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Biomedical subjects

G A Richards

Publications and source records attributed to G A Richards.

At least 19 recordsLinked to original sources
PubMed2005

The therapeutic challenge of Gram-negative sepsis: prolonging the lifespan of a scarce resource.

Mortality from severe bacterial sepsis remains high. The pathogenesis involves production of pro and anti-inflammatory cytokines which mediate: neutrophil adhesion to the endothelium, diffuse capillary leak, disseminated intravascular coagulation, vasodilatation and mitochondrial dysfunction, all of which culminate in microcirculatory failure. Therapy is multifaceted. As described in 'the surviving sepsis guidelines', many therapeutic interventions, such as early goal-directed resuscitation, low dose intravenous steroids, strict glucose control, recombinant activated protein C and ventilation according to ARDS- net criteria are critical to survival. However appropriate empiric antibiotic therapy initiated early is pivotal. Empiric therapy should be designed with regard to the bacterial epidemiology within the unit and the aim should be to optimise outcome while yet attempting to reduce the potential for resistance development. Antibiotic therapy for resistant organisms consists of the carbapenems, including ertapenem for ESBL's, cefepime, piperacillin/tazobactam and, on occasion, the Gram-negative quinolones, ciprofloxacin and levofloxacin. Consideration should be given to the possibility of 'collateral damage', where overuse of an antibiotic predisposes to multi-drug resistance. Antibiotics should be limited, where possible, to those organisms that are pathogens and not colonisers and should be discontinued if sepsis is not confirmed or there is rapid resolution of clinical indicators of sepsis. De-escalation strategies should be consistently employed and the duration of therapy should be tailored to clinical response. Continuation beyond 8 days is generally detrimental in terms of the potential for superinfection with resistant organisms. Failure of response necessitates, initially, a re-evaluation of source control and obsessive culturing of likely sites of sepsis prior to random antibiotic changes.

Animals↗
PubMed2004

Appropriate use of the carbapenems.

The carbapenems are a group of broad-spectrum beta-lactam antibiotic agents of which there are three parenteral preparations currently available in South Africa, namely imimpenem/cilastatin, meropenem and ertapenem. Owing to the fact that imipenem/cilastatin and meropenem have a broad spectrum of activity that includes Pseudomonas and Acinetobacter species, they are ideal antibiotics for treatment of severe nosocomial infections. In contrast, ertapenem has limited in vitro activity against the latter non-fermentative gram-negative bacteria and is therefore more suitable for the treatment of certain severe community-acquired infections. This statement arises out of concerns about the general abuse of antibiotics such as the carbapenems, with the primary intention of highlighting the appropriate use of these agents.

Anti-Bacterial Agents↗
PubMed2000

Unexpected Ebola virus in a tertiary setting: clinical and epidemiologic aspects.

OBJECTIVES: To describe the clinical manifestations of viral hemorrhagic fever, and to increase clinicians' awareness and knowledge of these illnesses. DESIGN: Retrospective study of the clinical and laboratory data and management of two cases of Ebola virus infection with key epidemiologic data provided. SETTING: Two tertiary care hospitals. PATIENTS: Two adult patients, the index case and the source patient, both identified as having Ebola, one of whom originated in Gabon. INTERVENTIONS: One patient was admitted to the intensive care unit. The other was managed in a general ward. MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data are reported. One patient, a healthcare worker who contracted this illness in the course of her work, died of refractory thrombocytopenia and an intracerebral bleed. The source patient survived. Despite a long period during which the diagnosis was obscure, none of the other 300 contacts contracted the illness. CONCLUSIONS: Identification of high-risk patients and use of universal blood and body fluid precautions will considerably decrease the risk of nosocomial spread of viral hemorrhagic fevers.

Adult↗
PubMed2000

Long-term domiciliary oxygen therapy--the Johannesburg Hospital experience.

OBJECTIVES: To assess the clinical and demographic characteristics of patients attending an oxygen clinic, to assess the relevance of the current clinical criteria determining the need for domiciliary oxygen, to assess the cost-effectiveness of an oxygen clinic and to assess compliance with the oxygen prescription. DESIGN: Descriptive study with a retrospective review of data. SETTING: Tertiary-level academic hospital. SUBJECTS: All patients attending a newly established oxygen clinic. RESULTS: Data were analysed for 679 patients (361 male and 318 female), of whom 543 were ex- or current smokers, and 136 were non-smokers. Of the total number, 576 had chronic obstructive pulmonary disease. Oxygen was given to 425 patients and denied to 254. Forced expiratory volume in 1 second (FEV1) is probably not of value in determining requirement for oxygen as there was no correlation between severity of lung disease and partial arterial oxygen pressure (PaO2). There was also no correlation between PaO2 and litres of oxygen prescribed. Compliance with the oxygen prescription was 39%. Cost savings to the State from the oxygen that was not prescribed was in the region of R125,000 per month. CONCLUSIONS: Each patient should be assessed individually using clinical parameters to classify the disease severity and to assess the degree of tissue hypoxia. Oxygen clinics are of value and should be established more widely within each province. Compliance is suboptimal and continued follow-up to motivate patients to use the oxygen as prescribed should be instituted.

