By M. Anktos. Syracuse University.

Why it has this specific influence I do not propose to say discount xanax 1 mg visa, but the fact I have proven in scores of cases generic xanax 1mg free shipping. Given buy 1 mg xanax visa, a case in which boils are being continually developed order xanax 1 mg with mastercard, the use of lime-water will effect a radical cure. In small doses it is stimulant to the cerebro-spinal centers; in large doses it produces intoxication, and finally arrest of function. It exerts an influence upon the urinary and reproductive apparatus that may be rendered available in practice, and also to some extent upon the skin. I have employed the Cannabis specially to relieve irritation of the kidneys, bladder, and urethra. It will be found beneficial in vesical and urethral irritation, and is an excellent remedy in the treatment of gonorrhœa. Camphor in small doses is a stimulant, in large doses a sedative, to the nervous system. I do not regard it as having a very extended use in medicine, though for the purpose named, it may sometimes be employed with advantage. In low forms of disease, with insomnia and restlessness, I have used it alone, and in combination with stimulant doses of opium or morphia, and quinine. As a topical stimulant, it may be employed with advantage, when the integrity of the part is threatened from enfeebled circulation. As an internal remedy, Cantharis will have but one use - as a stimulant to the urinary apparatus, especially the bladder. As Capsicum, it never gains admission to the circulation, and, in the process of digestion, it almost wholly loses its properties as a remedy. Capsicum is used as a topical stimulant to the skin, and with advantage where the circulation is feeble, and there is need of such stimulation. In torpid states of the gastric mucous membrane, such action may be very desirable, may even be essential to life, as in congestive intermittent. It is the topical action upon the gastric mucous membrane that is beneficial in some cases of delirium tremens. The solar plexus, the most important of the vegetative nerve centers, may be thus influenced from the stomach. The stimulant influence of Capsicum may, therefore, be extended through this, and be of marked advantage in states of great and sudden prostration with tendency to congestion. Given in water-brash, or where there is decomposition of the food, it is sometimes beneficial. So in topical disease - with free secretion and tendency to sepsis - its local application absorbs the one and checks the other. Why this checks it I can not tell; that it does it, I have the evidence of my own eyes. For several years I have employed the second decimal trituration as a remedy in passive hemorrhage, with most marked benefit. I employ it in threatened hemorrhage during typhoid fever, in menorrhagia, especially when chronic, in prolonged menstruation, the watery discharge that sometimes follows menstruation, hemorrhage from the kidneys, hemorrhage from the lungs, and in some cases of leucocythemia. A good indication for this remedy is a small pallid tongue, with lenticular spots, and with this it may be given in any form of disease. The dose of the first or second trituration will be one grain, repeated as often as necessary. In this form it is easily carried, and dispensed by adding the proper portion to water, so that the dose may be one teaspoonful. Carbolic Acid exerts a specific influence in those cases in which, with a broad moist tongue, there is a cadaverous odor of the breath. It makes little difference what the name of the disease is - whether bilious or typhoid fever, cynanche, pneumonia, diarrhœa, dysentery, disease of the urinary apparatus, or whether the disease is acute or chronic. In these cases it is used in small doses as - ℞ Solution of carbolic acid in glycerine, gtt. We employ it with marked advantage in cases of irritable stomach, and to check nausea and vomiting, when the symptoms above named present. As far as my experience goes, it cannot be used with advantage where the mouth is dry, or if the tongue is contracted, or enlongated and pointed. As a topical application, we employ carbolic acid when we need an antiseptic and a stimulant. Even here there must be the local symptoms, fullness and relaxation of tissues; whenever there is contraction, shrinking and dryness, it will prove harmful. These rules hold good, whether as a dressing for wounds, for erysipelas, for burns, for a chancre, for a gargle, a vaginal injection, or for the treatment of a gonorrhœa or gleet. As a local application in full strength we use this agent to destroy warts, and epidermal growths of this character. It is also a remedy in epithelial cancer, and in some cases it will exert a better influence than the stronger escharotics. The strength of the solution, in