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Biomedical subjects

R D Meyer

Publications and source records attributed to R D Meyer.

At least 19 recordsLinked to original sources

A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group.

BACKGROUND: After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS: We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS: Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS: Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.

Acquired Immunodeficiency Syndrome

Medical management of AIDS patients. Bacterial and fungal infections.

The rapid and thus far generally inexorable rise in HIV infections has led to a series of opportunistic infection that includes those caused by bacteria, yeasts, and members of the Eumycetes. The infections range in prevalence from occasional to highly prevalent, in severity from trivial to fatal, and in anatomic areas involved from local to disseminated. They occur as isolated, concurrent, or sequential infections with regard to other opportunistic diseases. Some vary in their geographic distribution. They may be newly acquired or reactivated and occur early or late in the course of HIV infection. Bacterial infections are usually easily treated, although they frequently disseminate and often recur after seemingly appropriate treatment. In contrast, all but the mildest fungal infections are difficult to treat and even more difficult or impossible to eradicate. The diagnosis of bacterial and fungal infections begins with clinical suspicion and involves relatively standard methodology. Treatment of the systemic mycoses and some bacterial infections in HIV infected patients is punctuated by exaggerated side effects of therapy, frequent relapses, and the need for maintenance suppressive therapy.

Acquired Immunodeficiency Syndrome

Community-acquired pneumonia.

The aetiology of community-acquired pneumonia is reviewed, and the identification of the most likely pathogens, based on clinical presentation, is discussed. By far the major pathogen in community-acquired pneumonia is Streptococcus pneumoniae; the relative frequency of other pathogens, and particularly the atypical pneumonias caused by Mycoplasma and Legionella spp., will depend on local epidemiological factors. The diagnostic tests to confirm diagnosis and subsequent treatment of these infections are reviewed.

Anti-Bacterial Agents

Endoscopic carpal tunnel release: a cadaveric study.

Five surgeons performed endoscopic (Dyonics) carpal tunnel releases on 24 fresh cadaver wrists. In 50% of the specimens, transection of the transverse carpal ligament was incomplete. The average amount of incomplete release was 31% (range, 0% to 53%). Three types of incomplete release were noted: (1) release of Guyon's canal release--one, (2) incomplete distal ligament release--five, and (3) incomplete central or superficial release--six. Other technical errors were noted in nine of 24 specimens. There were no nerve lacerations. Endoscopic carpal tunnel release is either a technically demanding procedure, commonly results in incompletely released ligaments, or both. Proper training, followed by practice on several cadaver specimens before its clinical use, is recommended.

Anthropometry

Septic arthritis and bacteremia due to Mycoplasma resistant to antimicrobial therapy in a patient with systemic lupus erythematosus.

We report a case of septic arthritis caused by Mycoplasma hominis in a patient with systemic lupus erythematosus. The infection started as monarthritis but spread to at least four joints despite apparently suitable therapy with various antimicrobial agents, including doxycycline, clindamycin, and ciprofloxacin; subsequent bacteremia was documented. Control was ultimately achieved with use of the experimental fluoroquinolone temafloxacin in combination with doxycycline administration, arthroscopic drainage of a persistently infected joint, several intravenous infusions of immunoglobulins (which led to increases in levels of antibodies specific to M. hominis), and discontinuation of corticosteroid therapy. Antimicrobial susceptibility testing of various mycoplasmal isolates showed the presence of the tetM gene, disparity between susceptibility to tetracycline and doxycycline, and increasing resistance to most antimicrobial agents used (including to fluoroquinolones before clinical use), although the patient ultimately had a favorable clinical response to treatment with combined modalities.

Adult

Evaluation of new anti-infective drugs for the treatment of respiratory tract infections. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines deal with the evaluation of anti-infective drugs for the treatment of respiratory tract infections. Five clinical entities are described: streptococcal pharyngitis and tonsillitis, otitis media, sinusitis, bronchitis, and pneumonia. A wide variety of microorganisms are potentially pathogenetic in these diseases; these guidelines focus on the bacterial infections. Inclusion of a patient in a trial of a new drug is based on the clinical entity, with the requirement that a reasonable attempt will be made to establish a specific microbial etiology. Microbiologic evaluation of efficacy requires isolation of the pathogen and testing for in vitro susceptibility. Alternatively, surrogate markers may be used to identify the etiologic agent. The efficacy of new drugs is evaluated with reference to anticipated response rates. Establishment of the microbial etiology of respiratory tract infections is hampered by the presence of "normal flora" of the nose, mouth, and pharynx, which may include asymptomatic carriage of potential pathogens. This issue is addressed for each category of infection described. For example, it is suggested that for initial phase 2 trials of acute otitis media and acute sinusitis tympanocentesis or direct sinus puncture be used to collect exudate for culture. Acute exacerbations of chronic bronchitis also present difficulties in the establishment of microbial etiology. These guidelines suggest that clinical trials employ an active control drug but leave open the possibility of a placebo-controlled trial. For pneumonia, the guidelines suggest the identification and enrollment of patients by the clinical type of pneumonia, e.g., atypical pneumonia or acute bacterial pneumonia, rather than by etiologic organism or according to whether it was community or hospital acquired. For each respiratory infection, the clinical response is judged as cure, failure, or indeterminate. Clinical improvement is not acceptable unless quantitative response measures can be applied.

