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Biomedical subjects

C Feldman

Publications and source records attributed to C Feldman.

At least 19 recordsLinked to original sources

The clinical significance of Haemophilus influenzae and H. parainfluenzae isolated from the sputum of adult patients at an urban general hospital.

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.

Adult

Effect of immunization with Freund's adjuvant and pneumolysin on histologic features of pneumococcal infection in the rat lung in vivo.

Immunization with Freund's adjuvant and pneumolysin and stimulation with Freund's adjuvant alone both reduced the severity of the pneumonia caused by injections of bacteria into the apical lobe bronchi of rats. Neither protocol influenced the incidence of pneumococcal bacteremia. Illness sufficiently severe to require sacrifice was delayed from 2.8 days in nonimmunized animals to 5.7 days in those immunized with Freund's adjuvant and pneumolysin (P < 0.05) and 4.5 days in those stimulated with Freund's adjuvant alone (P, not significant).

Adjuvants, Immunologic

Does primary Streptococcus viridans pneumonia exist?

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.

Adult

The interaction of Streptococcus pneumoniae with intact human respiratory mucosa in vitro.

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.

Cilia

Sarcoidosis in Johannesburg--a comparative study of black and white patients.

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.

Adult

Septic shock in the Intensive Care Unit, Hillbrow Hospital, Johannesburg.

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.

Bacterial Infections

Comparison of bacteraemic community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae in an intensive care unit.

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.

Adult

Pneumolysin induces the salient histologic features of pneumococcal infection in the rat lung in vivo.

Streptococcus pneumoniae infections are common, but how they cause host tissue injury and death is incompletely understood. Immunization with pneumolysin, a thiol-activated toxin produced by the pneumococcus, partially protects animals during subsequent infection. The mechanism by which pneumolysin contributes to disease is not known. The aim of the present investigation was to determine the histologic changes induced by recombinant pneumolysin in the rat lung and to compare them with the changes induced by live organisms. Injection of either toxin (200 or 800 ng) or bacteria into the apical lobe bronchus was associated with the development of a severe lobar pneumonia restricted to the apical lobe. The changes induced by the toxin were greater at the higher concentration, and changes were most severe in those animals in which there was partial ligation of the apical lobe bronchus. The pneumonitis was less severe following injection of a modified toxin with decreased hemolytic activity, generated by site-directed mutagenesis of the cloned pneumolysin gene, indicating that this property of the toxin was important in generating pulmonary inflammation. There was still considerable pneumonitis after injection of a modified toxin with decreased capacity to activate complement.

Animals

Metaproterenol (Alupent) metered dose inhaler in children 5-12 years of age.

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.

Administration, Inhalation

Ciliary beat frequency and structure of recipient and donor epithelia following lung transplantation.

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.

Bronchi

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?

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'.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Alternation of two doses of intravenous gammaglobulin in the maintenance treatment of patients with immune thrombocytopenic purpura: more is not always better.

Intravenous infusion of gammaglobulin (IVGG) has been shown to be effective in the maintenance treatment of children and adults with immune thrombocytopenic purpura (ITP). The objective of this treatment is not to increase the platelet count into the normal range but rather to keep the platelet count above a safe level, usually 20,000-30,000/microliters. This use requires periodic infusion whenever the platelet count falls. The dose of gammaglobulin in previous studies was 1 gm/kg/infusion in the majority of patients. This study compared doses of 0.5 and 1.0 gm/kg/infusion by alternating the two doses in the maintenance treatment of 11 patients with ITP. There was no significant difference in the duration of response following single IVGG infusion between these two doses. This finding suggests that there is no advantage to the greater dose of IVGG and will substantially lower the cost of as well as facilitating IVGG maintenance treatment. It was not possible to determine whether a lower dose would impact adversely on the curative potential of IVGG. This effect of IVGG has never been proved and, if it exists, may be mediated by a different mechanism from the acute platelet response.

Dose-Response Relationship, Drug

The effect of Streptococcus pneumoniae pneumolysin on human respiratory epithelium in vitro.

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.

Antibodies, Bacterial

Klebsiella pneumoniae bacteraemia at an urban general hospital.

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).

Adolescent

Cryptogenic fibrosing alveolitis. A study of an indigenous African population.

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.

Adrenal Cortex Hormones