By G. Altus. University of Arkansas at Monticello. 2018.

The term environmental encompasses discount pariet 20 mg with mastercard, in this case buy pariet 20mg without prescription, many different processes and conditions occurring outside but entering in contact with the organism cheap pariet 20 mg on-line. Obviously purchase pariet 20mg without prescription, these factors become increasingly relevant with aging to the healthy or pathological status of an individual, due to the increased possibility to encounter different environmental hits or to cumulate the reiterated effects of one of these factors. Since monozygotic twins are genetically identical, they are considered as ideal experimental models to study the role of environmental factors as determinants of complex diseases and phenotypes. Another example of association between acute environmental stimuli and epigenetic-dependent disease phenotypes is given by the observed increase of CpG-island promoter hyper- methylation in tumor-suppressor genes in the oral mucosa of smokers (reviewed in [125]). These alterations can be responsible for deviations from the normal aging processes, resulting in higher susceptibility to age-associated disease. Epigenetics in Human Disease behavioral stress (since it does not involve a physical contact of the individual with any chemical species), could result in a long-lasting alteration of epigenetic markers, leading to functional alterations. Another mild environmental factor that seems involved in the development of healthy or pathological aging is represented by the physical exercise. Physical exercise improves the efciency of the capillary system and increases the oxygen supply to the brain, thus enhancing metabolic activity and oxygen intake in neurons, and increases neurotrophin levels and resistance to stress. Similarly, studies in animal models show that physical activity has positive physiological and cognitive effects that correlate with changes in tran- scriptional proles possibly mediated by epigenetic modications [130]. Nutrition and diet represent another environmental factor that can exert its inuence on aging. Dietary exposures can have consequences even many years later and this observation raises questions about the mechanisms through which such exposures are remembered and how they can result in altered disease risk. There is growing evidence that epigenetic mechanisms may mediate the effects of nutrients, micronutrients, and even non-nutrient dietary factors may be causal for the development of complex diseases [131]. However, other nutritional factors seem able to determine epigenetic modications without 532 directly perturbing the core of the methylation reactions. One example is given by the link between under- and overnutrition during pregnancy and the consequent (later in life) development of diseases such as diabetes and obesity. Epigenetic modications may be one mechanism by which exposure to an altered intrauterine milieu may inuence the onset of these disturbances much later in life. As a matter of fact, it was demonstrated that epigenetic modications affecting processes important to glucose regulation and insulin secretion are present in the pancreatic b-cells and muscle of the intrauterine growth-retarded offspring, characteristics essential to the pathophysiology of type 2 diabetes. Moreover, epigenetic regulation of gene expression contributes to both adipocyte determination and differentiation in in vitro models [132]. As previously discussed, a modern and developing concept points out the fetal or perinatal origin of adult diseases and the adaptation response to environmental stimuli leading to increased susceptibility to age-associated diseases [134]. Although the mechanisms mediating and expressing this memory of the early life throughout aging are not clearly unraveled, it is clear that an epigenetic basis exists. Apparently, the consequent increased susceptibility to the disease recapitulates as well the mechanisms typical of the decline observed in normal aging. The involvement of multiple organ systems in the pathological aging phenotype can be assimilated to the frail syndrome. Identication of the role of epigenetic drift in the onset of frail status also represents the opportunity to underline the connection between epigenetics and other age-associated diseases. Part of the frail phenotype is, in fact, connected to other diseases typical of old age and characterized by evident epigenetic bases. An emerging theory identies an epigenetic basis also for the chronic low-grade inammation typical of aging, generated by the increase in the production of proinammatory cytokines and other markers that lead to the denition of inamm-aging status. Finally, this complex picture involving inammation and multi- organ contribution to the aged phenotype, nds a further piece of the jigsaw in the epigenetic basis of another complex disease like diabetes. A very important concept emerging from these studies is that malnutrition is often associated with aging