Taken as a class, long-term survival rates in BAC tend to be higher than those of other forms of NSCLC. BAC generally carries a better prognosis than other forms of NSCLC, which can be partially attributed to localized presentation of the disease. Though other factors might play a role. Prognosis of BAC depends upon the histological subtype and extent at presentation but are generally same as other NSCLC.

Recent research has made it clear that nonmucinous and mucinous BACs are very different types of lung cancer. Mucinous BAC is much more likely to present with multiple unilateral tumors and/or in a unilateral or bilateral pneumonic form than nonmucinous BAC. The overall prognosis for patients with mucinous BAC is significantly worse than patients with nonmucinous BAC.

Although data are scarce, some studies suggest that survival rates are even lower in the mixed mucinous/non-mucinous variant than in the monophasic forms.

In non-mucinous BAC, neither Clara cell nor Type II pneumocyte differentiation appears to affect survival or prognosis.

When BAC recurs after surgery, the recurrences are local in about three-quarters of cases, a rate higher than other forms of NSCLC, which tends to recur distantly.

Carcinoma "in situ" is, by definition, a localized phenomenon, with no potential for metastasis unless it progresses into cancer. Therefore, its removal eliminates the risk of subsequent progression into a life-threatening condition.

Some forms of CIS (e.g., colon polyps and polypoid tumours of the bladder) can be removed using an endoscope, without conventional surgical resection. Dysplasia of the uterine cervix is removed by excision (cutting it out) or by burning with a laser. Bowen's disease of the skin is removed by excision. Other forms require major surgery, the best known being intraductal carcinoma of the breast (also treated with radiotherapy). One of the most dangerous forms of CIS is the "pneumonic form" of BAC of the lung, which can require extensive surgical removal of large parts of the lung. When too large, it often cannot be completely removed, with eventual disease progression and death of the patient.

Carcinoma "in situ (CIS), also known as in situ" neoplasm, is a group of abnormal cells. While they are a form of neoplasm there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, breast). Some authors do not classify them as cancer, however, recognizing that they can potentially become cancer. Others classify certain types as a non-invasive form of cancer. The term "pre-cancer" has also been used.

These abnormal cells grow in their normal place, thus ""in situ"" (from Latin for "in its place"). For example, carcinoma "in situ" of the skin, also called Bowen's disease, is the accumulation of dysplastic epidermal cells within the epidermis only, that has failed to penetrate into the deeper dermis. For this reason, CIS will usually not form a tumor. Rather, the lesion is flat (in the skin, cervix, etc.) or follows the existing architecture of the organ (in the breast, lung, etc.). Exceptions include CIS of the colon (polyps), the bladder (preinvasive papillary cancer), or the breast (ductal carcinoma "in situ" or lobular carcinoma "in situ").

Many forms of CIS have a high probability of progression into cancer, and therefore removal may be recommended; however, progression of CIS is known to be highly variable and not all CIS becomes invasive cancer.

In the TNM classification, carcinoma "in situ" is reported as TisN0M0 (stage 0).

Research on the risk for developing schizophrenia in Ashkenazi Jews and other populations showed that 3q29 microdeletion syndrome leads to a significant higher rate of schizophrenia.

3q29 microdeletion syndrome is a rare genetic disorder resulting from the deletion of a segment of chromosome 3. This syndrome was first described in 2005.

Socioeconomic correlates of health have been well established in the study of heart disease, lung cancer, and diabetes. Many of the explanations for the increased incidence of these conditions in people with lower socioeconomic status (SES) suggest they are the result of poor diet, low levels of exercise, dangerous jobs (exposure to toxins etc.) and increased levels of smoking and alcohol intake in socially deprived populations. Hesdorffer et al. found that low SES, indexed by poor education and lack of home ownership, was a risk factor for epilepsy in adults, but not in children in a population study. Low socioeconomic status may have a cumulative effect for the risk of developing epilepsy over a lifetime.

Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (AD-RVCL) (previously known also as Cerebroretinal Vasculopathy, CRV, or Hereditary Vascular Retinopathy, HVR or Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke, HERNS) is an inherited condition resulting from a frameshift mutation to the TREX1 gene. This genetically inherited condition affects the retina and the white matter of the central nervous system, resulting in vision loss, lacunar strokes and ultimately dementia. Symptoms commonly begin in the early to mid-forties, and treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause. The overall prognosis is poor, and death can sometimes occur within 10 years of the first symptoms appearing.

AD-RVCL (CRV) Acronym

Autosomal Dominance (genetics) means only one copy of the gene is necessary for the symptoms to manifest themselves.

Retinal Vasculopathy means a disorder that is associated with a disease of the blood vessels in the retina.

Cerebral means having to do with the brain.

Leukodystrophy means a degeneration of the white matter of the brain.

Pathogenesis

The main pathologic process centers on small blood vessels that prematurely “drop out” and disappear. The retina of the eye and white matter of the brain are the most sensitive to this pathologic process. Over a five to ten-year period, this vasculopathy (blood vessel pathology) results in vision loss and destructive brain lesions with neurologic deficits and death.

Most recently, AD-RVCL (CRV) has been renamed. The new name is CHARIOT which stands for Cerebral Hereditary Angiopathy with vascular Retinopathy and Impaired Organ function caused by TREX1 mutations.

Treatment

Currently, there is no therapy to prevent the blood vessel deterioration.

About TREX1

The official name of the TREX1 gene is “three prime repair exonuclease 1.” The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes.

Changes (mutations) to the TREX1 gene can result in a range of conditions one of which is AD-RVCL. The mutations to the TREX1 gene are believed to prevent the production of the 3-prime repair exonuclease 1 enzyme. Researchers suggest that the absence of this enzyme may result in an accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules may be mistaken by cells for those of viral invaders, triggering immune system reactions that result in the symptoms of AD-RVCL.

Mutations in the TREX1 gene have also been identified in people with other disorders involving the immune system. These disorders include a chronic inflammatory disease called systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin.

The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644

The immune system.

- The immune system is composed of white blood cells or leukocytes.

- There are 5 different types of leukocytes.

- Combined, the 5 different leukocytes represent the 2 types of immune systems (The general or innate immune system and the adaptive or acquired immune system).

- The adaptive immune system is composed of two types of cells (B-cells which release antibodies and T-cells which destroy abnormal and cancerous cells).

How the immune system becomes part of the condition.

During mitosis, tiny fragments of “scrap” single strand DNA naturally occur inside the cell. Enzymes find and destroy the “scrap” DNA. The TREX1 gene provides the information necessary to create the enzyme that destroys this single strand “scrap” DNA. A mutation in the TREX1 gene causes the enzyme that would destroy the single strand DNA to be less than completely effective. The less than completely effective nature of the enzyme allows “scrap” single strand DNA to build up in the cell. The buildup of “scrap” single strand DNA alerts the immune system that the cell is abnormal.

The abnormality of the cells with the high concentration of “scrap” DNA triggers a T-cell response and the abnormal cells are destroyed. Because the TREX1 gene is identical in all of the cells in the body the ineffective enzyme allows the accumulation of “scrap” single strand DNA in all of the cells in the body. Eventually, the immune system has destroyed enough of the cells in the walls of the blood vessels that the capillaries burst open. The capillary bursting happens throughout the body but is most recognizable when it happens in the eyes and brain because these are the two places where capillary bursting has the most pronounced effect.

Characteristics of AD-RVCL

- No recognizable symptoms until after age 40.

- No environmental toxins have been found to be attributable to the condition.

- The condition is primarily localized to the brain and eyes.

- Optically correctable, but continuous, deterioration of visual acuity due to extensive multifocal microvascular abnormalities and retinal neovascularization leading, ultimately, to a loss of vision.

- Elevated levels of alkaline phosphatase.

