Toluene toxicity refers to the harmful effects caused by toluene on the body

6-Pyruvoyltetrahydropterin synthase deficiency is an autosomal recessive disorder that causes malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency.

It belongs to the rare diseases. It is a recessive disorder that is accompanied by hyperphenylalaninemia. Commonly reported symptoms are initial truncal hypotonia, subsequent appendicular hypertonia, bradykinesia, cogwheel rigidity, generalized dystonia, and marked diurnal fluctuation. Other reported clinical features include difficulty in swallowing, oculogyric crises, somnolence, irritability, hyperthermia, and seizures. Chorea, athetosis, hypersalivation, rash with eczema, and sudden death have also been reported. Patients with mild phenotypes may deteriorate if given folate antagonists such as methotrexate, which can interfere with a salvage pathway through which dihydrobiopterin is converted into tetrahydrobiopterin via dihydrofolate reductase. Treatment options include substitution with neurotransmitter precursors (levodopa, 5-hydroxytryptophan), monoamine oxidase inhibitors, and tetrahydrobiopterin. Response to treatment is variable and the long-term and functional outcome is unknown. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation and outcome of these diseases their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies a patient registry was established by the noncommercial International Working Group on Neurotransmitter Related Disorders (iNTD).

Patients affected by ADT tachyphylaxis experience a noticeably sudden progressive decrease in response to SSRIs. The reported rates of this condition vary from 9% to 33% of SSRI users, and the majority of those affected are less responsive to subsequent treatments. In most observational studies, these individuals suffer a recurrence or relapse of depression without changing the previously effective dose.

ADT tachyphylaxis incorporates drug sensitivity as a potential causal factor for the decreased response. However, tolerance provides a more accurate explanation. While the exact cause of ADT tachyphylaxis in individual cases is unknown, drug tolerance is a more comprehensive model, as it includes mechanisms of pharmacodynamic tolerance, metabolic tolerance, and others.

Drug-induced angioedema is a known complication of the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists (ARBs), and Angiotensin-Neprilysin Inhibitor LCZ969. The angioedema appears to be dose dependent as it may resolve with decreased dose.

Some common ACE Inhibitors are:

- Benazepril (Lotensin)

- Captopril (Capoten)

- Enalapril (Vasotec)

- Lisinopril (Prinivil, Zestril)

- Ramipril (Altace)

Some common ARBs are:

- Candesartan (Atacand)

- Losartan (Cozaar)

- Olmesartan (Benicar)

- Valsartan (Diovan)

Angioedema presents itself as an abrupt onset of non-pitting, non-itchy swelling that involves the mucosal layers. Some common locations of angioedema are the face, particularly the lips and around the eyes, hands and feet, and genitalia. A rare, yet serious complication is one inside the abdomen, the symptom usually being severe stomach upset, which is much less obvious than the other locations.

The chance of drug-induced angioedema is extremely uncommon, however, as studies show incidence of less than 1%. The reason this adverse effect may occur is due to the build-up of bradykinin, a vasodilator. This causes blood vessels to dilate and allow for fluid buildup in the mucosal surfaces.

Hippuric acid has long been used as an indicator of toluene exposure; however, there appears to be some doubt about its validity. There is significant endogenous hippuric acid production by humans; which shows inter- and intra-individual variation influenced by factors such as diet, medical treatment, alcohol consumption, etc. This suggests that hippuric acid may be an unreliable indicator of toluene exposure. It has been suggested that urinary hippuric acid, the traditional marker of toluene exposure is simply not sensitive enough to separate the exposed from the non-exposed. This has led to the investigation of other metabolites as markers for toluene exposure.

Urinary "o"-cresol may be more reliable for the biomonitoring of toluene exposure because, unlike hippuric acid, "o"-cresol is not found at detectable levels in unexposed subjects. o-Cresol may be a less sensitive marker of toluene exposure than hippuric acid. o-Cresol excretion may be an unreliable method for measuring toluene exposure because o-cresol makes up <1% of total toluene elimination.

