In vitro evaluation of cefpirome: an Australasian study of isolates from intensive care unit and hematology/oncology patients. The Cefpirome Study Group.
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Biomedical subjects
Publications and source records attributed to A Morris.
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Since the introduction of antibiotics, bacteria have not only evolved elegant resistance mechanisms to thwart their effect, but have also evolved ways in which to disseminate themselves or their resistance genes to other susceptible bacteria. During the past few years, research has revealed not only how such resistance mechanisms have been able to evolve and to rapidly disseminate, but also how bacteria have, in some cases, been able to adapt to this new burden of resistance with little or no cost to their fitness. Such adaptations make the control of these superbugs all the more difficult.
Sera from 77 patients with common variable immunodeficiency (CVID) were tested for GB virus C (GBV-C) RNA, because they are prone to unexplained chronic hepatitis, and from 28 patients with X-linked agammaglobulinemia (XLA) who have a similar primary antibody deficiency but are not prone to hepatitis. Eight CVID and 8 XLA patients were positive; 6 positive CVID and 3 XLA patients had abnormal liver enzymes, explained in 3 by either hepatitis B or C virus infection. Most patients tested had antibodies to the E2 antigen of GBV-C, apparently passively acquired from their immunoglobulin therapy. The high prevalence of GBV-C viremia in CVID and XLA patients is probably explained by their long-term exposure to blood products. Our data indicate that GBV-C does not cause chronic hepatitis in immunocompromised XLA patients and is not the cause of chronic non-B or -C hepatitis in the majority of CVID patients.
The influence of ascorbic acid on iron absorption from an iron-fortified, chocolate-flavored milk drink (6.3 mg total Fe per serving) was evaluated with a stable-isotope technique in 20 6-7-y-old Jamaican children. Each child received two test meals labeled with 5.6 mg 57Fe and 3.0 mg 58Fe as ferrous sulfate on 2 consecutive days. Three different doses of ascorbic acid (0, 25, and 50 mg per 25-g serving) were evaluated in two separate studies by using a crossover design. Iron isotope ratios were measured by negative thermal ionization mass spectrometry. In the first study, iron absorption was significantly greater (P < 0.0001) after the addition of 25 mg ascorbic acid: geometric mean iron absorption was 1.6% (range: 0.9-4.2%) and 5.1% (2.2-17.3%) for the test meals containing 0 and 25 mg ascorbic acid, respectively. In the second study, a significant difference (P < 0.05) in iron absorption was observed when the ascorbic acid content was increased from 25 to 50 mg: geometric mean iron absorption was 5.4% (range: 2.7-10.8%) compared with 7.7% (range: 4.7-16.5%), respectively. The chocolate drink contained relatively high amounts of polyphenolic compounds, phytic acid, and calcium, all well-known inhibitors of iron absorption. The low iron absorption without added ascorbic acid shows that chocolate milk is a poor vehicle for iron fortification unless sufficient amounts of an iron-absorption enhancer are added. Regular consumption of iron-fortified chocolate milk drinks containing added ascorbic acid could have a positive effect on iron nutrition in population groups vulnerable to iron deficiency.
We report a 53-year-old woman with ARDS who required positive pressure ventilation with positive end-expiratory pressure. She sustained an acute right ventricular myocardial infarction associated with cardiovascular instability. The next day she sustained a fatal cerebral arterial gas embolism. Intravascular gas was documented within the cerebral, coronary, and pulmonary arterial circulations. Clinicians need to be aware of venous and arterial gas embolism as a complication of mechanical ventilation.
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OBJECTIVE: To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994. DESIGN: Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland. SETTING: Scotland. SUBJECTS: 6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994. RESULTS: The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours. CONCLUSIONS: In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.
In this article the author explains how a benchmarking network for paediatric services was developed. The principles are described and the process for topic selection is discussed.
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OBJECTIVE: Congenital heart block (CHB), associated with antibodies to SS-A/Ro and SS-B/La, is most often detected between 18 and 24 weeks of gestation, yet the maternal heart is unaffected. We recently described an alternatively spliced 52-kd SS-A/Ro messenger RNA (mRNA) derived from the skipping of exon 4 which encodes a smaller protein, 52beta (MW 45 kd), recognized by CHB maternal antisera. This study was designed to identify whether cardiac expression of 52beta and full-length 52alpha relates to the development of CHB. METHODS: Reverse transcriptase-polymerase chain reaction was performed using primers flanking exon 4 and mRNA from 22 human fetal hearts (age 11-25 weeks) and 3 adult hearts. The brain, kidney, liver, lung, and spleen were similarly evaluated in a 15-week, an 18-week, and a 24-week fetus. RESULTS: Expression of 52beta was greatest and 52alpha lowest between 14 and 16 weeks of gestation. In fetal hearts ages 22-25 weeks and adult heart, the 52beta transcript was markedly diminished and 52alpha clearly dominated. The 52beta mRNA was observed in a 15-week brain, kidney, lung, and spleen; however, its expression relative to 52alpha was greatest in the heart. CONCLUSION: Since expression of the alternative product 52beta is maximal at the time of cardiac ontogeny when maternal antibodies gain access to the fetal circulation, just prior to the clinical detection of bradyarrhythmia, a role for 52beta in the development of CHB is implicated. Although other fetal tissues express 52beta, there may be differences in accessibility of antigen or regenerative capacities.
