Methotrexate pharmacogenetics in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory arthritis that can not only result in permanent joint damage, but is associated with high morbidity and mortality. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs improve the symptoms of joint pain and swelling, but more importantly, prevent the progression of joint damage. Methotrexate (MTX) is the first-line DMARD in RA with over two decades worth of excellent long-term efficacy and safety. However, there is significant variability in patients' response to MTX, both in efficacy and toxicity. Recent advances in genetics, particularly pharmacogenetics, may permit the prediction, a priori, of an individual patient's response to MTX. In this review, we highlight recent published literature on the pharmacogenetics of MTX in RA. Pharmacogenetics may be a useful means of optimising MTX therapy in patients with RA.

Biomechanical comparison of effects of supraspinatus tendon detachments, tendon defects, and muscle retractions.

BACKGROUND: Rotator cuff ruptures are frequently associated with loss of strength of the shoulder. However, the characteristics of the rotator cuff tear that are responsible for the loss of force generation and transmission have not yet been identified. The purpose of this study was to compare the effects of supraspinatus tendon detachments, tendon defects, and muscle retractions on in vitro force transmission by the rotator cuff to the humerus. METHODS: The rotator cuff tendons from ten cadaver shoulders were loaded proportionally to the respective cross-sectional areas of their muscles. A fiberglass rod was cemented into the medullary canal of the humerus and connected to a three-component load cell for the measurement of the forces transmitted by the rotator cuff to the humerus. This study was performed with the humerus in a hanging arm position and with various sizes of supraspinatus tendon detachments, tendon defects, and muscle retractions. RESULTS: Detachment or creation of a defect involving one-third or two-thirds of the supraspinatus tendon resulted in a minor reduction in the force transmitted by the rotator cuff (< or =5%), while detachment or creation of a defect involving the whole tendon resulted in a moderate reduction (11% and 17%, respectively). Simulated muscle retraction involving one-third, two-thirds, and the whole tendon resulted in losses of torque measuring 19%, 36%, and 58%, respectively. Side-to-side repair of the one-third and two-thirds defects nearly restored the force transmission capability, whereas a deficit remained after side-to-side repair following complete resection. CONCLUSIONS: Our results support the rotator cable concept and correspond to the clinical observation that patients with a small rupture of the rotator cuff may present without a loss of shoulder strength. Muscle retraction is potentially an important factor responsible for loss of shoulder strength following large rotator cuff ruptures. CLINICAL RELEVANCE: Supraspinatus muscle retraction diminishes glenohumeral abduction torque significantly more than either a defect in the tendon or a simple detachment of the tendon from the tuberosity. In cases of irreparable defects, side-to-side repair may be worthwhile to restore muscle tension and the integrity of the rotator cable.

Treatment and clinical management of recurrent knee empyema due to methicillin-resistant Staphylococcus aureus (MRSA) after total knee replacement.

We describe a patient with recurrent knee empyema and associated complications caused by methicillin-resistant Staphylococcus aureus (MRSA) after total knee replacement and the difficulties and limited options in its clinical management.

Delayed cervical epidural hemorrhage associated with silastic dural implant: case report.

OBJECTIVE AND IMPORTANCE: This is the first report of delayed cervical epidural hemorrhage caused by an onlay silastic graft placed over the dura after laminectomy. There are several reports of intracranial hemorrhage associated with silastic implants in the literature. CLINICAL PRESENTATION: A 49-year-old woman suddenly developed severe neck pain and quadriplegia during sexual intercourse. A C5-C7 laminectomy had been performed 17 years earlier for cervical stenosis. INTERVENTION: Magnetic resonance imaging showed an epidural mass compressing the cord at the level of the previous laminectomy. Laminectomy was performed within 5 hours of symptom onset. Postoperatively, the patient regained leg strength. After 2 months of physical therapy, she had minimal residual leg rigidity and returned to work. TECHNIQUE: At surgery, the cervical cord was compressed by a solid fibrous scar surrounding a silastic onlay graft and the dura. An epidural hematoma was beneath the silastic implant. The dense scar tissue, hematoma, and silastic implant were removed. CONCLUSION: Bleeding associated with silastic sheets starts with movement of this nonadherent implant. The movement disrupts the underlying fine vessels on the surface of an encasing connective tissue membrane. Overgrowth of this membrane can cause mass effect and simulate a tumor, even without associated bleeding, within weeks. Delayed hemorrhage is more common. We recommend removal of these implants electively, especially if a thick membrane surrounding the dura is detected with postcontrast-enhanced magnetic resonance imaging.

A comparative analysis of primate nasal airways using magnetic resonance imaging and nasal casts.

