By I. Irhabar. Nebraska Methodist College.
Transmission is especially efficient be- techniquesandavailableinavarietyofformats tween male homosexuals in whom receptive and are becoming more widely used buy capoten 25 mg line. A posi- anal intercourse and multiple sexual partners tive test should be confirmed by two further are particular risk factors cheap capoten 25 mg overnight delivery. Treat- public health education to reduce activities ment is aimed at reducing the plasma viral 134 Diseases load and is started before the immune system sexual or drug using networks purchase 25 mg capoten. Standard outbreak investi- infection control precautions for blood-borne gation methods should be adopted buy capoten 25 mg on line. Side room careisneededtopreservepatientconfidential- isolation is unnecessary unless there is a risk ity. Risksaregreaterwithhollowneedles,needlesthatarevisiblyblood-stainedorwhichhavebeen in an artery or vein, deep injuries and injuries from source patients who are terminally ill. Urine, vomit, saliva and faeces are low-risk materials unless visibly blood-stained. This course of action should be universally adopted with all significant exposures. Starter packs containing a 3-day course should be readily available at strategic locations. There should be weekly follow-up by an experienced occupational health practitioner. Allshould be encouraged to seek medical advice about any acute illness that occurs during the follow-up period. Pending follow-up, and in the absence of seroconversion, healthcare workers need not be subject to any modification of their working practices. They should, however, be advised about safer sex and avoiding blood donation during the follow-up period. It is a major cause of the specific marker infections or neo- of morbidity during epidemics and can be plasms. Those at particular Suggest case limits contact with non- risk of complications are those with under- vaccinated individuals who are at risk of lying chronic chest, heart or kidney disease, severe disease. Twenty per cent of infections are asymp- tomatic and 30% have upper respiratory symptoms but no fever. Influenza A (H3N2) may cause more severe disease than H1N1 or Influenza B, particularly in the elderly. Epidemiology Influenza causes both annual winter epi- Laboratory conrmation demics of varying size and severity, and occa- sional more severe pandemics. Results can be available variable times between November and March in 23 days, although 1 week is usual for rou- and tend to last 610 weeks, peaking at around tinesamples. Subtyping of influenza A is based on and causing a major pandemic, usually with a combination of H antigen (15 subtypes) and severe disease in all ages: these have occurred N antigen (9 subtypes), e. All in 1918 (causing 2040 million deaths world- recent common human pathogens are combi- wide), 1957 and 1968. Strains pactofpandemics,moredeathsresultfromthe may be further differentiated by serology and steady accumulation associated with yearly namedaftertheplaceandyearsoftheiridenti- non-pandemic influenza activity. Coughing and sneezing par- nausea, vomiting or diarrhoea if infected by ticularlypromotespread. The illness lasts itated by overcrowding and enclosed spaces, 27 days and may include marked prostration. The incubation period is short, usually 13 Transmissionmayalsooccurviadirectorin- days, occasionally up to 5 days. This may occasionally cause a tious period lasts from 1 day before until 35 slowlyevolvingoutbreakwithlowattackrates. Transmissiontohumans tice, they can return to school when clinically israrebutnewstrainsmaybespreaddirectlyor well. In recent years there has been much international concern over reports of human infection with avian influenza strains such as H5N1, H9N2 and H7N7. Some avian viruses cause serious infectionsinhumans(H5N1diseaseinHongKongin1997had33%mortality)butfortunately theydonotspreadeasily,ifatall,betweenhumans. However,influenzaviruseshavetheability toundergogeneticreassortmentandco-infectionwithbothavianandhumaninfluenzastrains in humans or pigs could produce a new strain with the increased virulence of the avian strain and the ability to spread easily from person to person like human influenza. Transmission of this highly pathogenic virus could then occur to a population with no existing immunity and, as yet, no vaccine to protect them. Rapidcontainmentofincidentswhereavianstrainsinfecthumansisthereforeessential to reducing the risk of future pandemics. Although most containment activities will take place in the source area, European countries can limit the risk to their population by measures aimed at early detection of cases and min- imising their contact with others. Exact measures would depend on the current risk but might include: information distributed at ports of entry; detection of symptomatic cases on entry to the country; high index of clinical suspicion in recent