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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 19 recordsLinked to original sources
PubMed1992

Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.

BACKGROUND AND METHODS: Toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with the acquired immunodeficiency syndrome (AIDS). To investigate its clinical course, we reviewed the records of 115 patients with AIDS and central nervous system toxoplasmosis treated at San Francisco General Hospital between 1981 and 1990. RESULTS: The most common presenting symptoms were headache (in 55 percent), confusion (52 percent), and fever (47 percent). Focal neurologic deficits were present in 79 patients (69 percent). The median CD4 cell count at presentation was 50 per cubic millimeter (50 x 10(6) per liter). Thirteen of 80 patients with clinical toxoplasmosis (16 percent) and 4 of 18 patients with pathologically proved disease (22 percent) had undetectable antitoxoplasma IgG antibodies by indirect immunofluorescence assay. Of 103 patients, 94 (91 percent) had enhancing lesions on CT. Single lesions were seen in 28 of 103 patients (27 percent) on CT, and such lesions were seen in 3 of 21 patients (14 percent) on magnetic resonance imaging. Over 90 percent of patients who eventually had clinical and radiographic improvement had evidence of improvement by day 14 of therapy. Adverse drug reactions occurred in 71 patients (62 percent) and led to a change in therapy in 50 patients (43 percent). Among the patients who survived a first episode of toxoplasmosis, the median survival was 265 days. CONCLUSIONS: Toxoplasmosis occurs in advanced stages of human immunodeficiency virus infection, and the absence of antitoxoplasma antibodies on immunofluorescence assay does not exclude the diagnosis. The clinical and radiographic response to therapy is usually rapid, but treatment is frequently limited by adverse drug effects.

AIDS-Related Opportunistic Infections↗
PubMed1992

The microbial etiology and antimicrobial therapy of adults with acute community-acquired sinusitis: a fifteen-year experience at the University of Virginia and review of other selected studies.

Pretreatment sinus puncture was performed on 339 patients with acute community-acquired sinusitis (ACAS) between 1975 and 1990. Bacterial species recovered in titers of greater than or equal to 10(4) colony-forming units per milliliter (CFU/ml) from 383 sinus aspirates included Streptococcus pneumoniae, 92 (41%); Haemophilus influenzae, 79 (35%); anaerobes, 17 (7%); streptococcal species, 16 (7%); Moraxella catarrhalis, 8 (4%); Staphylococcus aureus, 7 (33%); and other, 8 (4%). Viruses (rhinovirus, parainfluenza virus, and influenza virus) and fungi (Aspergillus, zygomycoses, Phaeohyphomycis, Pseudallescheria, and Hyalohyphomycis) have also been reported to cause ACAS. Posttreatment sinus puncture was performed on 220 of the 339 patients in six studies to evaluate efficacy of selected antimicrobial agents in producing bacteriologic cure. Ampicillin, 500 mg four times daily; amoxicillin, 500 mg three times daily; trimethoprim-sulfamethoxazole, twice a day; cefaclor, 500 mg four times daily; bacampicillin, 800 mg twice a day; cyclacillin, 500 mg three times a day; cefuroxime axetil, 250 mg twice daily; amoxicillin-clavulanate, 500/125 three times daily; and loracarbef 400 mg twice daily, given in 10-day courses, produced bacteriologic cure in more than 90% of patients. Early studies were done before beta-lactamase-producing strains of H. influenzae were a frequent cause of ACAS in Charlottesville. Management of therapeutic failures is a difficult problem for which diagnostic and therapeutic sinus puncture and lavage, prolonged antimicrobial therapy, steroid therapy, and evaluation of allergy, immunodeficiency, and surgically correctable lesions of the osteomeatal complex are recommended.

Acute Disease↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of acute bacterial meningitis. Infectious Diseases Society of America and the Food and Drug Administration.

Predisposing conditions for acute bacterial meningitis include prematurity, young age, management in an intensive care setting, low socioeconomic background, and crowded living conditions. Clinical findings vary with age and may be nonspecific (altered feeding behavior) or specific (Kernig and Brudzinski signs). Examination and culture of cerebrospinal fluid (CSF) are essential for diagnosis. Antigen identification in CSF, serum, or urine by latex agglutination or other techniques can be useful in the identification of the pathogen. Randomized, controlled studies with a single-, double-, or evaluator-blinded design are encouraged. Among neonates, infants, and children, CSF should be examined again 24-36 hours after initiation of therapy. Outcomes should be judged by both clinical and microbiological criteria. Assessment of microbiological outcome is paramount.