Benzylmercapturic acid, a minor metabolite of toluene, is produced from benzaldehyde. In more recent years, studies have suggested the use of urinary benzylmercapturic acid as the best marker for toluene exposure, because: it is not detected in non-exposed subjects; it is more sensitive than hippuric acid at low concentrations; it is not affected by eating or drinking; it can detect toluene exposure down to approximately 15 ppm; and it shows a better quantitative relationship with toluene than hippuric acid or "o"-cresol.

The symptoms can occur anywhere between days to months after administration of the offending medication, depending on the dose and speed of administration (Baack and Burgdorf, 1991; Demirçay, 1997). The patient first experiences tingling and/or numbness of the palms and soles that evolves into painful, symmetric, and well-demarcated swelling and red plaques. This is followed by peeling of the skin and resolution of the symptoms (Apisarnthanarax and Duvic 2003).

Chemotherapy-induced acral erythema (also known as palmar-plantar erythrodysesthesia, palmoplantar erythrodysesthesia, or hand-foot syndrome) is reddening, swelling, numbness and desquamation (skin sloughing or peeling) on palms of the hands and soles of the feet (and, occasionally, on the knees, elbows, and elsewhere) that can occur after chemotherapy in patients with cancer. Hand-foot syndrome is also rarely seen in sickle-cell disease. These skin changes usually are well demarcated. Acral erythema typically disappears within a few weeks after discontinuation of the offending drug.

M2 is a subtype of AML (Acute Myeloid Leukemia).

It is also known as "Acute Myeloblastic Leukemia with Maturation".

Antidepressant treatment tachyphylaxis (ADT tachyphylaxis), also known as Prozac poop-out, is a medical condition in which progressive or acute tolerance effects are seen following chronic administration of a drug. ADT tachyphylaxis specifically refers to a sudden decrease in response to selective serotonin reuptake inhibitors (SSRIs), which are the most commonly prescribed antidepressants. Although less commonly prescribed as antidepressants (having lost popularity following the introduction of SSRIs), monoamine oxidase inhibitors, or MAOIs, have also incurred a "poop-out" effect among depressed patients.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Clostridial necrotizing enteritis (CNE), also called enteritis necroticans and pigbel, is an often fatal type of food poisoning caused by a β-toxin of "Clostridium perfringens", Type C. It occurs in some developing countries, but was also documented in Germany following World War II. The toxin is normally inactivated by certain proteolytic enzymes and by normal cooking, but when these protections are impeded, the disease emerges.

Apitoxin, or honey bee venom, is a bitter colorless liquid containing proteins, which may produce local inflammation. It may have similarities to sea nettle toxin.

Clonal hypereosinophilia, also termed Primary hypereosinophelia or clonal eosinophilia, is a grouping of hematological disorder characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell, in the bone marrow, blood, and/or other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

The clone of eosinophils bear a mutation in any one of several genes that code for proteins that regulate cell growth. The mutations cause these proteins to be continuously active and thereby to stimulate growth in an uncontrolled and continuous manner. The expanding population of eosinophils, initially formed in the bone marrow may spread to the blood and then enter into and injure various tissues and organs.

Clinically, clonal eosinophilia resembles various types of chronic or acute leukemias, lymphomas, or myeloproliferative hematological malignancies. However, many of the clonal hypereosinophilias are distinguished from these other hematological malignancies by the genetic mutations which underlie their development and, more importantly, by their susceptibility to specific treatment regiments. That is, many types of these disorders are remarkably susceptible to relatively non-toxic drugs.

HIV-associated lipodystrophy commonly presents with fat loss in face, buttocks, arms and legs.

There is also fat "accumulation" in various body parts. Patients often present with "buffalo hump"-like fat deposits in their upper backs. Breast size of patients (both male and female) tends to increase. In addition, patients develop abdominal obesity.

HIV-associated lipodystrophy, also known as lipodystrophy in HIV-infected patients (LD-HIV), is a condition characterized by loss of subcutaneous fat associated with infection with HIV.

Apitoxins are under preliminary research for their potential biological effects, such as in cancer.