the treatment of cancers, will vary in different cases. In some the full strength of the solution in glycerine can be continually applied; in a few the full strength of the acid, rendered fluid by heat; but in others it will require dilution with glycerine. Use that strength that gives greatest ease, and leaves the parts in best condition. One of the principal objects is relief from pain, carbolic acid being a true anæsthetic in these cases, and the strength of the solution will be adapted to this use. It exerts, however, a special influence in colic, which renders it an important remedy. We have generally employed it in the form of the Compound Powder of Jalap and Senna, in doses of five or ten grains, frequently repeated until relief is obtained. An infusion of senna - or the tincture will answer the same purpose - for the relief of colic, whether the common wind colic or that known as bilious, I regard as one of our best remedies. Chestnut leaves exert a specific influence in some cases of whooping cough, so much so, that the relief is apparent in twenty-four hours. They have usually been employed in infusion, but the tincture will be found as good, and is more easily dispensed. In convulsive cough or paroxysmal cough, resembling whooping cough, it has also proven a successful remedy. It may also be tried in cases where there is unsteadiness in the gait, and a disposition to turn to one side. This remedy has been regarded as so valuable that it was monopolized by the government of Cashmere. A tincture is prepared from the root which is administered in doses of one drop; and is employed in giddiness, salivation, and as an antidote to poisonous bites and stings. In small doses the tincture of Catalpa relieves irritation of the bronchial tubes, and gives freedom to respiration.

The vaginal absorption of insulin was studied in ovariectomized rats and in the absence of any enhancer 1mg xanax with amex, no decrease in blood glucose was observed purchase xanax 1mg visa. Co-administration of various absorption enhancers was able to significantly increase the degree of hypoglycemia generic xanax 1mg with mastercard. The histological changes in the vaginal epithelium after treatment with the enhancer systems were variable and often severe: • palmitoylcarnitine chloride exhibited the greatest local toxicity including reduction of epithelial thickness and cell death 1 mg xanax free shipping. However, no conclusions can be drawn at this stage about the likely tolerability, safety and efficacy of the gel in the context of sexual intercourse. Antiviral vaginal devices Nonoxynol-9 is an approved spermicide with strong antiviral activity. The device, available as a diaphragm or a disk pessary, is fabricated from silicone elastomer matrix system. The drug release profile demonstrates square root time kinetics (M ∞ t / ) (see1 2 Section 4. While the spermicide-containing reusable diaphragms currently on the market are relatively effective when used in combination with a spermicidal formulation, they require careful fitting, insertion and maintenance. Moreover, adverse reactions, such as urinary tract infections, alterations in vaginal flora and occurrence of toxic shock syndrome, have been associated with their use. In contrast the silicone-based device described above has been reported to be stable, non-irritating and non-toxic. A vaginal sponge has also been recently developed comprising a soft poly(urethane) sponge impregnated with a gel containing 1% benzalkonium chloride, 0. The sponge therefore combines the actions of: • a physical barrier that blocks the cervix; • a material that absorbs the ejaculate; • a spermicide; • an antiviral agent. Antiviral liposomal preparations Intramuscular injection of α interferon was shown to be fairly efficacious in the treatment of genital warts; however, this route was associated with a number of side-effects including fever, myalgia, headache, nausea and fatigue. A liposomal preparation of α interferon for topical vaginal delivery has been developed, which offers the advantage of treating latent human papillomavirus infections as well as visible genital warts. The liposomal preparation can be self-administered intravaginally, without the need for multiple painful local, or im, injections. In the vagina, mucosal immune responses are initiated by the uptake of antigens from the vaginal surfaces (Figure 11. Whereas the gastrointestinal tract has identifiable aggregates of lymphoid tissue within the epithelium known as the Peyer’s patches (see Section 6. Antigen-specific effector lymphocytes (B cells and T cells) migrate through the lymphatics and exit via the thoracic duct into the bloodstream. The primed B and T cells home to various mucosal sites including the genital mucosa, where they undergo maturation and secretion. A vaginal