Disorders of the Musclar System

Neuromuscular disease is a very broad term that encompasses many diseases and ailments that either directly (via intrinsic muscle pathology) or indirectly (animal muscle in general.

Neuromuscular diseases are those that affect the muscles and/or their nervous control. In general, problems with nervous control can cause spasticity or paralysis, depending on the location and nature of the problem. A large proportion of neurological disorders leads to problems with movement, ranging from cerebrovascular accident (stroke) and Parkinson's disease to Creutzfeldt-Jakob disease.

Symptoms
Symptoms of muscle disease may include weakness or spasticity/rigidity, myoclonus (twitching, spasming) and myalgia (muscle pain). Diagnostic procedures that may reveal muscular disorders include testing creatine kinase levels in the blood and electromyography (measuring electrical activity in muscles).

Causes
Diseases of the motor end plate include myasthenia gravis, a form of muscle weakness due to antibodies to the acetylcholine receptor, and its related condition Lambert-Eaton myasthenic syndrome (LEMS). Tetanus and botulism are bacterial infections in which bacterial toxins cause increased or decreased muscle tone, respectively.

The myopathies are all diseases affecting the muscle itself, rather than its nervous control.

Muscular dystrophy is a large group of diseases, many of them hereditary, where the muscle integrity is disrupted. It leads to progressive loss of strength, high dependence and decreased life span.

Inflammatory muscle disorders
Polymyalgia rheumatica (or "muscle rheumatism") is an inflammatory condition that mainly occurs in the elderly; it is associated with giant-cell arteritis. It often responds dramatically to glucocorticoids (e.g. prednisolone).
Polymyositis, dermatomyositis and inclusion body myositis are autoimmune conditions in which the muscle is affected.
Rhabdomyolysis is the breakdown of muscular tissue due to any cause. While it may not lead to any muscular symptoms at all, the myoglobin thus released may cause acute renal failure.

Tumors
Tumors of muscle include:

Smooth muscle: leiomyoma (benign, very common in the uterus), leiomyosarcoma (malignant, very rare)
Striated muscle: rhabdomyoma (benign) and rhabdomyosarcoma (malignant) - both very rare
Metastasis from elsewhere (e.g. lung cancer)
Smooth muscle has been implicated to play a role in a large number of diseases affecting blood vessels, the respiratory tract (e.g., asthma), the digestive system (e.g. irritable bowel syndrome) and the urinary tract (e.g., urinary incontinence). These disease processes are not usually confined to the muscular tissue.

Injury
Injuries of muscles include wounds and strains.

Disorders of the Musclar System

Medulla Blastoma

Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.

Originally considered to be a glioma, medulloblastoma is now known to be of the family of cranial primitive neuroectodermal tumors (PNET).

Tumors that originate in the cerebellum are referred to as infratentorial because they occur below the tentorium, a thick membrane that separates the cerebral hemispheres of the brain from the cerebellum. Another term for medulloblastoma is infratentorial PNET. Medulloblastoma is the most common PNET originating in the brain.

All PNET tumors of the brain are invasive and rapidly growing tumors that, unlike most brain tumors, spread through the cerebrospinal fluid (CSF) and frequently metastasize to different locations in the brain and spine.

Incidence
Brain tumors are the second most common malignancy among children less than 20 years of age. Medulloblastoma is the most common malignant brain tumor, comprising 14.5% of newly diagnosed cases. In adults, medulloblastoma is rare, comprising less than 2% of CNS malignancies.

The incidence of childhood medulloblastoma is higher in males (62%) than females (38%). Medulloblastoma and other PNET tumors are more prevalent in younger children than older children. 40% of medulloblastoma patients are diagnosed before the age of 5, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19.

Pathogenesis
Medulloblastomas usually form in the fourth ventricle, between the brainstem and the cerebellum. Tumors with similar appearance and characteristics originate in other parts of the brain, but they are not identical to medulloblastoma.

Although it is thought that medulloblastomas originate from immature or embryonal cells at their earliest stage of development, the exact cell of origin, or "medulloblast" has yet to be identified.

It is currently thought that medulloblastoma arises from cerebellar "stem cells" that have been prevented from dividing and differentiating into their normal cell types. This accounts from the varying histologic variants seen on biopsy. Rosette formation is highly characteristic of medulloblastoma and is seen in up to half of the cases.