Aged↗
PubMed2000

Critically ill obstetric and gynaecological patients in the intensive care unit.

OBJECTIVES: To document mortality among critically ill obstetric and gynaecological patients requiring intensive care unit (ICU) admission and to investigate whether any poor prognostic features could allow for earlier and more aggressive intervention. STUDY DESIGN: A retrospective study of all obstetric and gynaecological patients admitted to the ICU of Johannesburg Hospital between 1985 and 1996. Sixty-one patients were analysed both as a group and as two subgroups--those with incomplete abortions and those with other pregnancy-related diagnoses. RESULTS: Derangements in platelet counts, serum creatinine levels and prothrombin international normalised ratio (INR) were present in all patients on the day of admission to hospital. In the group with incomplete abortions absolute levels of these parameters may be used to identify those patients with a worse outcome. The mortality rate was 38%. CONCLUSION: Early ICU admission and aggressive surgical intervention are strongly recommended in patients with septic incomplete abortions presenting with more than a single organ dysfunction.

APACHE↗
PubMed1998

Corticosteroids in life-threatening varicella pneumonia.

BACKGROUND: Varicella pneumonia that results in respiratory failure or progresses to the institution of mechanical ventilation carries a significant morbidity and mortality despite intensive respiratory support and antiviral therapy. There has been no reported study of the role of corticosteroids in life-threatening varicella pneumonia. DESIGN AND METHODS: This was an uncontrolled retrospective and prospective study of all adult patients with a diagnosis of varicella pneumonia who were admitted to the ICUs of the Johannesburg group of academic hospitals in South Africa between 1980 and 1996. Patient demographics, clinical and laboratory features, necessity for mechanical ventilation, and complications were reviewed. The outcome and therapy of varicella pneumonia was evaluated with particular reference to the use of corticosteroids. Patients with comorbid disease and those already taking immunosuppressive agents were excluded. Key endpoints included length of ICU and hospital stay and mortality. MEASUREMENTS AND RESULTS: Fifteen adult patients were evaluated, six of whom received corticosteroids in addition to antiviral and supportive therapy. These six patients demonstrated a clinically significant therapeutic response. They had significantly shorter hospital (median difference, 10 days; p<0.006) and ICU (median difference, 8 days; p=0.008) stays and there was no mortality, despite the fact that they were admitted to the ICU with significantly lower median ratios between PaO2 and fraction of inspired oxygen than those patients (n=9) who did not receive corticosteroid therapy (86.5 vs 129.5; p=0.045). CONCLUSION: When used in addition to appropriate supportive care and early institution of antiviral therapy, corticosteroids appear to be of value in the treatment of previously well patients with life-threatening varicella pneumonia. The observations presented in this study are important and should form the basis for a randomized controlled trial, as no other relevant studies or guidelines are available.

Acyclovir↗
PubMed1996

Increased levels of autoantibodies to cardiolipin and oxidised low density lipoprotein are inversely associated with plasma vitamin C status in cigarette smokers.

In this study we have measured circulating levels of autoantibodies to cardiolipin and oxidised low-density lipoprotein (ox-LDL) and correlated these with plasma concentrations of the anti-oxidant nutrients vitamin C, vitamin E and beta-carotene, in a group (79) of asymptomatic, male cigarette smokers and in non-smoking control subjects. Cigarette smoking, a well-known risk factor for development of atherosclerosis, was found to be associated with moderately elevated levels of autoantibodies to both cardiolipin and ox-LDL. Increased levels of these autoantibodies were most evident in the older smokers (> 30 years) and were significantly and inversely correlated with plasma vitamin C, but not with vitamin E or beta-carotene. Absorption studies designed to investigate the specificity of these autoantibodies demonstrated a high degree of cross-reactivity of cardiolipin antibodies with ox-LDL, while antibodies to the oxidatively modified lipoprotein tended to be specific for this antigen. These findings suggest that cigarette smoking promotes formation of autoantibodies to both cardiolipin and ox-LDL and that these may be involved in the initiation and/or perpetuation of atherosclerosis. Dietary intake of vitamin C may be a determinant of susceptibility to development of this cardiovascular disorder.

Adult↗
PubMed1996

Health effects of passive smoking in adolescent children.

OBJECTIVE AND DESIGN: To study the effects of passive smoking on health in adolescent schoolchildren by questionnaire, spirometry and laboratory investigations. SETTING: Two schools in the Vanderbijlpark area. PARTICIPANTS: Seven hundred and twenty-six high-school children of average age 16 years. OUTCOME MEASURES: Lung function, serological abnormality or historical (i.e. questionnaire) evidence of ill health. RESULTS: The prevalence of respiratory illness before and after 2 years, respiratory symptoms, earache over the past year, low birth weight and learning difficulties were found to be significantly increased in the children exposed to parenteral smoke in the home, especially those exposed to maternal smoking. Spirometric and laboratory parameters, however, were not affected by passive smoking.

Adolescent↗
PubMed1995

Plasma levels of beta-carotene are inversely correlated with circulating neutrophil counts in young male cigarette smokers.