vaccine has been developed for the treatment of recurrent urinary tract infections. The multi- strain vaccine, composed of 10 heat-killed bacterial uropathogenic strains, has been shown to be efficacious against cystitis in non-human primates when administered by the vaginal route. Bladder infections were significantly reduced and both systemic and local immune responses were generated. It was determined that vaginal immunization resulted in two different types of immune responses in mice: high and low. High responders to the immunizations had been immunized in the diestrous phase of the cycle. As explained above, the vaginal epithelium is thin and porous during this phase, which facilitates vaccine uptake. Similarly, rectal immunization induced high levels of specific IgA and IgG in rectal secretions, but not in female genital tract secretions. Thus, generation of optimal immune responses to sexually transmitted organisms in both the rectal and the genital mucosa of women may require local immunization at both of these sites. Association of an antigen with an appropriate microparticulate carrier may enhance antigen uptake by vaginal antigen-presenting cells. The effect was further enhanced when the penetration enhancer lysophosphatidylcholine was used. Hyaluronan ester microspheres Hyaluronan is a naturally occurring mucopolysaccharide, consisting of repeating disaccharide units of D- glucuronic acid and N-acetyl-D-glucosamine. By esterification of the carboxyl groups of the glucuronic acid residue with alcohols, modified biopolymers can be produced which are biocompatible, mucoadhesive and biodegradable. The degradation rate can be controlled by the degree of esterification and by the type of alcohol substituent. Experiments using radio-labeled microspheres have shown that after vaginal administration the microspheres are dispersed along the length of the vagina for prolonged periods, thereby demonstrating their potential as a long-acting intravaginal delivery system. Suppocire, a mixture of semi-synthetic polyethylene triglycerides, melts at 35–37 °C. After administration of the pessary, the formulation forms a fine emulsion on contact with the aqueous environment of the vagina, thus encouraging the dispersion of microspheres throughout the vaginal cavity. It has been proposed that the bioadhesive microspheres may induce transient widening of intercellular junctions when applied nasally, or added to Caco-2 cell monolayers. It is thought that drug microspheres take up water from the cells, causing the cells to dehydrate and “shrink”, thereby inducing the transient widening of the intercellular junctions and increased drug transport. Work in this field has concentrated on the use of poly(lactide-co-glycolide) microparticles, which have the advantages of being biocompatible, biodegradable and well tolerated in humans. Promising results have also been obtained with the use of biodegradable starch microspheres in conjunction with the absorption enhancer lysophosphatidylcholine. However, in general, only low levels of antibodies have been induced by intravaginal immunizations and the antibodies generated have been predominantly localized in the genital tract, even in the presence of potent antigen delivery systems. Such formulations are prone to leakage, which can result in: • low efficacy, due to limited contact time with the absorbing surface; • poor compliance. Bioadhesive polymers can be used to prolong the contact of a drug with a mucosal surface, without inducing adverse local effects on the epithelium. Other beneficial effects conferred by the use of bioadhesive polymers include: • increasing the local drug concentration at the site of adhesion/absorption; • protecting the drug from dilution and possible degradation by vaginal secretions; • prolonging the contact time of the dosage form near the absorbing surface. Thus such polymers have attracted considerable interest as a means of improving drug delivery at mucosal sites, including the vagina. Reference has already been made to the promising results obtained using bioadhesive hyaluronane ester microspheres for vaginal drug delivery. Other bioadhesive polymers under investigation include: Polycarbophil Polycarbophil, a poly(acrylic acid) lightly cross-linked with divinyl glycol, can remain on vaginal tissue for extended periods and has demonstrated many potential clinical applications: 296 Dry vagina: the bioadhesive gel can hydrate vaginal tissue for 3–4 days after a single application. Tissue hydration is caused by an increased blood flow, thus increasing transudation of vaginal fluid though the intercellular channels of the vaginal epithelium. Clinical assessment of local tissue pH in postmenopausal women shows a reduction in pH from about 7 to 4 and maintenance of this acidic pH for about 3–4 days.