but that this decit should be seen in terms of quality and variety of foods rather than in terms of quantity [141]. Epigenetics, disease, and aging are connected also in another complex relationship represented by the telomere attrition and the onset of cancer. Recently, different models of transgenic mice deleted for the shelterin proteins (the major complex bound to telomeres) have been generated and could help the future study on the role of telomeric attrition and instability in aging and cancer [146]. Epigenetic changes associated with aging and very often induced by environmental stimuli, seem therefore responsible for the possible onset of different, although strictly interconnected, pathologies typical of the elderly. It was discovered that brain-specic promoter-related sequences are surprisingly enriched in CpG sites. This leads to the conclusion that it is likely that brain-specic tran- scription is regulated by methylation at an epigenetic level much more frequently than tissue- specic expression in other organs. Low methylation status is strongly associated with 535 neurological and cognitive decits. Many epidemiological studies have shown that factors connected to low methylation status such as elevated total homocysteine, low folate or low vitamin B12 levels are associated with increased risk of cognitive decline, dementia, and brain atrophy. Methyl deciency results in global Epigenetics in Human Disease hypomethylation of the genome. Interestingly, the aging process leads to similar changes in the methylation pattern. Despite the fact that it is already well known that epigenetic changes could act in several physiological and pathological processes, few papers pointed the attention on epigenetic regulation of aging and neurodegeneration. As a matter of fact, the epigenetic mechanisms can be considered as a link between environmental stimuli and their effect on the genome and on the pathologies. Moreover, one-carbon metabolism alteration and consequent methylation reactions unbalance (i. Experimental evidences in this sense are given by the nding that exogenous Ab 1-40 seems to induce the hypermethylation of the Neprilysin gene [191]. This ability opened the window, in recent years, on a previously hidden scenario where epigenetics retains a causal role in mediating the effects that environmental stimuli exert in the organism. This growing area of the science is particularly relevant to the study of aging-associated processes, because the aging organism is increasingly exposed to continuous and different external stimuli. Now that the window is open on the mechanisms possibly responsible for the shifting from healthy to pathological aging, new questions rise together with the rst results. How many, and how long, stimuli are necessary to induce changes in the normal aging processes? In which manner does the organism translate these stimuli in processes that alter epigenetic modications? Alternatively, is this different susceptibility an endogenous characteristic of these tissue, cells, or sequences? And, in this case, are these modications druggable, in order to hypothesize epigenetic intervention and therapies? Deciphering the epigenome and its Epigenetics in Human Disease relevance to the aging processes is probably one of the most promising challenges for the researchers in the coming years and, due to its extreme complexity, it surely requires the interaction of different skills and knowledge in an interdisciplinary effort. Gene silencing through methylation: an epigenetic intervention on Alzheimer disease. Replicative senescence: considerations relating to the stability of heterochromatin domains. The dynamics of myogenin site-specic demethylation is strongly correlated with its expression and with muscle differentiation. Early demethylation of non-CpG, CpC- rich, elements in the myogenin 50-anking region: a priming effect on the spreading of active demethylation.

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Then calyces and pelvis become dilated order 20 mg pariet with amex, and pressure develops in the pelvicalyceal system Then renal parenchyma undergoes pressure atrophy and even chronic renal failure could develop in bilateral obstructions Clinical features Right side and males are commonly affected Insidious onset of mild pain or dull aching pain in the loin Sensation of drugging and heaviness Enlargement of kidney may be evident on palpation Attacks of acute renal colic may occur Features of chronic renal failure in untreated cases discount pariet 20 mg with mastercard. Clinical features General nonspecific such as headache purchase 20mg pariet fast delivery, lassitude and nausea may occur order pariet 20mg on-line. Choice should be based on clinical and epidemiological evidences, and then tailored by the results of culture and sensitivity. Vesico-ureteric reflux Repeated courses of antibiotic treatment may be necessary Perinephric abscess Definition Perinephric abscess is an infection of the perinephric fat resulting in pus