Relationships between plasma levels of beta-carotene (BC) and the numbers and oxidant-generating activities of circulating neutrophils have been investigated in a group of asymptomatic young male cigarette smokers (N = 40) and in a group of nonsmoking control subjects. Plasma BC levels were measured using HPLC, while oxidant generation was measured using a phorbol myristate acetate (PMA) activated whole blood luminol-enhanced chemiluminescence (LECL) method. Relative to nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were increased by 41% (p = 0.0001) and 47% (p = 0.004), respectively, while plasma BC levels were decreased by 24% (p = 0.01). In cigarette smokers, but not in nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were significantly and inversely correlated with plasma BC levels (r = -0.36, p = 0.02; and r = -0.33, P = 0.04 respectively). Diminished plasma levels of BC in cigarette smokers probably reflect the increased numbers and prooxidative activities of circulating neutrophils. Intake of this antioxidant nutrient may be a determinant of susceptibility to smoking-related pulmonary dysfunction mediated by oxidants derived from smoke-activated phagocytes.

Adult↗
PubMed1995

Vitamin E, pulmonary functions, and phagocyte-mediated oxidative stress in smokers and nonsmokers.

Relationships among the plasma levels of vitamin E (VE), the numbers and prooxidative activities of circulating phagocytes, serum alpha-1-protease inhibitor (API), and pulmonary functions were investigated in 83 asymptomatic male cigarette smokers and 65 nonsmoking controls. Plasma levels of VE, of cholesterol, and of API were measured using high performance liquid chromatography, spectrophotometry, and nephelometry, respectively, whereas reactive oxidant (ROS) generation by activated blood phagocytes was measured using a whole blood luciginen-enhanced chemiluminescence method. Smoking was associated with significantly increased circulating neutrophil counts (p 0.0001), serum API (p 0.0001) and phagocyte-derived ROS-generation (p 0.0001), and decreased spirometric values (FEV1: p 0.0138 and FEF25-75: p 0.0654). Plasma VE and cholesterol levels were not significantly different between smokers and nonsmokers. However, in smokers both plasma VE and cholesterol correlated significantly and positively with serum API (r 0.24, p 0.03 and r 0.30, p 0.005, respectively), neutrophil counts (r 0.24, p 0.03 and r 0.25, p 0.03, respectively), and phagocyte-derived ROS-generation (r 0.32, p 0.003 and r 0.32, p 0.003, respectively), and significantly and inversely with FEV1 (r -0.23, p 0.03 and r -0.22, p 0.04, respectively) and FEF25-75 (r -0.32, p 0.003 and r -0.26, p 0.02, respectively). In nonsmokers plasma VE, but not cholesterol, was positively correlated with FEV1 (r 0.34, p 0.007) and FEF25-75 (r 0.40, p 0.001). The results suggest that VE protects the lungs of both smokers and nonsmokers and may act as a mobilizable antioxidant in response to smoking-induced oxidative stress.

Adult↗
PubMed1995

Relationship between the plasma levels of beta-carotene and lung functions in cigarette smokers.

Relationships between the plasma levels of beta-carotene (BC) and spirometry were studied in 30 asymptomatic male cigarette smokers and 34 age-matched non-smoking control subjects. Plasma BC-levels, determined by high performance liquid chromatography (HPLC), were decreased on average by 18% (p 0.1251) in the smokers relative to the non-smokers and by 28% (p 0.015) following correction for blood cholesterol. The spirometric values, FEV1 and FEF25-75, determined from the flow-volume loops of each subject, were decreased by 5% (p 0.095) and 12% (p 0.0072) respectively in the smokers relative to the non-smokers. In the smokers, but not in the non-smokers, the plasma levels of BC correlated significantly and positively with the spirometric values, FEV1 (r 0.48, p 0.01) and FEF25-75 (r 0.58, p 0.0008). The results suggest that BC-status may determine susceptibility to oxidant-mediated pulmonary dysfunction in cigarette smokers.

Adult↗
PubMed1994

Investigation of the relative contributions of cigarette smoking and mineral dust exposure to activation of circulating phagocytes, alterations in plasma concentrations of vitamin C, vitamin E, and beta carotene, and pulmonary dysfunction in South African gold miners.

OBJECTIVES: To determine the relative effects of cigarette smoking and mineral dust exposure on numbers and activity of circulating phagocytes, plasma nutritional antioxidant state, and pulmonary function in South African gold miners. METHODS: Pulmonary function was assessed spirometrically, whereas reactive oxidant generation by circulating phagocytes, and plasma concentrations of the nutritional antioxidative nutrients vitamin C and vitamin E and beta carotene were measured with chemiluminescence, spectrophotometry, or high performance liquid chromatography respectively. RESULTS: Cigarette smoking, but not mineral dust exposure, was associated with increased numbers and pro-oxidative activity of circulating neutrophils and monocytes, decreased plasma concentrations of vitamin C, and pulmonary dysfunction. DISCUSSION: In this study group occupational exposure to mineral dust has not been found to promote increases in the numbers or reactivity of circulating phagocytes or to be a significant cause of pulmonary dysfunction, the changes found being due primarily to cigarette smoking.

Adult↗