travellers, appropriate microbiological testing and reporting to public health authorities; voluntary home isolation of infected cases; effective infection control measures in hospitalised cases; general education messages; particular information for ethnic minorities with links to affected area of world; in addition, if person-to-person spread reported for this strain: identification of contacts of cases, voluntary home isolation and prompt prophylaxis may be considered. Primarycarestaff clinical illness with the same strain for many can increase uptake by compiling an at-risk years. A letter should be sent to each of these patients, preferably from their family doctor, recommending vaccina- Prevention tion. Education on the benefits of vaccina- tion is required both for the target population Basic personal hygiene to reduce transmis- and for healthcare workers. Health authori- sion by coughing, sneezing or contaminated ties should appoint a co-ordinator to lead on hands. Asefficacyin National and local planning prior to oc- elderly people may be lower than the 7090% currence of a pandemic (see Box 3. This may cause perhaps a 50% increase in the total number of deaths from all causes at the height of the pandemic. Twenty-three Response to a case countries participate in the European In- fluenza Surveillance Scheme. Weekly updated Althoughspreadmayoccurbeforediagnosis, bulletins are available at www. However, these samples are heavily biased Control of an outbreak in terms of age (particularly children) and severity (hospitalisation). Timelylocalfeed- for 2 weeks until vaccine induced protection back of interpreted data is particularly use- present (influenza A or B). If not available, ful to local health service planners during the consider zanamivir (A or B) or amantadine or winter. Twenty to twenty-five per cent of upper or lower respiratory tract infection untreatedchildrendevelopcoronaryarteryab- without other identified cause in person normalities. Incidence rates in North America are highest in children of East Asian (especially Japanese This is a mosquito-borne viral encephalitis or Korean) ethnicity. It occurs throughout round; a greater number of cases are reported south-east Asia and the Far East. Several regional out- tions are inapparent, although the illness can breaks have been reported since 1976 in North be severe with high mortality and permanent America. Transmis- sion to man is via a mosquito that lives in rice- Clinical features growing areas. In the absence of a specific diagnostic test, Travellers to endemic countries are only at Kawasaki disease is a clinical diagnosis based risk if they spend long periods (more than a on the characteristic history and physical month) in rural areas where pig farming and findings. An unlicensed, inacti- swollen, fissured lips; strawberry tongue; cer- vatedvaccineisavailable. Thescheduleisthree vical lymphadenopathy; erythematous rash; dosesatdays0,714and28;twodosesatdays0 peeling of fingers and toes. Clinical criteria and 714 gives short-term protection in about havebeendevelopedbytheJapaneseKawasaki 80% of vaccines. Its Acquisition public health importance lies in its ability to cause outbreaks, including large outbreaks in The incubation period and infectious period the community and hospital outbreaks with are both unknown. Prevention Suggested on-call action Currently based on secondary prevention: ini- If linked to other cases, consult Outbreak tial therapy is directed at reducing fever and Control Plan. CasespeakfromJunetoOctober,although Investigation of a cluster and there is usually a smaller secondary peak in control of an outbreak spring. Within tailed investigation to learn more about the Europe those travellers most commonly af- aetiology. Large outbreaks have re- water and so routine environmental testing cently occurred in Spain, the Netherlands, is not helpful. Such sys- tems include hot water systems (especially Thereare41namedspeciesofLegionella,com- showers), wet cooling systems (e. Over 90% of le- towers and evaporative condensers), plastics gionellosis in immunocompetent individuals factories, whirlpool spas, indoor and outdoor is due to L.
I suggested calling his wife; she had said earlier she wanted her husband home for his last days order capoten 25 mg overnight delivery. There was no opportunity to say goodbye or let him know that his wife had been calling buy capoten 25mg. I obtained the next set of blood test results from his kind doctor at the new hospital buy cheap capoten 25 mg on line. He died of aflatoxin [from opening tumors] and dye in dental plastic which blocked conjugation of bilirubin 25mg capoten, all made worse by copper, cobalt and malonates. As long as the body can carry out its functions it can also put up with these obstructions. Norman had the following toxins in his prostate: freon, arsenic (pest- icide), cobalt, and patulin (from common moldy fruit). Arsenic