Causation in the Indian region Well-designed, population-based analytical studies on the causation of mental disorders are lacking in India. Complex methodological issues have further added to the existing problems in undertaking research. A review of the current research efforts in the country reveals that there has been a gradual shift and progress in identifying the social, demographic and cultural correlates of disorders (Gururaj and Isaac 2004). Apart from this, the different variables studied include: age, gender, sex, place of dwelling, education, occupation, income, religion, migration, marital status, caste, type of family (nuclear, non-nuclear). There was a female preponderance in the ratio of males to females (1:3); in addition, the age at onset was significantly higher for females for all mental disorders. There was a male preponderance in two of the centres (Bangalore and Baroda) and a female preponderance in the Patiala centre. Ganguli (2000) found a small difference (rural 71/1000 and urban 73/1000 population). However, considering the fact that a large part of the population of India lives in rural areas, the burden of mental morbidity and need for services will be higher in these areas. However, it continues to be debated whether income levels are a result of the mental illness or a cause. The Calcutta centre found a higher prevalence among the extremes of income levels. Income levels only need to be considered as a proxy for lack of resources among the mentally ill, the result of which would drive them further down the income categories (the social causation versus the downward drift hypotheses-Mueser and McGurk 2004). Thus, despite there being no conclusive evidence from available studies for severe mental disorders, those with low-income levels need to considered as a more vulnerable group. Education: Education as variable of study is important both from identifying the at-risk group and in guiding the planning of interventions, including continuity of care. The different definitions adopted in defining the education levels among various studies pose problems in comparison. Marital status: All reports indicate that those who are widowed, separated or divorced have greater mental morbidity. Contrary to western data, the Indian married population have a greater proportion of the mentally ill. Various reasons have been ascribed for this finding, a major one being the possibility of not differentiating but accommodating a mentally ill person in day-to-day activities. Migration: Migration as a specific variable of study has been reported by Dube (1970). It has been observed that Punjabi refugees were more afflicted than Sindhi refugees. Reviewing the literature on migration and mental health, Bhugra (2004) implores that the role of social and cultural factors is paramount in both aetiology and management of psychiatric illnesses. The former reports a greater risk among the joint family while the latter report a greater risk among nuclear families. In the absence of longitudinal studies that would help to identify the time-trends of the disease and evaluate causal mechanisms, interval studies are invaluable. However, the change, which has been documented over a period of two decades, is a definite pointer. The finding of a lesser proportion of morbidity among those healthy in the earlier surveys further bolsters this point.
Running on a slight downhill grade of two to three degrees is excellent for honing sprint speed. The effect of gravity forces the neuromuscular system to respond faster than normal. Such running is usually done at a time in the season where peak speed development is appropriate. Sprint-assisted training is an effective method of developing speed which lets the athlete run faster than possible under his or her own power. Tension in the mechanism pulls the athlete faster than he or she would sprint unassisted, training the body to move at greater speed. As with downhill running, the overload principle is satisfied by reducing the time period in which the sprinting motion must be completed. This form of 126 ChapTer 5 Plyometric Training for Speed-Strength training is specific to sprinters and jumpers and not particularly recommended for long distance runners. The tension should not be so great that the athlete loses good technique or control or needs to brake with each stride. For best results, another athlete should run with the tubing or cord at the same time as the first athlete sprints. This is a pure speed exercise, so the athlete should be fresh for all repetitions of the drill. Note: Some forms of sprint-assisted training can be dangerous, especially being towed by a vehicle. Athletes should always have enough control over the drill that they may stop it at any time. Incorporating Plyometric Training the key to successful use of plyometric training is a carefully planned and supervised program that is properly integrated into the overall training. The general and specific principles of training mentioned earlier must guide the structure of the training. Coaches should pay specific attention to the concepts of gradual progression, recovery and individuality; furthermore, they should always be aware that they are training the capacity for explosive power. Finally, the rate of stretch of the muscle is more important than the degree of stretch. Coaches must explain underlying principles and teach the methods of training correctly. Plyometric 127 ChapTer 5 Plyometric Training for Speed-Strength training is not mysterious. Physical maturity, fitness, propensity to injury, and event specialities are different for each athlete. A coach could find he or she may be working with an 18-year-old senior boy while at the same time working with a 14-year-old freshman girl in the same event. The volume and intensity of a plyometric session must also be determined in light of other training. The nature of plyometric exercises demands they be included as part of the body of a workout, not merely as warm-up or drills. Combining a hard power plyometric session with fast sprint repeats, for example, will most likely exhaust, overtrain, and even injure the athletes. Periodization and event specialities also determine the volume and intensity of a session. Eventually, plyometrics are sharply reduced during the peak competitive phase of the season. This formula is shaped, 128 ChapTer 5 Plyometric Training for Speed-Strength though, by event demands. Sprinters, jumpers and especially throwers will perform a good deal more plyometric work than distance runners. In especially heavy periods of training or competition, one session may be adequate.
