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By: Richard N Mitchell, MD, PhD

  • Lawrence J. Henderson Professor of Pathology and Health Sciences and Technology, Department of Pathology, Harvard Medical School, Staff Pathologist, Brigham and Women's Hospital, Boston, Massachusetts

https://meded.hms.harvard.edu/people/richard-n-mitchell-md-phd

Overall survival is better with postoperative radiotherapy diabetes test vårdcentral order metformin online now, which is delivered within 7 weeks of surgery diabetes mellitus type 2 en alcohol buy discount metformin 500 mg line. Partial frontolateral laryngectomy: Excision of vocal cord and anterior commissure diabetes mellitus case study buy line metformin. Partial horizontal laryngectomy: Excision of supraglottis diabetes mellitus quais os sintomas metformin 500mg with visa, which include epiglottis, aryepiglottic folds, false cords and ventricle. Total Laryngectomy: the entire larynx is removed along with hyoid bone, preepiglottic space, strap muscles, and one or more rings of trachea. Pharyngeal wall is closed primarily, and lower tracheal stump is sutured to the skin. The indications include T3­4 lesions and failure after radiotherapy or conservation surgery. Hemithyroidectomy or Subtotal Thyroidectomy: the Endoscopic significant debulking with laser or surgical forceps temporarily relieves the airway. The most common sites are free edge and upper surface of vocal cord in its anterior and middle third. Spread Local: Fixation of vocal cord is a bad prognostic sign and indicates involvement of thyroarytenoid muscle. Anterior: Anterior commissure and then to the opposite cord Posterior: Vocal process and arytenoid region Upward: Ventricle and false cord Downward: Subglottic region Lymphatic: There are not much lymphatic in vocal cords. Spread clinical Features Hoarseness of Voice: An early and most common presentation, because of which glottic cancer is detected early. Airway Obstruction: Large growth, accompanying edema or cord fixation may result in stridor. Extension to anterior commissure: Radiotherapy or frontolateral partial laryngectomy. Normal cord mobility suggests growth limited to the surface whereas impaired mobility indicates invasion into intrinsic laryngeal muscles or paraglottic space. Invasion of paraglottic or subglottic space may be associated with undetected invasion of laryngeal cartilages. With normal cord mobility, radiation gives 86% cure rate while it drops to 63% if cord mobility is impaired. In a case of postradiation edema, which persists for longer than 6 months, deep invasive recurrence must be ruled out. Cord mobile and anterior commissure or arytenoids not involved: Radiotherapy gives good results (upper neck nodes are included in the radiation field). In cases of radiation failure, laryngectomy or partial vertical laryngectomy is indicated. Anterior commissure and/or arytenoids involved or cord mobility impaired: Vertical hemi-laryngectomy or frontolateral laryngectomy. More advanced T 4: these lesions may be treated by combined therapy or palliative treatment. Anterior: Growths of infrahyoid epiglottis and anterior ventricular band extend into preepiglottic space, and penetrate the thyroid cartilage. Most common symptoms: Throat pain Dysphagia Referred ear pain Mass of lymph nodes in the neck Late symptoms: Hoarseness of voice Weight loss Airway obstruction-stridor Halitosis Lesion: Either exophytic (suprahyoid epiglottis) or ulcerative (infrahyoid epiglottis). Patient must be able to tolerate SupraglottIc cancEr It is less common than glottic cancer. Prognosis is poor because patients report late, and lymphatic spread occurs early. Other surgical procedures include subtotal laryngectomy with cricohyoidopexy and supracricoid partial laryngectomy. T3 and T4: Total laryngectomy with neck dissection and postoperative radiotherapy. Studies have shown that there is no difference in survival rate between the cases of total laryngectomy and combined chemotherapy+radiotherapy. The patients who are candidates for total laryngectomy are given a course of chemotherapy. Those who have complete response (some include even partial response) are given complete radiotherapy. Those who have no response (some include even partial response) are treated with surgery, usually followed by radiotherapy. No difference in survival was found in these two groups; those who went for radiotherapy or surgery