Molecular genetics reveal a loss of genetic information on the distal part of chromosome 17, distal to the p53 gene, possibly accounting for the neoplastic transformation of the undifferentiated cerebellar cells. Medulloblastomas are also seen in Gorlin syndrome as well as Turcot syndrome. Another research has strongly implicated the JC virus, the virus that causes multifocal leukoencephalopathy.

Clinical manifestation
Symptoms are mainly due to secondary increased intracranial pressure due to blockage of the fourth ventricle and are usually present for 1 to 5 months before diagnosis is made. The child typically becomes listless, with repeated episodes of vomiting, and a morning headache, which may lead to a misdiagnosis of gastrointestinal disease or migraine. Soon, the child will develop a stumbling gait, frequent falls, diplopia, papilledema, and sixth cranial nerve palsy. Positional dizziness and nystagmus are also frequent and facial sensory loss or motor weakness may be present. Decerebrate attacks appear late in the disease.

Extraneural metastases to the rest of the body is rare, but usually only after craniotomy.

Diagnosis
The tumor is distinctive on T1 and T2-weighted MRI with heterogeneous enhancement and typical location adjacent to and extension into the fourth ventricle.

Histologically, the tumor is solid, pink-gray in color, and is well circumscribed. The tumor is very cellular, many mitoses, little cytoplasm, and has the tendency to form clusters and rosettes.

Correct diagnosis of medulloblastoma may require ruling out atypical teratoid rhabdoid tumor (ATRT) and primitive neuroectodermal tumor (PNET).

Treatment and prognosis
Treatment begins with maximal resection of the tumor. The addition of radiation to the entire neuraxis and chemotherapy may increase the disease-free survival. This combination may permit a 5 year survival in more than 80% of cases. The presence of desmoplastic features such as connective tissue formation offers a better prognosis. Prognosis is worse if child is less than 3 years old, inadequate degree of resection, or if presence of any CSF, spinal, supratentorial or systemic spread.

Medulla Blastoma

Insulin Resitance

Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin resistance in fat cells results in hydrolysis of stored triglycerides, which elevates free fatty acids in the blood plasma. Insulin resistance in muscle reduces glucose uptake whereas insulin resistance in liver reduces glucose storage, with both effects serving to elevate blood glucose. High plasma levels of insulin and glucose due to insulin resistance often lead to metabolic syndrome and type 2 diabetes.

Pathophysiology
In a person with normal metabolism, insulin is released from the beta (β) cells of the Islets of Langerhans located in the pancreas after eating ("postprandial"), and it signals insulin-sensitive tissues in the body (e.g., muscle, adipose) to absorb glucose to lower blood glucose to a normal level (approximately 5 mmol/L (mM), or 90 mg/dL). In an insulin resistant person, normal levels of insulin do not trigger the signal for glucose absorption by muscle and adipose cells. To compensate for this, the pancreas in an insulin resistant individual releases much more insulin such that the cells are adequately triggered to absorb glucose. Occasionally, this can lead to a steep drop in blood sugar and a hypoglycemic reaction several hours after the meal.

The most common type of insulin resistance is associated with a disease state known as metabolic syndrome. Insulin resistance can progress to full type 2 diabetes. This is often seen when hyperglycemia develops after a meal, when pancreatic β-cells are unable to produce adequate insulin to maintain normal blood sugar levels (euglycemia). The inability of the β-cells to produce more insulin in a condition of hyperglycemia is what characterizes the transition from insulin resistance to type 2 diabetes.

Various disease states make the body tissues more resistant to the actions of insulin. Examples include infection (mediated by the cytokine TNFα) and acidosis. Recent research is investigating the roles of adipokines (the cytokines produced by adipose tissue) in insulin resistance. Certain drugs may also be associated with insulin resistance (e.g., glucocorticoids).

Elevated blood levels of glucose regardless of cause leads to increased glycation of proteins.

Insulin resistance is often found in people with visceral adiposity (i.e., a high degree of fatty tissue underneath the abdominal muscle wall - as distinct from subcutaneous adiposity or fat between the skin and the muscle wall), hypertension, hyperglycemia and dyslipidemia involving elevated triglycerides, small dense low-density lipoprotein (sdLDL) particles, and decreased HDL cholesterol levels.

Insulin resistance is also often associated with a hypercoagulable state (impaired fibrinolysis) and increased inflammatory cytokine levels.

