Tuberculosis: the beginning of the end?
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Antitubercular Agents↗
Biomedical subjects
R G Douglas
Publications and source records attributed to R G Douglas.
Phytophotodermatitis in pigs exposed to parsley (Petroselinum crispum).
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Animals↗
Interpretation of ANCA serology.
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Antibodies, Antineutrophil Cytoplasmic↗
Prevalence of severe ant-venom allergy in southeastern Australia.
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Adolescent↗
The Jeremiah Metzger Lecture. Vaccine prophylaxis today: its science, application and politics.
In summary, I have addressed 5 key issues concerning vaccines today. First is the essentially empiric nature of vaccinology. Vaccinology is not a rational science. Each idea must be tested by experiment. This need for trial and error experimentation is a substantial barrier to new vaccines. The proven track record of existing vaccines to eradicate disease, to reduce occurrence of disease, reduce human suffering and contain health care spending--when coupled with the potential for new discoveries against significant disease targets--is unparalleled by other therapeutic areas. The complexity of vaccine delivery today in clinical practice with 15-17 injections in the first two years of life emphasizes the need for development of combination pediatric vaccines, for example, putting DTaP, HBV, HIB, and IPV together. This has proved to be far more difficult than previously believed due to unpredicted immune interference and incompatibilities on mixing of different components, demonstrating again the inadequacy of our understanding of how vaccines work and the empiric nature of the science. Similar complexity will face adult vaccines in the future, as new adult vaccines are developed. Next, vaccines remain undervalued by people, by government, and by society. Government-controlled prices in many areas of the world prohibit a return on investment that supports innovative R&D. New vaccines may be unavailable in certain markets because of pricing restraints. Prices of new vaccines in the developed world will rise as will prices in the developing world for products currently available only in the developed world. Reluctance to use vaccines is an especially disturbing symptom of the undervaluation issue. In the U.S., school entry requirements have kept childhood immunization rates high by five years of age. But this is a new phenomenon, driven in part by the measles outbreaks. The risk is that history will repeat itself. In the absence of disease and lack of public knowledge of these diseases, complacency sets in, immunization rates fall, with the expected result on occurrence of disease. For adults, we may hope that managed care with its interest in cost saving and disease prevention may actually help in achieving the goals of the Year 2000. Finally, I have talked about the anti-vaccine attitudes and forces that impede control of disease by vaccines. It is important that new initiatives be undertaken that will be successful in providing a balanced view of vaccine safety, efficacy and benefits to the public, to the provider and to the payers.
Adult↗
The heritage of hepatitis B vaccine.
Pioneering development of the plasma-derived and yeast-derived recombinant hepatitis B vaccines represents a major contribution to preventive health care of this century. Current and expanding worldwide application of hepatitis B vaccine promises to eliminate and eventually eradicate hepatitis B infection from the human population and, with it, many cases of cirrhosis and cancer of the liver.
Hepatitis B↗
Infectious diseases.
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Communicable Disease Control↗
Anabolic and cardiovascular effects of recombinant human growth hormone in surgical patients with sepsis.
The clinical and metabolic effects of 7 days of recombinant human growth hormone (rhGH) and total parenteral nutrition (TPN) in surgical patients with sepsis were determined in a randomized controlled trial. In patients with a mean(s.e.m.) pretreatment rate of net protein catabolism (NPC) of 1.5 g per kg per day or less rhGH treatment decreased NPC from 0.93(0.14) to -0.20(0.24) g per kg per day (n = 5; P < 0.0005) and rendered these patients anabolic. TPN alone decreased NPC from 1.12(0.11) to 0.61(0.11) g per kg per day (n = 5; P < 0.001). In patients with an initial NPC of more than 1.5 g per kg per day rhGH treatment decreased NPC from 2.72(0.12) to 1.08(0.24) g per kg per day (n = 5; P < 0.001) while TPN alone decreased it from 2.41(0.32) to 1.28(0.28) g per kg per day (n = 5; P < 0.005). Use of rhGH was not associated with any adverse effects or improvement in clinical course but did decrease the mean systolic and diastolic pressures during the study period. Thus rhGH is a useful anabolic agent and may have a role in the haemodynamic management of the catabolic patient with sepsis.