after the course of chemotherapy. SubglottIc cancEr Subglottic region lies below the glottic area, and extends up to the lower border of cricoid cartilage. Spread Local: One side growth of subglottis spreads around the anterior wall, and to the opposite side. Lymphatic: Prelaryngeal (Delphian node), pretracheal, paratracheal and lower jugular nodes. Hoarseness of voice due to infiltration of thyroarytenoid muscle or recurrent laryngeal nerve at the cricoarytenoid joint. T3 and T4: Total laryngectomy and postoperative radiation, which include superior mediastinum. Significant inflammation surrounds the lesion, and lead to enlarged inflammatory neck nodes. Esophageal Speech Patient learns how to swallow air, and hold it in the upper esophagus. Then patient slowly ejects the air from upper esophagus, and speaks 6­10 words which are even though rough, are loud and understandable. Some patients learn to store air in stomach, which greatly improves duration of speech. After Artificial Larynx Artificial larynx is useful when patients fail to learn esophageal speech. They are least socially acceptable because they draw 508 unwanted attention to the speaker. It produces low-pitched sound which is further modulated into speech by the tongue, lips, teeth and palate. The vibrating disc of artificial larynx is held against the soft tissues of the neck or oral cavity. Transoral Pneumatic Device: the expired air from the tracheostome vibrates the diaphragm of this pneumatic device. These rubber diaphragm vibrations are carried by a plastic tube into the back of the oral cavity where modulators convert the sound into speech. The current prosthesis shunts the air from trachea to esophagus, and their inbuilt one-way valves prevent problems of aspiration. In comparison to supraglottis, nasopharynx and subglottic cancers, carcinoma glottis is the most radiosensitive tumor. Supraglottic cancer: It is the most aggressive of laryngeal cancers and has highest incidence of cervical nodal metastases. Synchronous second primary: In cases of carcinoma larynx the most common site of second primary (synchronous second primary) is bronchus. Esophageal speech: the dynamic component of phonation in esophageal speech in a case of laryngectomy lies at pharyngoesophageal segment. Near total laryngectomy in advanced cancers of the larynx and pyriform fossa-a much suited procedure for the Indian Milieu. Role of combined therapy of surgery and radiotherapy versus salvage surgery following radiation failures in advanced carcinoma of the larynx. Survival patterns in treated cases of carcinoma larynx in north India: A 10-year follow up study. Failure to achieve a patent airway in cases of impaired airway, inevitably results in hypoxic brain injury and death. The various means of airway control in the anesthetized or unconscious patients are discussed in chapter Anesthesia. The tracheotomy means opening the trachea, which is a step of tracheostomy operation. Tracheostomy facilitates suctioning, feeding, mobility, early return of speech, and decrease work of breathing.

Syndromes

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Treatment: Facial nerve function usually recovers with systemic antibiotics and wide-field myringotomy or tympanostomy tube diabetes pills vs insulin generic 500 mg metformin amex. Persistent headache diabetes type 2 pregnancy complications buy cheap metformin on line, which disappears with free flow of pus from the ear (spontaneous abscess drainage) occurs on the side of otitis media blood glucose sensor purchase genuine metformin line. High-resolution computed tomography of temporal bone: It is essential in the evaluation of facial nerve palsy early signs diabetes child cheap metformin 500mg with visa. Facial canal should be examined from the geniculate ganglion (processus cochleariformis) to the stylomastoid foramen. In cases of granulation tissue and cholesteatoma, bony facial canal is uncapped in the area of involvement. Granulation tissue surrounding the nerve is removed without damaging the nerve sheath. The nerve grafting is usually preferred in the second stage when infection is controlled and fibrosis has matured. Mastoidectomy (cortical, radical or modified radical): the overlying bone is removed until the healthy dura appears. In cases of strong suspicion overlying intact tegmen tympani or sinus plate is deliberately removed to evacuate any collection of pus. Follow-up