Zollinger–Ellison syndrome results from a gastrin-secreting tumor order xanax 1 mg with mastercard, gastrinoma purchase xanax 1mg online, usually originating in the pancreas buy xanax 1mg. It is characterized by very high levels of plasma gastrin and excessive gastric acidity 1mg xanax fast delivery. In duodenal ulcers, increased gastric acidity occurs, but fasting plasma gastrin levels are normal. In stomach cancer, gastric volume is increased but acidity is not, and plasma gastrin levels are variable. A Plasma gastrin levels greater than 1,000 pg/mL are usually diagnostic of Zollinger–Ellison Body fluids/Correlate clinical and laboratory data/ syndrome. Smaller elevations can occur in other Pancreatic function/2 types of hyperacidity, including gastric ulcers, in renal disease, and after vagotomy. Zollinger–Ellison syndrome can be differentiated from the others by the secretin stimulation test. In Zollinger–Ellison syndrome, at least one specimen should show an increase of 200 pg/mL above the baseline for gastrin. It may be measured to diagnose intestinal malabsorption, or used along with tests of other gastric regulatory peptides to evaluate dysfunction. Urinary trypsinogen is increased in acute pancreatitis, while fecal trypsin and chymotrypsin are decreased in cystic fibrosis due to pancreatic duct obstruction. B The xylose absorption test differentiates pancreatic insufficiency from malabsorption syndrome (both cause deficient fat absorption). Which of the following is commonly associated Answers to Questions 29–30 with occult blood? However, the test is nonspecific and contamination with Body fluids/Correlate clinical and laboratory data/ vaginal blood is a frequent source of error. Which test is most sensitive in detecting persons and children with pancreatic insufficiency as a with chronic pancreatitis? Perform a turbidimetric protein test and report Select the most appropriate course of action. Request a new specimen with microscopic results Body fluids/Evaluate laboratory data to recognize B. Report biochemical results only; request a new problems/Urinalysis/3 sample for the microscopic examination C. C Highly buffered alkaline urine may cause a contaminated in vitro false-positive dry reagent strip protein test by B. C A positive nitrite requires infection with a Body fluids/Evaluate laboratory data to recognize nitrate-reducing organism, dietary nitrate, and inconsistent results/Urinalysis/3 incubation of urine in the bladder. When volume is below 12 mL, the sample should be diluted with saline to 12 mL before concentrating. Results are multiplied by the dilution (12 mL/mL urine) to give the correct range. Perform a quantitative urine glucose; report as control trace if greater than 100 mg/dL C. Request a new urine specimen ketone result Body fluids/Evaluate laboratory data to determine D. Request a new sample and repeat the urinalysis possible inconsistent results/Glucose/3 Body fluids/Evaluate laboratory data to recognize problems/Urinalysis/3 Answers to Questions 4–7 5. The trace ketone does not require Other findings: confirmation, provided that the quality control Color: Amber Transparency: Microscopic: Crystals of the reagent strips is acceptable. Perform a tablet test for bilirubin before dry reagent test and will confirm the presence of reporting bilirubin. Reduced possible inconsistent results/Urinalysis/3 renal blood flow causes increased urea reabsorption 6. A The urine glucose is determined by the blood All other results are normal and all tests are in glucose at the time the urine is formed. Report these results Body fluids/Evaluate laboratory data to recognize problems/Renal function/3 6. Urinalysis results from a 35-year-old woman are: patient gives positive tests for blood and protein. Support the finding of an extravascular transfusion reaction Select the most appropriate course of action. Recheck the blood reaction; if negative, look for transfusion reaction budding yeast D. Request a list of medications Body fluids/Correlate clinical and laboratory data/ Urinalysis/3 Body fluids/Evaluate laboratory data to recognize sources of error/Urinalysis/3 9. D The plasma free hemoglobin will be increased Body fluids/Select routine laboratory procedures to immediately after a hemolytic transfusion reaction, verify test results/Transfusion reaction/3 and