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Biomedical subjects

C B Wofsy

Publications and source records attributed to C B Wofsy.

31 records · Page 2Linked to original sources

Use of a specific and sensitive assay to determine pentamidine pharmacokinetics in patients with AIDS.

The first-dose pharmacokinetics of pentamidine were studied in patients with AIDS. Pentamidine isethionate (4 mg/kg) was administered intramuscularly or intravenously to two groups of six patients each. Serial plasma and urine concentrations were measured by high-performance liquid chromatography, which is accurate and precise (sensitivity limits, 2.29 ng/ml in plasma and 229 ng/ml in urine). The mean peak concentrations in plasma after intramuscular and intravenous administration were 209 ng/ml and 612 ng/ml, respectively. Plasma concentrations, which declined biexponentially, were detectable throughout the 24-hr dosing interval and fell to less than 25 ng/ml after 8 hr. The mean plasma clearance, elimination half-life, apparent volume of distribution, and apparent volume at steady state for intramuscularly treated patients were 305 liters/hr, 9.36 hr, 924 liters, and 2,724 liters, respectively; these parameters for intravenously treated patients were 248 liters/hr, 6.40 hr, 140 liters, and 821 liters, respectively. Renal clearance of pentamidine was 5.0% of the plasma clearance for intramuscularly treated patients and 2.5% for intravenously treated patients. We found significant differences in the pharmacokinetic parameters between intramuscularly and intravenously treated patients.

Acquired Immunodeficiency Syndrome↗

Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial.

Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate. The two groups did not differ significantly in the severity of pulmonary or systemic processes at enrollment. Five patients treated initially with trimethoprim-sulfamethoxazole and one patient treated initially with pentamidine died during the 21-day treatment period (p = 0.09, Fisher's exact test). No significant differences were seen between groups in rates of improvement, pulmonary function tests, or 67Ga uptake by the lungs in the survivors at completion of therapy. Adverse reactions necessitated changing from the initial drug in 10 patients in the trimethoprim-sulfamethoxazole group and 11 in the pentamidine group. Minor reactions occurred in all patients. In patients with AIDS, trimethoprim-sulfamethoxazole and pentamidine do not have statistically significant differences in efficacy or frequency of adverse reactions.

Acquired Immunodeficiency Syndrome↗

Once-daily ceftriaxone for skin and soft tissue infections.

We prospectively compared once-daily administration of ceftriaxone with cefazolin given every 8 h for the treatment of skin and soft tissue infections. Thirty-one patients received cefazolin for a mean of 4.5 days, and 26 patients received ceftriaxone for a mean of 4.0 days. All patients had a satisfactory response. Adverse reactions were few and reversible. Ceftriaxone given as a single daily intramuscular injection is effective therapy for skin and soft tissue infections.

Adult↗

Abdominal CT findings of disseminated Mycobacterium avium-intracellulare in AIDS.

Disseminated infection from Mycobacterium avium-intracellulare (MAI) has recently been recognized as a common and serious complication of the acquired immunodeficiency syndrome (AIDS). The authors report the computed tomographic (CT) findings of 17 patients with AIDS and disseminated MAI referred for abdominal CT examination. Multiple large retroperitoneal and mesenteric lymph nodes were demonstrated in 14 patients (82%). MAI involvement was confirmed within abdominal lymph nodes in six patients by fine-needle percutaneous aspiration (five patients) or postmortem examination (one patient) and within enlarged peripheral lymph nodes in two other patients. The authors concluded that large, bulky, intraabdominal adenopathy in AIDS patients should suggest the diagnosis of MAI infection as well as other known causes of adenopathy, including lymphoma and metastatic Kaposi sarcoma. The authors recommend percutaneous aspiration of enlarged intraabdominal lymph nodes to establish the correct diagnosis.

Acquired Immunodeficiency Syndrome↗

The acquired immune deficiency syndrome: an international health problem of increasing importance.