Anti-Bacterial Agents

Current role of therapy with amphotericin B.

Systemic antifungal chemotherapy frequently is more difficult to conduct than antibacterial therapy. Factors that make it difficult include, but are not limited to, common biosynthetic pathways among the eukaryotes and humans, a relative lack of agents, imprecise modes of use, general lack of standardization of in vitro susceptibility tests that have clinical correlations, and, with certain exceptions, lack of clinical correlations with in vitro results of combination antifungal chemotherapy. Amphotericin B has been available for intravenous administration for greater than 30 years and, despite its shortcomings, remains the drug of choice or reference agent in the therapy for many specific systemic fungal infections in various clinical settings. The current role of amphotericin B therapy in these situations and the need for additional controlled, comparative clinical trials with azoles, liposomal amphotericin B, and amphotericin B complex are discussed.

Amphotericin B

Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection.

BACKGROUND: The rapidly evolving clinical picture of primary infection with the human immunodeficiency virus type 1 (HIV-1) suggests that a better understanding of the kinetics of viral replication in vivo during the short period before seroconversion may provide insight into the pathogenesis of the acquired immunodeficiency syndrome (AIDS). METHODS AND RESULTS: Titers of infectious HIV-1 were determined by end-point-dilution culture in sequential samples of plasma and peripheral-blood mononuclear cells from four patients with primary infection, with peak titers of 1000 to 10,000 tissue-culture-infective doses per milliliter of plasma and 100 to 10,000 infective doses per 10(6) peripheral-blood mononuclear cells. The high viral burden in mononuclear cells was confirmed by quantitative studies using a polymerase-chain-reaction method. In as little as 10 days, the high HIV-1 load in both plasma and cells decreased spontaneously and precipitously, at least 100-fold, in all four patients. CONCLUSIONS: Although p24 core antigenemia and viral isolation have previously been described during primary HIV-1 infection, this report documents the large viral burden during the acute phase of infection. The rapid and spontaneous decline in the viral load suggests an effective immune response in the host that, if understood, may be used to combat AIDS.

Acquired Immunodeficiency Syndrome

Brachial plexus microsurgery in children.

From this review, the following points have emerged: 1. The typical obstetrical palsy is a traumatic lesion caused by forced lowering of the shoulder during delivery. 2. While the lesion may affect all the roots, the upper roots are usually ruptured, whereas the lower roots (if involved) are always avulsed. 3. Spontaneous recovery is possible, but its quality depends on how early recovery of previously paralyzed muscles begins. If the biceps have not started to recover by 3 months, the final result will be poor. It is at this time interval that a surgical decision should be made. 4. Surgical repair is always possible, usually by grafting, though repair can be difficult if significant numbers of avulsions have occurred. 5. The results of surgical reconstruction are better than are the results of spontaneous evolution, at least in those patients who reach the age of 3 months without evidence of recovery of the biceps. For example, more than half of the patients recover a nearly normal shoulder after grafting C5, C6 lesions in Gilbert's series, whereas in the same control population of patients, none achieved this result spontaneously. 6. Palliative treatment of the sequelae of birth palsies is difficult, and the results obtained are rarely totally satisfactory. It is for these reasons that the initial surgical intervention should be on the plexus itself in those instances meeting the criteria established above. It is important to make this decision as quickly as possible before neuroplasticity is diminished and joint contractions have occurred.

Brachial Plexus

Inhaled or intravenous pentamidine therapy for Pneumocystis carinii pneumonia in AIDS. A randomized trial.