Aged↗
Fostering partnerships for vaccine development: a delicate fabric.
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Child↗
Infectious diseases.
Cryptosporidiosis is increasingly recognized to be a major cause of diarrheal disease in the United States. Improved strategies for prophylaxis of opportunistic infections in persons with advanced HIV disease have been identified. Zidovudine was shown to decrease perinatal transmission of HIV.
Communicable Disease Control↗
Infectious diseases.
Unlike the initial H influenzae type b vaccine, which contained polysaccharide alone, the conjugate vaccines effectively induce immunity in infants as young as 2 months. Multidrug-resistant strains of S pneumoniae are emerging as important pathogens in the United States.
Communicable Disease Control↗
New challenges in quality control and licensure. Regulation.
The Children's Vaccine Initiative (CVI) will result in profound changes in immunization practice. Before the CVI is fully developed, it will present numerous challenges to regulatory practice that will require new applications of existing ideas and innovative solutions to practical issues, especially in combining existing vaccines.
Child Welfare↗
Combination vaccines.
The availability of new vaccines for pediatric use provides an unprecedented opportunity to prevent serious infectious diseases and their associated morbidity and mortality. However, each new product entails the need for additional injections that could become so numerous as to discourage the administration of new vaccines. This challenge can be overcome by mixing individual vaccines before delivery such that multiple vaccines are administered as single combination vaccines. Technical, clinical, manufacturing, regulatory and marketing issues relative to combination vaccines in general are the major challenges for ongoing and future development.
Drug Design↗
The children's vaccine initiative: a public health solution or wishful thinking?
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Humans↗
Infectious diseases.
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AIDS-Related Opportunistic Infections↗
Growth hormone therapy initiated before starvation ameliorates the catabolic state and enhances the protein-sparing effect of total parenteral nutrition.
The effect of 7 days of subcutaneously administered bovine growth hormone (bGH) (0.2 mg kg-1 day-1; n = 4) or an equivalent volume of 0.15 mol l-1 saline (n = 3) on protein metabolism was assessed in lambs. The catabolic response to 48 h of starvation and subsequent hypocaloric total parenteral nutrition (TPN) was measured using primed constant intravenous infusions of [15N]urea and [14C]leucine. Following 48 h of starvation and 7 h of TPN, bGH-treated animals had a significantly decreased rate of net protein catabolism compared with controls (mean(s.e.m.) 2.4(0.2) versus 3.2(0.3) g kg-1 day-1, P < 0.01). The mean(s.e.m.) rate of whole-body protein catabolism was also significantly decreased in bGH-treated animals at 10.9(0.3) g kg-1 day-1 compared with 12.9(0.7) g kg-1 day-1 in saline-treated controls (P < 0.05). In addition, the rates of net and whole-body protein catabolism decreased significantly (P < 0.05) during the period of hypocaloric parenteral feeding to mean(s.e.m.) values of 2.3(0.2) and 8.6(0.6) g kg-1 day-1 respectively in bGH-treated animals. By contrast, in saline-treated controls net and whole-body protein catabolism continued to increase during hypocaloric parenteral feeding. There was a significant decrease (P < 0.05) in the rate of [14C]leucine uptake in tissues of the gastrointestinal tract, heart and diaphragm in bGH-treated animals compared with controls. These results demonstrate that daily administration of growth hormone decreases the catabolic response to a metabolic stress, resulting in the conservation of protein in the heart, diaphragm, gastrointestinal tract and musculoskeletal system by a primary anticatabolic action. In addition, growth hormone therapy initiated before induction of the catabolic state enhances the protein-sparing effects of TPN. Further study is justified to determine whether growth hormone therapy initiated before elective or urgent surgery in the nutritionally depleted patient may have a role in reducing the severity of the postoperative catabolic state, particularly in the patient in whom a complicated course is anticipated.
Animals↗