Diseases
Timed Approaches Run-ups are timed when foot leaves the ground at start until foot plants (about 3. High Jumping To train specifically, an athlete needs to high jump in training, though not more than twice per week. It is hard to high jump well while engaged in hard training, so schedule jump training accordingly. If the jumper is performing well, the bar can be raised one or two inches after several jumps. Endurance jumping develops specific jumping fitness and reinforces the need for consistency. This demands intense concentration and maximum effort; however, the coach should continue to emphasize good technical execution. If an athlete performs well in this training session, a new improvement in competition should be close at hand. These workouts should begin early in the competitive season and continue through mid-season. Do max jumping once every 363 ChapTer 15 Training High Jumpers two weeks in the early season and once per week with fewer jumps during mid-season. Remember, however, the central focus must be on the process of training, not jumping for height. Nonetheless, coaches should test the physical skills of their athletes periodically. Testing at the end of the season will provide returning high jumpers with training objectives for the following year. Sometimes it may be necessary to train through a meet, but when it comes to jumpers, nothing improves performance better than rest. A Training Periodization Plan for the Season As with other events, training for the high jump should be periodized over the course of the school year or season. Periodization is the division of training into phases or periods emphasizing different goals and types of training. Periodizing training frames the progress of training and skill development for the high jumper. Accordingly, coaches should integrate different types of training with each other. In a two- to four-week training phase, primary emphasis should be given to one type of training. Within any training plan, it is not recommended to have more than three quality, or hard, training days per week, including competitions. The goal of periodization is to manage the stress of training to produce improvement. Tactics and Strategy for High Jump Competition Athletes need to be well educated in the rules of the event to make smart tactical decisions during competition, For example, the procedure used for breaking first-place ties in the high jump will often dictate the heights a jumper will attempt or pass in the final stages of a competition. This nonproductive emotion can leave the athlete drained when it comes time to jump. Athletes must learn to keep nervous energy under control and in reserve for the competition. If an athlete is jumping well in warm-ups, three height progressions, or six inches below the personal best is usually a good opening height. If an athlete is struggling with his or her approach, the coach should have the jumper open at a lower height so he or she can work out problems early in the competition. If the opening height is higher than the athlete is accustomed to starting, have the jumper work his or her way up to 365 ChapTer 15 Training High Jumpers that height during his warm-up jumps. Never allow your jumpers to wear their warm-up suits in competition at lower heights! With one or two misses, any psychological or tactical advantage is reversed, and the stage is set for disaster! Determining Height Progressions In most high jump competitions, the bar is raised in increments of two inches until two or three jumpers remain. It is recommended coaches have their athletes jump at two-inch increments until they are going for the win. Then, the coach and athlete should make a tactical decision whether to proceed by one- or two-inch increments.