collection. Pathogenesis - The infection, once established in the kidney, tuberculous granuloma is formed. Differential diagnoses of opacity in X-ray film are: - calcified mesenteric lymph node - Gall stones or concretion in appendix - Phlebolith or any calcified lesion Treatment: Most small ureteric stones and non-obstructive kidney stones can be managed conservatively by treating the pain and any underlying infection with analgesics and antibiotics and then expecting the stone to be washed out by the urine and following the patient taking a follow up x-ray. Big stones, obstructing the urine outflow, and failure of expectant treatment are the indication for the following. Benign tumors of the kidney vary greatly, and have little significance most of the time. Renal injuries Renal injuries are relatively uncommon injuries partly due to the inaccessible location of the kidneys in the retroperitoneum. Injuries to ureters are extremely rare in traumas; however ureteric injuries are fairly common in endoscopic ureteric procedures. Renal injuries can be divided as mild, moderate severe or first, second and third degree renal injuries respectively. First degree renal injury is an injury limited to the kidney parenchyma resulting in only subcapsular hematoma, hematuria may not be there. Second-degree renal injury is said to happen when the injury involved the pelvicalyceal system but not the renal major vessels, hematuria is evident Third degree renal injury is characterized by renal artery or renal vein involvement Clinical features Hematuria: - the most important symptom in renal injuries, extent and duration of hematuria determines the severity Pain in the flank area and hypochondrium Fullness, tenderness and bruises in the flanks may be detected Hypotension and shock in third degree injuries are seen Treatment Conservative: - first degree and some second degree renal injuries replacement of fluid and blood transfusion if needed catheterization and follow up Surgery: - severe forms of renal injury 229 Urinary Bladder Bladder Injuries The bladder is one of the visceral organs that are commonly involved in either blunt or penetrating injuries. Bladder rupture can be either intra peritoneal where urine peritonitis occurs and needs laparotomy and closure, While extra peritoneal rupture can be managed conservatively by passing an indwelling catheter. Bladder outlet obstruction This is the commonest presentation of all urologic problems and quite diverse disorders produce bladder outlet obstruction. If the cause is urethral stricture, suprapubic cystostomy is done to relieve the acute retention. Bladder Stones Stones are also formed in the bladder, and if stone is formed without any predisposing factor it is called primary vesical calculus. Whereas, a stone formed in the presence of distal obstruction or foreign body acting as a nidus, is called secondary vesical calculus. Clinical Feature - Males are more effected than females - Pain characteristically occurs at the end of micturition - The pain is referred at the end of the penis or labia majora - In young boys, screaming and pulling of the penis with hand at the end of micturition - Interruption of urinary stream and changing of body position to resume micturition. Diagnosis Radio opaque stone or filling defect in X-ray film 230 Treatment Cystolithotomy (Open surgical removal) Bladder Cancer Bladder tumor is common in people exposed to chemical carcinogens. Occupational exposure to chemicals such as dye factory workers and cigarette smoking are considered to be strongly associated with bladder cancer. More than 80% of bladder cancer is transitional cell origin and only 25% of the tumors are muscle invasive. Muscle invasive transitional cell Carcinoma is solid tumor, large based and possesses potential of distant metastasis to the lungs, bones and liver. Possible treatment is radical surgery, removing the bladder and lymph nodes around it, then urinary diversion. Benign prostatic Hyperplasia starts in the periurethral zone and as it increases in size it compresses the outer peripheral zone. The gland is acted upon by testosterone, male hormone, incriminated to cause the enlargement. Prostatic carcinoma Prostatic cancer is most common malignant tumor in men over the age of 65 years. Clinical Feature Advanced disease gives rise to symptoms including - Bladder out let obstruction - Pelvic pain and hematuria - Bone pain, renal failure Diagnosis and assessment - Rectal examination stony hard gland with obliteration of the median sulcus. Bilateral orchidectomy The urethra and penis The urethra Congenital abnormalities Meatal stenosis This is a condition which usually follows fibrosis after circumcision and if left untreated leads to chronic retention then chronic renal failure Clinical Feature Spraying and dribbling in lesser degree of stenosis Urinary retention Treatment Meatotomy/meatoplasty (Plastic reconstruction of the meatus) Congenital valves of the posterior urethra This is a condition with presence of symmetrical of valves. It can cause