Biomedical subjects
Publications and source records attributed to M H Reed.
Restrictive dermopathy is an inherited syndrome characterized clinically by severe growth retardation, abnormal skin, characteristic facies, and multiple congenital contractures. Distinctive radiologic features include deficient mineralization of the clavicles and the skull, overtubulation and frequent modeling defects of the long bones, and occasional abnormalities of the ribs and scapulae.
The objective of our prospective study was to assess the role of contact thermography in children with migraine. Contact thermograms were done in 54 children aged 4.2-16.5 years (median 10.5 years), who were seen for headache and on 10 age-matched controls, between July and December 1991. Thermograms were interpreted as definitely normal, equivocally normal, equivocally abnormal, and definitely abnormal by a radiologist who was blinded to clinical information. Forty-eight children had the test between headaches; of these, four out of 26 patients (15%) who had migraine without aura and 3 out of 14 children (21%) who had migraine with aura had definitely abnormal thermograms. Nine out of 10 normal controls had definitely normal thermograms. The sensitivity of contact thermography in the diagnosis of childhood migraine, when done between headaches, was low in our study.
Normal ossification of the hyoid bone was studied on the basis of postpartum radiographs of 10 stillborn children and radiographs of the cervical spine or the lateral neck of 86 children ranging in age from newborn to 16 years old. None of the patients was suspected of having any abnormality of skeletal ossification. Ossification of the hyoid was seen only after 30 weeks' gestation. The body of the hyoid was ossified in all infants older than 4 months, and the greater cornua were ossified in all those older than 6 months. Ossification of the lesser cornua did not appear in children less than 15 years of age. Normal measurements for the body of the hyoid and the greater cornua were determined.
Radiographs of the hyoid region of 13 patients with cleidocranial dysplasia were reviewed. In all but one the hyoid bone was less ossified than normal. Delayed ossification, affecting the skull, the teeth, the pelvis and the extremities, is a known, frequent manifestation of this abnormality.
Heterotopic calcification or ossification of the soft tissues adjacent to the lesser trochanter was observed in the radiographs of 4 patients during a retrospective review of the records of 68 patients with Perthes' disease. This abnormality has since been seen in one other patient with Perthes' disease and in five with spastic quadriplegia. All 10 patients are known to have undergone iliopsoas release as part of adductor tenotomy. The authors believe that the heterotopic ossification is related to the surgery.
We report on a child with a unique constellation of congenital anomalies suggesting a new syndrome. These consist of developmental delay; craniofacial abnormalities, including bilateral cataracts, ptosis, median nasal groove, malformed ears with associated neurosensory hearing loss; dental anomalies consisting of anomalous cusp morphology with unusual pointed extensions and delayed tooth eruption; short stature with marked delay in epiphyseal ossification; coronal clefts involving vertebrae T11-S2; and dislocated hips. A literature search and use of a computer-assisted syndrome-identification program failed to uncover an identical case.
Sixteen patients with 20 forearm deformities were reviewed. The deformities were classified into three types. The degree of ulnar tilt of the radius, ulnar displacement of the carpus, and relative ulnar shortening were determined. The severity of the deformity correlated with these measurements. Metacarpal lengths were also measured. Significant metacarpal shortening without exostoses was seen in 10 of 11 patients and with exostoses remote from the metaphysis in 10 of 13 patients. Metacarpal shortening correlated with the type and severity of deformity.
Hand radiographs of 49 carriers of infantile hypophosphatasia and 67 non-carriers were evaluated using two Apple IIe Computer Programs and an Apple Graphics Tablet. CAMPS (1) was used to determine the bone lengths and calculate the metacarpophalangeal profiles. A newly developed program (ADAM) was used to determine bone density based on percent cortical area of the second metacarpal. Carriers of infantile hypophosphatasia had significantly less dense bones.