Insulin resistance is also occasionally found in patients who use insulin. In this case, the production of antibodies against insulin leads to lower-than-expected falls of glucose levels (glycemia) after a given dose of insulin. With the development of human insulin and analogues in the 1980s and the decline in the use of animal insulins (e.g., pork, beef), this type of insulin resistance has become very uncommon.

Investigation

Fasting Insulin Levels
A fasting serum insulin level of greater than the upper limit of normal for the assay used (approximately 60pmol/L) is considered evidence of insulin resistance.

Glucose tolerance testing (GTT)
During a glucose tolerance test, which may be used to diagnose diabetes mellitus, a fasted patient takes a 75 gram oral dose of glucose. Blood glucose levels are then measured over the following 2 hours.

Interpretation is based on WHO guidelines, but glycemia greater than or equal to 11.1mmol/L at 2 hours or greater than or equal to 7.0mmol/L fasting is diagnostic for diabetes mellitus.

OGTT can be normal or mildly abnormal in simple insulin resistance. Often, there are raised glucose levels in the early measurements, reflecting the loss of a postprandial (after the meal) peak in insulin production. Extension of the testing (for several more hours) may reveal a hypoglycemic "dip", which is a result of an overshoot in insulin production after the failure of the physiologic postprandial insulin response.

Measuring Insulin Resistance
Hyperinsulinemic euglycemic clamp

The gold standard for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp," so called because it measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. The test is rarely performed in clinical care, but is used in medical research - for example, to assess the effects of different medications. The rate of glucose infusion is commonly referred to in diabetes literature as the GINF value.

The procedure takes about 2 hours. Through a peripheral vein, insulin is infused at 10-120 mU per m2 per minute. In order to compensate for the insulin infusion, glucose 20% is infused to maintain blood sugar levels between 5 and 5.5 mmol/l. The rate of glucose infusion is determined by checking the blood sugar levels every 5-10 minutes. Low dose insulin infusions are more useful for assessing the response of the liver whereas high dose insulin infusions are useful for assessing peripheral (i.e. muscle and fat) insulin action.

The rate of glucose infusion during the last 30 minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. Very low levels (4.0 mg/min or lower) indicate that the body is resistant to insulin action. Levels between 4.0 and 7.5 mg/min are not definitive and suggest "impaired glucose tolerance," an early sign of insulin resistance.

This basic technique can be significantly enhanced by the use of glucose tracers. Glucose can be labeled with either stable or radioactive atoms. Commonly used tracers are 3-3H glucose (radioactive), 6,6 2H-glucose (stable) and 1-13C Glucose (stable). Prior to beginning the hyperinsulinemic period, a 3h tracer infusion enables one to determine the basal rate of glucose production. During the clamp, the plasma tracer concentrations enable the calculation of whole body insulin stimulated glucose metabolism as well as the production of glucose by the body (i.e. endogenous glucose production).

Modified Insulin Suppression Test

Another measure of insulin resistance is the modified insulin suppression test developed by Gerald Reaven at Stanford University. The test correlates well with the euglycemic clamp with less operator-dependent error. This test has been used to advance the large body of research relating to the metabolic syndrome.

Patients initially receive 25mcg of sandostatin in 5ml of normal saline over 3-5 min IV as an initial bolus and then will be infused continuously with an intravenous infusion of somatostatin (0.27microgm/m2/min) to suppress endogenous insulin and glucose secretion. Insulin and 20% glucose is then infused at rates of 32 and 267mg/m2/min, respectively. Blood glucose is checked at zero, 30, 60, 90 and 120 minutes and then every 10 minutes for the last 1/2 hour of the test. These last 4 values are averaged to determine the steady state plasma glucose level. Subjects with an SSPG greater than 150mg/dl are considered to be insulin resistant.

Alternatives
Given the complicated nature of the "clamp" technique (and the potential dangers of hypoglycemia in some patients), alternatives have been sought to simplify the measurement of insulin resistance. The first was the Homeostatic Model Assessment (HOMA), and a more recent method is the QUICKI (quantitative insulin sensitivity check index). Both employ fasting insulin and glucose levels to calculate insulin resistance, and both correllate reasonably with the results of clamping studies. Wallace et al point out that QUICKI is the logarithm of the value from one of the HOMA equations.