CNE is a necrotizing inflammation of the small bowel (especially the jejunum but also the ileum). Clinical results may vary from mild diarrhea to a life-threatening sequence of severe abdominal pain, vomiting, bloody stool, ulceration of the small intestine with leakage (perforation) into the peritoneal cavity and possible death within a single day due to peritonitis. Many patients exhibit meteorism. Treatment involves suppressing the toxin-producing organisms with antibiotics such as penicillin G or metronidazole. About half of seriously ill patients require surgery for perforation, persistent intestinal obstruction, or failure to respond to the antibiotics. An investigational toxoid vaccine has been used successfully in some developing countries but is not available outside of research.

Epithelioid sarcoma is a rare soft tissue sarcoma arising from Mesenchyme tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first clearly characterized by F.M. Enzinger in 1970. It commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) of young adults as a small, soft mass or a series of bumps. A proximal version has also been described, frequently occurring in the upper extremities. Rare cases have been reported in the pelvis, vulva, penis, and spine.

Histologically, epithelioid sarcoma forms nodules with central necrosis surrounded by bland, polygonal cells with eosinophilic cytoplasm and peripheral spindling. Epithelioid sarcomas typically express vimentin, cytokeratins, epithelial membrane antigen, and CD34, whereas they are usually negative for S100, desmin, and FLI-1. They typically stain positive for CA125.

Epithelioid sarcoma most commonly strikes young adults, yet no age group is immune. The disease has a tendency to develop local recurrences and metastasis thereafter to regional lymph nodes, lung, bone, brain, and other locations, including the scalp. Generally speaking, epithelioid sarcoma has a high rate of relapse after initial treatment and tends to recur locally (at or near the original tumor site). Epithelioid sarcoma also demonstrates lymphatic spread (in 22-48% of cases), and metastasis (in 21-63% of cases). These events, as well as advanced stage (progression) and grade (aggressiveness), are predictive of an overall worse outcome. The overall five-year survival rate for epithelioid sarcoma is anywhere from 25 to 78%. Importantly, the 10-year and 15-year survival rate drops off significantly. Associated with a more positive outcome are younger age, female vs. male sex, distal vs. proximal location, smaller tumor size, and negative margins upon tumor resection.

In general, epithelioid sarcoma is a slow-growing and relatively painless tumor, often resulting in a lengthy period of time between presentation and diagnosis. Due to its ambiguity, it is often misdiagnosed, mistaken as a persistent wart or cyst. It most commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) as a small, soft mass or a series of bumps. It is most often described as a firm-to-hard palpable mass, either in the deep soft tissue or in the dermis. Often, superficial lesions will ulcerate causing a mistaken diagnosis of a poorly healing traumatic wound or wart. About 13% of patients will present with multifocal tumors, and about 13% of patients will present with metastatic disease.

Antidepressant discontinuation syndrome is a condition that can occur following the interruption, dose reduction, or discontinuation of antidepressant drugs, including selective serotonin re-uptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs). The symptoms can include flu-like symptoms and disturbances in sleep, senses, movement, mood, and thinking. In most cases symptoms are mild, short-lived, and resolve without treatment. More severe cases may be successfully treated by reintroduction of the drug, provided reintroduction is done in a timely fashion. Symptoms, including tardive akathisia, and Post SSRI Sexual Dysfunction (PSSD) may persist for months to years, yet may spontaneously resolve after prolonged presence.

People with discontinuation syndrome have been on an antidepressant for at least four weeks and have recently stopped taking the medication, whether abruptly, after a fast taper, or each time the medication is reduced on a slow taper. Commonly reported symptoms include flu-like symptoms (nausea, vomiting, diarrhea, headaches, sweating) and sleep disturbances (insomnia, nightmares, constant sleepiness). Sensory and movement disturbances have also been reported, including imbalance, tremors, vertigo, dizziness, and electric-shock-like experiences in the brain, often described by sufferers as "brain zaps". Mood disturbances such as dysphoria, anxiety, or agitation are also reported, as are cognitive disturbances such as confusion and hyperarousal.