Patient should be closely observed for further intracranial complications, such as sinus thrombosis, meningitis or brain abscess. The subdural space is divided into several large compartments, which are anatomically confined, by foramen magnum, tentorium cerebelli, base of the brain and falx cerebri. An extradural abscess pathology Infection can spread either by erosion of bone and dura or by thrombophlebitic process (intervening bone remains intact). Thrombophlebitis of cortical veins of cerebrum: Aphasia, contralateral hemiplegia and hemianopia. Preformed pathways Patent petrosquamosal suture Perineural spaces to the internal auditory canal (uncommon via endolymphatic ducts) via labyrinth through round and oval windows Retrograde venous thrombophlebitis Direct erosion of bone (mastoiditis and petrositis) and dura microbiology Major pathogens are Hemophilus influenzae and Streptococcus pneumoniae. The raised intracranial tension and meningeal and cerebral irritations vary with the extent of disease. Earliest symptoms include­ Fever (102­104° F) often with chills and rigors Headache Vomiting (sometimes projectile) Photophobia Irritability and restlessness Seizures: Infants may have seizures. Lumbar puncture is contraindicated as it can result in herniation of cerebellar tonsil. If there is no satisfactory response to medical treatment, early surgery is required. Antibiotics: Crystalline penicillin, ampicillin, chloromycetin or third generation cephalosporin (drugs of choice) intravenously for 7­10 days. Stage of invasion (Initial encephalitis) of 1­3 days: the mild symptoms include headache, low grade fever, malaise and drowsiness. Stage of localization (Latent abscess) of 4­10 days: In this asymptomatic stage, which may last for several weeks, pus is getting localized by the formation of a capsule. Stage of enlargement or early capsule formation (manifest abscess) of 10­13 days: the enlarging abscess surrounded by a zone of edema aggravates the severity of clinical manifestations, which are due to raised intracranial tension and the focal involvement of brain. Stage of termination or late capsule formation (rupture of abscess) of 14 days: the enlarging abscess ruptures into either the ventricle or subarachnoid space. It is surrounded by an area of inflammation (encephalitis) · Fifty percent cases of brain abscesses in adults and 25% in children are otogenic. As the brain abscess is often associated with extradural abscess, perisinus abscess, meningitis, sinus thrombosis and labyrinthitis, the clinical picture may be overlapping. Clinical features are mainly due to raised intracranial tension and the area of brain affected. Raised intracranial tension Headache is severe and generalized, worse in the morning. Nausea and vomiting (usually projectile): It is more common in cerebellar abscess. Bimodal Age Distribution: Peak incidences are in pediatric age and 4th decade of life. Retrograde thrombophlebitis of dural vessels, which terminate in white matter, is usually caused by the osteitis and granulation tissue. Cerebral abscess: Cerebral abscess is often associated with extradural abscess that occurs due to erosion of the tegmen. It is often associated with extradural abscess, perisinus abscess, sigmoid sinus thrombophlebitis or labyrinthitis. Aerobic: Gram-positive: Pyogenic staphylococci, Streptococcus pneumoniae and Streptococcus haemolyticus Gram-negative: Proteus mirabilis, Escherichia coli, Klebsiella and Pseudomonas aeruginosa Anaerobic: Peptostreptococcus and Bacteroides fragilis. Localizing features of temporal lobe abscess Nominal aphasia: It occurs if the lesion is of dominant cerebral hemisphere, which is left side in right handed persons. Contralateral homonymous hemianopia: It indicates pressure on the optic radiations. Contralateral motor paralysis: They are: ­ Upward spread: Facial palsy is followed by palsy of arm and leg. Localizing features of cerebellar abscess Suboccipital headache associated with neck rigidity. Dysdiadokokinesia: Rapid pronation and supination movements become slow and irregular on the affected side. Raised intracranial tension: Dexamethasone, 4 mg intravenous 6 hourly or mannitol 20% in doses of 0. Neurosurgical: Life saving neurosurgical intervention takes precedence over the otologic management. Neurosurgeon may consider any of the following procedures: Burr hole: Repeated aspiration of pus Excision of abscess Open