the haptoglobin will be decreased. Given the following urinalysis results, select the hemoglobin will be eliminated by the kidneys, but most appropriate course of action: the haptoglobin will remain low or undetectable for 2–3 days. Call for a list of medications administered to the urine points to a patient with insulin-dependent patient diabetes. Perform a quantitative urinary albumin tolbutamide (Orinase) has been administered. Perform a test for microalbuminuria Body fluids/Evaluate laboratory data to determine 11. A A nonhemolyzed trace may have been overlooked possible inconsistent results/Urinalysis/3 and the blood test should be repeated. A routine urinalysis gives the following results: Answers to Questions 12–15 pH =6. Glucose= Trace Ketone = Neg These form yellow- or reddish-brown refractile Microscopic findings: deposits sometimes resembling blood or granular Blood casts: Mucus: Crystals: casts. False-negative blood reaction wall of the glomerulus, they become distorted, and B. False-negative protein reaction such cells are described as dysmorphic in appearance. Pseudocasts of urate mistaken for true casts They are characterized by uneven distribution of D. Mucus mistaken for casts hemoglobin, cytoplasmic blebs and an asymmetrical Body fluids/Evaluate laboratory data to determine membrane distinct from crenation. The cytoplasm possible inconsistent results/Urinalysis/3 may be extruded from the cell and may aggregate at 13. Intravascular hemolytic phenomenon is most often caused by: anemia causes hemoglobinuria rather than hematuria. Severe dehydration with extravascular hemolysis or hepatocellular Body fluids/Correlate clinical and laboratory data/ liver disease. A freshly voided specimen is needed Hematuria/2 to detect urobilinogen because it is rapidly photooxidized to urobilin. Urobilin does and turns brown after storage in the refrigerator not react with 2,4 dimethylaminobenzaldehyde or overnight. Te technologist requests a new 4-methoxybenzene diazonium tetrafluoroborate, specimen.

Lactose inactivates the repressor order 1mg xanax amex, initializing transcription of the genes for b-galactosidase and b-galactoside permease in the lactose operon generic 1mg xanax free shipping. These genesare normallynotread off because the repressor is bound to the operator generic 1mg xanax otc. The cell is not induced to pro- duce the necessary catabolic enzymes until the nutrient substrate is present order xanax 1 mg line. The signal molecule is the final product of an anabolic process, for instance an amino acid. If this acid is present in the me- dium, it can be obtained from there and the cell need not synthesize the anabolic enzymes it would require to produce it. In such a case, binding to the effector is what turns the regulator protein into an active repressor. A single regulator protein can also activate or repress several genes not integrated in an operon, i. Physiological cell status determines whether or not these alternative factors are produced. Based on the molecular mechanisms involved, bacte- rial recombinations are classified as homologous, site-specific, and transpo- sitional. The latter two in particular reflect the high level of mobility of many genes and have made essential contributions to the evolution of bacteria. Although sexual heredity is unknown in bacteria, they do make use of the mechanisms of intercellular transfer of genomic material known as parasex- ual processes. The Genetic Variability of Bacteria 171 chemically pure from a donor into a receptor cell. This process, made possible by con- jugative plasmids and transposons, can be a high-frequency one and may even occur between partners of different species, genera, or families. Conjugative structures carrying resistance or virulence genes are of considerable medical significance. The processes of restriction and modification are important factors 3 limiting genetic exchange among different taxa. Such mutations may involve substitution of a sin- gle nucleotide, frame-shifts, deletions, inversions, or insertions. The fre- quency of mutations is expressed as the mutation rate, which is defined as the probability of mutation per gene per cell division. The rate varies de- pending on the gene involved and is approximately 10–6 to 10–10. The integration of bacteriophage genomes is an example of