Surgical management of patent ductus arteriosus in pre-term infants - a british paediatric surveillance study.

BACKGROUND: This study aimed to provide UK data describing the incidence of patent ductus arteriosus (PDA) surgery in the neonatal population, including: pre-ligation management, and outcomes until discharge. We used British Paediatric Surveillance Unit (BPSU) methodology; collecting data via questionnaires for preterm neonates undergoing PDA ligation (PDAL) between 1st Sept 2012 - 30th Sept 2013. Infants born less than 37 weeks gestation, who underwent PDAL prior to discharge home, with no other structural cardiac abnormality, were included. Information collected included: patient demographics, pre and post-operative clinical characteristics, pre-operative medical management, post-operative complications and outcome. RESULTS: Over the study, 263 infants underwent PDAL an incidence of 3.07 per 10,000 live births. 88% were born extremely preterm (< 28 weeks) and 60% were male. The commonest reasons for ligation were inability to wean respiratory support (83.7%) and haemodynamically significant PDA (87.8%). Pre-operatively 65.7% received medical therapy. Surgery was performed at a median age of 33 days (range 9-260, IQR 24-48); the corrected age was less than 31 + 6 week in 50.6% babies at PDAL. Most, (90%), of procedures were open ligation; only 9 (3.4%) were catheter occlusions (PDACO). 20.5% of patients had post-operative complications. The 30-day mortality was 3%, with 93.5% surviving to hospital discharge. CONCLUSION: This study showed there was little consensus over medical and surgical management of the PDA or timing of surgery.

The inhibition of free radical generation by preparations of Harpagophytum procumbens in vitro.

Harpagophytum procumbens (Hp), commonly known as Devil's Claw has been used as a traditional treatment for a variety of illnesses for centuries. Since the early twentieth century, it has become a popular antiinflammatory and analgesic preparation amongst European herbalists for supportive or adjuvant treatment of degenerative joint diseases. Extracts of Hp tubers have demonstrated antiinflammatory and analgesic effects in animal models of inflammation and in human trials. The mechanism(s) of action responsible for these attributes, however, remain to be elucidated. Reactive oxygen species generated in acute and chronic inflammatory diseases are known to be cytotoxic and can cause tissue damage. In this study, a root tuber extract (Hp extract) and commercially available tincture (Hp tincture) were investigated for antioxidant characteristics using in vitro test systems. Both preparations were found to effectively scavenge DPPH radical, inhibit nitrite levels in supernatants harvested from LPS-stimulated RAW 264.7 macrophages, and cause dose-dependent suppressions in the detection of fMLP- and AA-induced neutrophil MPO. The antioxidant effects demonstrated for both preparations of Hp may contribute to the antiinflammatory and analgesic properties observed for the plant.

Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs. monotherapy.

INTRODUCTION: The aim of this meta-analysis was to systematically review the effectiveness of co-therapy compared with monotherapy for people with bipolar mania. METHOD: MEDLINE, Embase, Psychinfo, The Cochrane Library and reference lists of retrieved studies were searched without language restrictions for randomized controlled trials evaluating co-therapy compared with monotherapy for acute bipolar mania. Each trial was assessed for susceptibility to bias. Data on mania outcomes, withdrawals, extrapyramidal symptoms and weight were extracted and pooled effect estimates summarized as relative risks (RR) or differences in mean values (MD) where appropriate. RESULTS: Eight eligible studies were included (1124 participants). Significant reductions in mania (Young Mania Rating Scale, YMRS) scores were shown for haloperidol, olanzapine, risperidone and quetiapine as co-therapy compared with monotherapy with a mood stabilizer. For atypical antipsychotics combined, the pooled difference in mean scores was 4.41 (95% CI: 2.74, 6.07). Significantly more participants on co-therapy met the response criterion (at least 50% reduction in YMRS score), RR 1.53 (1.31, 1.80). With some drugs, co-therapy decreased tolerability compared with monotherapy, and resulted in greater weight gain. There were insufficient data to compare one co-therapy regimen with another. CONCLUSION: The addition of antipsychotic treatment to established mood-stabilizer treatment is more effective than mood-stabilizer treatment alone.

A review of the biological and potential therapeutic actions of Harpagophytum procumbens.

Harpagophytum procumbens (Hp), commonly known as Devil's Claw is a perennial plant which thrives in arid conditions. For centuries, it has been used as a traditional treatment for a variety of illnesses, including fevers, skin complaints, arthritis and diseases of the digestive tract as well as an appetite stimulant. Since its introduction to Europe in the early twentieth century, it has become a popular antiinflammatory and analgesic preparation amongst herbalists for supportive or adjuvant treatment of degenerative joint diseases, tendonitis, headache, backache and menstrual pain. The validity of Hp as an effective antiinflammatory and analgesic preparation, particularly in the relief of arthritic symptoms, has been investigated in numerous animal, clinical and in vitro studies. Although some contradictory evidence exists, the majority of animal studies appear to indicate Hp as an effective antiinflammatory and analgesic preparation in the treatment of acute and subacute inflammation. Clinical trials support Hp as a beneficial treatment for the alleviation of pain and improvement of mobility in a variety of musculoskeletal conditions. Analysis of the in vitro and ex vivo studies that currently exist, indicate that Hp has significant effects on numerous proinflammatory markers. However, the exact mechanism(s) by which Hp may reduce inflammation remain to be elucidated.

