A search for hepatitis C virus polymerase chain reaction-positive but seronegative subjects among blood donors with elevated alanine aminotransferase

BACKGROUND: Previous studies reported the existence of hepatitis C virus (HCV) polymerase chain reaction (PCR)-positive but seronegative sera. This is not surprising in the case of window-phase specimens, because PCR can detect HCV RNA many weeks before the appearance of antibody. To determine whether such sera can also be found in chronically infected subjects, a high-risk population of blood donors with elevated alanine aminotransferase was studied. STUDY DESIGN AND METHODS: Freshly frozen plasma from 301 donors with alanine aminotransferase > 100 IU per L was tested with PCR assays that were rigidly controlled for specificity and contamination, and with current and newer versions of assays for anti-HCV. Sera were classified as seropositive if positive in two screening assays and one supplemental assay or if positive in two screening assays and PCR. RESULTS: New versions of screening assays detected 100 percent of seropositive samples. A second-generation immunoblot assay detected 98 percent of seropositive sera, a second-generation recombinant immunoblot assay detected 96 percent, and an enzyme immunoassay for antibody to the envelope protein of HCV detected 98 percent. Fifty-one of 54 seropositive sera were PCR positive. None of the 247 seronegative samples was reproducibly positive on PCR. CONCLUSION: No PCR-positive but seronegative donors were found in this high-risk donor population. The possible benefit of PCR screening of blood donors can be determined only by large-scale comparative testing of donor populations and may be limited to the detection of window-phase infections.     

Caring for the wounded healer—nurturing the self

Health professionals have to deal with a “wounded society”, for example, violence, natural disasters and displaced people. Shortage of health professional groups and the high use of complementary therapies may reflect professional wounds, such as stress and burnout. Self-care is an important aspect of health professionals’ lives, given modern-day work stressors that can affect an individual's physical, mental and spiritual health. Often people become healers through personal suffering. Each person wounded or not, needs to understand his or her own need to be nurtured, and develop and implement a self-care health programme. Personal and professional reflection are important to understanding the nature of events that lead to “wounds” and how they can be transcended and the experiences used in holistic care. Aromatherapy can be a useful addition to self-care especially in managing stress and minor self-limiting conditions.     

Laparoscopic and robotic partial nephrectomy without renal ischaemia for tumours larger than 4?cm: perioperative and functional outcomes

Purpose

To evaluate the technical feasibility, safety and functional outcomes of zero ischaemia laparoscopic and robotic partial nephrectomy with controlled hypotension for renal tumours larger than 4?cm.

Methods

We evaluated 121 consecutive patients with American Society of Anaesthesiologists (ASA) scores 1–2 who underwent laparoscopic (n?=?70) or robotic (n?=?51) partial nephrectomy with controlled hypotension with either tumour size ≤4?cm (group 1, n?=?78) or tumour size >4 cm (group 2, n?=?43) performed by a single surgeon from December 2010 to December 2011. Operative data, complications, serum creatinine, estimated glomerular filtration rates and effective renal plasma flow calculated from 99mTc-mercaptoacetyltriglycine renal scintigraphy were compared. Differences between groups were evaluated by the Chi-square test and the Student’s t test.

Results

A significant difference in mean intraoperative blood loss and postoperative complications was found between the two groups: 168?ml (range: 10–600?ml in group 1) and 205?ml (range: 90–700?ml in group 2); p?=?0.005, and 6.4?% versus 18.6?%; p?=?0.004, respectively. The mean percentage decrease of ERPF of the operated kidney was 1.8?% in group 1 and 4.1?% in group 2.

Conclusions

Laparoscopic and robotic partial nephrectomy with controlled hypotension for tumours >4?cm in ASA 1–2 patients was feasible with significant higher intraoperative blood loss and postoperative complications compared to smaller renal masses. The benefits of avoiding hilar clamping to preserve kidney function seem excellent.     

Chronic myelocytic leukemia: eosinophils involved in the malignant clone

Chronic myelocytic leukemia (CML) is a clonal disorder involving neutrophil, monocyte, erythrocyte, and platelet precursors. In order to determine if the eosinophils are also involved in the leukemic clone, we purified the eosinophils from a woman heterozygous for the common electrophoretic variants of the G6PD gene. Only type B enzyme was demonstrable in the eosinophils, neutrophils, and red cells, but both A and B enzymes were found in the fibroblasts. The data provide evidence that the eosinophil is involved in the malignant clone.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.     

Demonstration of reversible priming of human neutrophils using platelet- activating factor

Exposure of neutrophils to agents such as lipopolysaccharide, tumor necrosis factor-alpha (TNF-alpha), and the granulocyte-macrophage colony-stimulating factor causes a major upregulation of subsequent agonist-induced NADPH oxidase activation. This priming effect is a prerequisite for neutrophil-mediated tissue damage and has been widely considered to be an irreversible process. We have investigated the potential for neutrophils to recover from a priming stimulus by studying the effects of platelet-activating factor (PAF). PAF did not stimulate respiratory burst activity directly, but caused a rapid (maximal at 10 minutes) and concentration-dependent (EC50 50.2 nmol/L) increase in N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated superoxide anion release. At time-points > 10 minutes, this priming effect spontaneously declined, with return to basal levels of fMLP- stimulated superoxide anion generation by 120 minutes. An identical priming time-course was observed with N-methyl carbamyl PAF, a nonmetabolizable analogue of PAF, indicating that the transient nature of PAF-induced priming was not secondary to PAF metabolism. Two structurally diverse PAF receptor antagonists (UK-74,505 and WEB 2086), added 10 minutes after PAF addition, increased the rate of decay of the priming effect. In contrast, TNF-alpha-induced priming, which was of a similar magnitude to that observed for PAF, was slower to evolve (maximal at 30 minutes) and remained constant for at least 120 minutes. The reversible nature of PAF-induced priming was confirmed by demonstrating that PAF-, but not TNF-alpha-, induced cell polarization (shape change) and CD11b-dependent neutrophil binding of albumin-coated latex beads was also transient, with return to basal, unstimulated levels by 120 minutes. Furthermore, cells that had spontaneously deprimed following PAF exposure retained their capacity to be fully reprimed by a subsequent addition of either PAF or TNF-alpha. These data imply that neutrophil priming is not an irreversible event: the demonstration of a cycle of complete priming, depriming, and repriming offers the potential for functional recycling of neutrophils at sites of inflammation.