Prof C Feldman - Publications

Title: Klebsiella pneumoniae bacteraemia at an urban general hospital.
Author: Feldman C; Smith C; Levy H; Ginsburg P; Miller SD; Koornhof HJ
Address: Department of Internal Medicine, Hillbrow Hospital, Johannesburg, South Africa.
Source: J Infect, 20: 1, 1990 Jan, 21-31
Abstract: Of 47 patients with Klebsiella pneumoniae bacteraemia admitted to the Hillbrow Hospital, Johannesburg during a period of 18 months, 31 were males and 16 were females. Features predisposing to illness were found in 89.4% patients, chronic alcoholism, neoplastic disease and diabetes mellitus being the most common. Twenty-five infections were acquired in hospital and 22 in the community. Most patients (59.6%) had pneumonia. All isolates of K. pneumoniae were resistant to ampicillin (100%); several (42.6%) were resistant to other antibiotics also. The overall mortality rate was 55.3%. A higher mean initial blood pressure and lower concentrations of serum urea and bilirubin were found in survivors. None of the 28 patients, surviving more than 48 h who received combined therapy with an aminoglycoside and a beta-lactam antibiotic (to which the organism was susceptible) died. Among the remaining patients treated with either an appropriate beta-lactam agent alone, an appropriate aminoglycoside alone or ciprofloxacin the combined mortality rate was 83.3% (P = 0.007).

Title: Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter s syndrome. A spectrum of metabolic madness, or new lights on an old disease?
Author: Meyers AM; Feldman C; Sonnekus MI; Ninin DT; Margolius LP; Whalley NA
Address: Department of Medicine, Johannesburg Hospital.
Source: S Afr Med J, 78: 11, 1990 Dec 1, 631-6
Abstract: The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter s syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17-54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter s syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed metabolic madness . Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of autonomous pseudo-Bartter s syndrome .

Title: Communication within low income families and the management of asthma.
Author: Clark NM; Levison MJ; Evans D; Wasilewski Y; Feldman CH; Mellins RB
Source: Patient Educ Couns, 15: 2, 1990 Apr, 191-210
Abstract: This study examines the effects of communication between low income urban parents and children about a chronic disease on the extent to which parent and child effectively manage the illness. Four asthma communication factors were identified by principal component analysis. We found that mothers whose preferred language was Spanish, and families who were not receiving public assistance, communicated more frequently about asthma in general. Spanish speaking mothers and their children communicated more about potential home treatments for asthma, and the more adults in the household the less there was communication about the need for emergency services for asthma. Mothers who preferred to speak Spanish had higher levels of management of the most recent asthma attack. Those whose children communicated with them about asthma in general were higher level managers. Children who influenced their parents decisions about school attendance, and those whose mothers were more highly educated, had higher levels of asthma attack management. More educated mothers, ones whose children were younger at the time of the onset of asthma, and one who received public assistance, were more involved "in general" in their child s asthma care.

Title: The effect of Streptococcus pneumoniae pneumolysin on human respiratory epithelium in vitro.
Author: Feldman C; Mitchell TJ; Andrew PW; Boulnois GJ; Read RC; Todd HC; Cole PJ; Wilson R
Address: Department of Thoracic Medicine, National Heart and Lung Institute, London, U.K.
Source: Microb Pathog, 9: 4, 1990 Oct, 275-84
Abstract: Streptococcus pneumoniae culture filtrates and pneumolysin both slow human ciliary beating and damage respiratory epithelium in vitro. A polyclonal pneumolysin antibody bound to sepharose beads removed pneumolysin from culture filtrates and showed that pneumolysin alone was responsible for the effects on epithelium. In a 48-h organ culture pneumolysin caused ciliary slowing and epithelial disruption in a dose-dependent manner down to 5 ng/ml. Comparison of the ciliary slowing activity and pneumolysin concentration in filtrates in a continuous broth culture showed a maximal effect at 16 h (pneumolysin 7.5 micrograms/ml). Later the activity decreased while the pneumolysin concentration increased (8.8 micrograms/ml). This loss of activity was prevented by neutralisation of the acid pH of the culture medium. Eight different culture filtrates produced significant (P less than 0.05) ciliary slowing which correlated (r = 0.95) with simultaneously measured haemolytic (pneumolysin) activity. Substitution of tryptophan (position 433) by phenylalanine reduced the haemolytic and ciliary slowing activity of pneumolysin, but did not affect its ability to activate complement. There was no correlation between the ciliary slowing produced by the culture filtrate and that produced by the autolysate of a particular strain, nor between ciliary slowing and the extent of autolysis or the serotype of the strain.