The nasal cavity is an intricate part of the respiratory tract. It is not only the site of olfaction, but also serves as a filter to protect the lower respiratory tract from inhaled pollutants. A substantial fraction of inhaled particles deposit in this region and may pose potential health risks. To predict possible sites of inhaled aerosol deposition and better understand health risks associated with inhaled aerosols in this region, it is necessary to examine the morphometry of the nasal passage. Magnetic resonance imaging (MRI) of the nose was done from the anterior to the posterior, in 3-mm sections, on five anesthetized rhesus monkeys and on two nasal casts (one human and one rhesus monkey). The MRI images were analyzed for perimeter and cross-sectional areas of each section. Results indicated that the left and right nasal passages were very symmetric for the five monkeys but not for the human cast. The cross-sectional area and, consequently, the volume varied greatly among monkeys in vivo. Measurements from the monkey cast exhibited 1.4-fold differences normalized body weight in cross-sectional areas, but with smaller differences in perimeter when compared to the MRI in vivo images. The human cast exhibited a volume three times greater than that of the monkey cast, while the surface area was approximately doubled. Results from this comparison showed many similarities in the structure of the monkey and human nose suggesting that the rhesus monkey would be a good human surrogate in aerosol deposition studies.

Reversal of CNS-prophylaxis-related leukoencephalopathy after CSF shunting: case histories of identical twins.

We report the case histories of identical twin brothers who developed concordant acute lymphoblastic leukemia at the age of 4 years and who later developed leukoencephalopathy and hydrocephalus related to central nervous system prophylaxis by, in the first case intrathecally administered methotrexate and, in the second by intrathecally administered methotrexate and cranial irradiation. The delayed encephalopathy developed 9 and 22 months respectively after the first dose of intrathecal methotrexate. Both patients underwent cerebrospinal fluid shunting mainly for their hydrocephalus. The imaging studies have shown that both hydrocephalus and leukoencephalopathy have improved significantly after ventriculoperitoneal shunt insertion. We review the pathophysiology of prophylaxis-related encephalopathy in leukemia patients and summarize its clinical, histological, and radiological characteristics. We also discuss the possible contribution of altered cerebrospinal fluid dynamics in the development of leukoencephalopathy.

Spinal subdural haematoma as a complication of immediate epidural blood patch.

PURPOSE: The authors report a case of a patient who developed spinal subdural haematoma after a series of epidural blood patches to alert anaesthetists to this rare complication. CLINICAL FEATURES: The patient was a 35-yr-old woman without coagulopathy and was initially treated elsewhere for chronic pain by repetitive epidural phenol injections. When the dura was inadvertently punctured during subsequent attempts to inject phenol, immediate epidural blood patch was performed to treat or prevent headache. The patient developed cauda equina syndrome after six epidural blood patches. The clinical diagnosis was confirmed by magnetic resonance imaging and the intradural haematoma was evacuated surgically. The patient made a complete recovery. CONCLUSIONS: Epidural blood patch is not without complications. Transient backache and/or radiculopathy may occur in up to one-third of patients receiving a blood patch. If signs and symptoms continue or worsen, a spinal subarachnoid and/or subdural haematoma should be suspected and neurosurgical opinion sought. The technique used to identify the epidural space is important in preventing subdural injection of blood. The needle should be withdrawn after dural puncture and the epidural space identified at a different level. Blood patches may carry a higher risk of serious complications after multiple epidural phenol injections because of fibrosis and obliteration of the epidural space. Magnetic resonance scans reliably demonstrate the extent of the pathology. If diagnosed and treated before irreversible changes occur, spinal intradural haematoma can result in complete recovery.

Extradural tumor causing spinal cord compression in Klippel-Trenaunay-Weber syndrome.

BACKGROUND: Myelopathy in Klippel-Trenaunay-Weber syndrome is uncommon but has been reported secondary to spinal vascular malformations. REPORT: A patient with Klippel-Trenaunay-Weber syndrome who presented with spinal cord compression from a spinal extradural mass lesion (angiomyolipoma) is described. DISCUSSION: This association has not been reported previously but is consistent with the segmental vascular abnormalities observed in Klippel-Trenaunay-Weber syndrome.

An ordinal pattern analysis of four hypotheses describing the interactions between drug-addicted, chronically disadvantaged, and middle-class mother-infant dyads.

This study investigated mother-infant interactions in 18 dyads. All participants were African American and enrolled in an early intervention program because the infants (2-26 months of age) had developmental disabilities or were at high risk for developmental disability. Some mothers had used drugs during their pregnancy, and all mothers were of low or middle socioeconomic status. Dyads were videotaped interacting at 4 different times, separated by at least 5 months in time. Videotapes were rated in terms of infant involvement and maternal responsivity in the interaction. 4 hypotheses concerning the pattern of maternal interaction across time were tested using ordinal pattern analysis. The hypothesis that mothers would become less responsive to infants over time (HD) as a function of drug addiction, poverty, or serious developmental delay was supported for only 4 of the 18 dyads. There was support for the hypothesis (H(I)) that mothers naturally increase their responsivity over time (N = 6) and support for the hypothesis (HT) that mothers' interactive sensitivity fluctuates in relation to infants' involvement in the interaction over time (N = 7). Ordinal pattern analysis has advantages in determining how well competing hypotheses describe individuals within populations relative to approaches that identify differences that apply to entire populations.