- Subtle vascular changes in the retina resembling telangiectasia (spider veins) in the parafovea circulation.

- Bilateral capillary occlusions involving the perifovea vessels as well as other isolated foci of occlusion in the posterior pole of the retina.

- Headaches due to papilledema.

- Mental confusion, loss of cognitive function, loss of memory, slowing of speech and hemiparesis due to “firm masses” and white, granular, firm lesions in the brain.

- Jacksonian seizures and grand mal seizure disorder.

- Progressive neurologic deterioration unresponsive to systemic corticosteroid therapy.

- Discrete, often confluent, foci of coagulation necrosis in the cerebral white matter with intermittent findings of fine calcium deposition within the necrotic foci.

- Vasculopathic changes involving both arteries and veins of medium and small caliber present in the cerebral white matter.

- Fibroid necrosis of vessel walls with extravasation of fibrinoid material into adjacent parenchyma present in both necrotic and non-necrotic tissue.

- Obliterative fibrosis in all the layers of many vessel walls.

- Parivascular, adventitial fibrosis with limited intimal thickening.

Conditions with similar symptoms that AD-RVCL can be misdiagnosed as:

- Brain tumors

- Diabetes

- Macular degeneration

- Telangiectasia (Spider veins)

- Hemiparesis (Stroke)

- Glaucoma

- Hypertension (high blood pressure)

- Systemic Lupus Erythematosus (SLE (same original pathogenic gene, but definitely a different disease because of a different mutation in TREX1))

- Polyarteritis nodosa

- Granulomatosis with polyangiitis

- Behçet's disease

- Lymphomatoid granulomatosis

- Vasculitis

Clinical Associations

- Raynaud's phenomenon

- Anemia

- Hypertension

- Normocytic anemia

- Normochromic anemia

- Gastrointestinal bleeding or telangiectasias

- Elevated alkaline phosphatase

Definitions

- Coagulation necrosis

- Endothelium

- Fibrinoid

- Fibrinoid necrosis

- Frameshift mutation

- Hemiparesis

- Jacksonian seizure

- Necrotic

- Necrosis

- Papilledema

- Perivascular

- Retinopathy

- Telangiectasia

- Vasculopathy

- Vascular

What AD-RVCL is not:

- Infection

- Cancer

- Diabetes

- Glaucoma

- Hypertension

- A neurological disorder

- Muscular dystrophy

- Systemic Lupus Erythematosis (SLE)

- Vasculitis

Things that have been tried but turned out to be ineffective or even make things worse:

- Antibiotics

- Steroids

- X-Ray therapy

- Immunosuppression

History of AD-RVCL (CRV)

- 1985 – 1988: CRV (Cerebral Retinal Vasculopathy) was discovered by John P. Atkinson, MD at Washington University School of Medicine in St. Louis, MO

- 1988: 10 families worldwide were identified as having CRV

- 1991: Related disease reported, HERNS (Hereditary Endiotheliopathy with Retinopathy, Nephropathy and Stroke – UCLA

- 1998: Related disease reported, HRV (Hereditary Retinal Vasculopathy) – Leiden University, Netherlands

- 2001: Localized to Chromosome 3.

- 2007: The specific genetic defect in all of these families was discovered in a single gene called TREX1

- 2008: Name changed to AD-RVCL Autosomal Dominant-Retinal Vasculopathy with Cerebral Leukodystrophy

- 2009: Testing for the disease available to persons 21 and older

- 2011: 20 families worldwide were identified as having CRV

- 2012: Obtained mouse models for further research and to test therapeutic agents

There are no currently known causes of this disease. There are studies currently proposing several theories of the causes which include inflammation of the adipose tissue, nervous system malfunction and endocrine malfunction. None of the theories that are currently proposed have been found viable. Since little is known about Dercum's disease, there are currently no known modes of prevention. Some hypotheses state that maintaining a healthy weight and diet can help prevent Dercum's although it has not been proven.

