Patterns of weight distribution under the metatarsal heads.
The longitudinal arch between the heel and the forefoot and the transverse arch between the first and fifth metatarsal heads, absorb shock, energy and force. A device to measure plantar pressure was used in 66 normal healthy subjects and in 294 patients with various types of foot disorder. Only 22 (3%) of a total of 720 feet, had a dynamic metatarsal arch during the stance phase of walking, and all had known abnormality. Our findings show that there is no distal transverse metatarsal arch during the stance phase. This is important for the classification and description of disorders of the foot. (+info)
Interdigitated deletion complexes on mouse chromosome 5 induced by irradiation of embryonic stem cells.
Chromosome deletions have several applications in the genetic analysis of complex organisms. They can be used as reagents in region-directed mutagenesis, for mapping of simple or complex traits, or to identify biological consequences of segmental haploidy, the latter being relevant to human contiguous gene syndromes and imprinting. We have generated three deletion complexes in ES (Embryonic Stem) cells that collectively span approximately 40 cM of proximal mouse chromosome 5. The deletion complexes were produced by irradiation of F(1) hybrid ES cells containing herpes simplex virus thymidine kinase genes (tk) integrated at the Dpp6, Hdh (Huntington disease locus), or Gabrb1 loci, followed by selection for tk-deficient clones. Deletions centered at the adjacent Hdh and Dpp6 loci ranged up to approximately 20 cM or more in length and overlapped in an interdigitated fashion. However, the interval between Hdh and Gabrb1 appeared to contain a locus haploinsufficient for ES cell viability, thereby preventing deletions of either complex from overlapping. In some cases, the deletions resolved the order of markers that were previously genetically inseparable. A subset of the ES cell-bearing deletions was injected into blastocysts to generate germline chimeras and establish lines of mice segregating the deletion chromosomes. At least 11 of the 26 lines injected were capable of producing germline chimeras. In general, those that failed to undergo germline transmission bore deletions larger than the germline-competent clones, suggesting that certain regions of chromosome 5 contain haploinsufficient developmental genes, and/or that overall embryonic viability is cumulatively decreased as more genes are rendered hemizygous. Mice bearing deletions presumably spanning the semidominant hammertoe locus (Hm) had no phenotype, suggesting that the classic allele is a dominant, gain-of-function mutation. Overlapping deletion complexes generated in the fashion described in this report will be useful as multipurpose genetic tools and in systematic functional mapping of the mouse genome. (+info)
Pads and flexion creases on the plantar surface of hammertoe mutant mouse (Hm).
The purpose of the present work was to determine the effects of the hereditary malformation of Hammertoe mutant mice (gene symbol Hm) on the surrounding morphological structures and, specifically, on the volar pads, i.e., the sites of the epidermal ridge patterns (dermatoglyphics). The hindlimbs of the wild-type (+/+) Hammertoe mice show no anomalies and their major pad and flexion crease configurations correspond to those of normal mice. The heterozygous (Hm/+) and homozygous (Hm/Hm) mice display a fusion of the interdigital tissues involving all digits with the exception of digit I. In Hm/Hm mice, this webbing extends to the distal phalanx and the markedly flexed digits form a shape resembling a hammer. In Hm/+ mice, the interdigital webbing does not extend as far and the digits show moderate flexion compared to those of Hm/Hm mice. Both Hm/Hm and Hm/+ have a rudimentary extra digit in the postaxial area of the hindlimbs. The ventral volar skin of the flexed digits is incompletely developed. The more posterior digits show the more severe camptodactyly. These aberrant configurations are related to the abnormal occurrence of the programmed cell death (PCD) in the interdigital zones II-IV and the proximal part of the postaxial margin during hindlimb development. They are limited to the pads on the plantar surface of the postaxial area; the preaxial area is not affected. As a result of a severe camptodactyly of digit V, its volar skin is shifted into the distal portion of the hypothenar area. This shifting affects the number, size, and location of the pads, especially of the hypothenar pad, resulting in varying pad configurations, such as a displacement of the distal and proximal components of the hypothenar pad, or a fusion of the two components of the hypothenar pad, leading to a reduced final pad number. These pad modifications are induced by the postaxial plantar surface shifting proximally and are not affected by the presence of an extra rudimentary digit. The pad modifications in Hammertoe mice with webbed digits and postaxial polydactyly resemble closely those of the previously studied mice with genetic preaxial polydactyly. (+info)
Perinatal development of endothelial nitric oxide synthase-deficient mice.