Acute Disease↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of cryptococcal meningitis. Infectious Diseases Society of America and the Food and Drug Administration.

Cryptococcus neoformans may infect persons with intact or compromised host defenses. Clinical manifestations generally correlate directly with the degree of immunosuppression. Treatment is prescribed on the basis of the severity of disease and the degree of immunosuppression. Cryptococcal meningitis is the most common clinical form of cryptococcal infection and the most amenable to study in clinical trials. The current standard of care for cryptococcal meningitis is therapy with amphotericin B. Despite clinical improvement and microbiological suppression of the organism at the completion of therapy, the microbiological outcome will be identified as presumptive persistence if treatment is continued. Patients should be observed for 1 year after completion of therapy before a final assessment is made.

Anti-Infective Agents↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of viral encephalitis. Infectious Diseases Society of America and the Food and Drug Administration.

Viral encephalitis may develop subsequent to viremia, via neuronal spread, or by arthropod vector. Diagnosis often requires invasive studies such as lumbar puncture and brain biopsy. This guideline addresses herpes simplex, rabies, and arbovirus infections of the central nervous system. Clinical trials should be designed according to the availability of approved therapeutic agents. Study designs with an active control (herpesvirus), a placebo control (arbovirus), or no control (rabies virus) are recommended. Outcome should be assessed 4-6 weeks, 4-6 months, and 11-13 months after the completion of therapy. For newborns with encephalitis, outcome should be assessed yearly through the age of 5 years. Assessment of clinical outcome is paramount.

Anti-Infective Agents↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of toxoplasma encephalitis. Infectious Diseases Society of America and the Food and Drug Administration.

Toxoplasma gondii is a protozoan that exists in three forms, all of which are potentially infectious for humans. After acute infection, cysts persist in the central nervous system and extraneural tissue. Human hosts with compromised immunity, particularly those with the acquired immunodeficiency syndrome, are vulnerable to reactivation and dissemination. The most common clinical expression of toxoplasma infection is encephalitis. The diagnosis is established by clinical presentation, computed tomography and/or magnetic resonance imaging, and detection of antibodies to T. gondii in serum of patients positive for human immunodeficiency virus. Brain biopsy may be performed. Protocols may be developed for the evaluation of new regimens for the treatment of acute encephalitis, the suppression of disease after treatment, or the prevention of reactivation before the onset of clinical disease. Assessment of clinical outcome is paramount.

Anti-Infective Agents↗
PubMed1992

Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin.

We examined the effect of azithromycin (CP-62,993), a new oral macrolide-like antibiotic, alone and in combination with rifampin, as treatment for experimental staphylococcal osteomyelitis. Clindamycin was used as a comparison drug. Rats (n = 10 to 15 per group) were infected by direct instillation of Staphylococcus aureus into the tibial medullary cavity. After 10 days, 21-day treatments with azithromycin (50 mg/kg of body weight, once daily, by the oral route), rifampin (20 mg/kg, once daily, subcutaneously), or clindamycin (90 mg/kg, three times daily, by the oral route) were started. The drugs were used singly or in combination (azithromycin plus rifampin or clindamycin plus rifampin). Peak azithromycin concentrations in bone were > 30 times higher than levels in serum, but the drug had little effect on final bacterial titers (5.13 +/- 0.46 log10 CFU/g of bone; for controls, 6.54 +/- 0.28 log10 CFU/g). Clindamycin was more active than azithromycin (3.26 +/- 2.14 log10 CFU/g of bone; 20% of sterilized bones), but rifampin was the most active single drug (1.5 +/- 1.92 log10 CFU/g; 53% of sterilized bones). Therapy with rifampin or clindamycin alone was associated with the emergence of resistance. Rifampin plus azithromycin (0.51 +/- 1.08 log10 CFU/g of bone; 80% of sterilized bones) and rifampin plus clindamycin (0.87 +/- 1.34 log10 CFU/g of bone; 66% of sterilized bones) were the most active regimens. Thus, azithromycin is ineffective as a single drug for the treatment of experimental staphylococcal osteomyelitis, despite high levels in bone that markedly exceeded the MIC, but it may be an attractive partner drug for rifampin.

Animals↗
PubMed1992

Effect of hydration status on cerebral blood flow and cerebrospinal fluid lactic acidosis in rabbits with experimental meningitis.