incision of the abscess and evacuation of pus C. Otologic: Only neurologically stabilized patients are taken for tympanomastoid surgery. Ear surgery is planned only after the abscess has been managed by antibiotics and neurosurgery. Cholesteatoma needs radical mastoidectomy, which removes the irreversible disease and exteriorizes the infected area. With the advent of new range of antibiotics, the incidence of this complication has declined yet mortality remains high. It detects not only the subtle changes in brain parenchyma but also spread of abscess into the subarachnoid space or into the ventricle. Endophlebitis and mural thrombus: Inflammation of the inner wall of the venous sinus results in thrombus formation (deposition of fibrin, platelets and blood cells) within the lumen of sinus. Obliteration of sinus and intrasinus abscess: Expanding mural thrombus occludes the sinus lumen. Organisms invade the thrombus and form intrasinus abscess that releases infected emboli into the blood stream (septicemia). It may spread to confluence of sinuses, superior sagittal sinus, cavernous sinus, mastoid emissary vein, jugular bulb or internal jugular vein. Medical: the different medical treatments are: Antibiotics: Parenteral chloromycetin, penicillin or its derivatives. Aminoglycoside, such as gentamicin, covers bacteriology Acute otitis media: Hemolytic streptococcus, Pneumococci. Cholesteatoma: Bacillus proteus, Pseudomonas pyocynea, Escherichia coli and Staphylococci. Fever: Hectic type of fever with chills and rigors coincides with the release of septic emboli into blood stream. Profuse sweating follows during the fall of temperature and patient becomes alert with a sense of well-being. Headache becomes severe when venous obstruction increases the intracranial pressure. Cavernous sinus thrombosis: Chemosis, proptosis, fixation of eyeball and papilledema. Otitic hydrocephalus: Thrombus extends to superior sagittal sinus through the transverse and confluence of sinuses. Papilledema: It is seen when clot extends to superior sagittal sinus, which is in the continuation of right sigmoid and transverse sinus.

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This earlier case also involved an application from a foreign father for the return of children who had been abducted by their mother diabetes zwangerschap buy 500 mg metformin free shipping. The mother had opposed this application by contending that the father had sexually abused one of the children while he had custody of her vorbereitung diabetes test order cheap metformin line. The Family Court judge who heard this application agreed that there was a grave risk that the child would be exposed to diabetes normal range purchase 500 mg metformin otc physical or psychological harm or would be placed in an intolerable situation if she was returned to diabetes type 1 foot problems order discount metformin her habitual residence in Denmark. On appeal, the High Court held that Family Court judges are not to treat applications for return of children as custody hearings. Instead, the courts must consider whether the foreign legal system contains adequate safeguards for children. In the instant case, the High Court found that the Danish legal system provides that, in family matters, the best interests of children are paramount and that Denmark would take steps to protect the child if there was a reasonable possibility that she would be sexually abused. The Court of Appeal agreed with these findings and cited Australian, Scottish, and American cases in support of its interpretation of the Hague Convention. In reaching this decision, the judge found that the fact that Australia provides protection to children through its social services did not eliminate the risk in the instant case. However, the judge was careful to note that most cases in which such concerns are raised will not result in an exception being granted to allow a child to stay in New Zealand. The major reason for this decision was that the child was a teenager who had indicated a strong preference to remain in the country. The above cases demonstrate that New Zealand courts have applied the Hague Convention in aid of foreign parents who have had children abducted by former spouses, but they have also found that certain cases fall within the exceptions under the agreement. In the latter cases, the courts have tended to stress the unusual facts to avoid the impression