Computed tomography rarely demonstrates the fracture line, although it may delineate increased marrow density and endosteal/ periosteal new bone formation and soft tissue edema. Magnetic resonance imaging may demonstrate a localized band of very low signal intensity continuous with the cortex. Classification Stress fractures may be classified as complete versus incomplete or acute versus chronic or recurrent. Treatment the treatment of a child presenting with a tibia or fibula stress fracture begins with activity modification. The cast should be maintained for 4 to 6 weeks until the fracture site is nontender and radiographic evidence of healing occurs. Nonunion may be addressed with open excision of the nonunion site with iliac crest bone grafting or electrical stimulation. Fifty-eight percent of ankle physeal injuries occur during athletic participation. Ligamentous injuries are rare in children because their ligaments are stronger relative to the physis. All ligaments attach distal to the physes of the tibia and fibula-important in the pathoanatomy of pediatric ankle fracture patterns. The distal tibial ossific nucleus appears between the ages of 6 and 24 months; it fuses with the tibial shaft at about age 15 years in girls and 17 years in boys. Over an 18-month period, the lateral portion of the distal tibial physis remains open while the medial part has closed. The distal fibular ossific nucleus appears at the age of 9 to 24 months and unites with the fibula shaft 12 to 24 months after tibial physis closure. Secondary ossification centers occur and can be confused with a fracture of either the medial or lateral malleolus; they are often bilateral. Ligamentous instability may be present, but it is usually difficult to elicit on presentation owing to pain and swelling from the acute injury. Ankle sprains are a diagnosis of exclusion and should be differentiated from a nondisplaced fracture based on the location of tenderness. Neurovascular examination is essential, with documentation of dorsalis pedis and posterior tibial pulses, capillary refill, sensation to light touch and pinprick, and motor testing. Dressings and splints placed in the field should be removed and soft tissue conditions assessed, with attention to skin lacerations that may indicate open fracture or fracture blisters that may compromise wound healing. Clinical examination will dictate the possible indication for obtaining views of the knee and foot. Stress views of the ankle may be obtained to determine possible undisplaced transphyseal fractures. The presence of secondary ossification centers (a medial os subtibiale in 20% of patients or a lateral os subfibulare in 1% of patients) should not be confused with fracture, although tenderness may indicate injury. A Tillaux fragment represents an osseous fragment from the lateral distal tibia that has been avulsed during injury. Chapter 51 Pediatric Ankle 745 Magnetic resonance imaging has been used to delineate osteochondral injuries in association with ankle fractures. The classification aids in determining the proper maneuver for closed reduction. The short oblique distal fibular fracture occurs 4 to 7 cm proximal to the fibula tip. These are intra-articular fractures that exhibit the highest rate of growth disturbance. Diagnosis is often delayed until premature physeal closure is found with a leg length discrepancy. External rotation force causes the anterior tibiofibular ligament to avulse the fragment.
Localized cranial hyperostosis of meningiomas: a result of neoplastic enzymatic activity Most intracranial meningiomas are not cleavable tumors: anatomic-surgical evidence and angiographic predictability. Aggressive surgery and focal radiation in the management of meningiomas of the skull base: preservation of function with maintenance of local control. Meningiomas: genetics, malignancy, and the role of radiation in induction and treatment. The natural history and growth rate of asymptomatic meningiomas: a review of 60 patients. Preoperative embolisation of intracranial meningiomas: a 17-years single center experience. Delayed surgical resection reduces intraoperative blood loss for embolized meningiomas. Clinicopathologic assessment and grading of embolized meningiomas: a correlative study of 64 patients. Meningioma: analysis of recurrence and progression following neurosurgical resection. Factors affecting operative and excess long-term mortality in 935 patients with intracranial meningioma. Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases. Primarily resected meningiomas: outcome and prognostic factors in 581 Mayo Clinic patients, 1978 through 1988. Risk factors predicting recurrence in patients operated on for intracranial meningioma: a multivariate analysis. Meningiomas invading the sagittal or transverse sinuses, resection with venous reconstruction. Atypical and anaplastic meningiomas: radiology, surgery, radiotherapy and outcome. Management of atypical and malignant meningiomas: role of high dose 3D-conformal radiation therapy. Efficacy of external fractionated radiation therapy in the treatment of meningiomas: a 20 year experience. Management of atypical and malignant meningiomas; role of high-dose, 3D conformal radiation therapy. Management of petroclival meningiomas by stereotractic radiosurgery: clinical study. Meningioma radiosurgery: tumour control, outcomes and complications among 190 consecutive patients. Judicious resection and/or radiosurgery for parasagittal meningiomas: outcomes from a multicenter review. High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas. Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy. Preliminary visual outcomes after three-dimensional conformal radiation therapy for optic nerve sheath meningioma. Stereotactic fractionated radiotherapy in patients with optic nerve sheath meningioma. Stereotactic radiosurgery provides equivalent tumour control to Simpson Grade 1 resection for patients with small to medium size meningiomas. Meningioma treated with interferon-alpha, evaluated with [(11)C]-L-methionine positron emission tomography. Lack of efficacy of megestrol acetate in the treatment of unresectable meningiomas. Gutmann2 and Guido Reifenberger3 1 Division of Neuropathology, School of Medicine, St. This review summarizes the most important features of meningioma pathology and provides an up-to-date overview about the molecular mechanisms involved in meningioma initiation and progression.
