PubMed Health⌕ Search

Biomedical subjects

H Douglas

Publications and source records attributed to H Douglas.

At least 37 records · Page 2Linked to original sources
PubMed1985

Characteristics and satisfaction of the patients of male versus female dentists.

With rising numbers of women entering dental practice, and relatively little known about these practices, this study seeks to characterize the practices of female dentists. Characteristics and satisfaction differences of patients between male and female practitioners were examined. A matched-pair design of 13 men and 13 women in general private practice in Connecticut was conducted. Questionnaires, designed to evaluate satisfaction and patient sociodemographics, were distributed to 25 patients from each practice. Patients were similar to utilizers as described by the US National Health Interview Survey, and scored slightly higher on the Dental Satisfaction Questionnaire than a national sample. Few differences were found between the patients of male and female dentists, but significant differences were found in patient incomes, satisfaction with cost, and satisfaction with access, with the patients of women giving more favorable satisfaction ratings on cost and access. These findings are encouraging to women entering private practice as they are perceived by patients to deliver care equal in quality to their male counterparts.

Adult↗
PubMed1983

Killing of Aspergillus spores depends on the anatomical source of the macrophage.

To resolve the controversy over the capacity of macrophages to kill or inhibit germination of Aspergillus spores, we compared this function in peritoneal and alveolar macrophages. Alveolar macrophages from rabbits killed 82 to 90% and completely digested 72 to 82% of spores of Aspergillus fumigatus in 30 h. In contrast, peritoneal macrophages could not even inhibit the germination of ingested spores; more than 85% transformed into mycelia within 24 h. Killing by alveolar macrophages was delayed for 3 to 6 h after phagocytosis and was independent of oxidative killing mechanisms and immune activation. The ability of alveolar macrophages to kill Aspergillus spores without modulation by T lymphocytes or the generation of oxygen intermediates points out that concepts built on studies of peritoneal macrophages may be misleading and underscores the importance of studying the role of macrophages in immunity with cells from the appropriate anatomical site.

Animals↗
PubMed1983

Models of T cell deficiency in listeriosis: the effects of cortisone and cyclosporin A on normal and nude BALB/c mice.

It is often difficult to test the role of T lymphocytes in resistance to infection because most models of T cell deficiency are associated with altered nonspecific resistance. In an attempt to address this problem, we compared the effects of cyclosporin A (CyA), cortisone (CA), and the athymic state on the course of murine listeriosis. We chose listeriosis because resistance to Listeria monocytogenes occurs in two phases. Bacterial multiplication is controlled by nonspecific defense mechanisms in the early phase and by acquired T cell-dependent immunity in the second phase. Mice treated with CA died during the early phase, probably because of inhibition of the antimicrobial activity of nonimmune macrophages. Accordingly, the immunosuppressive effect of CA was similar in athymic and normal mice. Untreated nude mice developed chronic low grade infection, probably because of heightened activity of nonimmune macrophages. In contrast, immunosuppression with CyA did not affect early resistance but induced overwhelming, fatal disease in the later phase when control mice began to acquire resistance. CyA did not change the course of listeriosis in nude mice, confirming its specificity for T cell-dependent immunity. Thus, this study shows that CyA is a potent and specific inhibitor of T cell-mediated immunity and that T cell-dependent resistance is essential for survival from listeriosis, a conclusion that could not have been established by studies of the nude mouse or immunosuppression by CA.

Animals↗
PubMed1982

Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli.

In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.

Adolescent↗
PubMed1982

Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes.

