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1.  The Opposing Roles of Cellular Inhibitor of Apoptosis Proteins in Cancer 
ISRN Oncology  2012;2012:928120.
Cellular inhibitors of apoptosis proteins 1 and 2 (cIAP1/2) are members of the inhibitor of apoptosis protein (IAP) family that has been implicated in the pathology of human cancers due to their overexpression and function as blockers of cell death in various cancers. As a result, small molecule IAP antagonists have been developed and are currently under clinical evaluation for potential therapeutic use. In contrast, recent evidence has indicated a tumour-suppressing role for the cIAPs. Mutations in or loss of cIAPs have been identified as molecular lesions that contribute to constitutive activation of NF-κB in hematopoietic malignancies. These studies reveal a context-dependent role for the cIAPs wherein both their overexpression and loss may contribute to tumourigenesis.
doi:10.5402/2012/928120
PMCID: PMC3425795  PMID: 22934195
2.  Neonatal resuscitation 2: an evaluation of manual ventilation devices and face masks 
Background: The key to successful neonatal resuscitation is effective ventilation. Little evidence exists to guide clinicians in their choice of manual ventilation device or face mask. The expiratory tidal volume measured at the mask (VTE(mask)) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation.
Aim: To compare the efficacy of (a) the Laerdal infant resuscitator and the Neopuff infant resuscitator, used with (b) round and anatomically shaped masks in a model of neonatal resuscitation.
Methods: Thirty four participants gave positive pressure ventilation to a mannequin at specified pressures with each of the four device-mask combinations. Flow, inspiratory tidal volume at the face mask (VTI(mask)), VTE(mask), and airway pressure were recorded. Leakage from the mask was calculated from VTI(mask) and VTE(mask).
Results: A total of 10 780 inflations were recorded and analysed. Peak inspiratory pressure targets were achieved equally with the Laerdal and Neopuff resuscitators. Positive end expiratory pressure was delivered with the Neopuff but not the Laerdal device. Despite similar peak pressures, VTE(mask) varied widely. Mask leakage was large for each combination of device and mask. There were no differences between the masks.
Conclusion: During face mask ventilation of a neonatal resuscitation mannequin, there are large leaks around the face mask. Airway pressure is a poor proxy for volume delivered during positive pressure ventilation through a mask.
doi:10.1136/adc.2004.064691
PMCID: PMC1721950  PMID: 15871989
3.  Neonatal resuscitation 3: manometer use in a model of face mask ventilation 
Background: Adequate ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation (PPV) is initiated with manual ventilation devices via face masks. These devices may be used with a manometer to measure airway pressures delivered. The expiratory tidal volume measured at the mask (VTE(mask)) is a good estimate of the tidal volume delivered during simulated neonatal resuscitation.
Aim: To assess the effect of viewing a manometer on the peak inspiratory pressures used, the volume delivered, and leakage from the face mask during PPV with two manual ventilation devices in a model of neonatal resuscitation.
Methods: Participants gave PPV to a modified resuscitation mannequin using a Laerdal infant resuscitator and a Neopuff infant resuscitator at specified pressures ensuring adequate chest wall excursion. Each participant gave PPV to the mannequin with each device twice, viewing the manometer on one occasion and unable to see the manometer on the other. Data from participants were averaged for each device used with the manometer and without the manometer separately.
Results: A total of 7767 inflations delivered by the 18 participants were recorded and analysed. Peak inspiratory pressures delivered were lower with the Laerdal device. There were no differences in leakage from the face mask or volumes delivered. Whether or not the manometer was visible made no difference to any measured variable.
Conclusions: Viewing a manometer during PPV in this model of neonatal resuscitation does not affect the airway pressure or tidal volumes delivered or the degree of leakage from the face mask.
doi:10.1136/adc.2004.064709
PMCID: PMC1721943  PMID: 15871988
4.  Volume guarantee ventilation, interrupted expiration, and expiratory braking 
Archives of Disease in Childhood  2005;90(8):865-870.
