Orthopaedic manifestations of familial dysautonomia. A review of one hundred and thirty-six patients

BACKGROUND: Familial dysautonomia is a hereditary multisystemic disease primarily affecting people of Ashkenazi Jewish descent. Musculoskeletal problems are related to gait disorders, spinal deformities, foot deformities, fractures, and arthropathies. METHODS: The charts and radiographs of 136 patients who ranged in age from three months to forty-six years (mean, sixteen years) were reviewed. Sixty-four patients were available for follow-up examination. RESULTS: Spinal deformity was the most common orthopaedic problem and was diagnosed in seventy-eight patients starting at the age of four years, with a prevalence of 86 percent (forty-eight of fifty-six) by the age of fifteen years. Forty-one (53 percent) of the seventy-eight patients had scoliosis only, thirty-four (44 percent) had kyphoscoliosis, and three (4 percent) had kyphosis only. Bracing was accompanied by emotional, pulmonary, and skin problems, leading to a high rate of noncompliance and progression of the curve. Twenty-four patients had an operation at a mean age of thirteen years (range, five to eighteen years): twenty patients had posterior spinal arthrodesis, and four had combined anterior and posterior arthrodesis. Fifteen patients had a total of nineteen complications, of which seven were systemic and twelve were related to the spinal fixation. Eight patients had revision surgery. At the time of the surgery, scoliosis was corrected from a mean of 55 degrees to a mean of 35 degrees and kyphosis was corrected from a mean of 69 degrees to a mean of 61 degrees. After a mean duration of follow-up of sixty-five months, scoliosis measured 49 degrees (range, 18 to 62 degrees) and kyphosis measured 67 degrees (range, 30 to 115 degrees). Postoperative progression of the deformity was caused by failure of the instrumentation or progression in unfused segments. Walking was delayed in 72 percent (ninety-four) of the 130 patients who were of walking age. All sixty-four of the patients who were examined had an ataxic gait. Foot deformities were found in sixteen patients, six of whom were treated surgically. Two patients had Charcot joints. Fifty-five patients sustained at least one fracture before skeletal maturity, with a mean of 1.5 fractures per patient. All but one of the fractures was treated nonoperatively, and fracture-healing was often accompanied by profuse callus formation. CONCLUSIONS: Spinal deformity is common in patients with familial dysautonomia. Bracing is of questionable benefit, and surgical intervention should be considered once curve progression is well documented. Arthrodesis should be extended as far proximally as possible to prevent junctional kyphosis. Swelling and warmth in a limb should raise suspicion of an undiagnosed fracture.     

Short-term wound complications after application of flaps for coverage of traumatic soft-tissue defects about the tibia. The Lower Extremity Assessment Project (LEAP) Study Group

