Time-based analysis of the apheresis platelet supply chain in England.

During 2009/2010 loss of platelets within NHS Blood and Transplant (NHSBT) due to time expiry was 9.3%. Hospitals remain reluctant to hold stocks of platelets due to the poor shelf life at issue. The purpose of this study was to identify areas for time compression in the apheresis platelet supply chain to extend the shelf life available for hospitals and reduce wastage in NHSBT. This was done within the context of NHSBT reconfiguring their supply chain and moving towards a consolidated and centralised approach. Time based process mapping was applied to identify value and non-value adding time in two manufacturing models. A large amount of the non-value adding time in the apheresis platelet supply chain is due to transportation and waiting for the next process in the manufacturing process to take place. Time based process mapping provides an effective 'lens' for supply chain professionals to identify opportunities for improvement in the platelet supply chain.

Rosai-Dorfman disease: a report of eight cases in a tertiary care center and a review of the literature.

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

Transient blood-brain barrier permeability following profound temporary global ischaemia: an experimental study using 14C-AIB.

The influence of reperfusion after profound incomplete forebrain ischaemia on blood-brain barrier (BBB) permeability to a small protein tracer was studied in male Sprague-Dawley rats. The mean cortical blood to brain transfer constant (Ki) for 14C-amino isobutyric acid (AIB) was significantly greater at 3 and 6 h of reperfusion, 2.5 times the mean values of controls (p less than 0.05) (2.5 microliter g-1 min-1 and 1.0 microliters g-1 min-1 respectively), but had returned to control values after reperfusion for 24 h. Analysis of distribution of Ki values showed that following 15 min and 30 min of profound ischaemia, there was a significant increase in transfer of AIB across the blood-brain barrier (BBB) after recirculation for up to 6 h, though there was no evidence of protein extravasation as assessed by Evans Blue (EB) dye. After 24 h of reperfusion, the BBB to AIB was restored, and Ki values had returned to control values. It is concluded that following transient global ischaemia, the BBB may recover rapidly.

19F imaging of cerebral blood oxygenation in experimental middle cerebral artery occlusion: preliminary results.

Fluorine (19F) nuclear magnetic resonance may be used to image cerebral perfusion in cats receiving perfluorocarbon blood substitutes. 19F relaxation times in these blood substitutes are dependent on oxygen tension (PO2) and may be used to calculate and spatially map cerebrovascular PO2 values in vivo. We have applied this noninvasive method to experimental middle cerebral artery (MCA) occlusion. Following MCA occlusion a perfusion defect is evident in the sylvian region, followed by the appearance of collaterals. Signal from the ipsilateral rete mirabilis is increased. Calculated cortical vascular PO2 values indicate a relative reduction in oxygenation in the ischaemic hemisphere. PO2 maps show a perfused hypoxaemic zone adjacent to the perfusion defect. These changes are partly reversed with reperfusion.

Incidence of retroviruses in some Brazilian groups.

The prevalence of human T lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) antibodies was evaluated in Brazil among 116 aboriginal Indians living in a pre-Amazonian region, and in 44 patients with haematological malignant disorders being treated in Rio de Janeiro. Screening for the presence of antibodies to HIV was performed routinely for 17,224 blood donors at the National Cancer Institute, Rio de Janeiro, from January 1986 to May 1987. The results demonstrated that HIV infection was not endemic among Brazilian Indians, as none of them had antibodies to HIV, in contrast with the population of Rio de Janeiro, which showed a high prevalence (0.34%) of positivity among normal individuals. In a small group of patients with haematological disease only one with acute lymphoblastic leukaemia proved to be HIV-positive, the infection having been acquired through previous blood transfusion. None of the serum samples reacted with HTLV-I, including those of 17 non-Hodgkin's lymphoma patients. HTLV-I infection does not seem to be endemic in this country, but further large scale studies are necessary, especially in patients with haematological disorders, homosexual individuals and drug users.

Massive epistaxis from nasal CPAP therapy.

A 75-year-old man with obstructive sleep apnea and secondary right heart failure was started on nasal CPAP therapy. Shortly thereafter he experienced massive life-threatening epistaxis requiring nasal packing and hospitalization. The epistaxis was thought to be due to the drying effect of nasal CPAP.

Detection of BCR-ABL transcripts by multiplex and nested PCR in different haematological disorders.

Single-step Multiplex RT-PCR was used as a rapid and highly sensitive method for screening patients with myeloproliferative conditions and ALL for the presence of underlying BCR-ABL gene fusions. Positive and negative results obtained with the multiplex assay were subsequently confirmed by nested PCR. We studied 21 patients for detecting the presence of b3a2, b2a2 and e1a2 BCR-ABL transcripts at diagnosis and following treatment with different therapeutical procedures. These studies allowed the molecular characterisation of patients with different haematological disorders and for demonstrating BCR-ABL transcripts in Ph-CML. In a Ph+ CML patient, a switch of isoforms was detected after bone marrow transplantation and infusion with donor lymphocytes, implying substitution of e1a2 for b3a2 coexisting with a myeloid/lymphoid biphenotypic profile. In ALL, one Ph+ patient showed coexpression of e1a2 and b2a2 at diagnosis followed by persistence of e1a2 after bone marrow transplantation. Our results were compared to previous findings in the literature on molecular diagnosis of leukaemias.

