Perioperative Antibacterial Prophylaxis in Urological Surgery The main aim of antimicrobial prophylaxis in urology is to prevent symptomatic / febrile genitourinary infections generic mysoline 250 mg otc, such as acute pyelonephritis mysoline 250 mg sale, prostatitis 250mg mysoline otc, edpididymitis and urosepsis as well as serious wound infections. Antibiotic prophylaxis is recommended only for a maximum of 24 hours after surgery in most situations. More rampant use leads to antibiotic resistance and places an additional economic burden. National patterns in the treatment of urinary tract infections in women by ambulatory care physicians. Effect of norfloxacin, trimethoprim- sulfamethoxazole and nitroffurantoin on fecal flora of women with recurrent urinary tract infections. Comparison of short-term treatment regimen of ciprofloxacin versus long-term treatment regimens of trimethoprim/sulfamethoxazole or norfloxacin for uncomplicated lower urinary tract infections: a randomized, multicentre, open-label, prospective study. The latest updates have been published in 2010 The significant differences in the socioeconomic and disease pattern (mode of presentation, stone bulk, health care delivery facilities) for urolithiasis in India make it imperative to formulate our own guidelines. Indian references have been cited, particularly so, if they are prospective randomized studies and/or metanalysis. Case definition The index patients are defined as follows:- Ureteral stones 18 A non pregnant adult patient with unilateral ureteral calculi (no renal stones) and normal functioning contralateral kidney, the body habitus, anatomy and medical condition should not (2) preclude the application of any of the available treatment options Staghorn calculi A staghorn calculi is defined as a stone with central body and at least one calyceal branch. Index patient (staghorn calculi):- Adult with a staghorn stone (non Cystine, non uric acid) who has two functioning kidneys (functioning both kidneys) or a solitary kidney with normal function. Any pelvic and /or calyceal calculi which do not fit in the definition of staghorn calculi Incidence in our country Although a few studies have been reported for a small group of subjects in screening camps. It is commonly seen in western states, hypothetically, attributable to high salinity of water. Renal stones Investigations:- Imaging is absolutely imperative if, the patient has a solitary kidney or a history of fever. Recommendation:-Excretory urography is the gold standard in work up for urolithiasis and is mandatory in solitary kidney, history of fever and when the diagnosis is in doubt. Analysis of stone composition Stone analysis is desirable in recurrent stone formers. Special investigations which are ordered on case to case merit are renal scintigraphy, antegrade, retrograde contrast study. Indications for intervention The indication for stone removal depends on the size, site and shape of the calculus. The likelihood of spontaneous passage, presence of obstruction should be assessed. The indications for intervention are:- 1) When the stone diameter is more than 7 mm (because of low rate of spontaneous passage). Recommendation:-For1, 2 stone removal with or without prior decompression(depending on the clinical situation) is recommended ,in situation ,3,4,5,6 emergency deobstruction of the collecting system is recommended. Various studies have attempted to show the correlation of geometry of the lower calyx to predict the clearance of stone in this location. However the calyceal stone burden is the most important factor in predicting the clearance. Specific stone compositions have different clearance rates because of the varying 22 fragility of stones. Better fragmentation can be achieved with starting the fragmentation (17) at lower energy setting and then ramping up the power. In case of infected stones, antibiotics should be given according to urine culture sensitivity, the (2) same should be continued after surgery for 4 days Clinical experience suggests that stones in the ureter rather than the kidney should be treated with shorter intervals between sessions. Antibiotics should be given according to urine culture sensitivity, the same should be continued after surgery for 4 days. The physicians should refer to the manufacturer recommendation regarding the decision of number, frequency and power of shocks. The tract should be the shortest possible tract from 24 the skin to the desired calyx traversing the papilla. Depending on the stone configuration a calyx should be selected (Supracostal, infracostal or subcostal) so that maximum stone bulk can (23) be cleared minimum number of tracts. Renal tract dilatation either balloon, amplatz or (2) metallic dilators are a matter of surgeon preference and availability. In uncomplicated cases, tubeless percutaneous nephrolithotomy with or without application of (25) (26) tissue sealants is a safe alternative i) Complications The patients should be counseled regarding the complications which are likely to be encountered such as life threatening bleeding with a possible need for angioembolisation or even nephrectomy. The patients should be counseled regarding the possibility of residual calculi and the consequences thereof. The procedure becomes challenging in complex stones, although the complications are not specific to them. Recommendations Technically, most of the renal stones can be managed with a percutaneous nephrolithotomy. The access to the collecting system 25 can be gained either ultrasound guided or fluoroscopy guided depending on the availability of instruments and expertise. Renal tract dilatation either balloon, amplatz or metallic dilators are a matter of surgeon preference and availability. In complicated cases or when secondary intervention is required a nephrostomy tube which serves the dual purpose of tamponade and a conduit for second look is placed.