Circulating levels of isoflavones and markers of 5alpha-reductase activity are higher in Japanese compared with New Zealand males: what is the role of circulating steroids in prostate disease?

Epidemiological evidence implicates dietary isoflavone intake as protective against prostate disease. A putative mechanism is attenuated circulating androgen levels in male populations consuming an isoflavone rich diet. We investigated this hypothesis by collecting plasma from 60 Japanese and 60 New Zealand males aged between 21 and 31 years each consuming their traditional diets. We measured plasma testosterone, dihydrotestosterone (DHT), androstenedione, dehydroepiandrosterone sulfate (DHEAS), the combined levels of androsterone sulfate and epiandrosterone sulfate (AoS/epiAoS), sex hormone-binding globulin, and cortisol and corticosteroid-binding globulin as well as the isoflavones genistein and equol. Plasma genistein and equol levels were several times higher in Japanese males as would be expected from an isoflavone rich diet. However, androstenedione, DHEAS, calculated free testosterone and paradoxically markers of 5alpha-reductase, DHT and AoS/epiAoS were all also significantly higher in Japanese rather than the New Zealand male counterparts. All other comparisons were not significant. Plasma DHT and DHEAS correlated positively with plasma equol and plasma AoS/epiAoS correlated positively with genistein levels. Taken together the results suggest that, rather than reduced levels of steroidogenesis, Japanese males may have increased 5alpha-reductase activity and possibly altered 17beta OH steroid dehydrogenase activity. Significantly the positive association between isoflavones levels and 5alpha-steroids is counter-intuitive to isoflavone intake offering prostate protection, unless this is postulated to occur through other mechanisms.

Comparison of trimethoprim-sulfamethoxazole, dapsone, and pentamidine in the prophylaxis of Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: To compare the incidence of Pneumocystis carinii pneumonia (PCP) in patients infected with the human immunodeficiency virus (HIV) receiving one of three prophylactic agents. DESIGN: Retrospective chart review. SETTING: A university-affiliated Department of Veterans' Affairs medical center HIV clinic. PATIENTS: All 200 HIV-infected patients enrolled in the clinic who were prescribed a PCP prophylactic drug during 18 months. INTERVENTIONS: Patients were administered oral trimethoprim-sulfamethoxazole (TMP-SMX) DS, oral dapsone, or aerosolized pentamidine in a heirarchic fashion. A subset of 110 patients received only one of the prophylaxis regimens for at least 6 months; they were examined separately for the purpose of statistical analysis. MEASUREMENTS AND MAIN RESULTS: One case of PCP was diagnosed in 1110 patient-months of oral TMP-SMX DS therapy, 6 in 418 patient-months of oral dapsone therapy, and 3 in 164 patient-months of aerosolized pentamidine therapy. In the subset population, the documented incidence of PCP was 0% among 71 TMP-SMX DS-treated patients, 16% among 25 dapsone-treated patients (p < 0.004), and 14% among 14 aerosolized pentamidine-treated patients (p < 0.03). For patients receiving primary prophylaxis, the incidence of PCP was 0% for 58 receiving TMP-SMX, 15% for 20 receiving dapsone (p = 0.015), and 17% for 6 receiving pentamidine (p = 0.094). CONCLUSION: We believe TMP-SMX DS was more effective than oral dapsone or aerosolized pentamidine in preventing PCP in these HIV-infected patients.

The provision of pharmaceutical care in a Veterans' Affairs Medical Center outpatient HIV clinic.

Recognizing the unique needs and demands of HIV-infected patients, it was decided to implement pharmaceutical care in a VAMC outpatient HIV clinic. Services provided to the patients by the pharmacist include drug information, medication counseling with the help of educational handouts, and drug-related problem identification and resolution. The pharmacist also serves as a liaison between the patient and the VAMC outpatient pharmacy if conflicts arise. Services provided to the other members of the HIV clinic team include the provision of drug information and participation in clinical research. In addition, the HIV clinic provides a training site for pharmacy practice residents and Doctor of Pharmacy students on their ambulatory care rotation.

Expression of the myc gene locus in populations of leukocytes from leukaemia patients and normal individuals.