Background: In volume guarantee ventilation with the Dräger Babylog 8000 ventilator, inspiratory and expiratory flows are monitored and the expiratory tidal volume calculated following each inflation. The pressure for the next inflation is modified to ensure the expired tidal volume is close to the set value.
Aim: To investigate interrupted expiration observed during volume guarantee ventilation of spontaneously breathing, ventilated infants.
Methods: Spontaneously breathing infants, ventilated with volume guarantee, had recordings of gas flow, ventilator pressures, tidal volume waveforms, oximetry, heart rate, and transcutaneous oxygen and carbon dioxide during 10 minute recordings.
Results: A total of 6540 inflations were analysed from 10 infants; 62% were triggered. Two different patterns were found: (1) Normal volume guarantee pattern with 97% of triggered and 91% untriggered inflations. It had a normal expiratory curve and a mean expired tidal volume within 3% of the set volume, but a large variation due to the babies' breathing. (2) A pattern of interrupted expiratory flow after ∼3% of inflations due to a small inspiration (∼1.3 ml/kg) during expiration. This led the ventilator to calculate an inappropriate total expired tidal volume for that inflation and an increase in the pressure for the next inflation.
Conclusions: After about 3% of inflations, with volume guarantee ventilation, interruption of the expiration causes an increased pressure for the next inflation of ∼4.9 cm H2O, compared with normal volume guarantee inflation. The interrupted expiration is most likely to be due to diaphragmatic braking.
doi:10.1136/adc.2004.061390
PMCID: PMC1720535  PMID: 15886260
6.  What do parents think about enrolling their premature babies in several research studies? 
Objective: To investigate parents' opinions about enrolling their premature baby into several research studies in the few days after birth.
Methodology: A questionnaire was given to parents of premature babies in the neonatal intensive care unit who had been invited to join several studies (two to seven).
Results: All 50 mothers and 42 of 48 fathers completed the questionnaire independently; 28% had been asked to join two studies, 32% three, 24% four, 14% five, and 2% six studies. There were 61 babies with mean (SD) gestational age 26.9 (1.6) weeks and birth weight 877 (249) g. Nearly three quarters (71%) of the parents thought it was very good for their baby to be in a hospital that was carrying out a lot of research. Most (93%) thought that their baby would get the same or better care in a study. Only 15% thought their baby was too small for research studies. Almost all (98%) wanted to be involved in the decision about their baby joining a study. Only 22% were worried about the number of studies; 10% would not enrol their baby in any studies, but 74% were willing for their baby to join two or more studies, and 10% would enrol in all the studies. Most (94%) believed that their baby's participation would improve care of future babies.
Conclusions: Most of these parents were willing to join several studies. The majority were not worried about their baby participating in the studies. The profession needs to be aware that parents are supportive of neonatal research and participation in multiple studies.
doi:10.1136/adc.2004.061986
PMCID: PMC1721889  PMID: 15846012
8.  www.chlamydiae.com 
doi:10.1136/sti.78.6.447
PMCID: PMC1758345
10.  In vitro comparison of nasal continuous positive airway pressure devices for neonates 
Objective: To compare the resistance in vitro of different devices used for the delivery of nasal continuous positive airway pressure (NCPAP) in neonates.
Design: Flows of 4–8 litres/min were passed through a selection of neonatal NCPAP devices (single prong, Duotube, Argyle prong, Hudson prong, Infant Flow Driver), and the resultant fall in pressure measured using a calibrated pressure transducer.
Results: The decrease in pressure (cm H2O) for each device (size in parentheses) at a constant flow of 6 litres/min was: Duotube: (2.5), 21; (3.0), 6.2; (3.5), 2.3; single prong: (2.5), 4.4; (3.0), 2.1; (3.5), 1.2; Argyle prong: (XS), 3.6; (S), 1.9; (L), 1.5; Hudson prong: (0), 3.1; (1), 1.8; (2), 0.6; (3), 0.4; (4), 0.3; Infant Flow Driver: (small), 0.3; (medium), -0.3; (large), -0.5.