A case of spondylometepiphyseal dysplasia congenita, Strudwick type is presented. At birth, this condition cannot be distinguished from spondyloepiphyseal dysplasia congenita. Features in common include delayed ossification of the public bones and proximal femoral epiphyses, coxa vara, odontoid hypoplasia and lumbar lordosis. The distinguishing radiologic feature of this condition is the striking irregularity of long bone metaphyses which develops during infancy.
The radiologic abnormalities seen in patients with juvenile rheumatoid arthritis (JRA) include disturbances of growth, various types of joint destruction, abnormalities of bone density, periostitis, and soft tissue abnormalities. We review the English language literature, which deals with the radiologic abnormalities in general, and at specific sites. We also review briefly radiologic abnormalities seen in other organ systems. The role of the other imaging modalities in the assessment of JRA is discussed.
The records of fifteen patients (11 girls and 4 boys) with a congenital transverse deficiency of the forearm were studied. In 11 patients the lesion was on the left. The deficiency occurred in the proximal third of the forearm in 13 patients. The radius and the ulna were usually bowed, and their shafts were sometimes irregular. The radial head was dislocated in six patients, and minor abnormalities occurred in the distal humerus in five and the proximal ulna in five.
The ability of RO 23-6457, a retinoid compound with marked in vitro immunosuppressive properties, to prolong vascularized allografts was examined in several in vivo transplantation models. In the murine heterotopic heart model, efficacy was shown in two H-2 incompatible strain combinations, with indefinite graft survival at some doses. In the rat heterotopic heart model, oral administration prolonged Wistar-Furth grafts in Lewis hosts an average of 1 week, with no long-term survivors at a variety of doses. Given subcutaneously, grafts were further prolonged, but the compound proved toxic. In a bilaterally nephrectomized renal transplant model in cynomolgus monkeys treated intravenously at a dose of 2 mg/kg/day, host survival was prolonged to 18, 32, 33, and 74 days, compared with 11, 11, 12, 13, and 26 days in untreated controls (P less than 0.05 by rank-sum testing). The three shorter surviving recipients died from anorexia and weight loss with normal renal function, while the longest survivor rejected its kidney when exhaustion of iv sites precluded further treatment. The toxic effects of the compound resemble the syndrome of hypervitaminosis A. RO 23-6457 will prolong graft survival as a single agent, justifying further preclinical testing and efforts to reduce toxicity.
The authors have reviewed our experience with 37 cases of toddler's fracture. This fracture of the distal tibia occurs in 1 to 4 year-old-children. History of trauma is usually trivial and the physical findings and radiological appearance are often subtle. The latter consists of a faint oblique lucent line crossing the distal tibia and terminating medially. It is usually seen on the anteroposterior view, poorly seen on the lateral and well seen on the internal oblique. Initial radiographs may be normal. A similar fracture of the midshaft of the tibia was associated with child abuse. Treatment consists of immobilization for a few weeks to protect the limb and to relieve pain. Diagnosis requires a high index of suspicion and is important because it obviates the need for investigations to rule out more sinister etiologies such as tumor or infection. The finding of a midshaft tibial fracture may indicate child abuse.
The radiographic findings in seven children with tarsal osteomyelitis are described. The bones involved were the calcaneus, talus, cuboid, and navicular. The lesions appeared as single, subchondral, reasonably well-defined round lucencies measuring up to 12 mm in diameter. Bone scans were positive. The lesions healed slowly with surrounding sclerosis but no periosteal reaction.
Abnormalities are described in the shoulders of 11 patients up to 17 years of age who have chronic brachial plexus paralyses from birth injuries. These abnormalities include a poorly formed and hypoplastic humeral head, a short abnormally formed clavicle, and a hypoplastic elevated scapula with a shallow glenoid fossa, inferiorly directed coracoid process, and abnormally tapered acromion. Four also had subluxated shoulders.
