathy. The present study was designed to assess the diagnostic role of upper extremity angiography in patients with disturbed circulation of the hand, according to a standardised protocol. METHODS: The study was carried out in an outpatient setting in 103 patients suffering from bilateral Raynaud's phenomenon without any obvious underlying disease and who were unresponsive to nifedipine and aspirin. All patients had angiographies taken according to a standardized technique using vasodilating medication, and reviewed according to a standardised protocol that covered all the known characteristics of angiopathy such as diminished flow, stops, tortuosity, irregularity of the wall, tapering, collaterals and blushing. RESULTS: Standardised angiograms showed vasculopathy compatible with primary vasospasm in 42 patients [all women; mean age 35.1 years], atherosclerotic vascular disease in 44 patients [M/F 9/35; mean age 46.7 years], peripheral embolism in 8 patients [M/F 4/4; mean age 38.4 years], vasculitis in 3 patients [3 women; mean age 38 years] and Buerger's disease in 3 patients [3 men; mean age 47 years]. Inter-observer differences were present in 4 cases, but consensus could be reached through open discussion. An unexpected 47% of patients with atherosclerotic vascular disease had dyslipidemia, frequently of familial origin. CONCLUSIONS: The standardised angiography protocol proved to be helpful in the assessment of upper extremity angiography. Surprisingly, a high prevalence of angiographic abnormalities compatible with atherosclerotic vascular disease could already be diagnosed in relatively young patients with Raynaud's phenomenon, of whom 47% showed hypercholesterolemia.

Familial multiple epiphyseal dysplasia due to a matrilin-3 mutation: further delineation of the phenotype including 40 years follow-up.

In this study, we followed-up the family with bilateral hereditary micro-epiphyseal dysplasia (BHMED) originally described by Elsbach [1959: J Bone Joint Surg [Br] 41-B:514-523]. Clinical re-examination of all available family members resulted in further delineation of the clinical and radiological phenotype, which is distinct from common multiple epiphyseal dysplasia (MED). Linkage analysis excluded EDM1, EDM2, and EDM3 as candidate genes. Linkage and mutation analysis of matrilin-3 (MATN-3) revealed a new pathogenic mutation confirming that BHMED is indeed a distinct disease entity among MED and MED-like disorders.

Orthopaedic sequelae in neurologically recovered obstetrical brachial plexus injury. Case study and literature review.

PURPOSE: Description of shoulder sequelae in obstetrical brachial plexus injury (OBPI) patients who had spontaneous functional recovery, in the context of historical and current conservative methods of treatment. METHOD: Case study of a baby with serious complications, followed by a review of the literature from 1900 until 2001 about conservative treatment of OBPI with respect to the prevention of shoulder complications. RESULTS: Description of contractures and bony deformities did not show important discrepancies over time, other than more detailed images because of new technical possibilities. There is no agreement on the explanation of the development of these deformities. Secondary changes caused by muscular imbalance and longstanding contracture are recognized by all authors. A primary osteoarticular lesion was recognized as a possible cause in the beginning of the twentieth century, then forgotten for a long time and only in the 1980s had gained interest again. The main change in treatment concerns the use of arm braces. This was strongly recommended in the first half of the twentieth century, then advised against and is at this moment not anymore mentioned. CONCLUSIONS: There is no consensus on the cause of contractures and bony deformities in children with OBPI. Conservative methods of treatment have changed over the years, without research on the outcome of these treatment changes.

[Radiologische Besonderheiten einer bilateral vererblichen Mikro-Epiphysendysplasie - deutliche Entität einer Skelettdysplasie]. / Radiological features of bilateral hereditary micro-epiphyseal dysplasia--a distinct entity in the skeletal dysplasias.

AIM: To prove that bilateral hereditary micro-epiphyseal dysplasia (BHMED), first described by Elsbach in 1959, is a distinct disorder radiologically as well as clinically, compared with multiple epiphyseal dysplasia (MED). MATERIAL AND METHODS: We used the data of the revised pedigree with 84 family members, performed a medical history, physical examination and made a radiological evaluation for defining a clinical and radiological phenotype of BHMED family members. We used blood samples for genetic analysis. RESULTS: Although there is a clear clinical picture of the dysplasia, the radiological signs are more reliable for making the diagnosis. Especially the typical deformity of the hip and knee joint are diagnostic for BHMED. By linkage analysis we excluded linkage with the three known MED-loci (EDM1, EDM2 and EDM3). CONCLUSION: BHMED is indeed an entity that is distinct from common multiple epiphyseal dysplasia (MED), clinically, as well as radiologically and genetically.

Bilateral hereditary micro-epiphyseal dysplasia: further delineation of the phenotype with 40 years follow-up.