Conclusions: A large variation in the potential fall in pressure may occur in the clinical setting. Devices with short double prongs had the lowest resistance to flow. These results have implications in the selection of the optimal device/s for clinical application and for future comparisons in randomised trials of NCPAP in neonates.
doi:10.1136/fn.87.1.F42
PMCID: PMC1721427  PMID: 12091290
11.  Homosexual men, HIV, and sexual risk in 2001 
Sexually Transmitted Infections  2001;77(5):325-326.
doi:10.1136/sti.77.5.325-a
PMCID: PMC1744385  PMID: 11588274
13.  Genitourinary medicine and the Internet No 8. 
Genitourinary Medicine  1997;73(5):415-417.
PMCID: PMC1195907  PMID: 9534758
14.  Genitourinary medicine and the Internet No 7. 
Genitourinary Medicine  1997;73(4):320-321.
PMCID: PMC1195869  PMID: 9389960
15.  Genitourinary medicine and the Internet no 6. 
Genitourinary Medicine  1997;73(3):221-222.
PMCID: PMC1195828  PMID: 9306906
16.  Genitourinary medicine and the Internet No 5. 
Genitourinary Medicine  1997;73(2):144-145.
PMCID: PMC1195793  PMID: 9215101
17.  Genitourinary medicine and The Internet No. 4. 
Genitourinary Medicine  1997;73(1):73-74.
The Internet provides a rapid facility for accessing a large amount of information which, once found, can be manipulated in a variety of ways. For example, with the authors' permission, Web pages can be retrieved, converted into text files and edited to produce patient leaflets of sexually-transmitted conditions, prescribing information leaflets, clinical guidelines and protocols, etc. Collections of relevant Web sites placed in bookmarks on a Web browser for students to refer to could also form the basis for self-directed learning, and tutorials and small group teaching on specific subjects.
PMCID: PMC1195766  PMID: 9155562
18.  Genitourinary medicine and the Internet No 3. 
Genitourinary Medicine  1996;72(6):443-444.
PMCID: PMC1195737  PMID: 9038645
19.  Genitourinary medicine and the Internet. No 2. 
Genitourinary Medicine  1996;72(5):380-381.
PMCID: PMC1195710  PMID: 8976859
20.  Genitourinary medicine and the Internet. 
Genitourinary Medicine  1996;72(4):298-300.
PMCID: PMC1195684  PMID: 8976840
21.  In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double gene marking trial. 
Journal of Clinical Investigation  1996;97(2):515-521.
Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and IL-2 appears to produce dramatic regressions in patients with metastatic melanoma and renal cancer. However, the in vivo mechanism of TIL function is not known. We conducted an UCLA Human Subject Protection Committee, Recombinant DNA Advisory Committee, and FDA-approved clinical trial using genetically-marked TIL to test the hypothesis that these cells have unique, tumor-specific in vivo trafficking patterns. TIL and PBL (as a control effector cell population) were isolated and expanded in parallel in vitro in IL-2-containing medium for 4-6 wk. During the expansion, TIL and PBL were separately transduced with the amphotropic retroviral vectors LNL6 and G1Na. Transduced TIL and PBL were coinfused into patients and their respective numbers measured in tumor, peripheral blood, and normal tissues; integrated provirus could be quantitated and distinguished by DNA PCR. Nine patients were treated (six melanoma, three renal) and received between 4.5 x 10(8) and 1.24 x 10(10) total cells. Both "marked" TIL and PBL could be detected circulating in the peripheral blood, in some patients for up to 99 d after infusion. Marked TIL and/or PBL could be detected in tumor biopsies in six of nine patients as early as day 6 and as late as day 99 after infusion. No convincing pattern of preferential trafficking of TIL vs. PBL to tumor was noted. Moreover, concurrent biopsies of muscle, fat, and skin demonstrated the presence of TIL/PBL in comparable or greater numbers than in tumor in five patients. The results of this double gene marking trial provide interesting insights into the life span and trafficking of adoptively transferred lymphocytes, but do not support the hypothesis that TIL specifically traffic to tumor deposits.
PMCID: PMC507045  PMID: 8567975
22.  AIDS in Africans living in London. 
Genitourinary Medicine  1995;71(6):358-362.