In an effort to produce specific immunosuppression through the targeting of those lymphocytes expressing cell surface interleukin 2 receptors in response to an allograft, the anti-human IL-2 receptor monoclonal antibody anti-Tac was administered to cynomolgus monkeys receiving renal transplants. The data demonstrate that anti-Tac produces a significant delay in renal allograft rejection and prolongs host survival in cynomolgus monkeys. Though higher doses of anti-Tac produce modest delays in rejection, there was a surprising finding of greatly prolonged survival in three of five monkeys treated with much lower doses of anti-Tac. Anti-Tac was not shown to be synergistic with cyclosporine in this model. Animals treated with anti-Tac developed high titers of antibodies against the murine monoclonal antibody after 6-8 days of treatment, associated with the disappearance of plasma anti-Tac staining of activated lymphocytes as measured by flow cytometry. The data confirm the utility of the IL-2 receptor as a target for immunosuppressive therapy, and suggest that investigations of dosage and of methods to reduce the immunogenicity of anti-IL-2 receptor agents may be beneficial.
Periodic assay of IL-2 receptor expression on the surfaces of peripheral blood lymphocytes might provide information predictive of in vivo immunologic events. This study compares two methods of determining IL-2 receptor expression after renal transplantation in cynomolgus monkeys. The first utilized single color staining of peripheral blood mononuclear cells with mouse anti-human IL-2 receptor monoclonal antibody followed by a fluorescein-labeled goat anti-mouse IgG antibody. Epics C cell sorter windows were set to count cells of the size and granularity of normal lymphocytes. The second utilized two-color staining with fluorescein-labeled anti-IL-2 receptor antibody, combined with phycoerythrin-labeled anti-CD4 antibody or with phycoerythrin-labeled anti-CD8 antibody. Two-color staining allowed the sorter windows to be enlarged to count all mononuclear cells, regardless of size or granularity, without introducing the contaminating effects of monocytes. Data obtained from single-color staining showed no consistent or significant expression of the IL-2 receptor on peripheral lymphocytes in association with the rejection process. Data obtained from two-color staining revealed an increase of IL-2 receptor expression on peripheral T cells of at least 10% from the postoperative baseline, which preceded the creatinine rise from allograft rejection in 13 of 13 animals. Increases in IL-2 receptor expression on T cells were not specific to rejection, however. Some animals in which treatment produced a delay of rejection showed a transient rise in IL-2 receptor expression around post-transplant day 5, which was not followed by a rise in creatinine. The two-color staining technique described provides a sensitive means of detecting IL-2 receptor expression in vivo and documents the association of increases in IL-2 receptor expression on T cells with rejection.
Monoclonal antibodies, either alone or conjugated to toxins, hold promise as important therapeutic agents. However, the immune response to these foreign protein agents may markedly limit their therapeutic utility in vivo. We have administered both an interleukin-2 receptor-specific monoclonal antibody (anti-IL-2R) and a CD2-specific monoclonal antibody linked to the ribosome-inactivating protein gelonin to macaque monkeys. The monkeys developed high-titer antibody responses to mouse Ig and, when immunotoxin was administered, to the toxin gelonin. Their antimouse Ig antibody responses were broadly reactive with mouse Ig of differing idiotypes and isotypes. Furthermore, sera from these monkeys blocked the in vitro cytotoxic effect of anti-IL-2R or immunotoxin. This blocking was mediated by both the antimouse Ig and the antigelonin antibodies. Serum from a monkey infused with one CD2-specific monoclonal antibody blocked the in vitro cytotoxicity of two other isotypically different CD2-specific monoclonal antibody conjugates. In addition, this serum blocked the in vitro cytotoxicity of a gelonin-monoclonal antibody conjugate of an unrelated specificity. These data indicate that the immune response to some monoclonal antibodies and toxins might preclude the later use of this class of substances in an individual. Therefore, strategies for the parental therapeutic use of monoclonal antibodies and immunotoxins must take into consideration the possible limiting effects of the humoral immune response to these agents.