BACKGROUND: The OX-40 antigen is a cell surface glycoprotein in the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells. Selective target organ expression of the OX-40 receptor on autoantigen specific T cells has been found in autoimmune disease. In order to evaluate whether OX-40 is expressed on T cells from patients with nodal-draining carcinomas, OX-40 expression was assessed in tumor infiltrating lymphocytes (TILs), draining lymph node cells (DLNCs), and/or peripheral blood lymphocytes (PBLs) of 13 patients with head and neck squamous cell carcinomas and 9 patients with melanomas. METHODS: Cell phenotype was determined by fluorescence cell analysis using a monoclonal antibody to human OX-40, and CD4+ T cell lymphokine production was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Expression of the OX-40 receptor was found in as many as 31% of the TILs and as many as 28% of the DLNCs tested. Conversely, no OX-40 expression was found in PBLs. In addition, CD4+ T cells isolated from DLNCs (but not from TILs or PBLs) secreted a Th1 pattern of cytokines (IL-2, gamma interferon). Co-culture of autologous CD4+ TILs with an MHC class II+ melanoma cell line transfected with OX-40 ligand cDNA resulted in T cell proliferation and in vitro tumor regression. CONCLUSIONS: These findings suggest that OX-40+ CD4+ T cells isolated from tumors and their adjacent draining nodes may represent a tumor-specific population of activated T cells capable of mediating tumor reactivity. These cells may play an exploitable role in future trials of immunotherapy.
OBJECTIVE: To determine the pulmonary vascular functional dose response to inhaled nitric oxide (NO) for infants and children with acute respiratory distress syndrome and pulmonary artery hypertension. DESIGN: Prospective, clinical observational study. SETTING: Thirteen-bed pediatric intensive care unit at a 168-bed children's hospital. PATIENTS: Infants and children requiring mechanical ventilation with an oxygenation index greater than 10. METHODS: Children with severe acute respiratory distress syndrome received inhalation therapy with NO after conventional mechanical ventilation failed to result in improvement. Inhaled NO was sequentially titrated from 10 parts per million to 20, 40, 60, and 80 ppm at 10-minute intervals. A reduction of at least 30% in the pulmonary vascular resistance index (PVRI), or a reduction in mean pulmonary artery pressure of at least 10%, or an increase in the hypoxemia score of at least 20%, or a decrease in the oxygenation index of at least 20% from pretreatment values was considered a therapeutic response. After sequential titration, children who responded received continuous inhaled NO at the lowest dose associated with a therapeutic response. RESULTS: Fourteen children received 15 trials with inhaled NO (median age, 63.4 months; range, 0.4 to 201 months). One patient's condition deteriorated during the titration phase, unrelated to NO treatment, and the patient was withdrawn from the study protocol. The mean (+/- SD) pretreatment oxygenation index was 35 +/- 15, which decreased to 32 +/- 20 at 80 ppm of inhaled NO (p = 0.01). Ten children had pulmonary artery catheter measurements. The PVRI decreased by 30% or greater in seven children (70%). One child had a minimal decrease in PVRI during the titration phase but demonstrated an increase of more than 30% after NO therapy was discontinued. Mean pretreatment PVRI (270 +/- 106) decreased to 207 +/- 92 dynes/sec per cubic centimeter per square meter at 80 ppm of inhaled NO (p = 0.06). Pretreatment mean pulmonary artery pressure (31 +/- 7) decreased to 28 +/- 5 mm Hg at 80 ppm of inhaled NO (p = 0.04). Six trials (43%) showed an increase of 20% or greater in their hypoxemia score. Maximum improvement in the hypoxemia score and reduction in OI, PVRI, and mean pulmonary artery pressure occurred at 20 to 40 ppm of NO. Ten trials led to continuous inhaled NO therapy ranging from 7 to 661.5 hours, with a median of 47 hours. Systemic hypotension was not observed in any patient, and the maximum methemoglobin level was 5%. CONCLUSION: Inhaled NO appears to be a safe, although variably effective, therapy for the treatment of infants and children with acute respiratory distress syndrome. The maximum dose response occurs between 20 and 40 ppm of inhaled NO. Systemic side effects did not occur in any child who received NO therapy.