However purchase 250mg mysoline mastercard, most pessary authors agree that routine follow up of women using pessaries is necessary to minimize the risk of complications associated with Contraindications to Pessary their use order mysoline 250 mg with visa. At each visit the pessary Insertion should be removed and cleaned • Severe untreated vaginal using mild antibacterial soap and atrophy warm water purchase mysoline 250 mg fast delivery. It should be examined • Vaginal bleeding of unknown 122 origin remain in place • Pelvic infammatory disease • Abnormal pap smear • Dementia without possibility of dependable follow-up care • Expected non-compliance with follow-up Types of Pessaries Often referred to as the “incontinence ring” since it has been designed for use in women with stress incontinence. Complications of pessaries All authors listed vaginal discharge and odor as the most common complication. Other complications which may occur are pelvic pain, Arch Heel Gehrung bleeding and development of • U-shaped device that provides urinary incontinence. The heel rests fat on the or failure of the pessary to vaginal foor hold the prolapse properly is • It avoids pressure on the rectum an obvious disadvantage. They state that early intervention using an estrogen-based cream or vaginal lubricant are essential to proper pessary care. Severe complications such as vesico-vaginal fstulae, hydronephrosis, sepsis, and even 124 small bowel incarceration were cited in the literature as the result of inadequate follow-up. Conclusion There is paucity of good randomized controlled trails that evaluate the use of conservative methods for the management of pelvic organ prolapse. Its treatment is one of the • Associated incontinence most common surgical indications symptoms in gynaecology, accounting for • Patient’s wishes 20% of elective major surgery with this fgure increasing to 59% in Important point the elderly population. Despite There is as yet no surgical numerous modifcations to the technique that can guarantee traditional surgical techniques and 100% success in treating prolapse the recent introduction of novel and some procedures such as procedures, the permanent cure of anterior colporrhaphy carry failure urogenital prolapse remains one of rates of up to 30%. Surgical Management General principles The following factors need to All women should receive be taken into account when prophylactic antibiotics to considering surgical intervention cover gram-negative and gram for prolapse: positive organisms, as well as 126 thromboembolic prophylaxis in fascial plication. Surgical options extensive dissection stretching for Anterior from the pubis anteriorly to the Compartment ischial spine posteriorly. The underlying Through a Pfannenstiel incision, pubocervical fascia is then reduced the retropubic space is opened using vicryl 3/0 sutures, known as and the bladder swept medially, 127 exposing the pelvic sidewall, very at the level of the hymenal similar to a burch colposuspension remnants, allowing the calibre procedure. The rectocele is mobilized pubis to just anterior to the ischial from the vaginal skin by blunt and spine. The rectovaginal fascia is then plicated using either an interrupted or continuous absorbable suture (Vicryl 3/0), to 2. Care Compartment should be taken not to create a Prolapse constriction ring in the vagina which will result in dyspareunia. Traditionally this compartment The redundant skin edges are is approached vaginally when then trimmed taking care not to operated on by the gynaecologist. The posterior that the colo-rectal surgeons vaginal wall is closed with a also operate on the posterior continuous Vicryl 2/0 suture. The patient should be specifc plication, place a number referred to a colorectal surgeon of interrupted lateral sutures for assessment if the following are that incorporate the Levator Ani present: concurrent anal or rectal muscles. This Levator plication has pathology such as hemorrhoids, been shown to be associated with rectal wall prolapse or rectal signifcant dyspareunia and is no mucosal redundancy. Finally a perineorrhaphy is performed by placing deeper absorbable sutures Posterior Colpoperineorrhaphy into the perineal muscles and Procedure fascia thus building up the perineal Two allis or littlewood forceps body to provide additional support are placed on the perineum 128 to the posterior vaginal wall and uterosacral ligament sutures are lengthening the vagina. Injury to therefore tied in the midline and the rectum is unusual but should brought through the posterior be identifed at the time of the part of the vault and tied after procedure so that the defect the vault has been closed. Middle the ureters at risk and therefore ureteric patency should be Compartment confrmed post-operatively by cystoscopy. This is a purse- string suture that goes through The cervix is circumscribed and the both corners of the vaginal vault, utero-vesical fold and pouch of through the uterosacral ligaments Douglas opened. The uterosacral and also through the posterior and cardinal ligaments are divided peritoneum to obliterate the and ligated frst, followed by the pouch of Douglas to prevent uterine pedicles and fnally the enterocele formation. The most (See a separate chapter on important part of the procedure Sacrocolpopexy) is support of the vault since these women are at high risk for post- This technique involves hysterectomy vault prolapse. It is not attached to the anterior aspect essential to open the enterocele of the sacral promontory using sac although care should be taken either an Ethibond suture or screw not to damage any loops of small tacks. The operation The vaginal vault can be supported has fallen from favour as long vaginally or abdominally. Both right and Modifed McCall cul-de-plasty (Endopelvic left Sacrospinous ligaments can fascia repair) be used to support the vagina. Iliococcygeus fascia fxation Some surgeons employ only one ligament but there is no evidence High uterosacral ligament suspension with fascial reconstruction to suggest that a uni-or bilateral is better. Vaginal obliterative procedures Colpectomy & colpocleisis Care must be taken to avoid Abdominal procedures that suspend the the sacral plexus and sciatic apex nerve which are superior to the Sacralcolpopexy ligament, and the pudendal New techniques vessels and nerve which are lateral to the ischial spine. The Transobturator- procedures including Prolift, Apogee and Avaulta sacrospinous sutures are then tied to support the vaginal vault 3. Success rates for this to expose the ischial spine using procedure are in the region of 80- sharp and blunt dissection.