OBJECTIVES--To investigate the presentation of HIV infection and AIDS amongst Africans diagnosed with AIDS living in London. METHODS--Identification of all AIDS cases of African origin attending four HIV specialist centres in South London--Guy's, King's, St George's and St Thomas' Hospitals--up to March 1994, by retrospective review of case notes of all HIV positive patients. RESULTS--Of 86 patients (53 women, 33 men) studied, 59 (69%) were from Uganda. The most frequent AIDS-defining diagnoses were: Pneumocystis carinii pneumonia (PCP) 21%, tuberculosis (TB) 20% (extrapulmonary TB 14%, pulmonary TB 6%), cerebral toxoplasmosis 14%, oesophageal candida 13%, cryptococcal meningitis 11%, wasting 6%, herpes simplex infection > 1 month 5%, Kaposi's sarcoma 5%, other 6%. Cytomegalovirus retinitis was diagnosed in one case. Late presentation was common; 70% were diagnosed HIV positive when admitted to hospital. The diagnosis of AIDS was coincident with a first positive HIV test result in 61%. The mean CD4 counts at both HIV and AIDS diagnoses were similar in both men and women: 87 x 10(6)/l and 74 x 10(6)/l in men and 99 x 10(6)/l and 93 x 10(6)/l in women respectively. Overall, TB 21 (24%) (extrapulmonary TB 12, pulmonary TB 9) was either the AIDS-defining diagnosis or was detected within three months of this event. Sixty-two per cent of TB cases were diagnosed within twelve months of entry to the UK compared to 34% of all other AIDS cases. The prevalence of STD was very low; genital herpes was the commonest STD: 17% of the women, 9% men; 28% of the men and 11% of the women tested had a positive TPHA test. In cases known to be HIV-positive prior to an AIDS diagnosis, 41% took prophylaxis for PCP and 45% had taken zidovudine (ZDV). Forty two of the study participants had 89 children: 59 of these children had mothers in the study. Overall, 37 (42%) of the children had lost at least one parent at the time of data assessment. CONCLUSIONS--PCP and TB were the most common initial AIDS-defining diagnoses. The majority of TB cases were diagnosed within 12 months of entry to the UK. An AIDS-defining diagnosis was the first manifestation of HIV-related illness in the majority of patients. Because of late presentation to medical services, access to treatments for HIV infection and prophylaxis against opportunistic infections was limited. Extending the role of clinics and staff into the community might facilitate both earlier presentation and access to services. Future provision of local services will need to be sensitive to the requirements of individuals from different cultures and backgrounds.
PMCID: PMC1196104  PMID: 8566973
23.  Differential splicing of Epstein-Barr virus immediate-early RNA. 
Journal of Virology  1992;66(10):6233-6236.
A variant form of splicing of RNA crossing the Epstein-Barr virus (EBV) BZLF1 gene was observed in the late productive cycle of EBV. This splice omits the middle exon of BZLF1 and joins the outer two exons of BZLF1 in frame, but the shortened form of BZLF1 protein (Z delta) could not be detected in natural EBV infections.
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PMCID: PMC283679  PMID: 1326670
25.  Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia. 
Journal of Virology  1991;65(6):2868-2874.
The BZLF1 protein of Epstein-Barr virus (EBV) is a key immediate-early protein which has been shown to disrupt virus latency in EBV-infected B cells. We have generated a monoclonal antibody, BZ1, to BZLF1 which reacts in immunohistology, immunoblotting, and immunoprecipitation and which recognizes both the active, dimeric form and the inactive, monomeric form of the protein. Biopsies of oral hairy leukoplakia, an AIDS-associated lesion characterized by high-level EBV replication, were examined by immunohistochemistry using the BZ1 monoclonal antibody. A differentiation-associated pattern of BZLF1 expression was observed, BZ1 reacting with nuclei of the upper spinous layer of the lesion. This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation. A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication. The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium.
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PMCID: PMC240913  PMID: 1851858

Results 1-25 (39)