Bilateral hereditary micro-epiphyseal dysplasia (BHMED) is a distinct skeletal dysplasia with specific clinical and radiological findings. It was first published in 1959. We have re-examined the original family for further delineation of the phenotype.

Differences in complexity of isolated brachydactyly type C cannot be attributed to locus heterogeneity alone.

Hereditary isolated brachydactyly type C (OMIM 113100) mostly follows an autosomal dominant pattern of inheritance with a marked variability in expression. This phenotype has been mapped to two different loci on chromosomes 12q24 and 20q11.2. The latter locus contains the cartilage-derived morphogenetic protein (CDMP)1 gene, in which a null mutation has been found in patients with malformations restricted to the upper limbs. A more complex brachydactyly type C phenotype has been mapped to chromosome 12q24. Differences in complexity of these phenotypes have been attributed to locus heterogeneity. Clinical subclassification based on the degree of complexity of the phenotype has therefore been suggested. We present patients with a complex brachydactyly type C phenotype in whom there is considerable intra- and interfamilial variability in expression. We show that clinical subclassification based on the complexity of the brachydactyly type C phenotype related to the genetic defect is not feasible. We present evidence that differences in complexity are not only due to locus heterogeneity, but that genetic modifiers and/or environmental factors must also play a role.

Assessment of ulnar variance: a radiological investigation in a Dutch population.

OBJECTIVE: A radiological study was performed to evaluate ulnar variance in 68 Dutch patients using an electronic digitizer compared with Palmer's concentric circle method. Using the digitizer method only, the effect of different wrist positions and grip on ulnar variance was then investigated. Finally the distribution of ulnar variance in the selected patients was investigated also using the digitizer method. DESIGN AND PATIENTS: All radiographs were performed with the wrist in a standard zero-rotation position (posteroanterior) and in supination (anteroposterior). Palmer's concentric circle method and an electronic digitizer connected to a personal computer were used to measure ulnar variance. The digitizer consists of a Plexiglas plate with an electronically activated grid beneath it. A radiograph is placed on the plate and a cursor activates a point on the grid. Three plots are marked on the radius and one plot on the most distal part of the ulnar head. The digitizer then determines the difference between a radius passing through the radius plots and the ulnar plot. RESULTS AND CONCLUSIONS: Using the concentric circle method we found an ulna plus predominance, but an ulna minus predominance when using the digitizer method. Overall the ulnar variance distribution for Palmer's method was 41.9% ulna plus, 25.7% neutral and 32.4% ulna minus variance, and for the digitizer method was 40.4% ulna plus, 1.5% neutral and 58.1% ulna minus. The percentage ulnar variance greater than 1 mm on standard radiographs increased from 23% to 58% using the digitizer, with maximum grip, clearly demonstrating the (dynamic) effect of grip on ulnar variance. This almost threefold increase was found to be a significant difference. Significant differences were found between ulnar variance when different wrist positions were compared.

Ulnar variance and the shape of the lunate bone. A radiological investigation.

The authors designed a study to test the hypothesis that the length of the ulna might affect the shape of the lunate bone because of long-term molding during life. This might then be useful to predict the presence or absence of a dynamic or static ulna plus by the shape of the lunate bone. In a prospective study, posterior-anterior wrist x-rays were taken in a standard fashion in 68 patients with a mean age of 34.5 years. Dominance, grip strength, ulnar variance and the shape of the lunate were recorded. Lunate shape, type 1, which is the least molded, was seen most frequently on both the left and right side and did not correlate with the dominant side. The most molded, type 3, was seen less frequently and almost exclusively on the nondominant side. No correlation was found between dynamic ulna plus and the type 3 lunate. Following statistical analysis, no correlation between ulnar variance and lunate shape was found, indicating that the shape of the lunate bone had no predictive value for predicting the presence or absence of a dynamic ulna plus variance. The hypothesis that the length of the ulna might influence the ultimate shape of the lunate could not be demonstrated.

A 100-year-old anatomical specimen presenting with boomerang-like skeletal dysplasia: diagnostic strategies and outcome.

The Museum Vrolik collection of human anatomy comprises 360 recently redescribed specimens with congenital anomalies. The specimen described here dated from 1881 and presented with a general embryonic appearance, disproportionate short stature, brachycephaly, widened cranial sutures, hypertelorism, microphthalmia, bilateral cleft lip and palate, micrognathia, short and curved limbs, polysyndactyly, and abnormal female genitalia. Conventional radiography was hampered by decalcification of the skeleton, due to acidification of the preservation fluid. The use of additional imaging techniques, i.e., mammography, computerized tomography with three-dimensional reconstruction, and magnetic resonance imaging eventually led us to conclude that the condition of our specimen was similar to Piepkorn type skeletal dysplasia, boomerang dysplasia, and a condition described by Carpenter and Hunter [1982: J Med Genet 19:311-315], though none of these diagnoses seemed fully applicable.

