Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
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Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.
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PMID:Toxoplasmic encephalitis in AIDS. 152 Jul 57

Treatment of cryptococcal meningitis in patients with AIDS with amphotericin B plus flucytosine is associated with a failure rate of 20%-30%. In the absence of chronic suppressive therapy, 40%-60% of patients develop recurrent disease. Recent comparative studies have evaluated fluconazole, a new triazole antifungal agent. In primary therapy, fluconazole is associated with response rates of 35%-60%, which are equivalent to those seen with amphotericin B alone. However, a smaller study suggested that amphotericin B plus flucytosine was superior to fluconazole alone. Both studies identified risk factors associated with a poor outcome; these factors include lethargy or obtundation at presentation, a high titer of cryptococcal antigen titer in the cerebrospinal fluid, and a low leukocyte count in the cerebrospinal fluid. Fluconazole is highly effective in suppressing relapses of cryptococcal meningitis. Itraconazole has been investigated less extensively in the treatment of cryptococcosis but offers promise. Future studies need to address alternative approaches to the management of acute cryptococcal disease and primary prophylaxis for cryptococcal infection in patients with AIDS.
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PMID:Therapy for cryptococcal meningitis in patients with AIDS. 156 96

Inpatient and community-based care can be complementary in relation to the management of HIV disease. Medical records from 200 inpatients of Chikankata Hospital near Lusaka, Zambia and 200 home based patients were examined and compared for the common symptoms of presentation of HIV disease, associated opportunistic infections, and treatment protocols. Drug costs of both groups were also compared. The most common respiratory symptoms in the 2 groups are cough, chest pains, weight loss, and hemoptysis. Treatment employed for these symptoms were cortimoxazole, penicillin V, erthromycin, and tetracycline. Acetyl saliclic acid and paracetamol were used for pain relief in both groups. Gastointestinal system symptoms for both groups were diarrhea, weight loss, abdominal pain, and vomiting. Cotrimoxazole and metronidazole were used in treating diarrhea. Additional treatment protocol for the 2 patient samples included oral rehydration therapy for dehydration, antacid or bismuth subsalicylate for diarrhea and enteritis, and mycostatin for oral candidiasis. Central nervous system symptomatology included headache, dementia, neckace, and lethargy. Chloramphenicol was employed in treating bacterial meningitis. Diazepam and chlorpromazine were effective for restless patients. Genito-urinary system symptomatology for the 2 groups included dysuria, genital ulcers, hematuria, viral warts, and buboes. Antibodies were used for sexually transmitted diseases and infections. Skin symptomatology included rash and dermatitis, herpes zoster, abscess, kaposi's sarcoma, ulcers, furunculosis, and discharging anal sinus. In treating these symptoms, hospital based care and home based care were similar. Overall, it was found that hospital treatment protocols were detailed, expensive, and time consuming. Furthermore, hospital treatment for HIV positive patients is more expensive than HIV negative patients; hospital costs for 50 HIV negative patients totaled US$415.94 compared to US$1204.98 HIV positive/PTB negative patients and US$1705.62 for HIV positive/PTB positive patients. Drug cost/patient admission is increased by 469% if HIV positive. (author's modified).
AIDS Care 1989
PMID:Clinical care as part of integrated AIDS management in a Zambian rural community. 248 94

Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV-2 and antibody received ddC prophylaxis prior to challenge with virus and continued to receive ddC therapy for up to 28 days postchallenge. All monkeys treated with a continuous intravenous dose of ddC, which maintained plasma concentrations of ddC at levels known to inhibit SRV-2 in vitro, developed dose-related toxic effects, including leukopenia, anemia, lethargy, and decreased appetite. Monkeys treated with a daily bolus injection of ddC experienced more severe toxic effects than those on the continuous intravenous regimen, including exfoliative dermatitis and peripheral neuropathy. At the concentrations of ddC administered, no significant inhibition of SRV-2 replication was detected in naturally infected macaques. However, a prophylactic regimen of ddC did have an inhibitory effect on SRV-2. Our findings suggest that ddC may be valuable as a short-term prophylactic treatment rather than as a long-term therapy.
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PMID:Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2. 255 13

In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.
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PMID:Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. 285 99

The clinical symptoms and signs were assessed in 20 consecutive patients developing infection with the human immunodeficiency virus (HIV). All were male homosexuals and all presented with a glandular-fever-like illness. Changes in laboratory values were compared with findings in 40 HIV negative male homosexual controls. In the 10 patients for whom date of exposure to the virus could be established the incubation period was 11-28 days (median 14). One or two days after the sudden onset of fever patients developed sore throat, lymphadenopathy, rash, lethargy, coated tongue, tonsillar hypertrophy, dry cough, headache, myalgia, conjunctivitis, vomiting, night sweats, nausea, diarrhoea, and palatal enanthema. Twelve patients had painful, shallow ulcers in the mouth or on the genitals or anus or as manifested by oesophageal symptoms; these ulcers may have been the site of entry of the virus. During the first week after the onset of symptoms mild leucopenia, thrombocytopenia, and increased numbers of banded neutrophils were detected (p less than 0.0005). The mean duration of acute illness was 12.7 days (range 5-44). All patients remained healthy during a mean follow up period of 2.5 years. Heightened awareness of the typical clinical picture in patients developing primary HIV infection will alert the physician at an early stage and so aid prompt diagnosis and help contain the epidemic spread of AIDS.
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PMID:Clinical picture of primary HIV infection presenting as a glandular-fever-like illness. 314 67