Adult T-cell leukemia/lymphoma and cluster of HTLV-I associated diseases in Brazilian settings.

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.

Otosyphilis and hearing loss: response to penicillin and steroid therapy.

Acquired and congenital syphilis are both known causes of potentially reversible sensorineural hearing loss. Various therapeutic regimens, including penicillin and/or corticosteroids have been used in the past as treatment for otosyphilis. Response rates have varied from 15% to 80%. In this retrospective study, 13 patients with otosyphilis were treated with a combined course of long-term penicillin and prednisone. A significant response was defined as a 15% improvement in the discrimination score and/or the pure tone average. Initial response rates were 35% with a lasting response rate of 15%. Discrimination scores improved more commonly than pure tone averages. No patient with congenital syphilis or profound deafness had a lasting response. An analysis of possible reasons for failure of therapy is discussed.

Long-term results with MACOP-B in the treatment of aggressive non-Hodgkin's lymphomas. The experience in Brazil.

From October 1984 to December 1989, 59 patients with aggressive non-Hodgkin's lymphomas (diffuse mixed, diffuse large cell, and immunoblastic) were treated with MACOP-B. All patients were previously untreated and most of them had advanced disease. Complete response (CR) was observed in 66%. Actuarial overall survival, failure-free survival (FFS), and relapse-free survival at 8 years were 54%, 52%, and 81%, respectively, with a median follow-up of 76 months (range: 28-92 months). The presence of B symptoms influenced significantly the CR rate, while FFS was affected by B symptoms, bone marrow involvement, and number of extranodal sites. Toxicity was high, with mucositis grade 2 or 3 occurring in 70%, leukopenia grades 3 or 4 in 80%, and death in 11.8% of the patients. MACOP-B was active in the treatment of aggressive non-Hodgkin's lymphomas, mainly in patients with few poor-prognosis factors, but other less toxic regimens would be more appropriate for this population. For poor-prognosis patients, new therapeutic modalities are necessary.

Adult T-cell leukemia/lymphoma associated with HTLV-1 infection in a Brazilian adolescent.

We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report.

Randomised controlled trial of brief intervention with biofeedback and hypnotherapy in patients with refractory irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common disorder associated with profoundly impaired quality of life and emotional distress. The management of refractory IBS symptoms remains challenging and non-pharmacological therapeutic approaches have been shown to be effective. We compared brief interventions with biofeedback and hypnotherapy in women referred by their GP with refractory IBS symptoms. Patients were randomised to one of two treatment groups, biofeedback or hypnotherapy, delivered as three one-hour sessions over 12 weeks. Symptom assessments were undertaken using validated, self-administered questionnaires. Two of the 128 consecutive IBS patients suitable for the study declined to consider nonpharmacological therapy and 29 patients did not attend beyond the first session. Of the 97 patients randomised into the study, 21 failed to attend the therapy session; 15 of 76 patients who attended for therapy dropped out before week 12 post-therapy. The mean (SD) change in IBS symptom severity score 12 weeks post-treatment in the biofeedback group was -116.8 (99.3) and in the hypnotherapy group -58.0 (101.1), a statistically significant difference between groups (difference=-58.8, 95% confidence interval [CI] for difference [-111.6, -6.1], p=0.029). In 61 patients with refractory IBS, biofeedback and hypnotherapy were equally effective at improving IBS symptom severity scores, total non-gastrointestinal symptom scores and anxiety and depression ratings during 24 weeks follow-up. Biofeedback may prove to be the more cost-effective option as it requires less expertise.

Rosai-Dorfman disease: a report of eight cases in a tertiary care center and a review of the literature

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

[3H]thymidine labels less than half of the DNA-synthesizing cells in the mouse tumour, carcinoma NT.

We have studied carcinoma NT, a transplantable mouse adenocarcinoma of spontaneous origin. Cells labeled with [3H]thymidine ([3H]TdR) were restricted to a narrow zone around the periphery of this tumour and were also found in rings up to 50 micrometers wide, around isolated blood vessels in the central necrotic area. Labelling with [3H]deoxyuridine ([3H]UdR), another DNA synthesis precursor, produced a very different pattern. The labelled zone around the periphery was much wider than with [3H]TdR, and [3H]UdR labelled cells were found up to 110 micrometers from isolated vessels. [3H]iododeoxyuridine ([3H]IUdR) gave the same pattern of labelling as [3H]UdR. In the heavily labelled zone, within 1 mm of the tumour periphery, the labelling index (LI) was 51% after [3H]UdR or [3H]IUdR injection, and only 36% with [3H]TdR. The data show that at least half of the DNA-synthesizing cells in this tumour did not incorporate [3H]TdR. Previous workers reported cell loss factors for carcinoma NT of 60% calculated from [3H]TdR labelling data and 30% from the rate of loss of [125I]UdR. The present work suggests that calculations based on [125I]UdR data are more likely to be accurate for carcinoma NT than those using [3H]TdR data.