Title: Cryptogenic fibrosing alveolitis. A study of an indigenous African population.
Author: Smith C; Feldman C; Levy H; Kallenbach JM; Zwi S
Address: Department of Medicine, Hillbrow Hospital, Johannesburg, South Africa.
Source: Respiration, 57: 6, 1990, 364-71
Abstract: Cryptogenic fibrosing alveolitis (CFA) has not been described previously in any large group of indigenous African patients. This was a retrospective study of 46 such patients diagnosed as having CFA during a 73-month period. The clinical spectrum of illness was similar to that of other groups studied worldwide. Cigarette smoking was associated with a poorer outcome and is a potentially preventable cause of deterioration.

Title: Septic shock in the Intensive Care Unit, Hillbrow Hospital, Johannesburg.
Author: Smith C; Arregui LM; Promnitz DA; Feldman C
Address: Department of Medicine, Hillbrow Hospital, Johannesburg.
Source: S Afr Med J, 80: 4, 1991 Aug 17, 181-4
Abstract: The records of all patients with septic shock admitted to an intensive care unit during a 15-month period were analysed retrospectively. The main purpose of the study was to describe the aetiology and clinical features of illness, and to determine the outcome of the patients, including those factors influencing prognosis. Thirty-five patients (46% medical, 54% surgical) fulfilling the criteria for the diagnosis of septic shock were admitted to the study. There were 21 male and 14 female patients. Most infections were community-acquired (69%). The two most common sources of infection were the respiratory tract and abdomen. All patients required inotropic blood pressure support. Most patients (94%) were mechanically ventilated and 7 required dialysis. Organisms, sometimes multiple, were isolated in 18 patients. Fifty percent of the isolates (12 of 24) were Gram-negative, 10 were Gram-positive and there were 2 associated Candida albicans bacteraemias. The overall mortality rate was 40%. There was no difference in outcome between community or hospital-acquired infections, infections with Gram-positive or Gram-negative organisms, or in patients with differing sources of sepsis. Features associated with a poorer prognosis were older age and higher bilirubin value.

Title: Metaproterenol (Alupent) metered dose inhaler in children 5-12 years of age.
Author: Storms WW; Bierman CW; Chai H; Dockhorn RJ; Eggleston P; Ellis EF; Feldman C; Fink JN; Hemstreet MP; Kniker WT; et al
Source: J Asthma, 28: 5, 1991, 369-79
Abstract: This multiclinic study was performed to evaluate the safety and efficacy of metaproterenol sulfate (Alupent) metered dose inhaler in children with asthma ages 5 to 12 years. A total of 268 children completed this study according to the protocol, having received either metaproterenol or placebo for 30 consecutive days. Full spirometric testing was done pre- and postdose on Days 1 and 30 for a total duration of 6 hours on each day. The results showed that metaproterenol was consistently superior to placebo in all pulmonary function parameters measured on Days 1 and 30. This difference was statistically significant for peak values and areas under the curves for both FEV1 and FEF25-75%. There were no significant side effects noted. We conclude that metaproterenol metered dose inhaler is safe and effective in the treatment of asthma in children ages 5 to 12 years.

Title: Sarcoidosis in Johannesburg--a comparative study of black and white patients.
Author: Smith C; Feldman C; Reyneke J; Promnitz DA; Kallenbach JM; Zwi S
Address: Department of Medicine, Hillbrow Hospital, Johannesburg.
Source: S Afr Med J, 80: 9, 1991 Nov 2, 423-7
Abstract: Fifty-one black and 31 white patients with histologically proven sarcoidosis were managed in the respiratory units of the Johannesburg and Hillbrow Hospitals between January 1965 and October 1987. A number of differences in the demographic, clinical and laboratory features of the disease were documented in the two groups. While none of the black patients presented with erythema nodosum, direct skin involvement was significantly more common (P less than 0.05), occurring in 59% of these patients. The mean serum angiotensin-converting enzyme level was raised in both groups, but hypercalcaemia occurred infrequently in black patients. Almost 60% of the patients received corticosteroids, and the clinical and objective response to therapy was not significantly different in the two groups. Before referral the diagnosis was often labelled tuberculosis in the black patients who had frequently received antituberculosis chemotherapy. The tuberculin skin test is helpful, since it was negative in all but 2 black patients with sarcoidosis.