Winterlien (Flaxseed). Serpina.
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He has a systolic blood pressure of 90 mmHg, pulse rate of 120 per minute and is cold and clammy with a tender distended abdomen and a pulsatile mass. B A 52-year-old man complains of a weak grip in his left hand with tingling and numbness along the inner side of his arm and palm. When using his arm he has pain, and his palm has a dusky discoloration of the fingertips. C A 73-year-old woman complains of attacks of sudden blindness in her right eye that last for a few minutes. D A 68-year-old man, who is a heavy smoker, complains of pain in his right thigh and buttocks on walking about 400 metres. Once he stops, the pain disappears and returns when he walks a similar distance again. E A 60-year-old woman, who is a heavy smoker and works as a domestic, gets syncopal attacks when she is working scrubbing floors using her right upper limb vigorously. F A 68-year-old woman complains of sudden onset of severe pain in her right thigh, calf and leg of 6 hours duration. She has lost sensations from the mid-thigh distally, cannot move her foot or knee, her skin feels very cold and she looks pale. G A 32-year-old woman complains of episodes of pain in the fingers of both her hands when it is cold. The fingers go white, swollen and dusky when she is unable to make any fine movements. H A 28-year-old man, who is a heavy smoker, complains of pain in his right lower limb on walking. He has developed a tender cord-like structure along his long saphenous vein with some tenderness and a generally swollen leg. I A 74-year-old man complains of epigastric discomfort and throbbing backache for 4 months. On examination he has a mass in his epigastrium extending on to umbilical region, which shows expansile pulsation. J A 64-year-old man, who is a postman, complains of intermittent claudication in his calf for 8 months. K A 70-year-old man, who is a long-term heavy smoker, complains of onset of severe pain in his left calf and thigh of 2 days duration. Prior to this he had suffered from intermittent claudication, with a claudication distance of 50 metres. L A 45-year-old woman complains of a lump on the left side of her forehead for many years. M A 55-year-old woman who has been an insulin-dependent diabetic for 35 years has developed necrotic skin patches in her right forefoot following a fall from a bicycle. The lump was there a couple of years, but only over the last couple of days it has become extremely tender, the leg has become cold and he is unable to walk. P A 65-year-old woman with atrial fibrillation underwent a successful lower limb embolectomy under local anaesthetic. A couple of days later she developed in the same limb severe throbbing pain over a period of 4 hours; the limb looked pink. N A 66-year-old man presented with a tender lump over his right popliteal fossa and severe pain Answers to multiple choice questions 1. This fact clinically differentiates it from arthritic pain, which comes on after taking the first step and is not relieved by rest. The pain-free distance that a patient can walk is called the claudication distance. The pain is relieved by keeping the foot dependent and hanging it by the bedside or sleeping in a chair. In aortoiliac disease, the patient complains of thigh and buttock claudication whilst calf claudication indicates superficial femoral artery obstruction.