that they do not take their obligations under the Hague Convention as seriously as was intended by its framers. Under the applicable section, a Family Court or District Court judge can issue a warrant that authorizes a police officer or social worker to take possession of a child and deliver him to a person or authority who will arrange for his return. To enforce such an order, a judge or the Registrar can direct that a child be taken into official custody and that any passports, tickets, and other travel documents be surrendered. Legal Assistance Programs the Guardianship Amendment Act, 1991 provides that where an applicant for the return of an abducted child is not represented by a barrister or solicitor, "the Authority shall, where the circumstances so require, appoint a barrister or solicitor to represent the applicant for the purposes of the application. The Court can order a party to reimburse the Crown such amount as it deems appropriate. It appears that this is not usually done when the dispute involves questions of law. Legal aid can be applied for by parties who are unable to pay the legal costs of bringing an application for the return of an abducted child. Conclusion Prior to 1991, several well-publicized cases gave New Zealand the reputation of being a country that at least sometimes harbored children who had been abducted in violation of foreign custody orders. However, New Zealand acceded to the Hague Convention of the Civil Aspects of International Child Abduction. The primary purpose of the Hague Convention is to ensure that, except in very special cases, 28 [2002] N. The Hague Convention was incorporated in New Zealand law through the adoption of the Guardianship Amendment Act, 1991. Domestic Laws and Regulations Implementing the Hague Convention In compliance with article 6, paragraph 1, of the Convention, 5 Panama has designated the Direcciуn General de Asuntos Jurнdicos y Tratados of the Ministry of Foreign Affairs as the Central Authority. According to the Political Constitution of Panama, the Convention became part of the legal order of the Republic upon its enactment, approval, and promulgation. Constituciуn Polнtica de la Repъblica de Panama (Editorial Publipan, Panama, 1993), art. Child Abduction the competent courts to decide on cases related to the wrongful removal and retention of a child are the family courts [juzgados seccionales de familia] of the city where the child resides. The procedure involves assigning each case to any of the six courts of the judicial district that is governed by the Judicial Code of Panama. Therefore, courts directly apply the text of the Convention to proceedings in these types of cases. Parental Visitation the competent courts to decide parental visitation include the juzgados seccionales de familia where the child resides. When there is no compliance with a custody agreement or a court resolution, or there is a violation of visitation rights, the Court may change its resolution or the terms of the agreement without prejudice to the criminal responsibility created by such conduct, which may be declared in contempt of court. Telephone inter view with Carla Ramirez, an attorney and an officer at the Central Authority of Panama (Dec. Cуdigo Penal de la Repъblica de Panama, Editorial Mizrachi & Pujol, Panama(1993), art. Court System and Structure - Courts Handling the Hague Convention the trial court is the juzgados seccionales de familia. In addition to the court, the Attorney General is the only other authority who may issues orders to prevent an individual from leaving the country. Legal Assistance Programs the Panamanian Central Authority after receiving a Hague Convention case presents the case to the Tribunal Superior de Familia, which then refers the case to the appropriate Juzgado Seccional de Familia. In addition, the Central Authority is present at court hearings and provides assistance to the judge on the interpretation and implementation of the Hague Convention if necessary. The Fiscalia de Familia, under the authority of the Attorney General (Ministerio Publico), represents the interest of the minor in court. Applicants are free to hire a Panamanian attorney to represent their interests in a Hague case. Conclusion Although Panama has not promulgated specific legislation to implement the Convention, by law it may be enforced directly by the courts. Telephone inter view with Ianna Quadri, head