By comparing natural immunity to Aspergillus fumigatus (AF) in vivo with the action of human or mouse phagocytes against AF in vitro, we delineated two sequential lines of defense against AF. The first line of defense was formed by macrophages and directed against spores. Macrophages prevented germination and killed spores in vitro and rapidly eradicated conidia in vivo, even in neutropenic and athymic mice. The second was the neutrophilic granulocyte (PMN), which protected against the hyphal form of AF. Human and mouse PMN killed mycelia in vitro. Normal, but not neutropenic mice, stopped hyphal growth, and eradicated mycelia. Either line of defense acting alone protected mice from high challenge doses. Natural immunity collapsed only when both the reticuloendothelial system and PMN were impaired. These findings are in keeping with the clinical observation that high doses of cortisone and neutropenia are the main risk factors for invasive aspergillosis. Cortisone inhibited the conidiacidal activity of mouse macrophages in vivo and of human or mouse mononuclear phagocytes in vitro. Cortisone damaged this first line of defense directly and not through the influence of T lymphocytes or other systems modifying macrophage function as shown in athymic mice and in vitro. In addition, daily high doses of cortisone in mice reduced the mobilization of PMN so that the second line of defense was also impaired. Thus, cortisone can break down natural resistance on its own. Myelosuppression rendered mice susceptible only when the first line of defense was overpowered by high challenge doses, by activated spores that cannot be killed by macrophages, or by cortisone suppression of the conidiacidal activity of macrophages. The host, thus, can call upon two independent phagocytic cell lines that form graded defense systems against aspergillus. These lines of defense function in the absence of a specific immune response, which seems superfluous in the control and elimination of this fungus.

Animals↗
PubMed1982

Induction of immunity against lethal Haemophilus influenzae type b infection by Escherichia coli core lipopolysaccharide.

Efforts to prevent Haemophilus influenzae type b (HIB) infections in infancy have been hampered by the low immunogenicity of capsular polysaccharide vaccines in children younger than 18 mos. In searching for alternate immunogens, we have studied the protective potential of polysaccharide-poor, lipid-rich endotoxin (LPS) core in experimental HIB infections. Because all gram-negative bacteria have similar LPS core structures, we were able to use as vaccine the J5 mutant of Escherichia coli 0111, the LPS of which consists only of core components, and thus to avoid problems in interpretation arising from vaccine contamination with non-LPS HIB immunogens. Mice were given graded inocula of HIB and developed lethal infection analogous to human HIB disease when virulence was enhanced with mucin and hemoglobin. After active immunization with heat-killed E. coli J5, 40/50 (80%) of infected mice survived, compared with 14/50 (28%) of saline-immunized controls (P less than 0.005). Passive immunization with rabbit antiserum against E. coli J5 prevented lethal HIB infection when administered 24 or 72 h before or 3 h after infection. This protection was abolished by adsorption of antiserum with purified J5 LPS, with survival reduced from 14/24 to 0/24 (P less than 0.005). Furthermore, rabbit antiserum to purified J5 LPS gave just as potent protection against death as antiserum to whole J5 cells. These studies demonstrate that immunity to core LPS confers protection against experimental murine HIB infection and provide the framework for a new approach to prevention of human disease from HIB.

Antibody Formation↗
PubMed1981

Immunization against nosocomial infection.

Overwhelming infection with gram-negative bacteremia has become the most serious nosocomial infection in compromised patients. Because gram-negative bacteria share a common core lipopolysaccharide, we tried to develop a single vaccine or antiserum that might control these infections regardless of species. We used a mutant of Escherichia coli 0111 (J5) deficient in uridine diphosphate-galactose (UDP-GAL) epimerase and thus unable to attach "0" side chains, so that core lipopolysaccharide was exposed. A vaccine composed of this mutant produced antibody that gave broad protection against lethal infections by different gram-negative bacteria in immunosuppressed animals. The J5 vaccine protected against 98 percent lethal doses of Pseudomonas aeruginosa, and J5 antiserum improved survival tenfold in animals dying of Esch. coli, Klebsiella and Pseudomonas bacteremia. The protection with vaccine or prophylactic antiserum was undiminished in animals challenged six weeks after immunization. Encouraged by these results, we conducted a double-blind trial in patients with gram-negative bacteremia. In those given J5 antiserum, the mortality rate was cut in half and survival from deep shock increased from 28 percent to 82 percent. Because of these preliminary results in 136 patients, the study has been extended to 300 patients and the double blind code will be examined again to see if the early favorable results are confirmed and extended.

Adult↗
PubMed1979

Pseudomonas aeruginosa vasculitis and bacteremia following conjunctivitis: a simple model of fatal pseudomonas infection in neutropenia.