Maternal, perinatal and childhood conditions account for another significant percentage of the disease burden, of particular importance for the poor. Although no direct estimates of the prevalence/incidence of these health conditions are available, we can indirectly assess their importance by looking at the neonatal, infant, under-5 and maternal mortality rates, which continue to be unacceptably high. These forecasts are, however, not reliable as these ignore trends in and interplay with factors that underlie changes in the rates of infant, under-5 and maternal mortality (Deolalikar, forthcoming). Malaria, dengue and other vector-borne conditions were estimated to account for 1. Unfortunately, these estimations lack credibility as reliable population-based data on these conditions do not exist in India. Underreporting occurs when a large number of patients visit private health care providers who are under no obligation to report cases to the public health authorities, and when record-keeping and case-finding are done by poorly monitored employees who may receive incentives for underreporting to demonstrate the success of a programme. Most of this increase will occur on account of coronary heart disease-a mix of conditions that includes acute myocardial infarction, angina pectoris, congestive heart failure and inflammatory heart disease, although these are not necessarily mutually exclusive terms. The prevalence rates among younger adults (age group of 40 years and above) are also likely to increase; and the prevalence rates among women will keep pace with those of men across all age groups. They refer to a group of diseases associated with uncontrolled cell growth that can affect normal body functions, often with fatal outcomes. These estimates will, however, change as many of the common risk factors for cancers, such as tobacco and alcohol consumption, continue to become more prevalent in India. Fairly conservative assumptions show that the number of people living with cancers will rise by nearly one-quarter from 2001 to 2016. Nearly 10 lakh new cases of cancer will be diagnosed in 2016, compared to about 800,000 in 2001. The incidence of cancers common to both men and women will also see a sharp increase during this period; nearly 670,000 people are expected to die of cancer in India in 2016. There is, however, increasing realization that conditions such as schizophrenia, mood disorders (bipolar, manic, depressive and persistent mood disorders) and mental retardation can impose a marked disease burden on Indians. It is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, especially tobacco smoke and air pollution-both indoor and outdoor. Although asthma can occur at all ages, in about half of the cases it occurs before the age of 10 years. Blindness Data on the current prevalence and future projections for blindness show that the number of blindness cases is expected to remain more or less the same during the next two decades. The projection, however, is based on extremely optimistic projections on cataract treatment that may not be realized. Oral and dental diseases Available data on the current prevalence and future projections for oral health conditions suggest an increase by 25% over the next decade. These data, together with other evidence presented previously on non-communicable diseases, suggest a major future health policy challenge for India. Unintentional injuries include road traffic injuries, poisoning, drowning, falls, etc. It is estimated that the number of deaths from accidents and injuries in 2005 would range from 730,000 to 985,000, with projections that deaths from injuries will increase by as much as 25% over the next decade. These estimates do not include the health impact of injuries with non-fatal outcomes (including permanent disability), which tend to be heavily underreported in India and could well be in the region of about 5 crore cases per year. Available evidence from India also shows that much of the mortality from injuries due to road traffic accidents, occupational accidents and suicide is concentrated among Disease burden in India: Estimations and causal analysis 5 adults in their peak work ages, i. In most cases, disease occurrence and progression can be avoided or significantly reduced/ contained if access to right information and/or early treatment is assured. In countries such as India where there are limited resources and competing demands, not all conditions can be treated and not every intervention provided at public expense. At some point prioritization of interventions or population groups that need to be supported with public funding becomes inevitable. The issue then arises as to the criteria that ought to be used for identifying such publicly supported interventions.