Title: Ciliary beat frequency and structure of recipient and donor epithelia following lung transplantation.
Author: Read RC; Shankar S; Rutman A; Feldman C; Yacoub M; Cole PJ; Wilson R
Address: Department of Thoracic Medicine, National Heart & Lung Institute, Royal Brompton and National Heart Hospital, London, UK.
Source: Eur Respir J, 4: 7, 1991 Jul, 796-801
Abstract: To investigate possible changes following lung transplantation, the structure and in vitro ciliary beat frequency (CBF) of airway epithelium from the cytology brushings of 9 heart-lung (HLT) and 5 single-lung (SLT) transplant recipients were examined. The CBF of brushings taken proximal and distal to the anastomosis was measured 2-10 months following transplant. There was no difference between the measured mean CBF at the two sites or between the two groups; HLT CBF: distal 11.0 /- 0.5 Hz (standard error of mean), proximal 10.5 /- 0.4 Hz, SLT CBF: distal 11.7 /- 0.9 Hz, proximal 12.0 /- 0.6 Hz. Mean CBF of bronchial brushings (except distal brushings from SLT patients) was significantly lower than that from controls: 13.6 /- 0.3 Hz (n = 7) (p less than 0.05). Transmission electron microscopy of epithelial brushings from 4 patients (3 HLT, 1 SLT) revealed epithelial abnormalities both proximal and distal to the anastomosis, particularly ciliary depletion, mitochondrial abnormalities and death of cells. No significant ciliary ultrastructural abnormalities were seen in any tissue. We conclude that epithelial abnormalities were observed both proximal and distal to the anastomosis following lung transplantation. These may contribute to impairment of mucociliary clearance.

Title: Comparison of bacteraemic community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae in an intensive care unit.
Author: Feldman C; Kallenbach JM; Levy H; Thorburn JR; Hurwitz MD; Koornhof HJ
Address: Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Source: Respiration, 58: 5-6, 1991, 265-70
Abstract: In a study of 41 consecutive patients with bacteraemia-associated community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae an attempt was made to determine whether distinguishing criteria of disease due to these organisms could be identified according to demographic features and the results of initial clinical and laboratory investigations. Such information would aid in the early initiation of appropriate antimicrobial therapy. The most significant difference between the two groups of patients was the lower platelet count in the K. pneumoniae group (p less than 0.005). In addition leucopenia (p less than 0.05), higher serum albumin (p less than 0.05), and the male sex (p less than 0.05) featured with an increased frequency in patients with pulmonary infection due to K. pneumoniae. Initial antimicrobial therapy in critically ill patients with community-acquired lobar pneumonia and thrombocytopenia, particularly when associated with leucopenia and in male patients, should include agents effective against K. pneumoniae.

Title: The clinical significance of Haemophilus influenzae and H. parainfluenzae isolated from the sputum of adult patients at an urban general hospital.
Author: Feldman C; Smith C; Kaka S; De Jong P; Promnitz DA
Address: Department of Medicine, Hillbrow Hospital, Johannesburg.
Source: S Afr Med J, 81: 10, 1992 May 16, 495-8
Abstract: Fifty-seven patients, from whose sputum Haemophilus influenzae (49 cases) or Haemophilus parainfluenzae (8 cases) was isolated during a 7-month period, were studied. In the majority of cases there were well-defined predisposing factors to respiratory tract colonisation or infection with the isolates, in particular bronchiectasis and chronic obstructive airways disease. Colonisation of the airways, bronchopneumonia in patients with underlying lung disease, acute lobar pneumonia, and postoperative chest infections were the commonest clinical diagnoses. Primary acute lobar pneumonia with these organisms alone was uncommon. All of the H. influenzae isolates were nontypeable, and there was a wide range of biotypes of both organisms. Three H. influenzae isolates produced beta-lactamase, and there was, in general, a low incidence of resistance to a wide range of antimicrobial agents on disc susceptibility testing.