Causes of insulin resistance
The cause of the vast majority of cases of insulin resistance remains unknown. However, insulin resistance might be caused by a high carbohydrate diet. [NIRC ED: While technically correct in the absence of proof from replicable scientific studies, one factor is highly implicated by epidemiological evidence: insulin resistance is coded in the genetics of about 10% of the population. This is inferred from the genetic risk inherent in indisputable family patterns of diabetes and heart disease occurrence, two of insulin resistance's bad outcomes. Further, there is scientific evidence that insulin resistance is probably triggered, and certainly enhanced, by excess weight.] Some physicians also believe that glucosamine (often prescribed for joint problems) may cause insulin resistance.

Associated Conditions
Several associated conditions include

Abnormally Sedentary Lifestyle, whether the result of the effects of aging on the body or lack of physical exercise (both of which can also produce obesity)
Haemochromatosis
Polycystic ovarian syndrome (PCOS)
Hypercortisolism (e.g. steroid use or Cushing's disease)
Drugs (e.g. rifampicin, isoniazid, olanzapine, risperidone, progestogens, many antiretrovirals, possibly alcohol, methadone)
Genetic causes
Insulin receptor mutations (Donohue Syndrome)
LMNA mutations (Familial Partial Lipodystrophy)

Therapy
The primary treatment for insulin resistance is exercise and weight loss. In some individuals, a low glycemic index or a low carbohydrate diet may also help. Fasting might also help. Both metformin and the thiazolidinediones improve insulin resistance, but are only approved therapies for type 2 diabetes, not insulin resistance, per se. [NIRC ED: Nevertheless, metformin, the 8th most often prescribed drug in the US, is often prescribed for pre-diabetes and insulin resistance, despite FDA instructions.] By contrast, growth hormone replacement therapy may be associated with increased insulin resistance.

The Diabetes Prevention Program showed that exercise and diet were nearly twice as effective as metformin at reducing the risk of progressing to type 2 diabetes.

Some types of Monounsaturated fatty acids and saturated fats appear to promote insulin resistance, whereas some types of polyunsaturated fatty acids (omega 3) can increase insulin sensitivity.

There are scientific studies showing that chromium picolinate can increase insulin sensitivity, especially in type 2 diabetics, but other studies show no effect. The results are controversial.

Naturopathic approaches to insulin resistance have been advocated including supplementation of vanadium, bitter melon (momordica) and Gymnema sylvestre.

History
The concept that insulin resistance may be the underlying cause of diabetes mellitus type 2 was first advanced by Sir Harold Percival Himsworth of the University College Hospital Medical Center in London in 1936.

Insulin Resitance

Intellix MO150 System Monitors Medium

A heart rate monitor is a device that allows a user to measure his or her heart rate in real time. It usually consists of two elements: a chest strap transmitter and a wrist receiver (which usually doubles as a watch). Strapless heart rate monitors are available as well, but lack some of the functionality of the original design. Advanced models additionally measure heart rate variability to assess a user's fitness.

The heart rate monitor was invented by the Australian physicist, Robert Treffene[citation needed]. He appeared on the television show The New Inventors with his device, which was made with swimmers in mind.

The first EKG accurate wireless heart rate monitor was invented by Polar Electro in 1977 as a training tool for the Finnish National Cross Country Ski Team. The concept of "intensity training" by heart rate swept the athletic world in the eighties. By the 1990's individuals were looking to heart rate monitors not only for performance training needs, but also for achieving everyday fitness goals. Today, the same concept of heart rate training is being used by world-class athletes as well as everyday people.

The chest strap has electrodes in contact with the skin to monitor the electrical voltages in the heart (see electrocardiography for more details). When a heart beat is detected a radio signal is sent out which the receiver uses to determine the current heart rate. More expensive monitors send a unique coded signal from the chest strap, and this prevents a user's wrist receiver from receiving signals from other nearby transmitters ("cross-talk.")

There are a wide number of receiver designs, with all sorts of advanced features. These include average heart rate over exercise period, time in a specific heart rate zone, calories burned, and detailed logging that can be downloaded to a computer.

Intellix MO150 System Monitors Medium

Eye Surgry

Eye surgery, also known as ophthalmic surgery or ocular surgery, is surgery performed on the eye or its adnexa, typically by an ophthalmologist. Although most eye surgery can be performed by an experienced general ophthalmologist, more complex procedures are usually done by one who is fellowship trained.

