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We report laboratory and clinical evaluations of a blood propofol concentration analyser. Laboratory experiments used volunteer blood spiked with known propofol concentrations over the clinically relevant concentrations from 0.5 to 16 µg.ml(-1) to assess linearity and the influence of haematocrit and concurrent drug administration. Analyser concentrations demonstrated excellent linearity (R(2) = 0.999). Blood spiked with commonly used drugs showed no significant variation compared to unspiked controls. Propofol measurements were largely independent of haemoglobin concentration. A 6% decay in propofol concentration was observed at the highest prepared concentration. Clinical performance of the analyser was assessed using 80 arterial blood samples from 72 patients receiving propofol infusions during cardiac surgery. Samples were processed using the propofol analyser, and high performance liquid chromatography (HPLC) used as a gold-standard comparator. These data demonstrated excellent agreement between the propofol analyser and HPLC with a bias of 0.13 µg.ml(-1) and precision of -0.16 to 0.42 µg.ml(-1).

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Hereditary multiple glomus tumours constitute an autosomal dominant skin disease which is known to demonstrate cutaneous mosaicism typified by type 1 and 2 segmental arrangements. We report a patient with type 2 segmental multiple glomangiomyomas who was disturbed by the pain of her lesions. A symptomatic lesion was successfully treated with the pulsed dye laser and to date there has been no recurrence of the pain. Possible explanations for the clinical response are discussed.

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BACKGROUND AND OBJECTIVES: The purpose of this study was to analyse the follow-up results for six blood donors who screened positive for hepatitis C virus (HCV) by nucleic acid amplification technology (NAT) but were non-reactive in the primary antibody immunoassay (HCV NAT yield). MATERIALS AND METHODS: Volunteer blood donations were screened, in parallel, for antibodies to hepatitis C virus (anti-HCV) and for human immunodeficiency virus (HIV)/HCV RNA using the Abbott PRISM HCV Chemiluminescent immunoassay (ChLIA) and the Chiron Procleix HIV-1/HCV RNA assays, respectively. NAT yield donor samples were further tested using supplemental assays, including an alternate HCV antibody enzyme immunoassay (EIA) (Abbott Murex anti-HCV Version 4), an immunoblot (Ortho RIBA-3 or Genelabs Diagnostics HCV Blot 3.0) and two alternative HCV NAT assays [Roche HCV Amplicor and an assembled HCV polymerase chain reaction (PCR)]. Five of the six donors were available for follow-up testing. RESULTS: The six NAT yield donations were identified as constituents of 24-member minipools among 2,212,695 donations screened over the 28-month study period. All samples were positive when tested, undiluted, using the Roche Amplicor and assembled reverse transcription-polymerase chain reaction (RT-PCR) alternate NAT assays. One of the donors, subsequent to seroconversion, showed RNA levels that fluctuated above and below the limit of detection of the NAT screening assay. Three of the six were reactive on the secondary EIA and showed reactivity to the core c22(p) antigen by immunoblot at the index donation. Two others subsequently became reactive in the ChLIA prior to the EIA, showing reactivity against c100 and/or c33c antigens by immunoblot. The remaining donor became reactive in the ChLIA and EIA at the same time, showing RIBA reactivity against all of the following three peptides: c100; c33c; and c22(p). CONCLUSIONS: This study demonstrated that at least five of six HCV NAT yield donors were in the pre- or early antibody seroconversion phase of infection. The observation that one yield donor demonstrated HCV RNA that fluctuated above and below the limit of detection of the primary NAT-screening assay supports the maintenance of both NAT and antibody screening for HCV. Follow-up testing of suspected yield donors revealed that the primary and alternate anti-HCV immunoassays had different performance characteristics, depending on the specificity of the donor's early anti-HCV response.

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The majority of newly diagnosed patients with Hodgkin's lymphoma are expected to survive because of effective therapies established during the last 40 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy that have contributed morbidity and excess mortality to Hodgkin's lymphoma survivors. As such complications have been recognized treatment approaches have been modified. Here we report a case of cervical neuropathy secondary to mantle radiotherapy, a complication not previously reported in the literature.

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BACKGROUND: Use of the polymerase chain reaction (PCR) for detection of the RHD gene can measure the RHD gene status for unborn babies at risk for hemolytic disease of the newborn (HDN). The occurrence of D gene variants has led to errors in prenatal typing. Previous reports have highlighted the danger of assigning a positive fetus as negative, resulting in intrauterine fetal deaths. OBJECTIVE: To evaluate the effectiveness of a testing strategy whereby PCR was not only performed to determine the presence/absence of the RHD gene, but also used to assess the D gene copy number (zero, one or two RHD genes) in family studies for at risk pregnancies. METHODS: Samples comprising maternal (57) and paternal (42) peripheral blood samples, amniotic fluid (64), and matching cord blood (64) were collected. Rhesus (Rh) serotyping was performed on all blood samples. For RHD genotyping, DNA was extracted from all samples except for 28 cord samples, where only serotyping was performed (total 199 DNA genotyping). RHD gene PCR amplified exon 4 and exon 7 regions of the RHD gene. The dosage of RHD gene was determined by comparing the intensity of the RHD gene to that of the RHCE gene. RESULTS: A total of 197/199 samples showed concordance between exon 4 and exon 7 PCR results. Two discrepant results occurred in one family: the father carried one normal D gene and one D gene variant where PCR was tested to be positive using exon 4 but negative using exon 7. One of a pair of dizygotic twins inherited this abnormal D gene and was mildly affected by HDN. This was correctly identified antenatally and the pregnancy successfully managed. The concordance rate between serotypes and genotypes for 135 blood samples was 100%. Amongst the family groups, 8/14 heterozygous fathers transmitted the D gene and 26/26 homozygous fathers transmitted the D gene to the babies. The concordance rate between RHD genotypes from amniotic fluid and Rh D serotypes from cord blood was also 100%. CONCLUSION: The present study demonstrates the effectiveness of using PCR in a clinical setting. It verifies the importance of testing more than one region of the gene, and also the need for a testing strategy where both maternal and paternal testing for RHD gene dosages are performed.