Sunburn discount mysoline 250mg, bee stings cheap mysoline 250mg with mastercard, tendinitis generic 250 mg mysoline amex, and arthritis are just a few examples of painful inflammation caused by the body’s release of certain types of prostaglandins in response to an injury. These kinds to this large class of medicines include Advil®, of experiments teach scientists about molecular Aleve®, and many other popular pain relievers function by providing clear pictures of how all the available without a doctor’s prescription. All these folds and bends of an enzyme—usually a protein drugs share aspirin’s ability to knock back the or group of interacting proteins—help it do its production of prostaglandins by blocking an job. Antibodies are spectacularly specific pro­ teins that seek out and mark for destruction anything they do not recognize as belonging to the body. Scientists have learned how to join antibody-making cells with cells that grow and divide continuously. This pro­ Recently, researchers have also figured out how to tection, however, can run afoul if the body produce monoclonal antibodies in the egg whites slips up and views its own tissue as foreign. This may reduce production costs of Autoimmune disease, in which the immune system these increasingly important drugs. A drug called The powerful immune army presents signifi­ Rituxan® was the first therapeutic antibody cant roadblocks for pharmacologists trying to approved by the Food and Drug Administration create new drugs. Another thera­ pursuing immunotherapy as a way to treat a peutic antibody for cancer, Herceptin®, latches wide range of health problems, especially cancer. Herceptin’s forms of antibodies—our immune system’s actions prevent breast cancer from spreading to front-line agents. The vaccines are not designed to prevent cancer, Medicines By Design I Body, Heal Thyself 25 but rather to treat the disease when it has already research will point the way toward getting a taken hold in the body. Unlike the targeted-attack sick body to heal itself, it is likely that there approach of antibody therapy, vaccines aim to will always be a need for medicines to speed recruit the entire immune system to fight off a recovery from the many illnesses that tumor. The body machine has a tremendously com­ plex collection of chemical signals that are relayed back and forth through the blood and into and out of cells. While scientists are hopeful that future A Shock to the System difficulty pumping enough blood, and body temper­ ature climbs or falls rapidly. Despite the obvious public health importance of finding effective ways to treat sepsis, researchers have been frustratingly unsuccessful. Kevin Tracey of the North Shore-Long Island Jewish Research Institute in Manhasset, New York, has identified an unusual suspect in the deadly crime of sepsis: the nervous system. Tracey and his coworkers have discovered an unexpected link between cytokines, the chemical weapons released by the immune system during sepsis, and a major nerve that con­ trols critical body functions such as heart rate and digestion. Further serious public health problem, causing more deaths research has led Tracey to conclude that produc­ annually than heart disease. The most severe form tion of the neurotransmitter acetylcholine underlies of sepsis occurs when bacteria leak into the blood­ the inflammation-blocking response. Tracey is stream, spilling their poisons and leading to a investigating whether stimulating the vagus nerve dangerous condition called septic shock. Blood can be used as a component of therapy for sepsis pressure plunges dangerously low, the heart has and as a treatment for other immune disorders. For decades, researchers have isolated and purified individual enzymes from cells, performing experi­ ments with these proteins to find out how they do their job of speeding up chemical reac­ tions. But to thoroughly understand a molecule’s function, scientists have to take a very, very close look at how all the atoms fit together and enable the molecular “machine” to work properly. Plants have for sure what the earliest humans did to treat also served as the starting point for countless drugs their ailments, but they probably sought cures in on the market today. Drug discovery scientists often refer to these ideas as “leads,” and chemicals that have desirable properties in lab tests are called lead compounds. Natural Cholesterol-Buster Having high cholesterol is a significant risk factor and his coworker David Moore of Baylor College for heart disease, a leading cause of death in the of Medicine in Houston, Texas, found that guggul­ industrialized world. This research, part of which first identified cholesterol receptors, led to the development of the popular cholesterol-lowering “statin” drugs such as Mevacor® and