Preparation and precautions
The eye is a delicate organ, requiring extreme care before, during and after a surgical procedure. An expert ophthalmologist must identify the need for specific procedure and be responsible for conducting the procedure safely. Many university programs allow patients to specify if they want to be operated upon by the consultant or the resident / fellow.

Proper anesthesia is a must for any eye surgery. Local anesthesia is most commonly used. Retrobulbar and peribulbar techniques for infiltrating the local area surrounding the eye muscle cone are used to immobilize the extraocular muscles and eliminate pain sensation. Topical anesthesia using lidocaine topical gel is preferred for quick procedures. In topical anesthesia, patient cooperation is a must for a smooth procedure. General anesthesia is recommended for children, traumatic eye injuries, major orbitotomies and for apprehensive patients. Cardiovascular monitoring is preferable in local anesthesia and is mandatory in general anesthesia. Proper sterile precautions are taken to prepare the area for surgery, including use of antiseptics like povidone-iodine. Sterile drapes, gowns and gloves are a must. A plastic sheet with a receptacle helps collect the fluids during phacoemulsification. An eye speculum is inserted to keep the eyes wide open. For anxious patients, supplementation with a facial nerve block using lidocaine and bupivacaine is recommended.

Laser eye surgery
Although the terms Laser Eye Surgery and Refractive surgery are commonly used as if they were interchangeable, this is not the case. Lasers may be used to treat nonrefractive conditions (e.g. to seal a retinal tear), while radial keratotomy is an example of refractive surgery without the use of a laser.

Cataract surgery
Cataract surgery, using a temporal approach phacoemulsification probe (in right hand) and "chopper"(in left hand) being done under operating microscope at a Navy medical centerA cataract is an opacification or cloudiness of the eye's crystalline lens due to aging, disease, or trauma that typically prevents light from forming a clear image on the retina. If visual loss is significant, surgical removal of the lens may be warranted, with lost optical power usually replaced with a plastic intraocular lens (IOL). Due to the high prevalence of cataracts, cataract extraction is the most common eye surgery.

Glaucoma surgery
Glaucoma is a group of diseases affecting the optic nerve that results in vision loss and is frequently characterized by raised intraocular pressure (IOP). There are many types of glaucoma surgery, and variations or combinations of those types, that facilitate the escape of excess aqueous humor from the eye to lower intraocular pressure, and a few that lower IOP by decreasing the production of aqueous.

Canaloplasty
Canaloplasty is an advanced, nonpenetrating procedure designed to enhance and restore the eye’s natural drainage system to provide sustained reduction of IOP. Canaloplasty utilizes breakthrough microcatheter technology in a simple and minimally invasive procedure. To perform a canaloplasty, a doctor will create a tiny incision to gain access to a canal in the eye. A microcatheter will circumnavigate the canal around the iris, enlarging the main drainage channel and its smaller collector channels through the injection of a sterile, gel-like material called viscoelastic. The catheter is then removed and a suture is placed within the canal and tightened. By opening the canal, the pressure inside the eye will be relieved.

Eye Surgry

Argentina Diabetes Reserch

Diabetes mellitus (IPA pronunciation: [daɪəˈbitiz], sometimes [ˌdaɪəˈbitəs]) is a metabolic disorder characterized by hyperglycemia (high blood sugar) and other signs, as distinct from a single illness or condition. The World Health Organization recognizes three main forms of diabetes: type 1, type 2, and gestational diabetes (occurring during pregnancy),[1] which have similar signs, symptoms, and consequences, but different causes and population distributions. Ultimately, all forms are due to the beta cells of the pancreas being unable to produce sufficient insulin to prevent hyperglycemia.[2] Type 1 is usually due to autoimmune destruction of the pancreatic beta cells which produce insulin. Type 2 is characterized by tissue-wide insulin resistance and varies widely; it sometimes progresses to loss of beta cell function. Gestational diabetes is similar to type 2 diabetes, in that it involves insulin resistance; the hormones of pregnancy cause insulin resistance in those women genetically predisposed to developing this condition.

Types 1 and 2 are incurable chronic conditions, but have been treatable since insulin became medically available in 1921, and today are usually managed with a combination of dietary treatment, tablets (in type 2) and, frequently, insulin supplementation. Gestational diabetes typically resolves with delivery.

Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease (doubled risk), chronic renal failure (diabetic nephropathy is the main cause of dialysis in developed world adults), retinal damage (which can lead to blindness and is the most significant cause of adult blindness in the non-elderly in the developed world), nerve damage (of several kinds), and microvascular damage, which may cause erectile dysfunction (impotence) and poor healing. Poor healing of wounds, particularly of the feet, can lead to gangrene which can require amputation — the leading cause of non-traumatic amputation in adults in the developed world. Adequate treatment of diabetes, as well as increased emphasis on blood pressure control and lifestyle factors (such as not smoking and keeping a healthy body weight), may improve the risk profile of most aforementioned complications.

Diabetes mellitus
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Types of Diabetes
Diabetes mellitus type 1
Diabetes mellitus type 2
Gestational diabetes
Pre-diabetes:
Impaired fasting glycaemia
Impaired glucose tolerance

Disease Management
Diabetes management:
•Diabetic diet
•Anti-diabetic drugs
•Conventional insulinotherapy
•Intensive insulinotherapy
Other Concerns
Cardiovascular disease
Diabetic comas:
•Diabetic hypoglycemia
•Diabetic ketoacidosis
•Nonketotic hyperosmolar

Diabetic myonecrosis
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy

Diabetes and pregnancy

Blood tests
Blood sugar
Fructosamine
Glucose tolerance test
Glycosylated hemoglobin

Terminology
The term diabetes was coined by Aretaeus of Cappadocia, diabaínein that literally means "passing through," or "siphon", a reference to one of diabetes' major symptoms—excessive urine production. In 1675 Thomas Willis added the word mellitus to the disease, a word from Latin meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, and Indians. In 1776 Matthew Dobson confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.

The ancient Indians tested for diabetes by observing whether ants were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs which mean "sugar urine disease".

Diabetes, without qualification, usually refers to diabetes mellitus, but there are several rarer conditions also named diabetes. The most common of these is diabetes insipidus (insipidus meaning "without taste" in Latin) in which the urine is not sweet; it can be caused by either kidney (nephrogenic DI) or pituitary gland (central DI) damage.

The term "type 1 diabetes" has universally replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes. "Type 2 diabetes" has also replaced several older terms, including adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes. Beyond these numbers, there is no agreed standard. Various sources have defined "type 3 diabetes" as, among others:

Gestational diabetes
Insulin-resistant type 1 diabetes (or "double diabetes")
Type 2 diabetes which has progressed to require injected insulin.
Latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes)

History
Although diabetes has been recognized since antiquity, and treatments of various efficacy have been known in various regions since the Middle Ages, and in legend for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900. The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards. In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.

The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not further clarified until 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs. Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases at the University of Toronto. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director MacLeod received the Nobel Prize in Physiology or Medicine in 1923; both shared their Prize money with others in the team who were not recognized, in particular Best and Collip. Banting and Best made the patent available without charge and did not attempt to control commercial production. Insulin production and therapy rapidly spread around the world, largely as a result of this decision.

The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir Harold Percival (Harry) Himsworth, and published in January 1936.

Despite the availability of treatment, diabetes has remained a major cause of death. For instance, statistics reveal that the cause-specific mortality rate during 1927 amounted to about 47.7 per 100,000 population in Malta.

Other landmark discoveries include:

identification of the first of the sulfonylureas in 1942
the determination of the amino acid order of insulin (by Sir Frederick Sanger, for which he received a Nobel Prize)
the radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)
the three-dimensional structure of insulin
Dr Gerald Reaven's identification of the constellation of symptoms now called metabolic syndrome in 1988
Demonstration that intensive glycemic control in type 1 diabetes reduces chronic side effects more as glucose levels approach 'normal' in a large longitudinal study, and also in type 2 diabetics in other large studies
identification of the first thiazolidinedione as an effective insulin sensitizer during the 1990s

Causes and types

Glucose metabolism

Much of the carbohydrate in food is converted within a few hours to the monosaccharide glucose, the principal carbohydrate found in blood. Some carbohydrates are not converted. Notable examples include fruit sugar (fructose) that is usable as cellular fuel, but it is not converted to glucose and does not participate in the insulin / glucose metabolic regulatory mechanism; additionally, the carbohydrate cellulose (though it is actually many glucose molecules in long chains) is not converted to glucose, as humans and many animals have no digestive pathway capable of handling cellulose. Insulin is released into the blood by beta cells (β-cells) in the pancreas in response to rising levels of blood glucose (e.g., after a meal). Insulin enables most body cells (about 2/3 is the usual estimate, including muscle cells and adipose tissue) to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Insulin is also the principal control signal for conversion of glucose (the basic sugar used for fuel) to glycogen for internal storage in liver and muscle cells. Reduced glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall, although only glucose thus recovered by the liver re-enters the bloodstream as muscle cells lack the necessary export mechanism.

