Immunologic status of hemophilia patients treated with cryoprecipitate or lyophilized concentrate

We evaluated 37 patients with moderate or severe hemophilia A and six patients with severe factor IX deficiency for clinical or laboratory evidence of immune abnormalities. Patients were assigned to one of four groups according to the type of clotting factor replacement. Twenty patients had received only cryoprecipitate during the two years preceding the evaluation (group I); 11 additional patients were treated predominantly with cryoprecipitate but had also received up to nine bottles of factor VIII concentrate (group II); six patients received factor VIII concentrate (group III); six patients received factor IX concentrate (group IV). There was no clinical or laboratory evidence of immunodeficiency among the 43 patients. The mean absolute number of Th cells was normal in all patient groups, but the mean absolute number of Ts cells was increased compared with controls, both in patients treated with cryoprecipitate and in patients treated with factor VIII or factor IX concentrate. There was no correlation between the Th/Ts ratio and patient age, alanine aminotransferase level, hepatitis serology, in vitro lymphocyte function, or amount of clotting factor administered. Our observations demonstrate that the volunteer or commercial origin of clotting factor replacement cannot fully explain the alterations in lymphocyte subset distribution previously described in patients with hemophilia A.     

A review of cervical spine injury associated with maxillofacial trauma at a UK tertiary referral centre

IntroductionThe aim of this study was to determine the incidence and patterns of cervical spine injury (CSI) associated with maxillofacial fractures at a UK trauma centre.MethodsA retrospective analysis was conducted of 714 maxillofacial fracture patients presenting to a single trauma centre between 2006 and 2012.ResultsOf the 714 maxillofacial fracture patients, 2.2% had associated CSI including a fracture, cord contusion or disc herniation. In comparison, 1.0% of patients without maxillofacial trauma sustained a CSI (odds ratio: 2.2, p=0.01). The majority (88%) of CSI cases of were caused by a road traffic accident (RTA) with the remainder due to falls. While 8.8% of RTA related maxillofacial trauma patients sustained a CSI, only 2.0% of fall related patients did (p=0.03, not significant). Most (70%) of the CSIs occurred at C1/C2 or C6/C7 levels. Overall, 455, 220 and 39 patients suffered non-mandibular, isolated mandibular and mixed mandibular/non-mandibular fractures respectively. Their respective incidences of CSI were 1.5%, 1.8% and 12.8% (p=0.005, significant). Twelve patients with concomitant CSI had their maxillofacial fractures treated within twenty-four hours and all were treated within four days.ConclusionsThe presence of maxillofacial trauma mandates exclusion and prompt management of cervical spine injury, particularly in RTA and trauma cases involving combined facial fracture patterns. This approach will facilitate management of maxillofacial fractures within an optimum time period.     

Unrelated donor marrow transplantation in children

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (n = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA- mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA- mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.     

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3- year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.     

Neuropsychiatric side-effects of lidocaine: examples from the treatment of headache and a review

Lidocaine has been used in treatment of patients with refractory headache. Personal observations of neuropsychiatric toxicity in these patients led us to review our cases and the literature systematically for lidocaine side-effects, especially neuropsychiatric symptoms. In our series of 20 patients, side-effects were observed in all, the most frequent being neuropsychiatric (75%) and cardiological (50%). When reviewing published series on intravenous lidocaine use, reports of side-effects range from 0 to 100%, with neuropsychiatric symptoms being reported in 1.8–100%. Thirty-six case reports of lidocaine-induced psychiatric symptoms were also analysed. Psychiatric symptoms of toxicity were similar in most patients, despite their differing ages, pathologies, co-therapies and lidocaine dosages. In conclusion, lidocaine neuropsychiatric toxicity has a well-recognized stereotypical clinical presentation that is probably unrecognized in headache series. As lidocaine represents an emerging alternative therapy in headache, particularly in short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, clinicians and patients should be aware of the extent of this problem.     

Construction of modern Australian first trimester ultrasound dating and growth charts

Accurate pregnancy dating is vital to obstetric management. However, first trimester fetal charts commonly used in Australia rely on data reported more than three decades ago. This study reports first trimester dating and growth charts for crown‐rump length between 5 and 14 weeks of gestation and biparietal diameter between 9 and 14 weeks of gestation on an Australia population using modern real‐time ultrasound equipment. All consenting eligible women attending a large Sydney clinic for first trimester ultrasound between March 2005 and December 2006 were recruited. Measurements were carried out to Australasian Society for Ultrasound in Medicine standard protocols. Statistical analyses were undertaken using polynomial regression models and thorough diagnostic checks made. Overall 396 eligible women consented to the study, with 268 between 9 and 14 weeks of gestation. The average participant age was 34 years (range 22–45 years), 371 and all yielded valid biometry measurements. Equations, means and 90% reference intervals for crown‐rump length measurements and biparietal diameter measurements were derived using polynomial regression models. Thorough residual and diagnostic checks were made. Once validated by others, we believe they will warrant consideration for use by Australasian Society for Ultrasound in Medicine.     

Cerebrospinal fluid exchange after intrathecal methotrexate overdose. A report of two cases

Two patients aged 11 and four years, were accidentally given a 10-fold overdose of intrathecal methotrexate while being treated for malignant disease. Neither patient developed any signs of neurotoxicity and exchange of lumbar cerebro-spinal fluid was started 3 and 5 h later, respectively. In one of the patients, who received 120 mg of methotrexate intrathecally, 31% of the given dose was recovered during 2 h of cerebrospinal fluid exchange that was started 3 h after the accidental overdosage. No sequelae were observed in any of the patients. Cerebrospinal fluid exchange is safe and can be recommended in all cases of intrathecal methotrexate overdosage. Ventriculo-cisternal perfusion is not necessary in cases of a 10-fold overdose if the patient has no signs of acute neurotoxicity.