Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The application of recombinant DNA technology to the production of tumor necrosis factor has resulted in the availability of large quantities of a highly purified protein product. This product has been evaluated extensively in preclinical studies, which have documented a direct cytostatic and cytotoxic effect on human tumor cells, as well as a variety of immunomodulatory effects on various immune effector cells, including neutrophils, macrophages, and T cells. In addition, a number of anti-infective and metabolic effects have been documented. In addition to its in vitro effects, rTNF has been shown to have antitumor activity in vivo in preclinical studies involving both transplantable murine tumors and human tumor xenografts. Such observations have led to the evaluation of rTNF as a potential antineoplastic agent in humans. Both single- and multiple-dose phase I studies have confirmed that rTNF can be safely administered to patients with advanced malignancies in a dose range associated with anticancer effect without concomitant serious toxicities such as shock and cachexia. The most commonly observed clinical toxicities include constitutional symptoms, such as fever, chills, headache, and fatigue, and toxicities, which can be at least partially controlled with concomitant administration of nonsteroidal anti-inflammatory drugs, such as acetaminophen and meperidine. Hypotension, which occurs at high doses administered by short intravenous infusion, can usually be prevented by prehydration with intravenous fluids or otherwise controlled by the administration. An intense local inflammatory reaction at the injection site as well as thrombocytopenia appear to be the dose-limiting toxicities after subcutaneous and intramuscular administration. Neurologic toxicity is infrequent, except following continuous intravenous infusion, where it may manifest as transient focal neurologic deficits or seizure. Prolonged administration of rTNF at higher doses may be associated with transient, subclinical decreases in diffusing capacity. Patients with underlying cardiopulmonary disease should be excluded from rTNF therapy in future clinical studies until the end-organ toxicities of this agent are better defined. For at least one preparation of rTNF there appears to be no evidence for the formation of antibodies to rTNF in patients who receive multiple administrations of the agent. Pharmacokinetic studies have shown a relatively rapid clearance following intravenous infusion with a half-life of 15 to 30 min and dose-dependent pharmacokinetics. rTNF can be detected in the serum following intramuscular or subcutaneous injection at only relatively high doses, suggesting a decreased bioavailability with the routes of administration. Early phase I studies defined tolerable dose ranges for each route of administration and began to explore immunomodulatory and metabolic effects of rTNF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human TNF-alpha: preclinical studies and results from early clinical trials. 155 Aug 75

Brain stem glioma is the third most common childhood brain tumor, comprising 10-15% of this group of neoplasms. Typical presenting symptoms include ataxia, diplopia and headache, while signs of increased intracranial pressure occur later in the clinical course. Although prolonged failure to thrive, characterized by cachexia and vomiting are rare manifestations of brain stem lesions, in this study we report a 9.5-year-old boy with failure to thrive since infancy which remitted after excision of a brain stem astrocytoma.
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PMID:Chronic dysphagia, vomiting and gastroesophageal reflux as manifestations of a brain stem glioma: a case report. 248 55

Septic shock and invasive infection are diseases caused by humoral mediators of both exogenous and endogenous origin. The search for and identification of these factors has led to the discovery and molecular cloning of cachectin. This pyrogenic cytokine is identical to tumor necrosis factor (TNF) and, when released into the circulation, causes profound shock and multiple organ injury. Cachectin antibodies protect against the lethal effects of mice given endotoxin and baboons given E. coli, a result suggesting that this mediator is both necessary and sufficient to provoke septic shock. Cachectin is produced in humans after endotoxin infusion; the infusion of small doses of TNF is associated with fever, rigors, headache, and hypotension. Septicemic patients also produce cachectin, and during meningococcal infection, patients with the highest serum levels of cachectin die. Chronic cachectin production causes a potentially lethal syndrome of cachexia, anemia, and protein and lipid wasting. Future investigation is being directed toward the development of cachectin antibodies for use in treating the humorally mediated systemic complications of infectious disease.
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PMID:Cachectin: a hormone that triggers acute shock and chronic cachexia. 327 61

