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.

Cerebral arteriovenous malformation and the primitive trigeminal artery.

A 27-year-old woman with a small cerebral arteriovenous malformation and a primitive trigeminal artery had subarachnoid hemorrhage. This case and a review of the literature suggest that some of the "spontaneous" subarachnoid hemorrhages reported in patients with a primitive trigeminal artery may have been due to rupture of an unrecognized small arteriovenous malformation or aneurysm.

Expanding the phenotype of the Proteus syndrome: a severely affected patient with new findings.

Here we report on a boy who died at 16 1/2 months with hemihypertrophy, eye abnormalities, macrodactyly, hamartomas, pigmented nevi, cerebral involvement, and other anomalies compatible with the Proteus syndrome. In addition, he also had abnormalities previously unreported in the Proteus syndrome including craniosynostosis and complex congenital heart defects. He seems to represent an extremely severe form of the Proteus syndrome and expands the already broad range of the phenotype.

Angiographic nephrectomy using iodinated contrast agent.

Diatrizoate meglumine and sodium (Renografin-76) was perfused in an obstructed renal artery in 13 dogs. Intense and prolonged accumulation of contrast agent ("contrast staining") was achieved in all animals. Repeat injection was frequently necessary to enhance staining. Renin output from the stained kidneys was lower than that from the opposite kidneys. Angiography at 14-18 weeks demonstrated a marked decrease in renal size in all dogs, with complete occlusion of the renal artery in two dogs. No collateral circulation was discerned. Grossly, all experimental kidneys were uniformly shrunken. Histologically, diffuse renal infarction was evident with coagulative necrosis. Contrast staining is an effective method for uniform destruction of renal tissue.

Antenatal diagnosis of Pena-Shokeir syndrome (type I) with ultrasonography and magnetic resonance imaging.

A case of Pena-Shokeir syndrome type I was diagnosed prenatally with ultrasonography and magnetic resonance imaging (MRI) in a woman with a possible previous occurrence. Initial ultrasonographic examination at 18.5 weeks' gestation demonstrated an unusual appearance of the fetal spine in an otherwise unremarkable fetus. However, subsequent sonographic examinations at 26 and 28.5 weeks demonstrated polyhydramnios and multiple skeletal, brain, and facial abnormalities. Magnetic resonance imaging, performed to further evaluate the fetal brain, confirmed the sonographic findings. However, MRI was not useful in further differentiating the diagnosis. A 1024-g, premature male fetus was delivered at 30 weeks' gestation and died within 30 minutes of delivery. The fetus had multiple congenital anomalies consistent with Pena-Shokeir syndrome type I.

Intracranial hemorrhage associated with meningioma.

Intracranial hemorrhage developed in two patients with meningioma without other apparent risk factors predisposing to hemorrhage. Bleeding has been reported to be associated with meningiomas regardless of the sex or age of the patient or the location of histological nature of the tumor. It can occur acutely without antecedent symptoms, often masking the tumor. The mechanism of hemorrhage is not clear. The complication has not been emphasized in the neurological literature and, although rare, should be considered in the differential diagnosis of intracranial hemorrhage.

Evaluation of brain death by contrast-enhanced computerized cranial tomography.

Four patients with clinical criteria of cerebral death were evaluated by computerized cranial tomography (CT). Upon intravenous infusion of meglumine diatrizoate, the intracranial vascular structures failed to enhance. Two of the patients also had electroencephalographic evaluation, and one patient underwent cerebral angiography, confirming the absence of cerebral blood flow. Contrast-enhanced CT may provide a contributory method in the establishment of cerebral death, in addition to elucidating the etiology of the ictus.

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.

Hydrocephalus and dementia complicating spinal tumor. Case report.

Hydrocephalus and dementia associated with spinal mass lesions are well recognized. Removal of the spinal mass has sometimes resulted in relief of the dementia. This case demonstrates that the ventricular size may also become smaller after removal of the spinal mass.

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.

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.

Traumatic pseudoaneurysm and arteriovenous fistula involving the middle meningeal artery.

Two cases of traumatic pseudoaneurysm and arteriovenous fistula involving the middle meningeal artery are reported with a review of the world literature on these specific entities. The two conditions appear to evolve through similar mechanisms and may lead to a confusing clinical picture. High quality angiography is important in making an early diagnosis, prior to performing a definitive surgical procedure.

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.

Preference and discrimination between response-dependent and response-independent schedules of reinforcement.

Four Asian quail (Coturnix coturnix japonica) were exposed to concurrent-chain schedules, the terminal links of which were either variable-interval 30 sec and variable-time 30 sec, or fixed-interval 30 sec and fixed-time 30 sec. Except for one bird that exhibited a preference for the variable-interval schedule over the variable-time schedule, no consistent preferences were demonstrated for response-dependent or response-independent schedules. However, response rates were three times greater on response-dependent than on response-independent schedules. The discrimination between terminal-link schedules was rapidly recovered after the schedule positions were reversed. Casual observations revealed that the birds engaged in stereotypic circling and pecking while the response-independent schedules were operative.

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.

[Thermography as an additional study method in the follow-up of reconstructive operations of the hand]. / Thermographie als ergänzende Kontrolluntersuchungsmethode nach Wiederherstellungsoperationen an der Hand.

The hand is very accessible to thermography. Disturbed circulation, vascular disease, tissue damage, or other causes of change in thermoproduction lead to deviation from a normal temperature chart. We found a high correlation between thermographic readings and prognosis after replantation. Thermography is, therefore, a method of examination that can be recommended.

[Apophyseal rupture of the pelvis and lower extremity caused by sports]. / Apophysenausriss am Becken und der unteren Extremität durch Sport.

Apophyses are secondary ossification centers and serve as the insertion or origin of tendons. They are under a dynamic but not static load. During sexual maturity, they represent a weak point in the locomotor system. Apophyseal injuries can apparently be attributed to an incongruity between load tolerance and increased strain on the seam of the apophysis. The majority of these injuries occur during sports and involve men more frequently than women. The injury is often primarily misinterpreted as a pulled-muscle. The treatment method is dependent on the localization of the injury and the extent of the fragment dislocation.

[Intramedullary nailing as an alternate method in the management of slow-healing or pseudarthrotic upper and lower leg fractures]. / Die Marknagelung als Methodenwechsel in der Versorgung verzögert heilender oder pseud-arthrotischer Ober- und Unterschenkelfrakturen.

Intramedullary nailing of delayed healing fractures and non-unions in the lower extremity is the method of choice in biological and biomechanical aspects. With the technic of interlocking screws the indication is extended to the metaphyseal areas of tibia and femur. By nailing as alternative method an ossification of fractures and non-unions can be reached at a rate of about 90 per cent. This result is rather unique in the literature. In the treatment of shaft non-unions after cast fixation or rigid stabilisation by plates or external fixation nailing must succeed throughout its weight-bearing system and only fails in the case of infection and wrong indication.