obstruction to the urethra of boys and is not visualized on urethroscope. Hypospadias This is the most common congenital malformation where meatus open onto the under side of the penis, perineum or prepuce. Treatment Surgical repair Urethral Injuries There are two types Rupture of the membranous urethra 233 Rupture of the bulbar urethra: blow to the perineum is the mechanism of injury Clinical Features - Retention of urine - Perineal hematoma - Bleeding from the external meatus Treatment - No attempts to catheterize should be made before urethroscopy or urethrography - Suprapubic catheter insertion then surgery (urethroplasty) after 3 months. Rupture of the membranous urethra: most commonly due to pelvic fracture or can also be due to penetrating injuries. Treatment: is circumcision Paraphymosis: Is a condition in which tight foreskin is retracted and causes constriction to the penis. The Testis and Scrotum The Testis Incomplete Descent This is a condition in which the testis is arrested in some part of its path to the scrotum. Clinical Features - Right side in 50% of the cases - Left 30%, - bilateral in 20% The position of the undescended testis is intra abdominal or inguinal canal or in the superficial inguinal pouch. Hazards The risks of incomplete descent of the testes include - Sterility in bilateral cases - Pain due to trauma - Associated inguinal hernia - Torsion - Epididymo-orchitis - Atrophy - Increased liability to malignant diseases Treatment: Orchidopexy Testicular Torsion Torsion of the spermatic cord may cause ischemia and necrosis of the testis 235 Predisposing conditions - Inversion of the testis (rotated testes, upside down, or transverse lie) - High investment of the tunica vaginalis (clapper-bell deformity) - Separation of epididymis from the body of testis Clinical Features Most common between 10-25 years of age. Vomiting is also common Treatment emergency exploration is mandatory orchidectomy if necrotic testis is found, orchidopexy if viable orchiopexy is advised on the unaffected side Hydrocele Hydrocele is an abnormal collection of serous fluid in the tunica. Types include:- Primary Secondary Etiology: - excessive production and defective absorption Treatment: - Hydrocelectomy Malignant tumors of the Testis 1-2% of all malignant tumors are Testicular Carcinoma. Classification Tumors are classified based on Histologic predominant cells - Seminoma (40%) - Teratoma (32%) - Combined seminoma and teratoma (14%) - Lymphoma (7%) - Other (7%) Seminoma - Occurs in age range between 35-45 years - Extremely rare in children before puberty - Tumor compresses the neighboring structure as it grows - In rapidly growing tumors there may be areas of necrosis - Spread is via the lymphatics, blood born is rare. Outline the important steps of investigating a patient with right flank mass and hematuria. Discuss the management of a 13 year-old patient with intermittent urinary retention and initial hematuria. Outline common causes of acute urinary retention and indicate the recommended treatment. Some people have it to reduce physical dysphoria strong discomfort with the mismatch between identity and body. The booklet Getting Surgery, available from the Transgender Health Program (see last page), explains the process. The details of top surgery and lower surgery are discussed on the following pages. We keep these terms in quotes to emphasize that they are artificial and imperfect concepts. Binding refers to the process of flattening your breast tissue to create a smaller and less noticeable chest. For others its only partially successful and is a short-term, stop-gap measure until surgery. The type of materials used depends on the size of your chest, 3 your overall build, and what you can afford. Many of the synthetic materials used for binding dont allow your skin to breathe (promoting rashes and fungal infections), and when binding is done too tightly it can cause pain and restrict your breathing. To reduce the potential risks of binding: Loosen your binder if it hurts, cuts your skin, makes it difficult to move, or makes it difficult to take a deep breath.

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The staff agonized over the prospect of another return under emergency circumstances order 20mg pariet with amex. She returned three weeks later with this news: Her follow up visit with the ophthalmologist at home who had done her eye surgery had said there was no sign of regrowth 20mg pariet. She was full of copper again order pariet 20mg without a prescription, as well as isopropyl alcohol (drinking bottled water on the airplane) discount pariet 20 mg overnight delivery. Mar 20 chest X-ray shows large tumor breakup was used before our discovery of the great folic acid deficiency in all cancer patients. And the enlarged lymph nodes in the right lung were no longer noted by the radiologist. But water accumulation had continued, as it must in the presence of maleic anhydride. I was begin- ning to see that we typically do not die from the malignancy or tumors