Mortality of 70% of all patients with tumors in the head and neck is linked with anorexia and cachexia. Two reasons for cachexia are well known: 1. local disease and local therapy preventing oral nutrition and 2. advanced tumors activating biochemical pathways of proteolysis, lipolysis, and gluconeogenesis. Five groups of substances are now used to treat tumor-induced cachexia: corticosteroids, progestational drugs, cyproheptadine, hydrazine sulfate, and anabolic steroids. Between 1992 and 1993 we treated 38 patients suffering from cachexia due to advanced cancers of the head and neck with 160 mg megestrol acetate per day for four months. The increase in body weight was significant after eight weeks. The mean increase after full therapy was 4.58 +/- 3.19 kg. Treatment of the five women in the series was very successful and all achieved their former body weight. Megestrol acetate therapy was best started after assuring enteral nutrition. Significant adverse events were loss of libido for the men, headache and, rarely, thrombophlebitis. Our first experiences suggest that megestrol acetate treatment is useful in cachectic patients with advanced squamous cell carcinomas of the head and neck.
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PMID:[Value of megestrol acetate in treatment of cachexia in head-neck tumors]. 757 3

Human immunodeficiency virus (HIV), is able to replicate in many human cells such as helper lymphocytes, monocytes/macrophages and glial cells. Monocytes/macrophages must be considered an important reservoir of HIV in vivo and a producer of cytokines such as Interleukin-1 (IL1) and tumor necrosis factor (TNF). These substances lead to an autocrine feedback loop that produces an increased virus replication and a secondary induction of other cytokines such as Interleukin 6 (IL6) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cytokines all together may be responsible for many clinical aspects of the disease such as headache, fever, anorexia, subtle cognitive changes, motor disfunctions and cachexia. The future strategies in the treatment of AIDS must be a combination of drugs acting on different points of viral replication and with synergistic potential. Omega 3 polyunsaturated fatty acids (omega-3) can be considered a candidate for their pleiotropic effects on immunological and metabolic systems. In particular, their use is considered for their ability to decrease IL1 and TNF production by monocytes/macrophages, as demonstrated by many authors. The decreased induction of these cytokines and consequently of IL6 and acute phase proteins may have beneficial effects on many clinical manifestations of AIDS such as cachexia.
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PMID:Omega-3 fatty acids as coadjuvant treatment in AIDS. 828 91