During attempts to create a realistic model of fatal bacteremia due to Pseudomonas aeruginosa during immunosuppression, it was found that the invasive as well as the disseminated phase of infection could be mimicked by gentle instillation of 10(8) colony-forming units of P. aeruginosa into the intact conjunctival sac of agranulocytic rabbits. Within 48 hr animals developed conjunctivits leading to severe necrotizing vasculitis and fatal bacteremia. Twelve of 26 strains from patients with P. aeruginosa infections were virulent, causing death in 50%--100% of animals. Nine (75%) of 12 isolates from blood but only two (15%) of 13 isolates from sputum and urine were highly lethal. Neither proteolytic enzyme production nor serum resistance alone accounted for virulence. No infection developed in animals and normal leukocyte counts or in neutropenic animals given Escherichia coli, Klebsiella pneumoniae, or non-aeruginosa pseudomonads. A rare vasculitic lesion was observed in animals inoculated with Serratia marcescens. This model, which illustrates the distinctive features of P. aeruginosa infection, is so simple and reproducible that it should be useful for evaluation of the efficacy of drugs and immunization against Pseudomonas in the compromised host.

Agranulocytosis↗
PubMed1977

Antibody to cell wall glycolipid of Gram-negative bacteria: induction of immunity to bacteremia and endotoxemia.

Antiserum to the core glycolipid of gram-negative bacteria was prepared by immunization of rabbits with vaccine composed of killed cells of the uridine diphosphate galactose-deficient mutant (J5) of Escherichia coli O:111. Antiserum to J5 not only prevented death of animals from endotoxin but also prevented the local and generalized Shwartzman reactions. Antiserum to endotoxin also prevented renal cortical necrosis and disseminated intravascular coagulation during the evolution of the generalized Shwartzman reaction. Antiserum to be J5 mutant was successful in the treatment of overwhelming bacteremia produced by other gram-negative bacteria; in addition to bacteremia cause by coliform organism, antiserum to J5 was dramatically effective in treatment of bacteremia due to Pseudomonas aeruginosa. One injection of rabbit antiserum to J5 improved the survival rate from 15% in controls to 59% in treated animals (P less than 0.002). Active immunization with J5 vaccine was even more effective against pseudomonas bacteremia: such immunization improved the survival rate from 13% in controls to 92% in vaccinated rabbits. Since an antiserum effective against the J5 mutant of E. coli can be prepared safely in human subjects, such immunotherapy should be considered for patients with gram-negative bacteremia.

Animals↗
PubMed1975

Prevention of lethal pseudomonas bacteremia with epimerase-deficient E. coli antiserum.

All of these experiments demonstrate that despite many microbiologic differences between Pseudomonas and the enteric rods, there is a close immunologic relationship between their endotoxin cores. These studies also show that by genetic manipulation we can unmask a protective antigen for preparing antiserum with a broad range of activity, even in the face of neutropenia. Production of potent human J5 antiserum is a safe, simple procedure, making it possible to consider endotoxin core antibody treatment of all Gram negative bacteremia in patients regardless of the causative organism.

Agranulocytosis↗
PubMed1973

Human antiserum for prevention of the local shwartzman reaction and death from bacterial lipopolysaccharides.

Bacterial lipopolysaccharides from dead bacteria have been blamed for the continuing high mortality from gram-negative infections despite antibiotic treatment. Because animal antiserum against these lipopolysaccharides has been shown to protect against several of the effects of endotoxin, we undertook the development of antiserum in human subjects. 21 men were immunized with a single injection of Salmonclla typhimurium or Escherichia coli 0:111 heat-killed cells and immune serum was collected at 2 wk. Preimmune serum was obtained as a control in all animal experiments. 1 ml antiserum given intravenously protected mice against a lethal intravenous dose of homologous endotoxin (P < 0.005 for both antisera). E. coli antiserum reduced the incidence of positive local Shwartzman reactions with E. coli endotoxin from 100 to 38%; S. typhimurium antiserum reduced the incidence from 92 to 35%. (P < 0.0005 for both antisera). There was no protection against heterologous endotoxin in either animal model. These experiments demonstrate for the first time that human antiserum confers exceedingly potent passive immunity to the effects of endotoxin.

Antitoxins↗