them- selves! Doing away with the tumors, either surgically or by alternative methods, does not do away with the toxicity that generated them. The dye causing all this had come out of the tu- mor but was not being detoxified or eliminated. It took till June 9 before Nikkis family began changing the plumbing at her home. On May 15 another chest X-ray was done (the quality was poor, so it is not shown). But she had stopped coughing blood and had enough breath to walk around at a swap meet so it was not a priority to her. Her retina tumor was gone, her neck nodule was gone, her lung tumor was gone, but a glance at her blood test on June 13 shows that her health was worse. She led us to discover malonic acid in foods after battling it for such a long time. Yet her blood test results, as is plain to see, were quite goodher body was still functioning well and she had every chance to recover. Now the cancer had Feb 13 chest X-ray shows large tumor (circled) spread all over her body in lumps under the skin like small mole hills every- where. And water had accu- mulated in the lung, the water level was clearly visible (all the dark area be- low the tumor). She was wearing a portacatheter (indwelling catheter), parts of which can be seen on the X-ray, to make it easy to inject things. But, it must be cleaned regularly and doused with heparin to prevent blood clots from forming around it. We tried to explain that it was morgue-medicine, intended only for the dying and would greatly inhibit her progress. It slowed bowel action, making laxatives necessary and for some unexplained reason, prevented weight gain. Her initial toxins included fiberglass, arsenic, and chlorine, all of which would be inhaled and feed the tumor in the lung. She also had mercury, thallium, and aluminum from dentalware and cosmetics, no doubt. Her dentalware was mostly goldthe very best goldsome amalgam and some plastic. She was extremely fatigued, due no doubt to lack of oxygen and to am- monia toxicity. But, clearly, her chief toxin was copper [and germanium]; iron levels were down to 22. And at no time during her stay did we manage to discover the source and remove it. All these metals could be part of the gold composition as well as in the amalgam and plastic. Yet, in spite of giving her 250 mg glutathione four times a day, we could not detect any reduced glutathione in her lungs. In five days her mood had improved so much she agreed to do dental workbut amalgam replacement only. Two weeks later, on March 4, she was feeling a lot better, but still very fatigued and pain ridden. New tests showed vanadium Positive at lung; mer- cury Positive at lung; thallium Positive at lung. Notice how parts of metabolism can be over-oxidized while other parts are under-oxidized. Glutathione, reduced and oxidized Positive at lung; cytochrome C Negative at lung (one of the links in the respiration chain). But cytochrome C, neces- sary to catch electrons in the respiratory chain is not high enough to appear positive. But the water-logged condition (pleural effusion) had not shown much reabsorbtionshe still had difficulty breathing. Mar 5 chest X-ray is missing the tumor The blood test of March 5 shows the effects of amalgam removal (gold was not removed) which probably removed quite a bit of copper and cobalt, too. But, although there was less copper, there was still some copper [or germanium], since iron stayed very low. The overall reduced edema could be seen along the margin of skin along the X- rays left side. We couldnt guess that she was back on morphine (procured from an- other hospital) and dreaded nothing more than running out of it. Just the sight of her colorful hat coming along the pathway stopped everybodys conversation. And when that was past, it would be living as usual for her, till her next crisis. From her first blood test we could see that her problem in the bone mar- row was mainly due to vanadium (albumin low, globulin high) and malonic acid derivatives (low calcium), not so much copper and cobalt. As the disease progresses, the bone marrow becomes totally incapable and all cell types drop, as we see here. In fact, her water samples tested Negative to copper; yet she was Posi- tive at her liver and parathyroids. She was being seen at several other alternative clinics as well as her oncologist at home in California. We also gave her coenzyme Q10, 3 gm to be taken every third day for 6 doses and gm daily in between to assist her heart. We had just found that ma- lonic acid could come from foods; we quickly warned her about orange juice, her favorite beverage. There was very little air capacity due to the enlarged heart and water effusate taking up lung space. Perhaps her bone mar- row was using the iron to make more cells, but the quinidine drug was sim- ply killing them. We quickly gave her an iron shot to be repeated weekly and a liquid supplement, iron booster, 1 tbs. The plan was to repeat the test in four days, since she did not want a transfusion, and yet was poised right at the transfusion level.