Dercum's disease can affect people of any gender and of any age. The majority of cases are linked to women between the ages of 45 and 60, who are overweight and postmenopausal. Due to the difficulty of diagnosis of this disease, many cases are underreported or misdiagnosed and it is difficult to understand what part of the population is affected by it the most.

There were also observations that hippocampal sclerosis was associated with vascular risk factors. Hippocampal sclerosis cases were more likely than Alzheimer's disease to have had a history of stroke (56% vs. 25%) or hypertension (56% vs. 40%), evidence of small vessel disease (25% vs. 6%), but less likely to have had diabetes mellitus (0% vs. 22%).

Infants who are colicky do just as well as their non colicky peers with respect to temperament at one year of age.

A complex mixture of genetic and environmental factors influences the risk of the development of alcoholism. Genes that influence the metabolism of alcohol also influence the risk of alcoholism, and may be indicated by a family history of alcoholism. One paper has found that alcohol use at an early age may influence the expression of genes which increase the risk of alcohol dependence. Individuals who have a genetic disposition to alcoholism are also more likely to begin drinking at an earlier age than average. Also, a younger age of onset of drinking is associated with an increased risk of the development of alcoholism, and about 40 percent of alcoholics will drink excessively by their late adolescence. It is not entirely clear whether this association is causal, and some researchers have been known to disagree with this view.

Severe childhood trauma is also associated with a general increase in the risk of drug dependency. Lack of peer and family support is associated with an increased risk of alcoholism developing. Genetics and adolescence are associated with an increased sensitivity to the neurotoxic effects of chronic alcohol abuse. Cortical degeneration due to the neurotoxic effects increases impulsive behaviour, which may contribute to the development, persistence and severity of alcohol use disorders. There is evidence that with abstinence, there is a reversal of at least some of the alcohol induced central nervous system damage. The use of cannabis was associated with later problems with alcohol use. Alcohol use was associated with an increased probability of later use of tobacco, cannabis, and other illegal drugs.

The tolerance to alcohol is not equally distributed throughout the world's population, and genetics of alcohol dehydrogenase indicate resistance has arisen independently in different cultures. In North America, Native Americans have the highest probability of developing alcoholism compared to Europeans and Asians.

Higher body masses and the prevalence of high levels of alcohol dehydrogenase in an individual increase alcohol tolerance.

Not all differences in tolerance can be traced to biochemistry. Differences in tolerance levels are also influenced by socio-economic and cultural difference including diet, average body weight and patterns of consumption.

An estimated one out of twenty people have an alcohol flush reaction. It is not in any way an indicator for the drunkenness of an individual. It is colloquially known as "face flush", a condition where the body metabolizes alcohol nearly 100-times less efficiently into acetaldehyde, a toxic metabolite. Flushing, or blushing, is associated with the erythema (reddening caused by dilation of capillaries) of the face, neck, and shoulder, after consumption of alcohol.

Although it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures are resistant to treatment. Studies do not support the widely held belief that seizure frequency early in life in patients who have SWS is a prognostic indicator.

Alcohol is the most available, widely consumed, and widely abused recreational drug. Beer alone is the world's most widely consumed alcoholic beverage; it is the third-most popular drink overall, after water and tea. It is thought by some to be the oldest fermented beverage.

Binge drinking is a more important factor rather than average alcohol intake, with regard to the severity of alcohol induced damage to the fetus. Alcohol has definite long-term adverse effects on the fetus, in particular impaired attentional skills and may lead to psychiatric disorders when the child grows up. Approximately one in five nonpregnant women binge-drinks and one in 25 pregnant women binge-drinks. Binge drinking during pregnancy is associated with fetal alcohol syndrome, alcohol-related birth defects as well as alcohol-related neurodevelopmental disorders. The affected children after birth can suffer mental retardation and problems with learning, memory, attention, problem solving and problems with mental health and social interactions. Deformities in facial features, skeletal and body organs as well as a smaller head circumference are also sometimes present in these children. Studies in sheep indicate that fetal neurotoxicity induced by alcohol may be due to acidaemia and hypercapnia. Binge drinking three or more times during pregnancy has been associated with an increased risk of stillbirth.