Lipitor®. New research from pharmacologist David Mangelsdorf, also at the University of Texas Southwestern Medical Center at Dallas, is pointing to another potential treatment for high cholesterol. Guggulsterone comes from the sap of the guggul tree, a species native to India, and has been used in India’s Ayurvedic medicine since at least 600 B. Medicines By Design I Drugs From Nature, Then and Now 29 Relatively speaking, very few species of living only a few of these organisms to see whether they things on Earth have actually been seen and harbor some sort of medically useful substance. Many of these unidentified Pharmaceutical chemists seek ideas for new organisms aren’t necessarily lurking in uninhab­ drugs not only in plants, but in any part of nature ited places. This includes identified a brand-new species of millipede in a searching for organisms from what has been called rotting leaf pile in New York City’s Central Park, the last unexplored frontier: the seawater that an area visited by thousands of people every day. Scientists estimate that Earth is home to at least 250,000 different species of plants, and that up to 30 million species of insects crawl or fly some­ where around the globe. Despite these vast numbers, chemists have tested Cancer Therapy Sees the Light A novel drug delivery system called photodynamic therapy combines an ancient plant remedy, modern blood transfusion techniques, and light. Some forms of cancer Photodynamic therapy has been approved by the can be treated with Food and Drug Administration to treat several photodynamic therapy, in which a cancer-killing cancers and certain types of age-related macular molecule is activated degeneration, a devastating eye disease that is the by certain wavelengths leading cause of blindness in North America and of light. The key ingredient in this therapy is psoralen, a plant-derived chemical that has a peculiar prop­ erty: It is inactive until exposed to light. Modern that exposes a psoralen-like drug to certain wave­ researchers explained this phenomenon by discov­ lengths of light, is approved for the treatment ering that psoralen, after being digested, goes of some forms of lymphoma, a cancer of white to the skin’s surface, where it is activated by the blood cells.

Due to a former hot spot in the Italian upper Po valley it was also referred to as ‘Lombardian disease’ purchase mysoline 250mg mastercard. Although Centanni and Savonuzzi 250mg mysoline sale, in 1901 discount mysoline 250 mg line, identified a filtrable agent responsible for causing the disease, it was not before 1955 that Schäfer characterised these agents as influenza A viruses (Schäfer 1955). In the natural reservoir hosts of avian influenza viruses, wild water birds, the infec- tion generally runs an entirely asymptomatic course as influenza A virus biotypes of low pathogenicity co-exist in almost perfect balance with these hosts (Webster 1992, Alexander 2000). However, in cases where the poultry species supports several cycles of infection, these strains may undergo a series of mutation events resulting in adapta- tion to their new hosts. Recently, however, avian influenza acquired world-wide attention when a highly pathogenic strain of the subtype H5N1, which probably arose before 1997 in South- ern China, gained enzootic status in poultry throughout South East Asia and unex- pectedly ‘traversed interclass barriers’ (Perkins and Swayne 2003) when transmit- ted from birds to mammals (cats, swine, humans). Although not an entirely un- precedented event (Koopmans 2004, Hayden and Croisier 2005), the substantial number of documented cases in humans, associated with severe disease and several fatalities raised serious concerns about a pandemic potential of the H5N1 strain (Klempner and Shapiro 2004; Webster 2006). There are several further lines of evi- dence – which will be discussed below – suggesting that the H5N1 virus has ac- quired increased pathogenic potency for several mammal species. Africa/2004 (H5N2) 1 Modified from Capua and Mutinelli, 2001 * Outbreaks with significant spread to numerous farms, resulting in great economic losses. Influenza viruses hold generic status in the Orthomyxoviridae family and are clas- siÞed into types A, B or C based on antigenic differences of their nucleo- and ma- trix proteins. Excellent reviews on the structure and replication strategy of influenza viruses have been published re- cently (e. On the basis of the antigenicity of these glycoproteins, influenza A viruses currently cluster into sixteen H (H1 – H16) and nine N (N1 – N9) subtypes. The conventional nomenclature for influenza virus isolates requires connotation of the influenza virus type, the host species (omitted in the case of human origin), the geographical site, serial number, and year of isolation. The