of the Panamanian Central Authority (Dec. Gutiйrrez Senior Legal Specialist November 2003 24 Information on international child abduction and the Panamanian law is available in the website of the Panamanian Ministry of Foreign Affairs, in the link of the General Directorate of Legal Issues and Treaties (Direcciуn General de Asuntos Jurнdicos y Tratados) The Convention, together with its Polish translation, was published in Dziennik Ustaw No. In the Declaration on Accession of Poland to the Hague Convention, the Polish Ministry of Foreign Affairs declared that pursuant to article 38 of the Hague Convention, the following contracting states had expressed their acceptance of the accession of the Republic of Poland to the Hague Convention: Holland, the United States of America, Luxembourg, and the United Kingdom of Great Britain and Northern Ireland. Between the United States and Poland, the Hague Convention became binding immediately on November 1, 1992. Due to the relatively short time span of the application of the Hague Convention by Polish courts, there are very few court cases available that have applied the Hague Convention. Generally accessible materials consist of the text of the two Polish Supreme Court decisions and an analysis of 12 district court decisions in a scholarly article by W. There are relatively few scholarly legal publications on the topic of the Hague Convention. Except for several publications on various aspects of the Hague Convention, cited in this report, there are no comprehensive analyses of its application in the Polish legal system. Although these terms are defined in the text of the Hague Convention, their application in the Polish domestic legal system may cause some problems. During the short time since the application of the Hague Convention in Poland, neither jurisprudence nor 1 See Oswiadczenie Rzadowe z dnia 17 maja 1995 r. This report, therefore, having a mainly informative character, does not attempt to undertake such a difficult task, except where it is absolutely necessary. Other International Agreements Aside from the Hague Convention, the Republic of Poland is also bound by other bilateral and multilateral agreements dealing with international child abduction. Poland has signed bilateral agreements relating to recognition and execution of civil and family judgments dealing with child custody with various countries, including, but not limited to: France, 5 former Czechoslovakia, 6 Hungary, 7 Lithuania, 8 Byelorussia, 9 and the former Union of the Soviet Socialist Republic. The Hague Convention states the following in article 26: Nothing in this Convention shall prevent two or more contracting states, in order to limit the restrictions to which the return of the child may be subject, from agreeing among themselves to derogate from any provisions of this Convention which may imply such a restriction. See Europejska Konwencja o uznawaniu i wykonywaniu orzeczen dotyczacych pieczy nad dzieckiem oraz o przywracaniu pieczy nad dzieckiem, Dz. See Konwencja o wlasciwosci organow i prawie wlasciwym w zakresie ochrony maloletnich, sporzadzona w Hadze dnia 5 pazdziernika 1961 r. As provided by the Preamble to the 1980 Hague Convention "interes" ["interest"] in the meaning of "dobro" ["best interest"] of a child is "of paramount importance in matters relating to its custody. In order to help Polish judges in the application of the new Conventions and other international agreements ratified by Poland, the Polish Ministry of Justice and the Dutch Ministry of Justice signed agreements on mutual cooperation. Pursuant to these agreements, Polish judges may refer, free of charge, 14 By their own decision, resolutions adopted by a bench composed of seven justices of the Supreme Court may become a binding legal principle which has a precedence value. The Constitution When the Hague Convention was ratified, the Polish Constitution that was in force at that time did not define the place or implementation of international agreements in the domestic legal order. The present Polish Constitution20 lists explicitly ratified international agreements as a source of universally binding law. Such categories are enumerated in article 89 of the Constitution and include those concerning "freedoms, rights, or obligations of citizens, as specified in the Constitution" and "matters regulated by statute or those for which the Constitution requires a statute.