The relative abundances of c-myc-related RNA in the total cellular RNA of peripheral blood leukocytes from 36 patients with leukaemia have been compared with those in normal peripheral blood leukocytes and in HL60 cells. Varying amounts of c-myc-related RNA were found in RNAs from leukocytes from patients with ANLL, CGL and ALL. High concentrations (comparable with that in HL60 cells) were found in 13 (36%) of the leukaemias and lower, but still significant, concentrations in a further 15 (42%). Low concentrations of c-myc-related RNA, comparable to that in normal leukocytes, were found in 2 of 8 CGLs, 1 of 12 ANLLs, and 5 of 5 CLLs. DNAs from 11 leukaemia patients' leukocytes, in which c-myc-related RNA concentrations ranged from very high to very low, were examined for rearrangements and/or amplification of the c-myc gene. No rearrangements were detected, and the small degree of amplification (2- to 4-fold at most) found was not correlated with increased levels of c-myc RNA. There was, however, a noteworthy (though incomplete) correlation between elevated levels of c-myc-related RNA and the occurrence of higher proportions of blast cells in leukocyte populations from leukaemic patients. It is suggested that high levels of c-myc-related RNA in a population of peripheral blood leukocytes indicate the presence of a high proportion of leukaemic leukocytes that are maturation-arrested at early stages of development.

Subdivision of the acute non-lymphoblastic leukaemias by measurement of the relative abundance of a specific RNA sequence.

A recombinant plasmid library representing the more abundant polyadenylated RNA of a relapsed acute myelomonocytic leukaemic (FAB class M4) has been constructed. One recombinant, designated pAM6, contains a DNA sequence complementary to an RNA of about 1100 nucleotides in length. The relative concentrations of pAM6 RNA in the RNAs from cloned human haematopoietic cell lines and from fractionated leukaemic leukocytes and normal bone marrow cells, measured by an RNA dot hybridization method, indicated that pAM6 RNA occurs in myeloid cells, probably those of the monocyte lineage at the earlier stages in differentiation. Similar assays showed that pAM6 RNA could not be detected in the peripheral blood leukocytes of normal individuals, or of ALL and CLL patients, but that the relative abundance of pAM6 RNA varied widely in leukocytes from CGL chronic phase, CGL acute phase, and ANLL. No correlation between pAM6 RNA occurrence and FAB classification of ANLL could be made; thus it would appear that the relative abundance of pAM6 RNA in ANLL leukocytes can be used to subdivide the ANLLs in a novel manner. It is suggested that this criterion, in conjunction with existing diagnostic markers, may provide a subclassification of the ANLLs that could be of some prognostic and therapeutic value.

Lineage-specific and differentiation-stage-specific gene expression in normal and leukaemic human myeloid cells.

One example of each of two approaches to the isolation of molecular hybridization probes and their use for the comparative investigation of gene expression and its control during differentiation of normal and leukaemic leukocytes is described. RNA preparations from the peripheral blood leukocytes of human leukaemias of various types were assayed for the relative abundance of the mRNA homologous with a cellular oncogene, c-myc. All types of leukaemia except chronic lymphatic leukaemia (CLL) showed varying levels of myc-related RNA; the highest concentrations occurred in cell populations in which blast cells predominated. In contrast, a recombinant plasmid (pCG14), isolated from a cDNA recombinant plasmid library that represented polyadenylated RNAs from the peripheral blood leukocytes of a chronic granulocytic leukaemia (CGL), hybridized with an mRNA whose occurrence is diagnostic of CGL leukocytes. This mRNA was also found in normal bone marrow cells; in both bone marrow and in CGL leukocytes, pCG14-homologous RNA occurs only in cells around the myelocyte stage in differentiation. It is suggested that these probes, and others for mRNAs whose occurrence is specific to a particular cell lineage and/or stage in differentiation, detect a new series of potential diagnostic markers. These might usefully supplement existing ones to provide a more detailed, objective subclassification of the leukaemias which could have important implications for diagnosis and therapy.

A new approach to the classification of human leukaemias: measurement of the relative abundance of a specific RNA sequence by means of molecular hybridisation.

A recombinant plasmid library representing polyadenylated RNAs in the leucocytes of a Ph1-positive chronic granulocytic leukaemia (CGL) has been constructed. One recombinant (designated pCG14) isolated from this library contains a DNA sequence complementary to a small polyadenylated RNA that is abundant in RNA from CGL leucocytes. The relative concentrations of pCG14 RNA in the RNAs from a variety of normal and leukaemic leucocytes and human haemopoietic cell lines have been measured with a molecular hybridisation assay. This has shown that pCG14 RNA is 10 to 50 times more abundant in RNA from CGL leucocytes than in the RNAs from these other cells. The data indicate that the occurrence of pCG14 RNA in high abundance is sufficiently characteristic of a CGL leucocyte population to distinguish it from other populations of leucocytes. They suggest that the measurement of the concentrations of specific RNA species in leucocyte RNA by means of molecular hybridisation with cloned complementary DNAs may provide additional markers for the objective classification of human leukaemias which could be particularly useful since the method exploits a criterion different from any currently in use.