Uniform fat suppression in hands and feet through the use of two-point Dixon chemical shift MR imaging.

PURPOSE: To assess the potential of two-point Dixon chemical shift magnetic resonance imaging to achieve uniform fat suppression in the distal parts of the extremities. MATERIALS AND METHODS: Two-point Dixon chemical shift imaging was performed in 31 consecutive patients clinically suspected to have bone marrow disease. In some patients, Dixon studies were performed before and after the intravenous administration of gadopentetate dimeglumine, and in some patients follow-up examinations were performed, for a total of 64 studies. Areas of interest were the hand, wrist, foot, ankle, and lower leg. There was a special interest in the neuropathic foot and osteomyelitis. The uniformity of fat suppression in the entire field of view, the frequency of displacement artifacts, and the applicability of the technique in routine patient treatment were evaluated. RESULTS: In 64 (100%) Dixon studies, uniform fat suppression was achieved. In 59 (92%) studies, there were no displacement artifacts. In five (8%) studies, displacement artifacts occurred; however, in only one (2%) study did they severely hamper the reading. Thus, in 63 (98%) studies, adequate diagnostic quality was obtained. CONCLUSION: Two-point Dixon chemical shift imaging is a good technique for achieving uniform fat suppression in the distal parts of the extremities. Because the frequency of displacement artifacts is low, the technique is applicable in a routine clinical setting.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. I: Syndromes with multiple congenital anomalies.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than 5,000 thousand specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies was recatalogued and redescribed according to contempory syndromological views. The original descriptions, as far as preserved, were compared with the clinical and radiographical findings. In 13 specimens the following multiple congenital anomalies (MCA) syndromes were diagnosed: acrofacial dysostosis, Apert syndrome, Brachmann-De Lange syndrome, ichthyosis congenita gravis, Jarcho-Levin syndrome, Meckel syndrome, oro-facio-digital syndrome type IV, Roberts syndrome, Smith-Lemli-Opitz syndrome, Treacher Collins syndrome, and trisomy 13. It appeared that the founders of the museum studied and described several of these syndromes many years before they became established as such. In some specimens a reliable diagnosis is still pending. The use of additional diagnostical techniques, such as MRI, CT scanning, and fluorescence in situ hybridization, in these specimens is currently being investigated.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. II: Skeletal dysplasias.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than five thousand specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies was recatalogued and redescribed according to contempory syndromological views. The original descriptions, as far as preserved, were compared with the clinical and radiographical findings. In 18 specimens the following skeletal dysplasias were diagnosed: achondrogenesis, achondroplasia, Blomstrand chondrodysplasia, Majewski syndrome, osteodysplastic primordial dwarfism, osteogenesis imperfecta type I, osteogenesis imperfecta type II, and thanatophoric dysplasia with and without cloverleaf skull. Radiography did not yield a diagnosis in 4 specimens. The use of additional diagnostical techniques, such as MRI and CT scanning and fluorescence in situ hybridization in these specimens, is currently being investigated.

Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group.

OBJECTIVE: To assess the efficacy, tolerability, and safety of sulfasalazine (SSZ) in the treatment of juvenile chronic arthritis (JCA). METHODS: We conducted a 24-week randomized, placebo-controlled, double-blind, multicenter study of patients with active JCA of both oligoarticular and polyarticular onset. Patients were treated with a dosage of 50 mg/kg/day of SSZ (maximum 2,000 mg/day) or placebo. The efficacy variables were joint scores, physician's, parents', and patient's overall assessments, and laboratory parameters of inflammation. RESULTS: Of the 69 patients enrolled, 52 (75%) completed the trial. Six patients (18%) withdrew from the placebo group, and 11 (31%) withdrew from the SSZ group (P = 0.18). In the intention-to-treat analysis of end point efficacy, between-group differences were significant for the overall articular severity score (P = 0.02), all global assessments (P = 0.01), and the laboratory parameters (P < 0.001). Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal (P < 0.001), but in all instances, these events were transient or reversible upon cessation of treatment. CONCLUSION: The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA, although it was not well tolerated in one-third of the patients.

The value of additional carpal box radiographs in suspected scaphoid fracture.