Sarsaparilla extracts are used extensively as flavor components in root beer even though they are essentially odorless and have hardly any taste; and it is doubtful that the reported average maximum use level of approximately 0 diabetes control vitamins buy genuine metformin. Other food products in which they are used include frozen dairy desserts diabetic diet popcorn purchase 500mg metformin mastercard, candy diabetes in dogs cost of treatment buy metformin 500 mg with amex, and baked goods diabetes association generic metformin 500mg line, with the highest average maximum use level of 0. Root used as a flavoring ingredient in teas; numerous product forms, including tablets, capsules, and nutritional powders touted as an anabolic enhancing dietary supplement for athletes and bodybuilders. Rhizome of Mexican sarsaparilla is reportedly used in Mexico in treating gonorrhea, skin diseases, rheumatism, fevers, and digestive disorders, usually as a decoction. In Chinese medicine, the roots and/or rhizomes of several related Smilax species native to China are used. As with sarsaparilla, they are used mainly in treating rheumatism, arthritis, sores, and skin problems. In clinical observations, its effectiveness on primary syphilis has been reported to be about 90% (negative blood test). It is sometimes decocted Sarsaparilla saponins have been reported to facilitate the absorption of other drugs when coadministered with sarsaparilla. Sarsaparilla has been used in the United States in treating syphilis and rheumatism, but its effectiveness has not been substantiated. Sarsaparilla products, along with other sterol containing plants, have in recent years been touted as performance-enhancing or body-building substitutes for anabolic steroids sold primarily to athletes. Plant sterols cannot be bio-chemically transformed in vivo into steroidal compounds, and have not been shown to promote anabolic effects in humans. Numerous Smilax species have been used in cancers both in the Old World and the New World. Subject of a German therapeutic monograph; not recommended since claims for skin diseases and psoriasis have not been substantiated. Other compounds 558 Sassafras present include a-pinene, a-and b-phellandrenes, methyleugenol, 5-methoxyeugenol, asarone, piperonylacrolein, apiole, coniferaldehyde, camphor, myristicin, thujone; l-menthone, caryophyllene, elemicin, copaene, anethole, and eugenol, among others. Sassafras is traditionally used in treating bronchitis, high blood pressure of elderly people, rheumatism, gout, arthritis, skin problems, and kidney problems, among others, usually as a tea or infusion, used both internally and externally. Safrole present in sassafras oil is used as a starting material for the synthesis of heliotropin (piperonal), an important fragrance and flavor chemical. Sassafras and its oil have been reported to have carminative and diaphoretic properties. Sassafras, its extracts, and oil were formerly extensively used in flavoring root beer; this use has been discontinued. Only safrole-free bark extract is reported used in nonalcoholic beverages and in candy, with average maximum use levels of 0. Parts used are the dried leaves and tender stems; summer savory oil is obtained by steam distillation of the whole dried herb. A hydroalcoholic extract, polyphenolic fraction, and the essential oil also displayed antinociceptive and anti-inflammatory effects when administered orally (50­2000 mg/kg) to mice and rats in different models of pain and inflammation. Summer savory oil and oleoresin are used in candy, baked goods, meat and meat products. Food products in which they are used include candy, baked goods, meat and meat products, and condiments and relishes. Both summer savory and winter savory are used as tonic, carminative, astringent, and expectorant in treating stomach and intestinal disorders. Summer savory is quite extensively used as a flavor component in baked goods, meat and meat products. Fruits reported to contain 1­2% essential oil (formed by reaction of alcohols and acids during distillation); fixed oil with 75% free fatty acids and 25% neutral substances including free or esterified sterols or esters of fatty acids with alcohols; acids including caproic, caprylic (ca. In mice experiments intraperitoneal administration of partially purified b-sitosterol fractions of the fruit extract showed significant estrogenic activity;7 an anti-estrogenic effect has also been demonstrated. Such reports include in vivo experiments in animal models,25­ 28 in vitro experiments in prostate cells, and human clinical trials. According to one source, the drug only relieves symptoms associated with prostrate enlargement, without reducing enlargement. Leaf wax investigated as a potential valuable material for wax-consuming industries, but was found to be of less value than the principal hard vegetable waxes currently available. Common/vernacular names: Wuweizi, meaning ``five-flavor seed' (general term for all varieties); northern schisandra or beiwuweizi (S. Part used is the fully