was gone; patulin was gone; but salmonellas were now present in the prostate. He had his new refrigerator, and patulin was still Negative, so he could eat a few more fruits. Rhizopus (fungus) was growing in his prostate and Peyers patches (the lymph nodes of the intestine). His next blood test showed exceptionally good results in spite of his poor condition. And deep inside, patulin fungus was again growing, as was Aspergillus mycelium, conidia and three other aspergillus varieties. Two weeks later, he appeared more bowed and shuffling than ever but still walked unassisted. His doctor at home, where the test was done, was calling him ur- gently for treatment. Six days later he arrived in a wheelchair, just a wispy shadow of his former self. He was given Lugols again to be taken four times a day for salmonella every- where. She related that he wanted to die on a piece of family propertymountainous landfar from his city home. He got out of the wheel- chair, began to cook for himself, went for walks on trails and enjoyed each sunrise and sunset. Later, as I absorbed this miracle I wondered: Was it his toxic home that he was getting away from? She kept her hair Iron 93 67 59 Sodium 138 136 133 dye and eyebrow pencil, Potassium 4. It has more hidden wisdom than we can understand; at the very least, a terminally ill patient should leave the dwelling where the disease was ac- quired. Three weeks earlier, his right arm began hurting and a bump arose on his forearm about half way up to the elbow. He slept most of the time (16-18 hours a day), the rest of the day he was dizzy and felt cold. A visit to the doctor at that time, March 9, got him a blood test and a di- agnosis of Epstein-Barre virus. He must have been suffering from certain parasites and pollutants for many years, perhaps from age four when he had Kawasaki disease. Creatine is made by the body from arginine and glycine and also requires methionine. Was he Brians arm in July not getting enough of these amino acids or was a parasite inhibiting their formation? It is normal to be high when your bones are growing, and Brian had grown 6 inches during the past year, but still, 378 is too high. The doctor had given an ominous prognosis: it was better to amputate than try to treat; this variety of cancer was lethal in children. On July 6 his family started him on our parasite killing recipe, using the book as guide. On July 10, another visit to his doctor brought only dire predictions if the surgery were not carried out quickly. These were Brians initial test results using the Syncrometer: isopropyl alcohol Positive. He was referred to the isopropyl alcohol list in The Cure For All Cancers; he agreed to be meticulous about compliance. Evidently he had killed the flukes and their stages already with the parasite program. A home air test (dust sample) was Positive for freon in liv- ing room and Brians bedroom. The parents planned to immediately move the refrigerator outdoors while finding a new non-freon replacement. They would make a homeopathic dilution of it (one part per million) and give Brian tsp. The final solution should not be more than 10 minutes old before Brian drank the tsp. New tests showed solvents Negative; Mucor Negative; copper still Positive at bone and parathyroid; mercury Positive at bone and parathyroid; freon still Positive at bone and parathyroid. The blood test (July 14) showed considerable improvement from the one done in March, especially in alk phos, creatinine level, and thyroid function (T4). Brians arm pain had not returned; the lump was visibly smaller, nearly normal-feeling. His new Syn- crometer tests showed: isopropyl and wood alcohol Negative; copper Posi- tive at bone and parathyroid; mercury Positive at bone; Penicillium spores (fungus) Positive at bone; Mucor and yeast fungi Negative at bone; freon Positive at bone and parathyroid. His household water continued to be Positive for copper; the plumbing had not yet been done. Final Syncrometer testing showed: Penicillium spores Negative at bone, mercury Negative at bone. They informed me that a second X-ray had been taken August 30, showing that the top part of the tumor was gone; the base was still there, maybe even larger, according to his doctor. The doctor now advised to keep doing whatever it is we are doing, something seems to be working and scheduled another X-ray for thirty days hence. The tumor had decreased in size again and texture appeared more bone-like; nevertheless, the doctor referred them to an orthopedic surgeon. Their regular doctor appointment had been on October 9, the doctor had compared all three X-rays stating he didnt usually see tumors do this, didnt usually see them get smaller, they usually get bigger. Nevertheless, the doctor recommended a total surgical bone biopsy in order to see it himself. They had become way too relaxed about all Brians instructions; he was consuming cold cereals and