The cause of colic is generally unknown. Fewer than 5% of infants who cry excessively turn out to have an underlying organic disease, such as constipation, gastroesophageal reflux disease, lactose intolerance, anal fissures, subdural hematomas, or infantile migraine. Babies fed cow's milk have been shown to develop antibody responses to the bovine protein, causing colic. Studies performed showed conflicting evidence about the role of cow's milk allergy. While previously believed to be related to gas pains, this does not appear to be the case. Another theory holds that colic is related to hyperperistalsis of the digestive tube (increased level of activity of contraction and relaxation). The evidence that the use of anticholinergic agents improve colic symptoms supports this hypothesis.

Psychological and social factors have been proposed as a cause, but there is no evidence. Studies performed don't support the theory that maternal (or paternal) personality or anxiety causes colic, nor that it is a consequence of a difficult temperament of the baby, but families with colicky children may eventually develop anxiety, fatigue and problems with family functioning as a result. There is some evidence that cigarette smoke may increase the risk. It seems unrelated to breast or bottle feeding with rates similar in both groups. Reflux does not appear to be related to colic.

Adiposis dolorosa, also known as Dercum's disease or Anders disease, is a rare condition characterized by generalized obesity and fatty tumors in the adipose tissue. The tumors are normally painful and found in multiples on the extremities. The cause and mechanism of Dercum's disease remains unknown. Possible causes include nervous system dysfunction, mechanical pressure on nerves, adipose tissue dysfunction, and trauma.

Dercum's disease was first described at Jefferson Medical College by neurologist Francis Xavier Dercum in 1892.

Age of Death: Stillborn fetuses and infants putrefy slowly due to their sterility. Generally, younger people putrefy more quickly than older people.

Condition of the Body: A body with a greater fat percentage and less lean body mass will have a faster rate of putrefaction, as fat retains more heat and it carries a larger amount of fluid in the tissues.

Cause of Death: The cause of death has a direct relationship to putrefaction speed, with bodies that died from acute violence or accident generally putrefying slower than those that died from infectious diseases. Certain poisons, such as potassium cyanide or strychnine may also delay putrefaction, while chronic alcoholism will speed it.

External Injuries: Antemortem or postmortem injuries can speed putrefaction as injured areas can be more susceptible to invasion by bacteria.

Acute intoxication, such as binge drinking and alcoholism, are known potent risk factors for suicide. Binge drinking is also associated with an increased risk of unplanned sex, unprotected sex, unplanned pregnancies, and an increased risk of HIV infection. 10 percent of women and 19 percent of men have reported being assaulted as a result of alcohol. Males who drink more than 35 units of alcohol per week report being physically hurt as a result of alcohol, and 15 percent report physically hurting others as a result of their drinking. Almost 16 percent of binge drinkers report being taken advantage of sexually, and 8 percent report taking advantage of another person sexually as a result of alcohol within a 1-year period. Heavy drinkers cause approximately 183,000 rapes and sexual assaults, 197,000 robberies, 661,000 aggravated assaults, and 1.7 million simple assaults each year. Binge drinking has been associated with high odds of divorce, spousal abuse, and poor job performance. Binge drinking can cause adverse effects on the body including effects on blood homeostasis and its circadian variation, cardiac rhythm, ischaemic heart disease, blood pressure, white blood cell activity, female reproductive hormone levels as well as adverse effects on the fetus. There is also evidence from animal studies that binge drinking causes brain damage. Binge drinking has been associated with lower abdominal pain in women. Ketoacidosis can occur in individuals who chronically abuse alcohol and have a recent history of binge drinking. Alcohol affects brain development quite significantly especially during adolescence when the brain is still developing. The main lobes that are involved in decision making and complex thought processes are undergoing their final development phase during adolescence and binge drinking can negatively stunt the growth of these frontal lobes.