BACKGROUND: The purpose of the present study was to compare the rate of short-term wound complications associated with rotational flaps and that associated with free flaps for coverage of traumatic soft-tissue defects about the tibia. METHODS: Of 601 patients prospectively enrolled in a multicenter study of high-energy trauma of the lower extremity, 190 patients (195 limbs) required flap coverage and had six months of follow-up. The injury data included the ASIF/OTA classification of the tibial fracture and the soft-tissue injury and the functional status of the neurovascular and muscular structures of the soft-tissue compartments at the time of soft-tissue coverage. The treatment data consisted of the type of flap, the timing of the flap coverage, and the type of fixation. The patient characteristics that were recorded included the age, gender, presence of comorbidities, and smoking status at the time of the injury. Short-term complications included wound infection, wound necrosis, and loss of the flap within the first six months after the injury. RESULTS: Eighty-eight limbs were treated with a rotational flap, and 107 limbs were treated with a free flap. Overall, complications occurred after fifty-three (27 percent) of the 195 flap procedures; forty-six (87 percent) of the fifty-three required operative treatment. The two treatment groups were similar with respect to age, gender, comorbidities, preinjury smoking status, ASIF/OTA classification of the fracture, and prevalence of vascular injury requiring repair (p>0.05). There were two important differences between the two groups. First, three of the four leg compartments--that is, the anterior, lateral, and deep posterior compartments--were more likely to be functionally compromised in the free-flap group than in the rotational flap group (p<0.05), suggesting that patients in the free-flap group had sustained more severe soft-tissue injuries. Second, the Injury Severity Score was significantly higher (p = 0.001) in the rotational flap group (mean, 14 points) than in the free-flap group (mean, 11 points), suggesting that patients in the former group had sustained more substantial total body trauma. Overall, there were no significant differences between the two groups with respect to the complication rates. However, among those with the most severe grade of underlying osseous injury (an ASIF/OTA type-C injury), 44 percent of the limbs that were treated with a rotational flap had a wound complication compared with 23 percent of the limbs that were treated with a free flap (p = 0.10). To control for any differences between the two groups with respect to the severity of the injury, the treatment methods, or the patient characteristics, multivariate regression modeling was performed. An interaction effect between the type of flap and the severity of the underlying osseous injury demonstrated significance (p<0.05) after controlling for other factors. Of the limbs that sustained an ASIF/OTA type-C osseous injury, those that were treated with a rotational flap were 4.3 times more likely to have a wound complication requiring operative intervention than were those treated with a free flap. No significant difference in the rate of complications was detected with respect to the type of flap used for the limbs that had lower-grade osseous injuries. CONCLUSIONS: We found that use of a free flap to treat limbs with a severe underlying osseous injury was significantly less likely to lead to a wound complication requiring operative intervention than was use of a rotational flap.     

Randomized phase II study of two doses of gefitinib in hormone-refractory prostate cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group.

PURPOSE: Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment. RESULTS: None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade 1 to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%; 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline. CONCLUSION: Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.     

Automated solid-phase extraction and two-step derivatisation for simultaneous analysis of basic illicit drugs in serum by GC/MS

A combination of automated solid-phase extraction (SPE) and subsequent two-step derivatisation has been developed for the simultaneous analysis of basic drugs of abuse and cocaine metabolites in serum samples. Substances included in this procedure are morphine, codeine, methadone, cocaine, benzoylecgonine, methylecgonine, amphetamine, methamphetamine, MDMA, MDEA and MDA. SPE with mixed-mode cartridges (RP-C8 and cation-exchange) was fully automated with a Zymark RapidTrace SPE robot. GC/MS analysis was performed after derivatisation with a new two-step reaction by trifluoroacetic anhydride and 2,2,3,3,3-pentafluoropropanol. High recoveries (> 85%) with high reproducibility (CV 1.1-3.8%) were found for all drugs. High correlation coefficients (r > 0.998) were obtained due to the addition of deuterated standards prior to extraction. Experience obtained over 2 years of applying this method to drug analysis in serum is discussed.     

Epipleurales H?matom

A 45-year-old man died from a ruptured aortic dissection as a consequence of cystic medionecrosis, which resulted in the formation of an epipleural hematoma of the left thoracic wall. Disruption of the detached parietal pleura was followed by exsanguination into the left pleural cavity. Epipleural or extrapleural hematoma is of clinical as well as of forensic importance as a relatively rare complication of blunt thoracic trauma which typically evolves from injured intercostal arteries. Non-traumatic epipleural hematomas are rare.     

Novel imaging techniques of the esophagus enhancing safety of left atrial ablation

This report describes different imaging techniques of the esophagus in four patients during radiofrequency catheter ablation of atrial fibrillation in the left atrium. A novel use of a mixture of barium cream and gadolinium diglutamate allowed esophageal imaging during magnetic resonance angiography of the left atrium and pulmonary veins. Barium cream used during computer tomography angiographic imaging of the left atrium and pulmonary veins allowed esophageal imaging. The esophagus was also imaged with an electroanatomic mapping system. Esophageal and left atrial imaging helped to avoid catheter ablation in left atrial tissue overlapping the esophagus.