soda pop (they contain traces of isopropyl alcohol antiseptic). He was to continue the maintenance parasite program once a week and give away his dog. He was reminded to boil all dairy products, avoid afla- toxins, stay away from salad bars (Salmonella, etc. The doctor was delighted, exclaiming it was like a ferocious beast had attacked but then decided to run away. We didnt actually see Brian and his family again till February 28 of the next year. This time we used coenzyme Q10 in 4 massive doses of 3,000 mg taken four days apart. Now we know he must remove the composites as well and even make a dedicated search for tattoos before he can be free of their toxicity. His last X-ray was taken on April 1: His doctor had come into the room and said, Well, its all gone now. After all, two radiologists knew exactly what it was, and two other doctors agreed. Summary: Of course, we know that the last quote, its gone now, should be changed to its gone for now. His parents, though, deserve A-1 grades for pulling their teenager through this experience, with arm intact.
Humans have one chemokine receptor that is promiscuous since it binds to numer- ous chemokines cheap 25 mg capoten otc. This receptor order 25 mg capoten, the Duffy blood group antigen cheap 25mg capoten with amex, was first identified on red blood cells but is also expressed by several nonerythroid cells order 25 mg capoten free shipping, e. Interestingly, the Duffy antigen is a factor in infections with Plasmodium vivax in which the parasite utilizes this receptor to invade erythrocytes (22). In people of African descent, this receptor may not be expressed on red blood cells, and they are resistant to infections with P. The mechanism by which expression of a chemokine receptor is advantageous to the virus is not clear (21). The signaling of cellular response to chemokines occurs through G proteins (gua- nine nucleotide binding regulatory proteins) coupling to initiate phosphoinositide 2 hydrolysis. The resultant increase in diacylglycerol and cytosolic Ca leads to activa- tion of protein kinase C (25). Despite the complex- ity of cytokine activity, it is important to appreciate the role of the interplay of the cytokines with their various target cells in the immune response to an inflammatory agent. The immune response during the early stages will either eradicate the infectious agent or set the stage for the type of chronic immune response. When the control mech- anism for the type of cytokine response is dysfunctional, the result may be the devel- opment of a chronic or progressive infection rather than eradication or containment of the infectious agent, e. The hosts genetic background is also a factor in the development of chronic inflammatory response and pathology. Autoimmune diseases result from perturbation of the immune system either intrinsically for unknown rea- sons, (e. The purpose of this section is to provide a background sketch of the role of the cytokine network in the responses of the immune system to an infectious agent prior to its commitment to the appropriate immune protective mechanism, i. Initial Inflammatory Response and Leukocyte Migration The bodys innate immune response to an invading organism results in the recruitment of leukocytes and phagocytosis of the organism. Numerous factors, including bacterial components, will stimulate migration of the leukocytes. Immunotherapies that are intended to interfere with the Cytokines, Cytokine Antagonists, and Growth Factors 125 activity of these cytokines and other inflammatory molecules, e. These cytokines in turn stimulate their target cells to produce a number of different mole- cules. These latter molecules are important in the recruit- ment of leukocytes from the circulation to the infected tissue. With expression of leukocyte adhesion molecules, the leukocytes loosely attach to the endothelial cells through the oligosaccharides on their membranes. With their movement slowed by this loose attachment, the leukocytes will begin to roll along the endothelial surface. The chemokines released from macrophages, the surrounding tissue cells, and the endothelial cells in response to the bacterial components bind to the endothelium, where they cause the rolling leukocytes to adhere more firmly to the endothelium through binding of the integrins to their ligand. The leukocytes then migrate through the endothelium and move up a gradient of chemokine concentrations to the inflammatory site. The types of leukocytes recruited to the inflammatory site can differ depending on the source of inflammation, (e. Activation of T-Helper Cells: Th1/Th2 Subsets When stimulated, T-cells produce different types and amounts of cytokines, which in turn, characterizes the functional response of the T-cells. The cytokines produced by each subset regulates the function and devel- opment of the other. Several immunotherapies for infectious diseases have