Auditory neuropathy spectrum disorder (ANSD) is a specific form of hearing loss defined by the presence of normal or near-normal otoacoustic emissions (OAEs) but the absence of normal middle ear reflexes and severely abnormal or completely absent auditory brainstem response (ABRs).

Individuals presenting with this recently recognised hearing loss appear to display sporadic windows of hearing and not. Very few (1 in 14) will go on to develop normal speech and language but with poor speech perception in background noise and in others, no speech perception and therefore language development is possible.

The condition was originally termed auditory neuropathy (AN) and in 2001 as Auditory Neuropathy / Auditory Dys-synchrony (AN/AD) (to include those cases where no true neuropathy was apparent). In 2008 at a meeting convened at Lake Como in Italy (Guidelines Development

Conference on the Identification and Management

of Infants with Auditory Neuropathy, International

Newborn Hearing Screening Conference, Como, Italy,

June 19–21, 2008), a group of leading authorities on the condition reached a consensus and renamed it as auditory neuropathy spectrum disorder.

The blood vessel formations associated with SWS start in the fetal stage. Around the sixth week of development, a network of nerves develops around the area that will become a baby’s head. Normally, this network goes away in the ninth week of development. In babies with SWS due to mutation of gene GNAQ, this network of nerves doesn’t go away. This reduces the amount of oxygen and blood flowing to the brain, which can affect brain tissue development.

Horizontal Gaze Nystagmus (HGN) testing is a common practice used by law enforcement in the United States in the identification of persons who are intoxicated or under the influence of a controlled substance. The key difference between recognizing PAN and horizontal gaze nystagmus is the position of the subject's head in relation to the body. PAN is identified when the head is tilted to one side or the other. In order for HGN to be properly identified, the head must be positioned in line with the spine. Because of this, if the head is tilted towards the side when an evaluation for HGN is given, PAN may be induced and give a "false positive" for HGN. Some defendants may claim or argue that the nystagmus observed by an officer was positional and not horizontal gaze.

Dietary causes account for about 12% of gout, and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. Other triggers include physical trauma and surgery.

Studies in the early 2000s found that other dietary factors are not relevant. Specifically, moderate consumption of purine-rich vegetables (e.g., beans, peas, lentils, and spinach) are not associated with gout. Neither is total consumption of protein. Alcohol consumption is strongly associated with an increased risk, with wine presenting somewhat less of a risk than beer and spirits.

The consumption of coffee, vitamin C, and dairy products, as well as physical fitness, appear to decrease the risk. This is believed to be partly due to their effect in reducing insulin resistance.

Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while prevalence is the total number of cases of the disease in the population at any given time.

Regarding incidence, cohort longitudinal studies (studies where a disease-free population is followed over the years) provide rates between 10 and 15 per thousand person–years for all dementias and 5–8 for AD, which means that half of new dementia cases each year are AD. Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every five years after the age of 65, the risk of acquiring the disease approximately doubles, increasing from 3 to as much as 69 per thousand person years. There are also sex differences in the incidence rates, women having a higher risk of developing AD particularly in the population older than 85. The risk of dying from Alzheimer's disease is 26% higher among the non-Hispanic white population than among the non-Hispanic black population, whereas the Hispanic population has a 30% lower risk than the non-Hispanic white population.

Prevalence of AD in populations is dependent upon different factors including incidence and survival. Since the incidence of AD increases with age, it is particularly important to include the mean age of the population of interest. In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65–74 age group, with the rate increasing to 19% in the 75–84 group and to 42% in the greater than 84 group. Prevalence rates in less developed regions are lower. The World Health Organization estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030. Other studies have reached similar conclusions. Another study estimated that in 2006, 0.40% of the world population (range 0.17–0.89%; absolute number , range ) were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by 2050.