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Rare individuals who lack all of the Rh blood group antigens are called Rhnull and may be classified as "regulator" or "amorph" types. The suppression of Rh antigen expression for regulator types may be attributed to mutations of the RH50 gene, which is independent of the RH locus. The RH50 gene encodes a glycoprotein that interacts with the Rh proteins to form a functional complex within the red blood cell membrane. This report describes an RH50 gene mutation for a previously unclassified Rhnull donor. Sequencing cDNA clones from Rh50 mRNA revealed a single base change (G836A) yielding a missense and nonconservative mutation (Gly279Glu) within a predicted hydrophobic domain for this membrane protein. Genomic DNA studies using polymerase chain reaction (PCR) restriction analysis and sequencing showed that the Rhnull propositus was a composite heterozygote for this mutation, carrying two alleles with the A and G at nucleotide 836, respectively. In contrast, cDNA studies showed that only the A836 sequence was present, suggesting that the second allele with G836 was apparently silent (no transcript detected). Family studies showed that the mutant RH50 allele (836A) was inherited maternally, whereas the silent RH50 allele (836G) was from paternal transmission. These findings provide further evidence that rare but diverse genetic alterations may occur along the RH50 gene where the Rhnull syndrome of the regulator type occurs. The single amino acid change (Gly to Glu) provides insight into the critical value of these residues for assembly of the Rh antigen complex within the membrane.

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BACKGROUND: This study was undertaken to assess the prevalence of hepatitis C virus (HCV) antibody and RNA in first-time blood donors and to examine the HCV genotype distribution. STUDY DESIGN AND METHODS: A third-generation enzyme-linked immunosorbent assay (ELISA) was used to screen 34,725 donors for HCV antibodies. Donors who were repeatably reactive were tested in two immunoblot assays-a second-generation and a third-generation recombinant immunoblot assay-as well as by a polymerase chain reaction (PCR) assay. PCR-positive donors were genotyped. All samples were screened for alanine aminotransferase levels. RESULTS: The ELISA repeat reactivity rate was 0.55 percent. PCR testing showed that 69 (38%) of the 183 ELISA-reactive samples contained HCV RNA. The third-generation recombinant immunoblot assay identified all 69 viremic samples as antibody positive; however, only 63 tested positive on the second-generation immunoblot. The remaining six PCR-positive donors tested antibody-indeterminate to the core peptide. All six of these donors had HCV subtype 3a infections. Genotype distribution among 58 samples showed that 34 were type 1, of which 22 could be further subtyped as 1a (16) and 1b (6); 2 were 2a; 5 were 2b; and 17 were subtyped as 3a. Donors infected with 2b and 3a had reduced antibody reactivity to the NS4 and NS3 peptides only on the second-generation immunoblot. CONCLUSION: The prevalence of confirmed anti-HCV and viral RNA in new donors is 0.29 and 0.2 percent, respectively. The third-generation recombinant immunoblot assay was more sensitive than the second-generation immunoblot assay in detecting 2b and 3a HCV subtypes. The inclusion of the NS5 peptide in the third-generation recombinant immunoblot did not result in positive tests in any additional donors. Rather, the improvement was due to the increased detection of NS3 and, to a lesser extent, NS4 antibodies. Subtypes 1a and 3a were most prevalent in this population.

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The presentation of prostatic carcinoma with pulmonary metastases is unusual. The patient reported here presented with nodular lung metastases from an unknown primary site and 3.5 years later became symptomatic with a prostatic carcinoma. Subsequent hormonal therapy led to radiological regression of the pulmonary metastases. This case report demonstrates the progression of asymptomatic prostatic lung metastases with time and their response to delayed hormonal therapy, which is discussed.

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The susceptibility of the skin of patients with seborrhoeic dermatitis to surfactant irritation was investigated and compared to that of a group of normal subjects and patients with a history of atopic eczema. Responses to six concentrations of sodium lauryl sulphate (SLS), applied to forearm skin, were assessed clinically and measured by laser Doppler flowmetry. Analysis of dose-response curves showed statistically significant increased susceptibility to SLS-induced irritation in patients with seborrhoeic dermatitis and atopic eczema compared with normal subjects. Increased susceptibility to chemical irritation may be important in the pathogenesis of seborrhoeic dermatitis.

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The hypothesis that sebum permits the growth of Pityrosporum ovale, and hence the development of seborrhoeic dermatitis, was tested by observing whether a reduction of sebum production by isotretinoin would improve the disorder. In 10 male patients with seborrhoeic dermatitis, treatment with isotretinoin for 6 weeks reduced the mean sebum excretion rate by 70% and improved the severity of the rash, but with a site difference in magnitude of response. It is concluded that the residual pool of sebum is important for the growth of P. ovale and that, within the physiological range, sebum has a permissive effect on the growth of this yeast. Variation in the pools of residual sebum explains a number of features of the disease such as site of involvement and greater prevalence in males than females. The pathological increase in the residual pool of sebum due to immobility explains the frequent occurrence of seborrhoeic dermatitis in patients with a variety of neurological disorders.

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