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In a young woman who complains of infertility pariet 20mg discount, menstrual irregularity purchase 20 mg pariet amex, and chronic pelvic discomfort generic 20mg pariet, N cheap pariet 20 mg on-line. The diagnosis is usually easy if the history is clear of an actual or recent pregnancy. Unfortunately, the woman may be so frightened that she denies having tried to induce an abortion, even when she is very ill. The only way to avoid a misdiagnosis is to remember that any acute pelvic inflammation in a woman of childbearing age may be the result of a miscarriage. Fortunately, the uterus is usually a good barrier to the spread of infection, but sepsis does sometimes spread as pelvic cellulitis or localized peritonitis. You can usually treat this without a laparotomy, although usually you should evacuate the uterus. If need be (no facilities, waiting list, the anaesthetist refuses to get involved because of anaemia), you can often do this digitally. One hand pushes down the uterus while the gloved index finger of the other hand evacuates the uterus. This is painful for the woman but better than waiting for possibly dangerous transfusions. Another advantage is that in this way you might detect a hole caused by an unskilled abortion before you have pushed instruments through it. You can deal with that A, acute salpingitis with swollen congested tubes and pus leaking rather painlessly with the help of a speculum and a sponge from the ostium. After Young J, A Textbook while waiting for an evacuation might easily reduce of Gynaecology, A&C Black 5th ed 1939. The uterus will be infected and soft, so be Examine the uterus bimanually: it is tender bilaterally, especially careful not to perforate it. Your main concern will be to know There should be a dramatic improvement, and fever should how far infection has spread, and if you should perform a settle in 48-72hrs. There may be haemolysis, jaundice and If there is no improvement within 24hrs after high fever from severe malaria or dengue. Avoid the lateral fornices, or you may injure the ureters or If the pulse is >120/min, the infection has probably spread the uterine arteries. A seriously infected uterus can be silent, general condition as best you can by rehydration, apart from a very sick patient. If the history suggests that the uterus has been perforated with some instrument, the prognosis is N. If it is leaking pus into the abdominal cavity, she has had an induced abortion (septic or otherwise) is you may ultimately have to perform a hysterectomy. If you perforate the uterus when you evacuate a septic miscarriage, there is no easy answer. If you stop with an If the patient is very ill, with signs of spread outside the incompletely evacuated uterus, the risk of sepsis remains. If you complete the evacuation, you may enlarge the hole Resuscitate with rapid infusion of Ringers lactate or and even damage bowel. Antibiotics will not control the infection if infected evacuation as best you can using your fingers, products of conception remain inside the uterus. If the tissues do not hold, try to plug the laceration with omentum, if there is minimal bleeding. The treatment of an accidental perforation of a Ask the woman to describe the bleeding pattern by giving non-pregnant uterus or a small perforation in the midline approximate dates and amounts. A D&C will not diagnose carcinoma of the cervix as it should, the corpus luteum does not develop and nor will a Papanicolau (Pap) smear (23. The endometrium grows always diagnose carcinoma advanced enough to bleed by abnormally thick under the influence of unopposed looking at the cervix with a speculum and taking a biopsy. In early pre-malignant cases you need to inspect it with 4% Courses of progestagen stop bleeding temporarily, acetic acid. However, if you need acetic acid to see if there and when these are stopped normal periods usually follow. These are inter-menstrual bleeding, and especially curettage to exclude carcinoma of the endometrium. Heavy regular periods are a common prolapsed submucosal fibroids (23-7), and atrophic complaint, and are usually benign but may result in severe vaginitis. Unfortunately, this is unlikely to be possible, so send Use the contraceptive pill bd for 10days, then od. At age <40yrs, sending curettings for Bleeding will probably stop while taking the medication. Review her again in a month, to see if treatment has worked, and bleeding has stopped. Although D&C is usually simple, the long list of Of course, if she needs contraception, continue the pill. Perform a suction curettage because this will be either (2);Injuring a nulliparous cervix. Although both operations have similar complications, they have different indications. D&C is complement to a carefully taken history and examination, and is not a substitute for them. It is also one of the commonest operations in gynaecology, and one of the most abused, so make sure that you only do it on the proper indications: (1) To diagnose the cause of abnormal bleeding. Perforation of the uterus is less likely if you use your finger as a guide and steadier like this, with the finger acting as a brake. When you dilate the Dilatation only, without curettage: cervix, you will need a mental picture of its shape. If necessary treat with and carefully try to find your way into the uterine cavity. Sometimes sideward pressure or massaging (2);Where menses have never occurred, check if there is a (up or down) is needed to make it possible to follow the uterus at all, after failing to produce a withdrawal bleed sound with a small dilator (for a D&C), a suction curette with hormones. Start by making sure that the buttocks are well over the Infection will have fixed the uterus; dilating it with end of the table. Then grasp the anterior lip of the cervix with a biphasic basal temperature curve or by examination of the vulsellum forceps transversely. Anovulation just under the surface of the vagina in the fornices beside outside pregnancy can be investigated not by D&C but by the cervix at 2,6,10 & 12 oclock. Or, perhaps better, seeing if you can initiate a withdrawal bleed with inject from inside out, i. If not there are anatomical problems (the Ascherman syndrome, a blocked vagina or absent Pull the cervix well down. If withdrawal from using anteverted or retroverted uterus towards the axial position, a combined oral contraceptive pill produces bleeding, and reduce the risk of perforation. If it is very soft, as after then the anatomy is in order (unless there is a bicornuate labour, use sponge forceps. If you only want to take an endometrial biopsy, the cervix, starting with the smallest dilator.

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