haemagglutinin, a glycosylated and acylated protein consisting of 562 – 566 amino acids, is incorporated in the viral envelope. The globular head of its mem- brane-distal, knob-like external domain is associated with binding to cellular re- ceptors composed of oligosaccharides which terminally carry derivates of neura- minic acid (Watowich 1994). This function prevents viral aggregation during egress, and possibly also facilitates the drifting of the virus through the mucus layers of the targeted epithelial tissues leading to viral attachment (Matrosovich 2004a). Attachment is stratiÞed by recognition of distinct terminal sialic acid species (N-acetyl- or N-glycolylneuraminic acid), the type of glycosidic linkage to penultimate galactose (α2-3 or α2-6) and the composi- tion of further inner fragments of sialyloligosaccharides present at the cell surface (Herrler 1995, Gambaryan 2005). A variety of different sialyloligosaccharides are expressed with restriction to tissue and species origin in the different hosts of influ- enza viruses. Avian influenza viruses generally show the highest affinities for α2-3 linked sialic acid as this is the dominating re- ceptor type in epithelial tissues of endodermic origin (gut, lung) in those birds that are targeted by these viruses (Gambaryan 2005a, Kim 2005). Human-adapted influ- enza viruses, in contrast, primarily access 2-6 linked residues which predominate on non-ciliated epithelial cells of the human airway. These receptor predilections de- fine part of a species barrier preventing hassle-free transmission of avian viruses to humans (Suzuki 2000, Suzuki 2005). Yet recently, it has been shown that there is a population of ciliated epithelial cells in the human trachea which also carry avian receptor-like glycoconjugates at lower densities (Matrosovitch 2004b), and also chicken cells carry human-type sialyl receptors at low concentrations (Kim 2005). This might explain why humans are not entirely refractory towards infection with certain avian strains (Beare and Webster 1991). In pigs, and also in quails, both receptor types are present at higher densities which renders these species putative mixing vessels for avian and human strains (Kida 1994, Ito 1998, Scholtissek 1998, Peiris 2001, Perez 2003, Wan and Perez 2005). Once successfully attached to a suitable receptor, the virion is internalised into an endosomal compartment by clathrin-dependent and -independent mechanisms (Rust 2004). The virus escapes degradation in this compartment by fusing viral and en- dolysomal membranes: mediated by proton transport through the viral matrix-2 (M2) tunnel protein at pH values in the endosome of around 5. Arrangements between helical nucleocapsids and viral envelope proteins are mediated by the viral matrix-1 (M1) protein which forms a shell-like structure just beneath the viral envelope. Viral reproduction in fully per- missive cells is a fast (less than ten hours) and efÞcient process, provided an ‘opti- mal’ gene constellation is present (Rott 1979, Neumann 2004). In case selective pressures (such as neutralising anti- bodies, suboptimal receptor binding or chemical antivirals) are acting during viral replication on a host or population scale, mutants with corresponding selective ad- vantages (e. This occurs in a cell which is simultaneously infected by two or more influenza A viruses of different subtypes. While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the ‘Spanish flu’ in 1918 appears to be entirely derived from an avian source (Belshe 2005). Natural hosts Wild aquatic birds, notably members of the orders Anseriformes (ducks and geese) and Charadriiformes (gulls and shorebirds), are carriers of the full variety of influ- enza virus A subtypes, and thus, most probably constitute the natural reservoir of all influenza A viruses (Webster 1992, Fouchier 2003, Krauss 2004, Widjaja 2004). While all bird species are thought to be susceptible, some domestic poultry species – chickens, turkey, guinea fowl, quail and pheasants – are known to be especially vulnerable to the sequelae of infection. Instead, the viruses remain in an evolutionary stasis, as molecularly signalled by low N/S (non-synonymous vs. Host and virus seem to exist in a state of a meticulously balanced mutual tolerance, clinically demonstrated by ab- sence of disease and efÞcient viral replication. However, strains of the subtypes H5 and H7 carry the potential to mutate to a highly pathogenic form after transmission and adaptation to the new poultry hosts. Nascency of highly pathogenic forms of H5 and H7 or of other subtypes has never been observed in wild birds (Webster 1998). Therefore, one may even come to look at the highly pathogenic forms as something artiÞcial, made possible only as a result of man-made interference with a naturally balanced system.