The paper describes the psychiatric status on the basis of 76 patients with acquired immune deficiency syndrome. There is considerable difference between the different stages of the disease. The disorders are divided into groups following the German and French psychopathological tradition, where the incidence is dependent on the underlying complaint. 50% of the patients suffered from chronic psychoorganic disorders (34% organic personality disorders, 16% dementia). 9% suffered from an acute psychosis caused by complications and founded on substantial physical illness. 3 patients showed symptoms of a (under given circumstances) hitherto unknown endoform psychosis. In 9% of the patients, psychoreactive disturbances (anxiety and reactive depression) were observed. Two infants had congenital development deficiencies. 25% of the patients were without any psychopathology. Patients showing organic personality disorders mostly resemble each other to such a degree as to form a separate group. We suggest to name this group according to the most prominent psychopathology as "AIDS-lethargy". This status is characterised by a specific apathy, tiredness and indolence of the patients combined with the lack of emotional participation related to their own destiny. AIDS-lethargy is the first manifestation in appearance of the HIV infection of the brain itself. Another sequel of the brain infection is AIDS dementia which can be classified as "subcortical dementia" and differs from the more current forms of dementia clinically. Affected are mainly neuropsychologic functions like arousal, attention, mood and motivation, whereas the hallmarks of cortical involvement-aphasia, agnosia and apraxia-are not present. Supplementary findings (EEG, CCT, CSF): The group of patients with chronic psychoorganic disorders differs significantly from the group with psychoreactive disorders and normals. Pathological EEG and CCT are more frequent in psychoorganic disorders. CSF-test-including the intrathecally synthesized antibodies against HIV-does not show traceable variation in either group. There are four problems which may be combined in a given acute psychopathological HIV-syndrome: 1. Being member of a risk group with its reactive, psychosocial and personality problems. 2. Individual mental and emotional reaction to the fact of infection 3. Chronic psychoorganic disturbances. 4. Acute organic psychoses as a result of complications and other physical illness.
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PMID:[Psychopathologic pictures in HIV infection: AIDS lethargy and AIDS dementia]. 340 94

Meningitis should be suspected in a patient who presents with fever, meningism, or severe headache. A careful physical examination should be performed of perimeningeal foci, with emphasis on the sinuses, ears, throat, neck, and lungs. A history of exposure to tuberculosis, viral disease, rodents, or suspicious dairy products or farm animals may give clues to the source of the meningitis. Immunosuppression through the use of corticosteroids or chemotherapy for such conditions as Hodgkin's disease, lymphoma, leukemia, malnutrition, or acquired immunodeficiency syndrome (AIDS) should also be noted and alert the clinician to the possible presence of an unusual pathogen. Meningitis associated with leukemia or most of the non-T-cell lymphomas is likely to be from a common bacterial agent (often Listeria), unless the patient is being treated with a steroid or is receiving other chemotherapy. Patients with Hodgkin's disease or AIDS or who have been treated with a steroid are more likely to have cryptococcal or tuberculous meningitis. Neonates and the very elderly may present with only irritability or lethargy and fever, without any of the other common symptoms. In neonates up to one week of age, group B streptococcal infection should be suspected. Gram-negative organisms should be suspected in elderly patients and those who have had neurosurgery. In patients with CSF shunts, infection with coagulase-negative Staphylococcus should be assumed and these patients are treated empirically until results of cultures are received. Several noninfectious conditions may mimic infectious meningitis, as may some unusual causes of infectious meningitis (eg, syphilis and schistosomiasis), which have not been discussed in this article.
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PMID:The many causes of meningitis. 361 11

We reviewed the clinical, neuroradiological, and serological findings in 27 patients with cerebral toxoplasmosis complicating the acquired immune deficiency syndrome, 19 of whom were also analyzed neuropathologically. The clinical manifestations of this disorder varied, ranging from headache and fever to coma. However, the characteristic presentation included focal neurological symptoms and signs, usually of subacute onset. In addition, two-thirds of the patients exhibited more generalized cerebral dysfunction with confusion and lethargy. The computed tomographic (CT) scan most commonly revealed ring contrast enhancement, which appeared to correlate best with the histological presence of vascular proliferation and inflammation surrounding the abscesses. However, in 5 patients the CT scan revealed either homogeneous enhancement or no enhancement, and in 3 patients the scans were negative. In general, CT scans underrepresented the number of lesions eventually documented pathologically. Double-dose contrast administration and preliminary experience with magnetic resonance imaging suggested that these techniques were superior to standard CT scanning in detecting Toxoplasma lesions. All patients were seropositive for IgG antibody against Toxoplasma gondii in blood, both before the onset of illness and at the time of presentation, although titers in some patients were as low as 1:8 and most patients did not exhibit rising titers. Prompt therapy resulted in rapid clinical improvement, documented by CT scan, associated with the development of an organizing tissue response in the host and elimination of free organisms. Response to treatment was sufficiently rapid in most patients to allow a trial of therapy as the favored approach to diagnosis.
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PMID:Cerebral toxoplasmosis complicating the acquired immune deficiency syndrome: clinical and neuropathological findings in 27 patients. 396 67

We evaluated clinical features of five cases of Toxoplasma encephalitis (TE) occurring in recent Haitian entrants into the United States. None of the patients had any underlying malignancy or known immunosuppressive therapy. Histopathologic findings of TE at autopsy were confirmed by peroxidase-antiperoxidase method. Four patients had an antecedent episode of disseminated tuberculosis and all five were receiving antituberculous therapy when neurologic manifestations of lethargy, seizures, and motor weakness first developed. These symptoms progressed into coma and death within 15 days. Peripheral lymphocytopenia was noted in all patients; three were anergic. Parenchymal lesions were identified by CT brain scans and total proteins were elevated in spinal fluid in all cases. TE appears to be a manifestation of the acquired immune deficiency syndrome in Haitians; it should be suspected in those with a febrile illness and multiple focal lesions of the central nervous system.
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PMID:Toxoplasma encephalitis in recent Haitian entrants. 662 28


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