The effects of hydration status on cerebral blood flow (CBF) and development of cerebrospinal fluid (CSF) lactic acidosis were evaluated in rabbits with experimental pneumococcal meningitis. As loss of cerebrovascular autoregulation has been previously demonstrated in this model, we reasoned that compromise of intravascular volume might severely affect cerebral perfusion. Furthermore, as acute exacerbation of the inflammatory response in the subarachnoid space has been observed after antibiotic therapy, animals were studied not only while meningitis evolved, but also 4-6 h after treatment with antibiotics to determine whether there would also be an effect on CBF. To produce different levels of hydration, animals were given either 50 ml/kg per 24 h of normal saline ("low fluid") or 150 ml/kg 24 h ("high fluid"). After 16 h of infection, rabbits that were given the lower fluid regimen had lower mean arterial blood pressure (MABP), lower CBF, and higher CSF lactate compared with animals that received the higher fluid regimen. In the first 4-6 h after antibiotic administration, low fluid rabbits had a significant decrease in MABP and CBF compared with, and a significantly greater increase in CSF lactate concentration than, high fluid rabbits. This study suggests that intravascular volume status may be a critical variable in determining CBF and therefore the degree of cerebral ischemia in meningitis.

Animals↗
PubMed1992

Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS.

To determine the efficacy and toxicity of SCH 39304 in the treatment and suppression of cryptococcal meningitis, we conducted a prospective, noncomparative study in three groups of patients: patients with acute cryptococcal meningitis, patients with acute cryptococcal meningitis in whom other therapies have failed (salvage), and patients who required maintenance therapy. As primary therapy, the patients received up to 14 days or 1 g of amphotericin B followed by SCH 39304 200 mg once daily for 12 weeks. As maintenance therapy, the patients received SCH 39304 600 mg once weekly for 12 months. Of five salvage patients, none completed the study. Two patients died, two patients clinically deteriorated, and one patient was noncompliant. Two of three patients with acute cryptococcal meningitis completed the 12-week primary therapy, and one patient was discontinued from therapy because of a skin rash (95% confidence interval, 14-100%). All four patients who were receiving weekly maintenance therapy followed up to 27 weeks were clinically stable with no change in their serum cryptococcal antigen titer from baseline when the study was prematurely terminated. Elevation of liver function test results developed in three patients and skin rash developed in one patient. The unique pharmacologic and pharmacokinetic properties of SCH 39304 (low incidence of toxicity, long serum half-life, and good penetration into the cerebrospinal fluid) lend promise to pursue other triazole antifungals at higher doses as primary therapy and less frequent dosing for maintenance therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection.

BACKGROUND AND METHODS: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Effect of indomethacin on the pathophysiology of experimental meningitis in rabbits.

The effects of indomethacin on central nervous system abnormalities in rabbits with experimental pneumococcal meningitis were studied. As expected, prostaglandin E2 levels in cerebrospinal fluid were significantly lower in the indomethacin-treated group, indicating that the drug effectively reduced prostaglandin synthesis. Brain edema was markedly attenuated in the indomethacin-treated group; however, cerebrospinal fluid white blood cell counts, lactate and protein concentrations, and intracisternal pressure were not significantly different between groups. It seems that indomethacin, while effective in reducing brain edema, does not significantly affect other important pathophysiologic alterations in experimental pneumococcal meningitis.

Animals↗
PubMed1991

Natural history of disseminated Mycobacterium avium complex infection in AIDS.

This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The pharmacokinetics of teicoplanin in varying degrees of renal function.

The pharmacokinetics of teicoplanin, a new glycopeptide antibiotic with activity against aerobic gram-positive bacteria, were characterized after intravenous administration of a single 3 mg/kg dose in five healthy volunteers and six patients with various degrees of stable renal insufficiency. Serum and urine samples were collected during a 15-day period and drug concentrations were assayed microbiologically. The mean elimination half-life of teicoplanin was 162.6 +/- 69.8 hours in healthy volunteers and was prolonged with decreased renal function. The mean plasma and renal clearances of teicoplanin in healthy subjects were 11.4 +/- 1.5 ml/min and 10.0 +/- 1.0 ml/min, respectively. Both values decreased in patients with renal failure and correlated significantly with measured creatinine clearances (r2 = 0.938 and 0.884, respectively). A nomogram for dosage adjustment in patients with varying degrees of renal failure is presented.

Adult↗