Compound heterozygosity of HLA‐DRB3*01:01 and HLA‐DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia

BACKGROUND: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life‐threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune‐dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)‐1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response. STUDY DESIGN AND METHODS: In this study our aims were to find whether other allele variants of the β subunit of the HLA‐DR family specifically focused on the HLA residues that bind Position 33 of the HPA‐1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti‐HPA‐1a and anti‐HLA Class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn. We examine the genotype of 23 mothers to newborns with FNAIT compared to a control group. RESULTS: Our results suggested that, when HPA‐1 incompatibility with the husband is found, the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of a preventive immunoglobulin G treatment. We provide a structural model for the molecular basis of the rational effects of the different HLA alleles. In addition, we found that the presence of both anti‐HPA‐1 and anti‐HLAs did not aggravate FNAIT in comparison to mothers harboring only anti‐HPA‐1. CONCLUSION: Overall, we suggest that a specific genotyping of the mother in relation to HLA‐DRB as well as HPA‐1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT.     

Detection of anomalous vertebral arteries by ultrasound as an alternative to radiological methods

In order to examine ‘ultrasound’ approach in detecting the course of the vertebral artery (VA) and its anomalies important for neck surgery. An observational study with retrospective analysis of ultrasound images. 500 VAs on 250 3D CT angiographies and 500 ultrasound images performed on the same set of patients were analyzed. The relationship between the extraosseous portions of the VA to the neck organs with a special emphasis to the thyroid gland area, and the abnormal position of the VA were detected. Ultrasound and CT 3D images were compared. Ultrasound detected that 29 out of 500 VAs were anomalous (5.8%), 3D CT detected 30 cases. These anomalies were found in 22 patients (8.8%) (23 for 3D CT; 9.2%), in 7 (31.8%) of them bilaterally. An abnormal level of entrance (C3, C4, and C5) was observed in all anomalous cases. An additional case detected by 3D CT indicated C7 level of entrance. The ultrasound data correspond the CT data in 96.7% of cases. In ten cases (33.3%) the anomalous VA run close to the thyroid gland even touching the lower pole (16.7%; n = 5) or the upper pole (10.0%; n = 3) of the gland. In ten cases (33.3%) the anomalous VA crossed common carotid artery and the internal jugular vein by a way of a median loop. The incidence of anatomic variations of the VA is significant. Preoperative ultrasound investigation allows precise identification of anomalous VAs. Radiation-free ultrasound investigation of blood vessels is as precise as CT 3D imaging.     

Assessing wound severity with color and infrared imaging of reactive hyperemia

This study examined the use of cutaneous reactive hyperemia as a means for noninvasive assessment of wound severity of newly formed temperature-modulated pressure injuries in a porcine model. Two methods to quantify the extent of the reactive hyperemic reflex were developed. First, color image analysis was used to measure the hue of injured tissue. The specific hue of the skin surface of the wounded site was found to provide an indication of the severity of the wounds. Second, infrared imaging, coupled with computer image processing, was used to detect differences in skin temperature. The relative surface temperature of the wounds showed a strong correlation with the presence or absence of deep tissue injury. Both techniques correlated with the severity of the injuries as determined by a histologic assessment of biopsied tissue, but infrared imaging provided the better means to assess wound depth.     

Phase I clinical trial of fludarabine phosphate (F-ara-AMP)

Summary F-Ara-AMP (fludarabine phosphate) is an adenosine analogue that is resistant to deamination; it is a more potent cytotoxic compound than ara-A in experimental tumor systems. F-Ara-AMP was given by continuous IV infusion over 5 days once every 4 weeks to 27 evaluable adult patients with advanced cancer. The median Karnofsky performance status was 70% (range 50%–90%), and the median age was 58 years (range 41–74). In addition to adequate blood counts, a creatinine clearance of at least 60 ml/min was required. The initial dose level was 35 mg/m²/day. Dose-limiting myelosuppression was seen in the first patient. Subsequent patients were treated at lower doses. Myelosuppression was the only major toxicity. Leukopenia was generally more prominent than thrombocytopenia, but 2 patients experienced prolonged thrombocytopenia which prevented further therapy. Nausea was minimal, and neither renal nor neurologic toxicity was encountered. In patients with good renal function a dose of 25 mg/m²/day can be safely administered. However, because of apparent cumulative myelosuppressive effects a lower dose is more appropriate for patients who have had extensive prior chemotherapy or radiotherapy.Supported by CCPP grant CA-05826 and Contract NO1-CM-27546 from the National Cancer Institute, National Institutes of Health, Bethesda, Md. The content of this paper was presented in part at the 76^th meeting of the American Association for Cancer Research, Toronto, 1984     

Dispensing habits of Johannesburg pharmacists in treating acute infantile diarrhoea

Sixty pharmacists in Johannesburg were randomly selected and questioned on their suggested treatment of acute infantile diarrhoea as well as their knowledge of oral rehydration therapy (ORT); 53 (88%) responded. Of 51 pharmacists who had treated diarrhoea in children, 8 (16%) had never heard of ORT, while 20 (39%) treated this condition with antidiarrhoeal drugs. These findings are perturbing, because acute diarrhoeal disease is the biggest cause of mortality of children aged 1-4 years in South Africa and ORT is recognised as an effective means of prevention of death.     

Phase II trial of ZD1694 (TomudexTM) in patients with advanced pancreatic cancer

SummaryBackground Currently available therapies for advanced pancreatic cancer offer only palliative benefits, and patients with this disease have a poor prognosis. We undertook a phase II trial of ZD1694 (Tomudex^TM), a quinazoline folate analogue that is a potent and selective thymidylate synthase inhibitor, to determine this analogue's efficacy and safety in patients with advanced pancreatic adenocarcinoma.Patients and methods ZD1694, 3.0 mg/m², was administered to 42 adult patients with pancreatic adenocarcinoma as a 15-minute intravenous infusion every 3 weeks for up to 6 doses. Objective tumor response was assessed every 6 weeks; clinical examinations, adverse event assessments, and clinical laboratory tests were performed every 3 weeks.Results ZD1694 produced an overall response rate of 5% (95% confidence limits [CI], 1% to 16%) in the study group. Of 42 patients, 2 (5%) had a partial response, 12 (29%) had stable disease, 21 (50%) had disease progression, and 5 (11%) could not be evaluated for response. Grade 3 vomiting, grades 3 and 4 fever, grade 3 leukopenia, grade 4 thrombocytopenia, and grades 3 and 4 liver function elevations were reported. Toxic effects with ZD1694 were reversible and manageable.Conclusions ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.Tomudex is a tradename, the property of Zeneca Limited. Supported by a grant from Zeneca Limited.