ripe, sun-dried fruit that yields northern schisandra; it is oval and wrinkled, with a diameter of 5­8 mm, ranging from bright red, dull red, to purplish red; flesh is soft, with a weak characteristic odor and tastes primarily sour and sweet, with a salty note; its 1­2 yellowish brown, kidneyshaped seeds are fragrant when crushed and taste simultaneously pungent, bitter, and salty; these five flavor elements give schisandra its name, ``five-flavor seed. Its fully ripe, sun-dried fruit yields southern or western schisandra, which is similar in properties to northern schisandra fruit, but is smaller, with thinner flesh and is reddish brown to dull brown. Southern schisandra is mainly produced in western, central, and southern provinces, including Gansu, Shaanxi, Henan, Hunan, Hubei, and Sichuan. Although several other Schisandra species also serve as commercial or potential commercial sources of schisandra fruit, its current major sources are S. The more important ones include: schizandrin (јschizandrol A), schizandrin A (јdeoxyschizandrin), schizandrin B (јgschizandrin), schizandrin C, schizandrol B, schisantherin D, schisandrene, schizandrer A, schizandrer B (јschisantherin), pseudoy-schizandrin, wuweizisu A (јschizandrin A), wuweizisu B, wuweizisu C, gomisins A­R and derivatives, wuweizi ester A (јgomisin C, schisantherin A, schizandrer A), wuweizi ester B (јgomisin B, schisantherin B, schizandrer B), wuweichun A (јschizandrin), wuweichun B, and others. Among these triterpenes are sphenadilactones A and B, lancifodilactones A­N, lancifoic acid A, nigranoic acid, rubriflordilactones A and B, schiprolactone A, schisanlactone B, schisandronic acid, micrandilactone A, micranoic acids A and B, and others. The most extensively studied effect of schisandra fruit is its antioxidant activity14,40­43 and ability to protect human and animal liver from toxins and diseases. Extracts and crude powder are used in preparations marketed mainly for their antioxidant and energy enhancing as well as adaptogenic effects. In traditional Chinese medicine, schisandra fruit is considered a lung astringent, and kidney and male tonic. It is used in treating cough, asthma, insomnia, neurasthenia, chronic diarrhea, Schisandra 567 night sweat, spontaneous sweating, involuntary seminal discharge, thirst, impotence, physical exhaustion, and excessive urination. Most extracts are expressed in weight-to-weight ratios with no uniform quality standards; some extracts are standardized to schizandrin content. Alexandrian senna leaves and pods are reportedly derived mostly from wild plants, while Indian senna leaves are collected at 3­5 months after planting and pods 1­2 months hence. Senna 569 the two species of senna are very closely related and have formerly been recognized as a single species, though later research data have established them as distinct species. Most of the senna currently used in the United States is Indian senna (Tinnevelly senna). Two benzophenone glucosides have recently been isolated from Tinnevelly senna pods and were characterized as 60 -carboxy20, 6-dihydroxy- 2 - b - glucopyranosyloxy-40 hydroxymethyl benzophenone and 40,60 -dicarboxy-20,6-dihydroxy-2-b-glucopyranosyloxy- 40 -hy-roxymethyl benzophenone (cassiaphenone A-2-glucoside and cassiaphenone B-2glucoside, respectively). The naphthalene glycoside tinnevellin-8-glucoside and kaempferol were also isolated. Senna pods normally contain 2­5% sennosides, with Alexandrian pods having higher values than Indian pods. In addition to sennosides A and B, a closely related glucoside, named sennoside A1, has been isolated from Alexandrian senna pods. Sennosides A and C have equal purgative potency in mice but sennoside C has potentiating effects on the activity of sennoside A, exerting a potentiating effect of about 1. Stimulating laxatives should not be used more than 1­2 weeks without medical advice. Chronic abuse can disturb electrolyte balance, leading to potassium deficiency, heart dysfunction, and muscular weakness, especially under concomitant use of heart-affecting glycosides, thiazide diuretics, corticoadrenal steroids, and licorice root. Senna does not induce specific lesions in the nerve plexus of the intestinal wall, and when used rationally, does not lead to electrolyte losses or habituation. Senna leaves, pods, their extracts, and sennosides are extensively used as active ingredients in laxative preparations (syrups, tablets, etc. Often termed a ``bowel irritant' or ``stimulant,' recent scientific consensus suggests such terms should be avoided, in favor of a more specific characterization as a prokinetic agent with a secretory component. Senna leaves or pods used in laxative formulations, usually in tablet, capsule or tea bag form. Senna leaves have been used for centuries in both western and eastern cultures as a laxative, usually taken as a tea or swallowed in powdered form. Senna leaf (both Indian and Alexandrian), its fluid extract, and sennosides A and B are official in U.

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