In cases associated with sudden discontinuation of MAO inhibitors, acute psychosis has been observed. Over fifty symptoms have been reported.

Most cases of discontinuation syndrome last between one and four weeks, are relatively mild, and resolve on their own; in rare cases symptoms can be severe or extended. Paroxetine ("Paxil") and venlafaxine ("Effexor") seem to be particularly difficult to discontinue and prolonged withdrawal syndrome lasting over 18 months have been reported with paroxetine.

A 2009 Advisory Committee to the FDA found that online anecdotal reports of discontinuation syndrome related to duloxetine ("Cymbalta") included severe symptoms and exceeded prevalence of both paroxetine ("Paxil") and venlafaxine ("Effexor") reports by over 250% (although acknowledged this may have been influenced by duloxetine being a much newer drug). It also found that the safety information provided by the manufacturer not only neglected important information about managing discontinuation syndrome, but also explicitly advised against opening capsules, a practice required to gradually taper dosage.

The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek. In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.

The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.

Tumor-associated macrophages (TAMs) are the multifarious group of cells that originate mainly from the peritumoral tissue or bone marrow and can be divided into two main types: M1 and M2. Among them are the infiltrating M1 tumor-associated macrophages present in the early stages of tumorigenesis, which can secrete proinflammatory cytokines and turn in inhibit tumor growth. On the contrary, M2 tumor-associated macrophages are predominant in the late stage of tumor formation. Type II cytokines, which are secreted by them, can promote anti-inflammatory reaction and thus promote tumor growth. However, it remains unclear when M1 tumor-associated macrophages are transformed to M2 tumor-associated macrophages, but tumor hypoxia is currently thought to be associated with such a shift. M2 tumor-associated macrophages secrete many proteases such as cathepsin, cytokines, and an epidermal growth factor. The presence of M2 TAMs make the tumor prone to growth and angiogenesis, which in turn damages other tissues.

Clinically, in 128 patients in the first or second stage of breast cancer it was found that more patients with M2 tumor-associated macrophages had a higher degree of histology, more angiogenesis, and worse overall survival. Patients with more M1 tumor-associated macrophages displayed the opposite effect. .

Macrophages are the most common cells in breast tumors. They have a profound effect on the immune status of tumor tissues. Macrophages act as professional phagocytes in the body, specifically killing and eliminating cells or microbes that are perceived to be a threat. They represent the first line of defence and the bridge of connecting the innate and adaptive arms of the immune system. However, the large number of tumor cells and the derived factors present within the tumour microenvironment (TME) act to attenuate the tumoricidal activity function of macrophages. The TME consists of hypoxic conditions, growth factors and immunosuppressive cytokines that convert trophic macrophages to tumor-associated macrophages (TAM). These features promote tissue growth and repair and are an integral part of development so that macrophages within breast tumors are inadvertently authorized to promote tumor growth and metastasis.

The way CML presents depends on the stage of the disease at diagnosis as it has been known to skip stages in some cases.

Most patients (~90%) are diagnosed during the chronic stage which is most often asymptomatic. In these cases it may be diagnosed incidentally with an elevated white blood cell count on a routine laboratory test. It can also present with symptoms indicative of hepatosplenomegaly and the resulting upper quadrant pain this causes. The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss. It may also present with mild fever and night sweats due to an elevated basal level of metabolism.

Some (<10%) are diagnosed during the accelerated stage which most often presents bleeding, petechiae and ecchymosis. In these patients fevers are most commonly the result of opportunistic infections.

Some patients are initially diagnosed in the blast phase in which the symptoms are most likely fever, bone pain and an increase in bone marrow fibrosis.

Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:

In 2008, the World Health Organization listed these diagnoses as types of MPD:

- Chronic myelogenous leukemia (BCR-ABL1–positive)

- Chronic neutrophilic leukemia

- Polycythemia vera

- Primary myelofibrosis

- Essential thrombocythemia

- Chronic eosinophilic leukemia (not otherwise specified)

- Mastocytosis