RATIONALE AND OBJECTIVES: Carpal Box (CB) radiographs, transverse and longitudinal, produce elongated and magnified views of the carpus. These radiographs can be used after carpal injury, in addition to conventional scaphoid x-rays. In this study, the use of CB radiographs was evaluated in patients with possible scaphoid fracture. METHODS: Seventy-one consecutive patients who presented at the First Aid department from May 1994 to May 1995 were included. All patients were examined for scaphoid fracture after a fall on the out-stretched hand. If a scaphoid fracture was seen on the scaphoid x-rays, patients were immobilized. If the x-rays remained negative or dubious for fracture, additional transverse and longitudinal CB radiographs were obtained. If CB radiographs remained negative or inconclusive, patients were referred for three-phase bone scintigraphy. The results of independent and masked judgment by three different observers were used for an inter- and intraobserver analysis. RESULTS: Twenty of 71 patients initially showed a scaphoid fracture on the conventional scaphoid x-rays, 41 were negative, and 10 inconclusive. All 41 negative patients remained negative on CB radiograph; however, the bone scintigraphy was positive for scaphoid fracture in 11 patients and in 9 patients a hot spot elsewhere in the carpus was found. Of the 10 patients with inconclusive x-rays, 2 showed a clear fracture of the scaphoid on CB radiograph, 5 were negative, and 3 remained inconclusive. The agreement between observers, calculated in kappa values, was highest in CB radiographs. CONCLUSIONS: In the diagnosis of scaphoid fracture, Carpal Box radiography is of limited value in patients with clinically suspected scaphoid fracture. In two of 10 patients with initial dubious scaphoid x-ray, bone scintigraphy can be avoided. Furthermore, the reliability of the interpretation of the radiographs is increased by additional Carpal Box radiography.

Metacarpophalangeal pattern (MCPP) profile analysis in a family with triphalangeal thumb.

Triphalangeal thumb (TPT) is a rare congenital disorder characterised by a long, finger-like thumb with three phalanges instead of two. It can occur as an isolated defect, in association with other abnormalities of the hands and feet, or as a part of a syndrome. Sporadic cases have been described, but it is usually inherited as an autosomal dominant trait. In order to examine skeletal morphology in different phenotypic variations of this disorder, we performed metacarpophalangeal pattern profile analysis in one kindred with this disorder. A characteristic profile occurred in all affected people, based on the individual lengthening or shortening of the thumb bones. Comparison of the affected and unaffected people from this family with people with a different genetic background suggests that the described profile is specific for TPT and could be used as a helpful diagnostic tool in syndromes which include TPT.

The role of metacarpophalangeal pattern (MCPP) profile analysis in the treatment of triphalangeal thumbs. Description of a method and a case report.

The metacarpophalangeal pattern (MCPP) profile analysis is a method of comparing the length of each of the 19 tubular bones of the hand on the X-ray with the standard length in the normal population according to age and sex. An MCPP plot is a graphic illustration of the MCPP analysis. It is not the exact height of the curve on the MCPP plot which is most important, but the profile which occurs because of the individual lengthening or shortening of the bones. This pattern profile appears to be specific for several congenital malformation syndromes. We have recently used MCPP analysis in planning surgery for triphalangeal thumbs. The percentage of excessive or reduced length of each individual bone of the hand can be read from the MCPP plot and is helpful in calculating a more accurate length for the newly created thumb. MCPP analysis can be used as a diagnostic tool in a number of congenital hand malformations, but may also be helpful in planning surgical treatment of congenital hand malformations when abnormal bone length is involved.

Autosomal dominant familial radial luxation, carpal fusion and scapular dysplasia with variable heart defects.

A family is described with skeletal abnormalities involving the shoulder, elbow, and hand, in combination with variable cardiac defects including conduction defects and anatomical anomalies. The disorder followed an autosomal dominant pattern of inheritance with apparently full penetrance for the skeletal abnormalities and reduced penetrance for the cardiac defects.

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis.

BACKGROUND: In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of methotrexate proved to have an adverse effect on bone metabolism, especially on osteoblast activity. OBSERVATIONS: Methotrexate osteopathy is a relatively unknown complication of low-dose methotrexate treatment. We describe three patients treated with low-dose oral methotrexate in whom signs and symptoms were present that were similar to those found in children treated with high doses of methotrexate. All three patients had a triad of severe pain localized in the distal tibiae, osteoporosis, and compression fractures of the distal tibia, which could be identified with radiographs, technetium Tc 99m scanning, and magnetic resonance imaging. CONCLUSIONS: Methotrexate osteopathy can occur in patients treated with low doses of methotrexate, even over a short period of time. As pain is localized in the distal tibia, it is easily misdiagnosed as psoriatic arthritis of the ankle, but the diagnosis can be correctly made by careful investigation and use of imaging techniques. The only therapy is withdrawal of methotrexate. It is important that more physicians become aware of this side effect of methotrexate therapy, which can occur along with arthritic symptoms.