This is a form of minimally invasive endovascular therapy that uses bipolar catheter to generate thermal energy to ablate the vein. These procedures might result in complications such as thrombophlebitis in about 5% and embolism in about 1%. Following open surgery of saphenofemoral ligation and long saphenous stripping or saphenopopliteal junction ligation and short saphenous vein stripping, complications occur in up to one in five patients, with wound infection being the most common. Following long saphenous vein stripping, injury to the saphenous nerve occurs in up to 7% whereas sural nerve neuropraxia occurs in 4% after short saphenous vein stripping. Deficiencies of antithrombin, activated protein C and protein S are predisposing factors in the young. Confirmation of the diagnosis on clinical suspicion is by duplex ultrasound examination of the deep veins, which should be located and compressed. Patients undergoing surgery are categorised as low risk, moderate risk and high risk (Figure 57. Moderate- and high-risk patients are given prophylaxis in the form of pharmacological and mechanical methods, the latter consisting of graduated elastic compression stockings and external pneumatic calf compression. Used by itself, pharmacological methods are more effective than mechanical methods although the downside is the slight increased risk of bleeding. Thrombolytic therapy might be considered in iliac vein thrombosis when diagnosed early. A, B, C, D, E Venous disease is the cause for up to 70% of all leg ulcers particularly when they occur in the lower leg. Nonvenous causes are ischaemia, rheumatoid arthritis, inflammatory bowel disease, trauma, diabetic neuropathy, neoplasm and infections (in developing countries). The hypertension leads to leakage of fibrin and red cells, the former causing the formation of a pericapillary fibrin cuff while the latter causes haemosiderin deposition and pigmentation. Pedal pulses might not be palpable because of the indurated skin; therefore, ankle-brachial pressure index should be assessed by Doppler studies. Therefore if the ulcer is seen on the foot or high up in the calf the diagnosis of a venous ulcer must be reconsidered. F Axillary vein thrombosis this patient has axillary vein thrombosis, which is typically seen in a young muscular man after heavy use of the arm. At the same time, an x-ray of the thoracic inlet is done to exclude a cervical rib that might have precipitated the thrombosis by compression of the vein. Hence, an attempt should be made to cannulate the vein and treat by thrombolysis using tissue plasminogen activator. If a cervical rib is confirmed, causing thoracic inlet syndrome, then it is removed in due course. This would show up the filling defects in flow and lack of compressibility, which indicates the presence of thrombosis. Treatment should be commenced immediately on low-molecular-weight heparin and anticoagulated with warfarin according to the local protocol. Usually it is 10 mg, 10 mg and 5 mg, on three consecutive days monitored by daily prothrombin time. It consists of cutaneous naevus, varicose veins and bone and soft tissue deformity. Superficial veins are removed if symptoms are not relieved by stockings after making sure the deep veins are normal. Excessive limb growth might have to be controlled by epiphyseal stapling or heel raise of the opposite limb. C Superficial thrombophlebitis this patient suffers from superficial thrombophlebitis. Common causes are trauma, intravenous infusion of hyperosmolar solutions or drugs and visceral malignancy (as in this patient).
Periodontal disease and cardiovascular disease: Epidemiology and possible mechanisms. Association of a vitamin D receptor gene polymorphism with localized early-onset periodontal diseases. The 5year survival rate is 75% for local lesions but only 17% for those with distant metastasis. Unfortunately, in India, most cancers are diagnosed at a very late stage, when treatment not only becomes more expensive, but the morbidity and mortality also increase. Prevention and treatment Strategies for prevention and treatment of oral cancer are summarized in Table 8. Impact of betel quid, tobacco and alcohol on three-stage disease natural history of oral leukoplakia and cancer: Implications for prevention of oral cancer. Prevalence of oral submucous fibrosis among the cashew workers of Kerala, South India. Solar radiation, lip protection, and lip cancer risk in Los Angeles County women (California, United States). A fluoride content higher than 1 ppm is known to cause dental and skeletal fluorosis. It manifests as unsightly, chalky white or yellowish-brownish discoloration of the teeth, sometimes with structural defects in the enamel such as pitting of the surface. Fluoride toxicity depends upon several factors such as (i) the total quantity of ingested fluoride from all sources- water, food and drugs with a high fluoride content, (ii) climatic conditions of the region-in tropical countries such as India, water consumption can be high causing higher ingestion of fluoride-containing water, (iii) nutritional status of the individual-deficiency of vitamin D, calcium and phosphate can aggravate the manifestations of fluoride toxicity, (iv) presence of advanced kidney disease and hyperthyroidism are associated with manifestations of fluoride toxicity. The concentration of fluoride in drinking water to give the point of minimum caries with maximum safety. Domestic water and dental caries including certain epidemiological aspects of oral L. Fluoride varnishes-a review of their clinical use, cariostatic mechanism, efficacy and safety. Project report, sponsored by Task Force on Safe Drinking Water, Government of India. Tertiary prevention Treat the discoloured/disfigured dentition by appropriate aesthetic treatment such as bleaching, micro-abrasion, laminate veneers, etc. Equipment, minimum manpower required and approximate cost for medical interventions for oral and dental diseases Medical interventions Dental check-up Equipment/instruments required Gloves, face mask, head light, mouth mirror, explorer, tweezers, cotton/ gauze, etc. Dental clinic set-up with micromotor/air-rotor and inventory of cutting and filling instruments Cost of clinic set-up, excluding the place, is minimum 2. Though not life-threatening, these diseases are often very painful, expensive to treat and cause loss of several mandays. Periodontal (gum) diseases are found to be closely associated with several serious systemic illnesses such as cardiovascular and pulmonary diseases, stroke, low birth-weight babies and preterm labour. Besides, poor oral health affects the functions of mastication and speech, and ultimately the overall well-being of an individual. The major oral and dental diseases/disorders are (i) dental caries, (ii) periodontal diseases, (iii) dentofacial anomalies and malocclusion, (iv) edentulousness (tooth loss), (v) oral cancer, (vi) maxillofacial and dental injuries, and (vii) fluorosis. Dental caries Dental caries is a universal disease affecting all geographic regions, races, both the sexes and all age groups.