We report two cases of trauma where a surgical airway was required. In both cases soft tissue swelling of the neck made modification of the Advanced Trauma Life Support (ATLS) airway guidelines necessary. A gum elastic bougie was used to guide a standard endotracheal tube into a cricothyroidotomy incision and secure the airway. Slight departure from standard techniques may be required in difficult circumstances to achieve a definitive airway.
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An important advance in the description and understanding of congenital heart block (CHB) came in the 1970s with the observation that mothers of affected infants frequently had autoimmune diseases and, in particular, that many maternal sera contained antibodies to SSA/Ro and SSB/La ribonucleoproteins. Although the molecular biology of the candidate antigens has been extensively defined, the arrhythmogenic and electrophysiological effects of their cognate antibodies on the human fetal heart are unknown. In the present study, we provide evidence that IgG-enriched fractions and anti-52-kD SSA/Ro antibodies affinity-purified from sera of mothers whose children have CHB induce complete atrioventricular (AV) block in the human fetal heart perfused by the Langendorff technique and inhibit L-type Ca2+ currents at the whole-cell and single-channel level. Immunization of female BALB/c mice with recombinant 52-kD SSA/Ro protein generated high-titer antibodies that crossed the placenta during pregnancy and were associated with varying degrees of AV conduction abnormalities, including complete AV block, in the pups. These findings strongly suggest that anti-52-kD SSA/Ro antibodies are causally related to the development of CHB.
OBJECTIVES: A randomized controlled study was conducted to assess the effects of case management and patients' characteristics on the use of inpatient psychiatric services. METHODS: Inpatients discharged from Harlem Hospital Center in 1984-1985 were randomly assigned to an outreach case management team or standard aftercare. Analysis of variance was used to assess the main effects and two- and three-way interaction effects of treatment status, gender, age, substance abuse, and diagnosis on the number of days of psychiatric rehospitalization in state and city community hospitals. RESULTS: In the follow-up period, 75 of the 146 patients in the case management group (51.4 percent) and 51 of the 143 patients in the control group (35.7 percent) were rehospitalized for psychiatric care. On average, patients spent 31.1 days in city hospitals and 26.6 days in state hospitals. Members of the case management team spent a mean total of 18.1 hours a month in direct and indirect care for each patient. They spent most time with substance-abusing older women. Significant three-way interaction effects were found between treatment status and diagnosis and gender, diagnosis and age, and diagnosis and substance abuse on the number of days patients spent rehospitalized for psychiatric care in city and state hospitals. CONCLUSIONS: It is unlikely that case management intervention will reduce rehospitalization rates unless appropriate and effective outpatient and community services are available. Effective surveillance of patient populations by case managers frequently results in rehospitalization as the only treatment alternative if other options for meeting the needs and resolving the crises of patients are not available.
OBJECTIVE: To evaluate outpatients from Toronto-area cardiology clinics for panic disorder (PD) and investigate differences between patients with and without PD. METHOD: Participants were diagnosed using both standard DSM-IV criteria and an altered formulation that identified a more fearful panic group. RESULTS: There was a prevalence of panic disorder (12.5%) in cardiac outpatients in keeping with previous studies. Patients with PD did not differ significantly from other patients with regard to the presence of significant heart disease. The higher prevalence of palpitations found in patients who met criteria for PD compared with those who did not reflects previous findings. PD cases did not differ significantly in family history from respondents without the disorder, but the more fearful group did (P < 0.05). CONCLUSION: PD often presents with cardiac symptoms, especially palpitations, and is often comorbid with heart disease.
The aim of this study was to estimate the direct annual healthcare costs to the UK National Health Service (NHS) of managing community-acquired pneumonia. Using a prevalence-based burden of illness approach, health service resource use and corresponding costs attributable to the management of community-acquired pneumonia during 1992/1993 in the UK were obtained from published sources and commercial databases, and supplemented by a telephone survey of general practitioners, finance directors, community nurses, receptionists and nurses in out-patient respiratory clinics, ambulance services, and consultant respiratory physicians. The study was appraised by a Peer Review Panel, representing a cross-section of experts from different locations. This study was a predefined subgroup analysis of a previous, larger study that estimated the annual cost to the NHS of treating all community-acquired lower respiratory tract infections. The analysis shows that there are 261,000 episodes of community-acquired pneumonia annually in the UK, costing 440.7 million pounds at 1992/1993 prices (32% of the annual cost for all community-acquired lower respiratory tract infections). Approximately 83,153 annual cases of community-acquired pneumonia are treated in hospital (32% of all episodes) and account for 96% of the annual cost. The average cost for managing pneumonia in the community is 100 pounds per episode, compared to 1,700-5,100 pounds when the patient is hospitalized, depending on the length of hospitalization. Hospitalization accounts for 87% of the total annual cost. In conclusion, community-acquired pneumonia in the UK incurs a direct healthcare cost of 440.7 million pounds annually at 1992/1993 prices. Developing and implementing strategies to prevent and minimize hospitalization will significantly reduce this annual cost and should be assessed in future studies.