Higher insulin levels increase many anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. Insulin is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, it is the trigger for entering or leaving ketosis (ie, the fat burning metabolic phase).

If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, glucose will not be handled properly by body cells (about ⅔ require it) or stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.

Argentina Diabetes Reserch

Blue Balls and Erectile Dysfunction

Blue balls is a slang term for a temporary fluid congestion in the testicles and prostate region caused by prolonged sexual arousal in the human male. It is often accompanied by a cramp-like ache of prostatic congestion and pain/tenderness of the testes. While the term is usually applied to men, the female homologue is usually referred to by the more general term "pelvic congestion," or "pink ovaries."

Cause
The cause is the prolonged sexual stimulation of the erect penis (intentional or unintentional), either by direct or indirect contact, that does not result in orgasm and ejaculation. This can, in some circumstances, be a consensual sexual act as part of erotic sexual denial.

During arousal in a sexually mature male, the parasympathetic nervous system increases its inputs to the genital tissues, resulting in increased blood flow to the testicles and prostate areas. As this happens, other fluid outflow muscles constrict, causing less bodily fluid to leave the area than enter, ensuring a high enough regional blood pressure to allow a sustained erection for penetration during sexual intercourse.

If orgasm is not achieved, blood and lymphatic fluid tend to pool, and the blood becomes oxygen-deprived. The technical term for this is vasocongestion. It can be extremely painful, like a hit to the testicles, but from the inside.

Some men may deprive themselves of an orgasm purposely, to prolong sexual activity, etc. Their sexual partner may also request that they refrain from ejaculation for a longer period to increase their duration of sex (or mutual satisfaction of both partners). If this is the case, massaging the testicles or using a vibrator on the testicles during the prolonged sexual activity may prevent the blood from pooling and actually prevent or decrease the severity of blue balls. Some men have also learned and practiced methods prolonging ejaculation for a stronger and more satisfying orgasm.

Men with priapism or orchalgia may experience an extreme, prolonged form of blue balls, which may require medical attention.

Treatment
The easiest way to relieve the symptoms of blue balls is through an orgasm [citation needed]. The resultant ejaculation jump-starts the sympathetic nervous system, which increases blood flow through the penis area, dissipating the fluid buildup. Even without orgasm, the symptoms of blue balls usually subside within an hour of onset, but they can also last much longer, up to 3 hours. While well known in folklore, there was scant information in the medical literature until an article by Chalett and Nerenberg in Pediatrics 2000 which found little formal data regarding the condition but concluded that "the treatment is sexual release, or perhaps straining to move a very heavy object — in essence doing a Valsalva maneuver."[1] Simply lying down can also sometimes help the pain associated with blue balls.

One folk remedy for blue balls is the cold shower. Putting cold substances (such as ice) on the crotch region significantly helps. One source [2] states that "the cool water of the shower would stimulate new warm blood to the scrotum," but local cooling might instead work by causing arterioles in the scrotal skin to constrict, thus decreasing blood flow to those tissues and allowing fluid to leave the congested areas. Also, physical exercise like walking or climbing stairs may ease the engorgement. Sometimes pseudoephedrine can help quicken the process; however, analgesics do not generally help as they do not involve prostaglandins.

The most common treatment is masturbating until climax.

One should attempt to return blood flow by any possible means. If pain doesn’t go away within a reasonable amount of time, one should seek medical attention to ensure that no serious injuries are present.

In women
Women can also experience discomfort due to unrelieved vasocongestion as their pelvic area also become engorged with blood during sexual arousal. They can experience pelvic heaviness and aching if they do not reach orgasm. The general term pelvic congestion refers to such pain as it occurs in either sex.

Blue Balls and Erectile Dysfunction