There have been reports of chemical attacks in which sulfur mustard might have been used (a) on Iranian soldiers and civilians during the Gulf War in 1984 and 1985 and (b) in an Iraqi chemical attack on the Iranian-occupied village of Halbja in 1988, resulting in many civilian casualties. Heavy use of chemical warfare in Afghanistan by the Soviet military is a recent innovation in military tactics that has been highly successful and may ensure further use of chemical agents in future military conflicts and terrorist attacks as a profitable adjunct to conventional military arms. Mustard is a poisonous chemical agent that exerts a local action on the eyes, skin, and respiratory tissue, with subsequent systemic action on the nervous, cardiac, and digestive systems in humans and laboratory animals, causing lacrimation, malaise, anorexia, salivation, respiratory distress, vomiting, hyperexcitability, and cardiac distress. Under extreme circumstances, dependent upon the dose and length of exposure to the agent, necrosis of the skin and mucous membranes of the respiratory system, bronchitis, bronchopneumonia, intestinal lesions, hemoconcentration, leucopenia, convulsions with systemic distress, and death occur. Severe mustard poisoning in humans is associated with systemic injury, which is manifested as headache, epigastric distresses, anorexia, diarrhea, and cachexia and is usually observed at mustard doses of 1000 mg/min/m3 with damage to hematopoietic tissues and progressive leucopenia. Sulfur mustard is a cell poison that causes disruption and impairment of a variety of cellular activities that are dependent upon a very specific integral relationship. These cytotoxic effects are manifested in widespread metabolic disturbances whose variable characteristics are observed in enzymatic deficiencies, vesicant action, abnormal mitotic activity and cell division, bone marrow disruption, disturbances in hematopoietic activity, and systemic poisoning. Indeed, mustard gas readily combines with various components of the cell such as amino acids, amines, and proteins. Although evidence of an association between lung cancer and mustard gas encountered on the battlefields of World War I is at best suggestive if not problematical (Case and Lea, 1955; Beebe, 1960; Norman, 1975), the epidemiological data accumulated from the poison gas factories in Japan (Yamada et al., 1953; Wada et al., 1968; Inada et al., 1978; Shigenobu, 1980; Nishimoto et al., 1983; Hirono et al., 1984; Takuoka et al., 1986), in Germany (Weiss, 1958; Hellmann, 1970a; Weiss and Weiss, 1975; Klehr, 1984) and in England (Manning et al., 1981; Easton et al., 1988) are substantial (International Agency for Research on Cancer, 1975). Unfortunately, attempts to seek confirmatory and substantial evidence in laboratory animals such as mice (Boyland and Horning, 1949; Heston, 1950; Heston, 1953a; McNamara et al., 1975) and rats (Griffin et al., 1951; McNamara et al., 1975; Sasser et al., 1996) have not been consistent. Sulfur mustard has been shown to be mutagenic in a variety of different species using many different laboratory techniques from fruit flies, microorganisms and mammalian cell cultures (Fox and Scott, 1980). Evidence is slowly accumulating from human data (Hellmann, 1970a; Lohs, 1975; Wulf et al., 1985). Evidence for the teratogenicity of mustard has been negative in assessment of fetotoxicity and adverse effects of mustard on the reproductive potential of both human and animal studies. Indeed, investigations of women adversely affected by mustard are minimal because most of the studies have been performed on former men employees of poison gas factories and have been negative or questionable. We have recently emphasized the need to assess the affect of a suspected teratogen on maternal toxicity in laboratory animals before any conclusions can be made.(ABSTRACT TRUNCATED)
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PMID:Toxicology and pharmacology of the chemical warfare agent sulfur mustard. 880 7

The authors present a very rare case of a child with anterior communicating artery aneurysm and symptoms of anorexia nervosa. Because of coexistence of subarachnoid haemorrhage and head trauma false diagnosis of temporal and frontal lobe contusion was initially established. Headaches, anorexia and cachexia occurred with aneurysm enlargement. Computed tomography and cerebral angiography allowed to indicate operation. After successful surgery all symptoms disappeared.
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PMID:[Anorexia as a symptom of cerebral aneurysm in a 14-year-old boy]. 1046 63

The cancer anorexia-cachexia syndrome is common, occurring in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death in patients with cancer. It is a complex problem involving abnormalities in protein, carbohydrate, and fat metabolism. Tumors have both direct and indirect effects that result in anorexia and weight loss. The disease burden does not necessarily correlate with the degree of cachexia. In addition to the physical manifestations, the resulting abnormalities have a significant psychologic effect on patients and their families. Although there is no treatment to reverse the process, pharmacologic and nonpharmacologic measures can enhance food intake and improve quality of life.
Curr Pain Headache Rep 2001 Jun
PMID:Modern management of the cancer anorexia-cachexia syndrome. 1130 13