Title: The interaction of Streptococcus pneumoniae with intact human respiratory mucosa in vitro.
Author: Feldman C; Read R; Rutman A; Jeffery PK; Brain A; Lund V; Mitchell TJ; Andrew PW; Boulnois GJ; Todd HC; et al
Address: Dept of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Source: Eur Respir J, 5: 5, 1992 May, 576-83
Abstract: The interaction of Streptococcus pneumoniae with human ciliated upper respiratory mucosa was studied in an agar-embedded organ culture of nasal turbinate tissue, which only exposed the intact epithelial surface and its secretion. The ciliary beat frequency, measured along the edge of the organ culture, was slowed by 13% in the presence of S. pneumoniae after 16 h (p less than 0.05) compared with the control, and by 24% after 24 h (p less than 0.01). Light microscopy showed bacteria in a thickened gelatinous layer, which obscured the surface of the organ culture. Transmission and scanning electron microscopy confirmed the association of bacteria with the gelatinous layer above an epithelial surface which showed only minor changes compared to uninfected control organ cultures. Contact between bacteria and normal or damaged epithelial cells was not seen. S. pneumoniae in organ culture developed projections from their surface, which were not present after broth culture. S. pneumoniae interactions with epithelial-derived secretions, the formation of a thickened gelatinous layer, and the effects of bacterial toxins on ciliary motility, may be important during colonization of the respiratory tract.

Title: Does primary Streptococcus viridans pneumonia exist?
Author: Goolam Mahomed A; Feldman C; Smith C; Promnitz DA; Kaka S
Address: Department of Medicine, Hillbrow Hospital, Johannesburg.
Source: S Afr Med J, 82: 6, 1992 Dec, 432-4
Abstract: In 4 adult black patients admitted to an urban general hospital with community-acquired pneumonia, Streptococcus viridans alone was isolated from blood culture (first subculture), in the absence of any other positive microbiological finding. Sputum examination by Gram staining and culture in 3 cases was reported as negative. Echocardiography was performed in 3 cases and was normal, without evidence of endocarditis. The clinical course of illness in the 4 patients is described. The chest radiograph showed a segmental or subsegmental consolidation in all cases; this appeared mass-like in 2 patients. Viridans streptococci may be a more important, if still uncommon, cause of community-acquired pneumonia than previously suspected. The organism should be considered as a possible cause of chest infection, particularly in patients with appropriately positive blood cultures and no other positive microbiological finding.

Title: A study of immunoglobulin G subclass levels in black and white patients with various forms of obstructive lung disease.
Author: Feldman C; Weltman M; Wadee A; Sussman G; Smith C; Zwi S
Address: Department of Medicine, Hillbrow Hospital, Johannesburg.
Source: S Afr Med J, 83: 1, 1993 Jan, 9-12
Abstract: The association of various respiratory disorders with disturbances in immunoglobulin G (IgG) subclass levels is increasingly being recognised. This was a prospective study of the IgG subclass levels in 71 patients (37 white, 34 black) with various respiratory disorders associated with obstructive airways disease. Ten white patients with adult cystic fibrosis were studied, 4 of whom were colonised with Pseudomonas aeruginosa. Alterations in individual subclass levels were seen in these patients and abnormalities noted included a decrease in IgG3 and/or an increase in IgG1 and/or IgG2 levels. Of the 17 black and 16 white patients with asthma, 2 had absent IgG4 levels associated with severe and recurrent respiratory infections, 2 had deficient IgG3 and 1 decreased IgG1 levels. Several patients had increased levels of several IgG subclasses, of which IgG1 was the most commonly affected. Both atopy and recurrent chest infections occurred most often in the latter group of patients. In the studies of 17 black and 11 white patients with bronchiectasis, all but 3 white patients were shown to have some alteration in IgG subclass levels. The commonest deficiencies were an absence of IgG4 (3 cases), and an absence of all subclasses (2 cases). One of the latter patients had an associated deficiency of total IgG and IgM, and the other demonstrated pan-hypogammaglobulinaemia. Abnormalities of IgG subclass levels appear to be commonly associated with several respiratory disorders including recurrent infections, atopy and bronchiectasis.