OBJECTIVE: To compare inhaled pentamidine with intravenous pentamidine for the treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome (AIDS). DESIGN: A randomized trial. SETTING: Community teaching hospital and hospital-based outpatient treatment center. PATIENTS: Twenty-one homosexual men with pneumocystis pneumonia; 11 received inhaled pentamidine and 10 received intravenous pentamidine. INTERVENTION: Inhaled (8 mg/kg body weight) or intravenous (4 mg/kg body weight) pentamidine administered daily for 21 days. MEASUREMENTS AND MAIN RESULTS: All patients responded to intravenous pentamidine, whereas 6 of 11 (55%; 95% CI, 23% to 83%; P = 0.02, Fisher exact test) responded to inhaled pentamidine therapy. Two patients who failed inhaled pentamidine therapy eventually died despite appropriate intravenous therapy (mortality rate, 18%; CI, -6% to 42%). Nonresponders to inhaled pentamidine had a greater severity of illness compared with responders to this therapy, as shown by a lower mean (+/- SE) Pao2 (8.0 +/- 0.4 kPa compared with 10.8 +/- 0.6 kPa; P = 0.005) and higher alveolararterial Po2 difference (6.8 +/- 0.6 kPa compared with 2.8 +/- 0.8 kPa; P = 0.003). CONCLUSIONS: Inhaled pentamidine is probably as effective as intravenous pentamidine in patients with mild pneumocystis pneumonia. However, its use as sole therapy in patients with moderate to severe pneumocystis pneumonia is not supported by the results of our study and is not warranted.

Acquired Immunodeficiency Syndrome

Triggering of the thumb with de Quervain's stenosing tendovaginitis.

Triggering with de Quervain's stenosing tenosynovitis has rarely been mentioned since de Quervain's original description. Either or both the abductor pollicis longus and extensor pollicis brevis tendons may be responsible. Without detailed examination testing specifically for triggering, the entity may be overlooked. We have encountered nine patients with triggering in the first dorsal compartment. The five with surgical release had complete resolution of symptoms; the four treated nonoperatively have improved but still have symptoms. Triggering may represent a more severe form of de Quervain's tendovaginitis.

Adult

Seroprevalence of human T cell leukemia viruses in selected populations of homosexual men.

This study sought to define the seroprevalence of human T cell leukemia virus (HTLV) types I and II in selected populations of homosexual men. Serum specimens were screened for antibodies to HTLV and to human immunodeficiency virus (HIV) by enzyme immunoassay; successive testing of specimens with positive results was done by Western blotting and radioimmunoprecipitation assay (RIPA) and then by polymerase chain reaction (PCR) assay on available peripheral blood mononuclear cells (PBMC). Of 1290 specimens, only 4 had antibodies against HTLV confirmed by RIPA. PCR analysis of DNA from PBMC from two subjects showed one to be HTLV-I and the other to be HTLV-II; both men also had HIV antibodies. These results demonstrate a lower seroprevalence rate for HTLV than some previous studies and emphasize the need for specific confirmatory tests.

Blotting, Western

Candidal pyarthrosis in an AIDS patient.

The unusual occurrence of a case of indolent Candida albicans pyarthrosis arising as a late complication in a 57-year-old male patient with AIDS, despite prior treatment with amphotericin B for candidemia, is reported. The case is discussed in the context of candidal pyarthrosis and of the rarely reported other fungal arthridites in AIDS patients.

Acquired Immunodeficiency Syndrome

Epithelioid angiomatosis or cat scratch disease with splenic and hepatic abnormalities in AIDS: case report and review of the literature.

Cat scratch disease (CSD) in the setting of HIV infection is associated with lesions of epithelioid angiomatosis but not with granulomatous lesions seen in the normal host. We report a case of CSD in a patient with AIDS and Kaposi's sarcoma with epithelioid angioma of skin, thrombocytopenia, and abnormalities of liver, spleen, lymph node, and pleura that responded to antimicrobial therapy. We also review reported cases of epithelioid angiomatosis in HIV infections. 12 of these resolved, including 3 without antimicrobial therapy; 18 demonstrated pleomorphic organisms with Warthin-Starry silver stain. Six involved visceral or bony as well as skin lesions. CSD should be considered in the setting of HIV infection with skin nodules even in the presence of biopsy-proven Kaposi's sarcoma. CSD may in these patients be responsible for a variety of disseminated lesions which respond to antimicrobial therapy.

Acquired Immunodeficiency Syndrome

[Legionaire's disease (author's transl)].

In a review of all cases of legionaire's disease known so far the epidemiology, diagnosis and therapy of this disease are discussed. Risk factors have been shown to be stays in hotels and hospitals, especially if the rooms were subject to faulty air conditioning, water containers or to earthworks. Furthermore, the male sex and an immunosuppressive therapy were established as risk factors. The diagnosis can only be confirmed by increased titer in the indirect fluorescence test. Erythromycin and Rifampicin (as a supplementary medication) have proved the antibiotics of choice.

Air Pollutants