A 41-year-old human immunodeficiency virus (HIV)-positive man was hospitalized with complaints of a 4-week history of nausea and vomiting, associated with decreased oral intake, and a 4-day history of frontal headache and fever. His medical history was significant for a gunshot wound to the head 3 years prior, with a residual seizure disorder. He also had two previous hospitalizations, both for culture-negative bacterial meningitis; the first episode occurred 12 months before admission and the second episode occurred 5 months later. At that time, he was found to be positive for serum antibodies against HIV and a CD4+ T-lymphocyte count of 126/mm3. He had no known drug allergies and was not receiving any medication. On admission, the patient was febrile (104.0 degrees F) and hypotensive (blood pressure, 92/40 mm Hg). Pertinent physical examination findings included cachexia with bitemporal wasting, dry mucus membranes, adherent white patches on the oral mucosa, and negative Kernig's and Brudzinski's signs. His laboratory results revealed macrocytic anemia, a decreased serum sodium of 125 mEq/L, and a normal total leukocyte count with a CD4+ T-lymphocyte count < 50/mm3. Lumbar puncture opening pressure was elevated at 160 mm Hg, and cerebrospinal fluid analysis showed an increased white cell count of 97/microL (84% lymphocytes), a decreased glucose level of 26 mg/dL, and a decreased protein level of 42 mg/dL. The patient was started on empiric therapy that included intravenous ampicillin and cefotaxime, oral Bactrim, and clotrimazole lozenges for thrush. Cerebrospinal fluid culture was positive for Escherichia coli, sensitive to cefotaxime. Two days later, the patient developed fine, erythematous, nonblanchable macules primarily on his abdomen, with minimal involvement of his thorax and back. His skin lesions remained unchanged for the next 2 weeks. Repeat lumbar puncture was performed after 14 days of cefotaxime. The cerebrospinal fluid analysis showed an elevated white cell count of 7/microL (100% lymphocytes), a decreased glucose level of 53 mg/dL, and a decreased protein level of 33 mg/dL. The cerebrospinal fluid culture was now positive for Pseudomonas aeruginosa resistant to cefotaxime. The patient was started on imipenem. On day 34 of his admission, the patient became tachypneic with complaints of dyspnea. A chest roentgenogram revealed bilateral patchy infiltrates. He was transferred to the intensive care unit and intubated for hypoxemic respiratory failure (arterial blood gas values on 6 L of oxygen: pH, 7.46; bicarbonate, 23; and oxygen saturation, 37). That evening, the patient was also noted to have diffuse petechiae and purpura in a reticulated pattern over his abdomen (Figure 1A and 1B), most heavily concentrated in the periumbilical region, extending to the axillae and upper thighs. A 3x3-mm punch biopsy from abdominal skin demonstrated Strongyloides stercoralis larvae in the dermis (Figure 2A and 2B). His sputum specimen was teeming with adult S stercoralis worms (Figure 3) and, subsequently, numerous S stercoralis larvae were observed not only from the bronchoalveolar lavage but also from the nasogastric fluid specimen. These findings confirmed the diagnosis of disseminated strongyloidiasis. On hospital day 35, the patient was doing poorly and was started on thiabendazole (1250 mg twice daily for 28 days). Nine days later, ivermectin (4.5 mg once daily for 3 days for 2 courses) was also added. He continued to clinically deteriorate. The patient died 31 days after systemic antihelminthic treatment was initiated.
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PMID:Cutaneous manifestations of Strongyloides stercoralis hyperinfection in an HIV-seropositive patient. 2167 5

An 82-year-old woman presented with bilateral, symmetric posterior circulation infarctions secondary to giant cell arteritis (GCA). Her atypical clinical presentation included a lack of headache and fever, but she exhibited signs of systemic illness including generalized weakness, cachexia, apathy, and anemia. Laboratory testing revealed a markedly elevated erythrocyte sedimentation rate, but only a borderline elevated C-reactive protein. Head and neck vascular imaging demonstrated a pattern of vertebral arterial narrowing consistent with GCA-a diagnosis confirmed by temporal artery biopsy. Her unusual symptomatic, laboratory, and imaging presentation highlights the importance of considering GCA in the differential diagnosis of unusual bilateral stroke syndromes, where early treatment decreases morbid outcomes.
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PMID:Giant cell arteritis causing symmetric bilateral posterior circulation infarcts. 2404 10


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