Title: Determinants of near fatality in acute severe asthma.
Author: Kallenbach JM; Frankel AH; Lapinsky SE; Thornton AS; Blott JA; Smith C; Feldman C; Zwi S
Address: Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Source: Am J Med, 95: 3, 1993 Sep, 265-72
Abstract: PURPOSE: The data extrapolated from cases of acute severe asthma that narrowly miss being fatal may prove valuable in the identification of the factors implicated in mortality. The purpose of this study was, therefore, to identify determinants of near fatality in patients with acute severe asthma. PATIENTS AND METHODS: We studied 81 patients with acute severe asthma in whom mechanical ventilation was required. Near fatality was defined as the occurrence of respiratory arrest and/or coma necessitating emergency tracheal intubation and resuscitation. In the cases that were not regarded as near fatal, tracheal intubation was performed electively because of deteriorating arterial blood gas values and/or the anticipation of exhaustion. Various continuous and categorical variables were compared in these two groups of patients. Patients with a hyperacute attack (period from onset of attack to mechanical ventilation less than 3 hours) were specifically sought and studied to determine the impact of such a course on near fatality. RESULTS: The "attack duration" (period from onset of attack to mechanical ventilation) was an important determinant of near fatality and of the subsequent clinical course. It was shorter in the group with a near-fatal episode (p < 0.03), and hyperacute attacks were uniformly near fatal. The attack duration correlated positively with the duration of the requirement for mechanical ventilation (p < 0.01). A longer attack duration was associated with an increased likelihood of the occurrence of major atelectasis (p < 0.01). There was no evidence of a relationship between near fatality and the side effects of bronchodilators as regards hypokalemia, arrhythmias, or cardiotoxicity. There was evidence of considerable under-treatment in the patient population as a whole, particularly in regard to the use of corticosteroids. CONCLUSIONS: A short attack duration is associated with an increased risk of near fatality in acute severe asthma. This is particularly evident in hyperacute attacks. Hyperacute attacks resolve rapidly once bronchodilator therapy has been instituted, suggesting that smooth muscle spasm is the predominant pathogenetic mechanism. The importance of routine anti-inflammatory therapy in mild to moderate asthma requires re-emphasis but, in addition, all patients should be provided with, and educated in the use of, bronchodilator rescue therapy, which should be available at all times. Despite current trends, the use of regular, prophylactic bronchodilator therapy in strict conjunction with anti-inflammatory agents may still be indicated. There is little evidence in the present data obtained from near-fatal cases to support the concept that cardiotoxicity related to bronchodilators contributes significantly to mortality from asthma.

Title: A study of acute community-acquired pneumonia, including details of cardiac changes.
Author: Seedat MA; Feldman C; Skoularigis J; Promnitz DA; Smith C; Zwi S
Address: Department of Medicine, Baragwanath Hospital, Johannesburg, South Africa.
Source: Q J Med, 86: 10, 1993 Oct, 669-75
Abstract: We prospectively studied 102 patients, aged 15-50 years, with acute community-acquired lobar pneumonia without underlying cardiorespiratory illness, admitted to Baragwanath Hospital May 1990-April 1991. Demographic, clinical, microbiological and laboratory data and negative prognostic features of these patients are described. In particular, we documented electrocardiographic changes and studied their possible relevance in patients with pneumonia. Electrocardiographic changes occurred in 32 patients (31%). The commonest changes were clockwise rotation (16%), followed by P. pulmonale (9.8%) and S1 Q3 T3 pattern (7.8%) Other changes included right axis deviation (n = 6), right bundle branch block (n = 3), ventricular extrasystoles (n = 2), atrial fibrillation (n = 1) and nodal rhythm (n = 1). These changes returned to normal in survivors after a mean of 2 days. The S1 Q3 T3 pattern was associated with cardiac enzyme leak (CK-MB fraction), hypoxia and a high Simplified Acute Physiology Score (SAPS). In addition, P. pulmonale, right axis deviation and clockwise rotation correlated with hypoxia and a high SAPS score. Clockwise rotation also correlated with serum (including cardiac fraction) enzymes leak (LDH and CK-MB fraction), and pulmonary artery pressure. The overall mortality rate was 10.8%, with no association between electrocardiographic changes and mortality. The negative prognostic factors documented were hypoxia (p < 0.0001), multilobar pulmonary consolidation (p < 0.0001), tachycardia (p = 0.0001), tachypnoea (p = 0.0002), renal dysfunction function (p = 0.0009), hypotension (systolic p < 0.02, diastolic p < 0.003), bacteraemia (p = 0.003), and serum (including cardiac fraction) enzymes leak: LDH (p < 0.02), CK (p < 0.002) and CK-MB fraction (p = 0.0002). These factors, with the exception of renal dysfunction, also correlated with the need for intensive care unit admission. Acute and reversible electrocardiographic changes are common in acute community-acquired lobar pneumonia. Electrocardiographic changes, especially those compatible with acute cor pulmonale and accompanied by cardiac enzyme (CK-MB fraction) leak, correlated with severity of illness but not with mortality.