focused on the manipulation of the type or degree of T-cell response, e. Although this response is intended to eradicate intracellular pathogens, it may also be associated with autoimmune diseases. Th2 cytokines activate mast cells, eosinophils, and elevation in IgE levels and are associated with the immune response to allergens and helminths. Chemokines have a role in lymphocyte response to infections with the orchestration of the movement of the right lymphocyte, i. The T-helper cell subsets tend to colocalize with different leukocytes (although not always). The Th1 subset of cells tends to colocalize with macrophages and neutrophils, whereas Th2 are more often associated with eosinophils and basophils. Much of the data on chemokine receptor expres- sion analysis in T-helper subsets are from in vitro experiments, and further studies are needed to improve our comprehension of the role of chemokines in lymphocyte migration. Since the elucidation of the Th1/Th2 subsets of helper T-cells, their function has probably been oversimplified in the assignment of a Th1 response to intracellular pathogens and a Th2 response to extracellular organisms. However, for many infectious Cytokines, Cytokine Antagonists, and Growth Factors 127 diseases a response by Th1 and Th2 cells at different time points is needed to control or eradicate the infection. In addition, unlike in the mouse, some cytokines are syn- thesized by both T-cell subsets in humans. This coproduction for some cytokines and the redundancy in the activity of the cytokine network suggest that the immune response to different pathogens represents a weighted response involving both T-cell subsets rather than one limited solely to either Th1 or Th2. Therefore, it is important to rec- ognize that the therapeutic effect of an immunotherapy intended to manipulate the effect of one cytokine will result not only from the modulation of that cytokine but also the effect that that modulation has on other cytokines in the network. Modulation of host defenses by cytokines: evolving adjuncts in pre- vention and treatment of serious infections in immunocompromised hosts. Regulation of immunoglobulin production in hyperim- munoglobulin E recurrent-infection syndrome by interferon-gamma. Airway epithelial cell expression of interleukin-6 in transgenic mice: uncoupling airway inflammation and bronchial hyperreactivity. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Purification of a human monocyte-derived neutrophil chemotactic fac- tor that has peptide sequence similarity to other host defense cytokines. Neutrophil activating peptide 1/interleukin 8, a novel cytokine that activates neutrophils. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Th1/Th2 subsets: distinct differences in homing and chemokine receptor expression? Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. This vaccine was based on the observation that subsequent to injection of a boy with cowpox, he was protected against two successive inoculations with smallpox virus. After 200 years, global administration of vaccinia has led to almost total eradication of the small- pox virus from the earth. There is no other example in medicine of a new drug or bio- logic substance leading to eradication of the causative agent and extinction of disease. Vaccinations against other bacteria or viruses prevents the death of millions of people yearly. This is why the development of new vac- cines is a permanent aim of medical research. This interest grew because scientists have understood that vaccines can be used not only for prevention of infectious diseases but also for therapy, leading to the concept of therapeutic vaccines. Classical vaccines pioneered by the discoveries of Jenner, Pasteur, and Ramon was based on the principle of inactivation of pathogenicity of a microbe without altering its capacity to induce a protective immune response. Developments during the past decades in biochemistry, molecular biology, and immunology have provided new tools for the development of a new generation of vac- cines. Biochemistry and Immunochemistry contributed to the identification of epitopes endowed with protective capacities. The identification of such antigenic determinants, also called epitopes, on antigens of protein origin allowed for preparation of synthetic peptides or subunit vaccines in the case of antigens of nonprotein origin. Immunology provided the framework for understanding the mechanisms responsible for the activation of lymphocytes fol- lowing vaccination as well as functional analysis of various epitopes that induce a pro- tective immune response. This is particularly important as antibodies mediate the protection against some bacteria; cellular immune responses are prevalent against obligatory intracellular microbes. The differences between B- and T-cells are not only func- tional but are also seen in the mechanism of recognition of antigens.