Relations among maternal stress, cognitive development, and early intervention in middle- and low-SES infants with developmental disabilities.

Relations between maternal stress and the development of infants with handicaps was examined in 72 middle-SES and 72 low-SES families who attended a weekly early intervention program. Measures of maternal stress and development of infants were obtained 10 months apart. Regression analyses predicted 81% of variance in later developmental level with initial Bayley MA, initial Mental Development Index (MDI), SES, initial stress, early intervention participation, and SES x Initial Stress x Attendance interaction. Subsequent maternal stress was predicted (42% variance explained) by initial stress, attendance, initial MDI, number of intervention agencies and MDI x SES x Attendance. Results were interpreted in terms of a transactional model.

[Corrective osteotomy of the femoral and tibial shafts using the interlocking nail]. / Korrekturosteotomien an Femur- und Tibiaschaft mit dem Verriegelungsnagel.

The indication for nailing a femur or tibia fracture has been extended by the method of interlocking up to the meta/diaphyseal zone. For the stabilisation of osteotomies in these regions, the nail was used in 19 cases of femur and 23 of tibia corrections between 1983 and 1988 in the Orthopedic University Clinic Berlin. The osteotomies were done with a small skin incision in open way. Although there were three infections, bone consolidation was succeeded in all but one patient with the planned axis. The first achieved gain in length could not be hold in five cases after removing the interlocking screws in order to give full weight bearing to the leg for callus formation. In situations of non-unions with wrong position or refracture of biologically troubled bones after plating the method of interlocking nail is stable and enables bone recovery after grafting by drilling. The possibility of early full weight bearing is a great advantage for the rehabilitation of patients, who had been suffering from delayed fracture healing before. The nail itself preserves the right position of the bone in two dimensions, even if there are not exact fitting osteotomy fragments, and the interlocking screws secure the shorter part of diaphysis against malrotation.

Prenatal diagnosis of autosomal dominant microcephaly and postnatal evaluation with magnetic resonance imaging.

A case of fetal autosomal dominant microcephaly was prenatally diagnosed with ultrasonography in a woman with previously undiagnosed microcephaly. At the time of initial ultrasonographic assessment, the mother was identified to have a markedly small cranium, consistent with maternal microcephaly. The ultrasonographic examination showed the fetal head size to be four standard deviations below the mean for gestational age. Gestational dating from the other biometric parameters and from the last menstrual period was consistent with 31 weeks' gestation. Neurosonographic evaluation of the fetus revealed no obvious structural abnormalities. Serial ultrasonographic examinations at 35 and 38 weeks' gestation showed no changes in the fetal head size. A 2.64 kg male fetus was delivered at term. Neonatal assessment showed the fetal head circumference to be less than the second percentile for gestational age. Neurologic assessment of the neonate with magnetic resonance imaging showed abnormal development of the brain, with small cerebellar and cerebral hemispheres, and pachygyria. These images are compared with the magnetic resonance images of the mother. Our findings of maternal and fetal microcephaly are consistent with autosomal dominant microcephaly. To our knowledge, this is the first report of the prenatal diagnosis of autosomal dominant microcephaly.

Comparison of computerized tomography with magnetic resonance imaging (MRI) in the evaluation of encephalic ventricular volume.

The volume of the encephalic ventricles was determined from computerized tomographic (CT) and magnetic resonance imaging (MRI) scans of seven subjects without apparent pathology and three subjects with enlarged ventricles. Since there are many conditions in which the encephalic ventricles become enlarged such as Alzheimer's disease and hydrocephalus, accurate measurement of these structures provides (1) a valuable and safe means of aiding in the diagnosis of such conditions and (2) important follow-up information on affected patients. This paper presents the data obtained from the second phase of a three phase study. The first phase demonstrated the possibility of measuring fluid filled spaces by MRI in three phantom preparations (small, medium, and large "ventricles"). The results were compared with those obtained from the computerized tomography (CT) scans of the same preparations. This phase of the study compares the volumes obtained from CT scans with those obtained from MRI scans of the same individuals. The volumetric calculations were done with the aid of a Calcomp 9000 digital analyser programmed to compensate for the scale factor and slice thickness of the images. The results obtained from the MRI scans correlated closely with those obtained from the CT scans of the same subjects. The third and final phase of the project is the development of an MRI volumetric data base for the encephalic ventricles using a larger number of subjects.

Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects.

Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for "normal" subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm3, while that for males was 16.3 cm3 and that for females was 18.0 cm3. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.