Title: Factors associated with airway colonisation and invasion due to Klebsiella spp [see comments]
Author: Feldman C; Smith C; Kaka S; de Jong P; Goolam Mahomed A; Frankel A; Koornhof HJ
Address: Department of Medicine, South African Institute for Medical Research, Hillbrow Hospital, Johannesburg.
Source: S Afr Med J, 83: 9, 1993 Sep, 643-6
Abstract: The clinical significance of a heavy growth of Klebsiella spp. in sputum was studied in 54 patients. All but 3 patients had significant factors potentially associated with respiratory tract colonisation or invasion. Risk factors identified for colonisation of the airway and for invasive disease were similar. Patients with community-acquired Klebsiella infections were more likely to have underlying chronic respiratory diseases. Prior antibiotic use was a risk factor for nosocomial infections which occurred more commonly with antibiotic-resistant organisms. The most common diagnoses were airway colonisation, acute community-acquired chest infections, and nosocomial chest infections. Primary acute community-acquired pneumonia was uncommon. The sensitivity and specificity of the sputum Gram stain (in the setting of positive sputum cultures) in suggesting the presence of invasive disease due to Klebsiella spp. were 42% and 69% respectively.

Title: Ethnic differences in the occurrence of the M1(ala213) haplotype of alpha-1-antitrypsin in asthmatic and non-asthmatic black and white South Africans.
Author: Gaillard MC; Zwi S; Nogueira CM; Ludewick H; Feldman C; Frankel A; Tsilimigras C; Kilroe-Smith TA
Address: Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Source: Clin Genet, 45: 3, 1994 Mar, 122-7
Abstract: An ethnic study of 175 individuals, comprising 65 black and 110 white South Africans, has shown a conclusive difference in the frequency of the M1(ala213) haplotype of alpha 1-antitrypsin (P < 0.00001). The M1(ala213) haplotype occurred more frequently in the black group. In the latter group, the frequency of the M1(ala213) haplotype was the same in both controls (0.55) and asthmatics (0.53). However, there was a significant difference in the frequencies (0.19 and 0.36) for the respective white groups (P < 0.01), the frequency of the M1(ala213) haplotype being much higher in the asthmatics. Apart from the above differences, there was also a difference in the elastase-inhibitory capacities of the homozygote phenotypes M1(val213) vs M1(ala213) (P < 0.0001), this capacity being lower in the latter phenotype. We conclude that the occurrence of the M1(ala213) allele of alpha 1-antitrypsin differs in various ethnic groups and may play a role in asthma.

Title: Oxidant-mediated ciliary dysfunction in human respiratory epithelium.
Author: Feldman C; Anderson R; Kanthakumar K; Vargas A; Cole PJ; Wilson R
Address: Department of Medicine, Hillbrow Hospital, Johannesburg, South Africa.
Source: Free Radic Biol Med, 17: 1, 1994 Jul, 1-10
Abstract: Exposure of human nasal ciliated epithelium to reactive oxidants generated by the enzymatic xanthine-xanthine oxidase superoxide/hydrogen peroxide (H2O2) and glucose-glucose oxidase H2O2-generating systems, or to reagent H2O2 or hypochlorous acid (HOCl) resulted in significant alterations in ciliary beating. The earliest change noted was the presence of ciliary slowing, progressing eventually to complete ciliary stasis in some areas. Ciliary dyskinesia was seen within the first hour, often from as early as 15 min after exposure of the cells to reactive oxidants. Using peroxidases, various antioxidant enzymes, and oxidant scavengers, we confirmed that these detrimental effects on ciliary function were mediated primarily by H2O2 and HOCl. Moreover, 3-aminobenzamide (3-ABA), an inhibitor of the DNA repair enzyme poly ADP ribose polymerase, prevented H2O2-mediated inhibition of ciliary function, indicating that oxidant-mediated damage to DNA may well be the basis of the effects of H2O2 on ciliated epithelium. Acute and chronic inflammatory responses may therefore present the possible threat of H2O2- or HOCl-inflicted injury on bystander respiratory epithelium, leading to ciliary dyskinesia and slowing.