In general, there is little incentive for pharmaceutical companies to evaluate their therapies in meningiomas because of the small potential market. Hopefully as the molecular pathogenesis of these tumors becomes better understood, a compelling case can be made for evaluating specific agents directed at critical molecular targets. Given the limited number of meningioma patients, and the increasing number of potential drug candidates and combinations, there will be a need to consider novel trial designs to effectively screen new agents. These may include small multi-arm trials using adaptive randomization, ``pick-the-winner' design, sequential accrual, or randomized discontinuation. These novel designs potentially allow more agents to be screened rapidly, reducing the overall number of patients that will be required. Since meningiomas are frequently resected and tissue is readily available, there may also be the opportunity to conduct phase 0 studies, which are increasingly used in drug development in many tumors, including glioblastomas. In these studies drug is administered for short periods prior to surgery and the tumor examined to determine if adequate drug concentrations were achieved and whether there is evidence that the putative molecular targets are inhibited. In the next section, targeted molecular drugs that have a potential role against meningiomas will be reviewed in detail. These therapies have also been discussed in recent review articles [4, 8, 11, 14, 15, 67, 79, 80]. Targeted molecular agents the importance of dysregulated cell signaling as a cause of neoplastic transformation is increasingly apparent. Emerging data have identified aberrant expression of critical signaling molecules in meningioma cells [14, 69], suggesting that molecular drugs designed to target pathways involved in cell growth, proliferation, and angiogenesis may prove valuable in therapy. However, in contrast to the extensive work on understanding the genetics of systemic cancers and gliomas, relatively little work has been conducted in understanding the growth factors and their receptors, and the signal transduction pathways that are critical to meningioma growth [4, 67, 68, 70, 79]. Patients were stratified into 2 cohorts: (1) grade 1 meningiomas or (2) grade 2 and 3 meningiomas. Patients initially received 600 mg/day of imatinib; the dose was increased in the second cycle to 800 mg/day if no significant toxicity was observed in the first cycle. Although the treatment was generally well-tolerated, and therapeutic plasma levels of imatinib were achieved, the agent had minimal activity [77]. A recent in vitro study suggests that combining imatinib with the protease inhibitor and pro-apoptotic agent nelfinavir may be lead to synergistic activity [88]. This study has completed accrual and results should be available in the near future (Table 1). These drugs may potentially be more effective than imatinib as monotherapy against meningiomas. In both studies, the drugs were reasonably well-tolerated; the main toxicities were the expected adverse effects of rash and diarrhea [78]. Overall, 25 eligible patients were evaluated, 16 patients received gefitinib and 9 erlotinib. Eight patients had grade I (benign) tumors, 9 grade 2 (atypical), and 8 grade 3 (malignant). There were no objective imaging responses; 8 patients (32%) had stable disease as their best response. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. To date very few studies have evaluated the therapeutic potential of these agents in meningiomas. No radiographic responses were detected, but efficacy data is difficult to interpret in a study with so few subjects [98]. Activation of Ras requires localization to the cytoplasmic surface of the cell membrane [100]. This subcellular localization is dependent on the addition of a hydrophobic farnesyl group to the ras protein, catalyzed by the enzyme farnesyltransferase. However, preliminary studies suggest that the activity of these agents may be limited in benign meningiomas [67]; in addition the development of this class of agents is in some doubt.
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