what this process fa- cilitates (p. Just as in site- specific recombination, transposition has always played a major role in the evolution of multi-resistance plasmids (see Fig. An integron is a ge- intI attI sulI gene netic structure containing + (without promoter) the determinants of a site- specific recombination sys- Integrase tem. This structure is capable 59 bp-element of capturing or mobilizing mobile gene cassettes. It Pant Pint also provides the promoter intI attI sulI for transcription of the cas- sette genes, which them- a selves have no promoter. Pint Pant The cassettes occur in both Resistance genes free circularized and inte- intI attI aacC1 orfE aadA2 cmlA sulI grated forms. In4 is the result of successive integration of several resistance genes at the att1 site. The target structures for this enzyme are the so- called direct repeats, nucleotide sequences comprising 5–9 bp that are duplicated in the integration process. In addition to the transposase gene tnpA, they contain the regulator sequence tnpR and the res site to which resolvase must bind. Tn3-like transposons are duplicated in the transposition process, so that one copy remains at the original location and the other is integrated at the new location. These genetic elements code in certain regions for factors that control the transfer (Tra) and transposition (Tn) processes. Conjugative transposons have been discovered mainly in Gram-positive cocci and Gram-negative anaerobes (Bacteroides). These mechanisms, which involve a unilateral transfer of genetic information from a donor cell to a receptor cell, are subsumed under the term parasexuality. In 1928, Griffith demonstrated that the ability to produce a certain type of capsule could be transferred between different pneumococci. This transformation process has been observed mainly in the genera Streptococcus, Neisseria, Helicobacter and Haemophilus. The Genetic Variability of Bacteria 175 Bacteriophages are viruses that infect bacteria (p. Conjugation is made possible by two genetic elements: the conjugative plasmids and the conjugative transposons. This initial step alone does not necessarily always lead to effective conjugation. However, these elements can also mobilize chro- mosomal genes or otherwise nontransferable plasmids. Conjugation is seen frequently in Gram-negative rods (Enterobacteriaceae), in which the phenomenon has been most thoroughly researched, and enterococci. This factor contains the so-called tra (transfer) genes responsible both for 3 Model of a Hypothetical Conjugative Multiple-Resistance Plasmid Fig. In4 Codes for chloramphenicol acetyltransferase (= cmlA), an aminoglycoside acetyltransferase (= aacC1) and an aminoglycoside adenylyltransferase (= aadA2); also contains an open reading frame (orfE) of unknown function. The Genetic Variability of Bacteria 177 the formation of conjugal pili on the surface of F cells and for the transfer process. The transfer of the conjugative plasmid takes place as shown here in schematic steps (Fig. Occasional integration of the F factor into the chromosome gives it the conjugative properties of the F factor. Such an integration produces a sort of giant conjugative element, so that chromosomal genes can also be trans- ferred by the same mechanism. Cells with an integrated F factor are therefore called Hfr (“high frequency of recombination”) cells. Conjugative plasmids that carry determinants coding for antibiotic resistance and/or virulence in addi- tion to the tra genes and repA are of considerable medical importance. Three characteristics of conjugative plasmids promote a highly efficient horizontal spread of these determinant factors among different bacteria: & High frequency of transfer. Due to the “transfer replication” mechanism, each receptor cell that has received a conjugative plasmid automatically be- comes a donor cell. Each plasmid-positive cell is also capable of multiple plas- mid transfers to receptor cells. Many conjugative plasmids can be transferred be- tween different taxonomic species, genera, or even families. Many conjugative plasmids carry several genes determining the phenotype of the carrier cell. The evolution of a hypothetical conjugative plasmid carrying several resistance determinants is shown sche- matically in Fig.

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