Title: The aetiology of severe community-acquired pneumonia and its impact on initial, empiric, antimicrobial chemotherapy.
Author: Feldman C; Ross S; Mahomed AG; Omar J; Smith C
Address: Division of Pulmonology, Hillbrow Hospital, South Africa.
Source: Respir Med, 89: 3, 1995 Mar, 187-92
Abstract: Of 259 patients admitted to an intensive care unit with severe acute community-acquired pneumonia, 173 had primary infections and 86 had secondary infections. The commonest organism isolated in each group was Streptococcus pneumoniae (51.3 and 36.6% of known isolates in each group respectively). Klebsiella pneumoniae was the next most common isolate (31.9 and 29.3% respectively). A variety of other Gram-negative organisms and Staphylococcus aureus accounted for most of the remaining pathogens. Based on retrospective analysis of data, there appeared to be no difference in the alcohol consumption of patients with infection due to S. pneumoniae and K. pneumoniae. The overall mortality rate for the primary infections was 47.4%, with 68.4% of these infections due to K. pneumoniae and 33.9% due to the pneumococcus (P < 0.002). Among the secondary infections, the overall mortality rate was 40.8% (not significantly different to that of primary infections) with 45.5% due to K. pneumoniae and 23.1% due to the pneumococcus (not significantly different on statistical analysis, probably due to low patient numbers). Our investigation confirms that severe community-acquired pneumonia due to K. pneumoniae is extremely common, even in patients without obvious risk factors for Gram-negative colonization. This organism is contributing to the high mortality rate seen in our intensive care unit among patients with pneumonia, and our empiric therapy for such cases routinely includes a combination of agents active against this organism (e.g. a cephalosporin and an aminoglycoside).

Title: Patterns of cytokine expression in community-acquired pneumonia.
Author: Puren AJ; Feldman C; Savage N; Becker PJ; Smith C
Address: Department of Medical Biochemistry, University of the Witwatersrand Medical School, South Africa.
Source: Chest, 107: 5, 1995 May, 1342-9
Abstract

BACKGROUND: Pneumonia continues to be a major cause of disease and death among patients worldwide. Aspects of the host response to infection, such as the release of cytokines, may be contributing to the persistent morbidity and mortality. METHODS: Plasma levels of cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured in critically ill patients with pneumonia (ICUP; n = 12) and less severely ill patients with pneumonia (NONICUP; n = 8), and in 2 additional control groups of patients, viz, severely ill postoperative patients without evidence of infection (POSTOP; n = 11) and less severely ill patients with nonpneumonia infections (NONP; n = 9). All four groups of patients were studied in a multivariate one-way analysis of variance using the parameter vector: plasma IL-1 beta, IL-6, TNF-alpha, systolic blood pressure, diastolic blood pressure, plasma urea, creatinine, and temperature. Thereafter the significance of individual parameters were assessed by univariate analysis and pairwise comparisons. RESULTS: All cytokine concentrations were highest in the ICUP group. In the case of IL-1 beta, levels were significantly higher in the ICUP group when compared with the noninfected POSTOP group. The acute physiology and chronic health evaluation (APACHE) II scores were identical in these two groups (17 /- 3 [SD] and 10 /- 1, respectively, not significantly different). Intermediate levels were found in those groups with intermediate levels of infection. The IL-6 levels were not significantly different between the groups and in particular, the levels in the ICUP and POSTOP groups were similar. The TNF-alpha levels tended to mimic those of IL-1 beta, although the significant difference found was between the ICUP and NONICUP groups which had significantly different APACHE II scores (17 /- 3 vs 4.4 /- 1, respectively). No association between cytokine levels and patient mortality was demonstrated. CONCLUSION: Among the cytokines, IL-1 beta appeared to be associated with the severity of infection, IL-6 appears to reflect severity of stress whether of infection or noninfective origin, and TNF-alpha may be a marker of severity of pneumonia.

Prof C Feldman - Publications

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