The purpose of this study was to evaluate the influence of endothelial nitric oxide synthase (eNOS) deficiency on fetal growth, perinatal survival, and limb development in a mouse model with a targeted mutagenesis of the Nos3 gene. Wild-type (Nos3+/+) and eNOS-deficient fetuses (Nos3-/-) were evaluated on Gestational Day (E)15 and E17, and newborn pups were observed on Day 1 of life (D1). The average term duration of pregnancy was 19 days. For the evaluation of postnatal development, a breeding scheme consisting of Nos3+/- x Nos3+/- and Nos3-/- x Nos3-/- mice was established, and offspring were observed for 3 wk. Southern blotting was used for genotyping. No significant differences in fetal weight, crown-rump lengths (CRL), and placental weight were seen between Nos3+/+ and Nos3-/- fetuses on E15. By E17, Nos3-/- fetuses showed significantly reduced fetal weights, CRL, and placental weights. This difference in body weight was also seen throughout the whole postnatal period. In pregnancies of Nos3-/- females, the average number of pups alive on D1 was significantly decreased compared to either E15 or E17. Placental histology revealed no abnormalities. On E15, E17, and D1, Nos3(-/-) fetuses demonstrated focal acute hemorrhages in the distal limbs in 0%, 2.6%, and 5.7%, respectively, of all mutant mice studied on the respective days. Bone measurements showed significantly shorter bones in the peripheral digits of hindpaws of Nos3-/- newborns. We conclude mice deficient for eNOS show characteristically abnormal prenatal and postnatal development including fetal growth restriction, reduced survival, and an increased rate of limb abnormalities. The development of this characteristic phenotype of eNOS-deficient mice dates back to the prenatal development during the late third trimester of pregnancy. (+info)
Screening diabetic patients at risk for foot ulceration. A multi-centre hospital-based study in France.
BACKGROUND: To determine the prevalence of risk factors for diabetic foot ulceration in diabetic patients free of active pedal ulceration in a hospital setting. METHODS: In sixteen French diabetology centres, a survey was conducted on a given day in all diabetic people attending the units, both as in- or out-patients. RESULTS: 664 patients were evaluated: 105 had an active foot ulcer and were excluded from the analysis as were four other patients due to lack of reliable data. From the 555 assessable patients, 40 (7.2%) had a history of foot ulcer or lower-limb amputation. Sensory neuropathy with loss of protective sensation, as measured by the 5.07 (10 g) Semmes-Weinstein monofilament testing, was present in 27.1% of patients, whereas 17% had a peripheral arterial disease mainly based on the clinical examination. On addition, foot deformities were found in 117 patients (21.1%). According to the classification system of the International Working Group on the Diabetic Foot, 72.8% of patients were at low-risk for pedal ulceration (grade 0) and 17,5% were in the higher-risk groups (grade 2 & 3). If patients with isolated peripheral arterial disease were considered as a separate risk group (as was those with isolated neuropathy), percentage of low-risk patients decreased to 65.6%. There was a clear trend between the increasing severity of the staging and age, duration of diabetes, prevalence of nephropathy and retinopathy. CONCLUSIONS: Prevalence of risk factors for foot ulceration is rather high in a hospital-based diabetic population, emphasising the need for implementing screening and preventive strategies to decrease the burden of diabetic foot problems and to improve the quality of life for people with diabetes. (+info)
A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24.
Split hand-split foot malformation (SHFM) is characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits. SHFM is usually an autosomal dominant condition and at least five loci have been identified in humans. Mutation analysis of the DACTYLIN gene, suspected to be responsible for SHFM3 in chromosome 10q24, was conducted in seven SHFM patients. We screened the coding region of DACTYLIN by single-strand conformation polymorphism and sequencing, and found no point mutations. However, Southern, pulsed field gel electrophoresis and dosage analyses demonstrated a complex rearrangement associated with a approximately 0.5 Mb tandem duplication in all the patients. The distal and proximal breakpoints were within an 80 and 130 kb region, respectively. This duplicated region contained a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and beta-TRCP genes, known to be involved in limb development. The possible role of these genes in the SHFM3 phenotype is discussed. (+info)
Evaluation of abnormal biomechanics of the foot and ankle in athletes.
Athletes often suffer from recurrent or chronic overuse symptoms of the lower extremities. During the office visit it is essential to analyse the patient's shoes, gait cycle, lower extremities and, especially, the talocrural, subtalar and more distal joints of the ankle and foot. The basic (clinical) biomechanical analysis can be supplemented by radiographs, treadmill and video analysis and mirror table (podoscope) examinations. Ideally, successful pain relief by correction of the observed abnormality with an orthotic device completes the diagnostic procedure, especially if symptoms return soon after the removal of the device. In treatment custom-made, expensive orthotics should not be prescribed for overuse symptoms without an obvious malalignment, for asymptomatic athletes with a malalignment, or for symptoms in which the causal relationship between the biomechanical abnormality and symptoms is difficult to see. Strict indications for prescription of orthotics and close cooperation between the attending physician, physical therapist and orthotist are prerequisites for obtaining good, long-lasting results. (+info)
Primary idiopathic osteolysis: description of a family.
A clinical, analytical, and radiological study was carried out on three members of the same family with multicentric idiopathic osteolysis. Transmission appeared to be via the dominant autosome present in the mother and two daughters. In the daughters osteolysis was seen in the carpal and tarsal bones, whereas in the mother radiology showed it to be in the phalanges of the hands and feet. (+info)