The Acquired Immune Deficiency Syndrome (AIDS) is a new disease which first appeared in human populations about 1979. The disease is defined by the development of unusual types of cancer (e.g. Kaposi's sarcoma), or severe cellular immunodeficiency manifested by opportunistic infections (e.g. Pneumocystis carinii infection), or both. Although the etiology of AIDS is unknown, the epidemiologic evidence is consistent with an infectious agent transmitted by blood (e.g. transfusion, needle sharing) or sexual intercourse. Over three-quarters of the cases have been in homosexual or bisexual males and in intravenous drug abusers; about 5% of cases do not have recognized risk factors. A small number of cases have resulted from transfusion of blood or blood products. The early clinical manifestations are non-specific, and may include asymptomatic skin lesions, dyspnea and dry cough, weight loss, chronic diarrhea, and focal and non-focal central nervous system findings. Treatment for the associated cancers and opportunistic infections may be successful in individual instances, but the underlying immunosuppression of AIDS appears to progress inexorably and the fatality rate approaches 100% within a few years from diagnosis. Although nosocomial transmission has not been documented, infection control guidelines have been developed by analogy with hepatitis B infection.

Acquired Immunodeficiency Syndrome↗

Adverse reactions to trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome.

We reviewed the charts of 38 patients with the acquired immunodeficiency syndrome who were treated for Pneumocystis carinii pneumonia. Only 5 of 37 patients started on trimethoprim-sulfamethoxazole were able to complete treatment; in 29 patients drug toxicity occurred and in 19 treatment was changed due to adverse reactions that included rash, fever, neutropenia, thrombocytopenia, and transaminase elevation. Pentamidine was given to 30 patients (1 as initial treatment); toxicity occurred in 13 but only 4 required a change in drug. Adverse reactions from pentamidine included fever, rash, neutropenia, transaminase elevation, azotemia, and hypoglycemia. Patients received trimethoprim-sulfamethoxazole a median of 9.5 days, and pentamidine, a median of 12.5 days. Toxicity from trimethoprim-sulfamethoxazole appeared earlier than toxicity associated with pentamidine (7.5 versus 9.5 days of treatment). In patients with the acquired immunodeficiency syndrome, trimethoprim-sulfamethoxazole has a higher incidence of adverse reactions than pentamidine (p less than 0.005).

Acquired Immunodeficiency Syndrome↗

An outbreak of Pneumocystis carinii pneumonia in homosexual men.

Pneumocystis carinii pneumonia has rarely been reported in previously healthy persons over the age of 6 months. Five cases of P. carinii pneumonia in adult homosexual men, confirmed by biopsy results, are reported. All five patients were seropositive when tested for antibodies to cytomegalovirus and four had evidence of active concurrent cytomegalovirus infections. Kaposi's sarcoma was shown in two of the patients and one had possible Pneumocystis infection of the central nervous system as well as P. carinii pneumonia. Three patients had second episodes of Pneumocystis pneumonia. Four of the five patients have died. Past or concurrent cytomegalovirus infection and homosexuality were the only common epidemiologic features in all five patients.

Adult↗

Effectiveness of nurse triage in the emergency department of an urban county hospital.

The effectiveness of patient triage by a specially trained registered nurse in the emergency department of an urban county hospital, San Francisco General Hospital, was evaluated over a three-month period. Ambulatory patients thought to have nonemergent illnesses were directed to the Walk-In Service for physician evaluation and treatment; the remainder were seen in the Emergency Service. In three months, 11,329 patients registered for care, and 4,150 (37%) were referred to the Walk-In Service. Of the 77 admitted patients, six were thought to require treatment within a few hours, 67 within hours to days, and four were considered elective admissions. There were no deaths. Error in triage was about equally divided between mistaken diagnosis and underestimated severity of illnes. The overall accuracy of triage was 98%.

Adolescent↗

Use of trimethoprim-sulfamethoxazole in the treatment of Pneumocystis carinii pneumonitis in patients with acquired immunodeficiency syndrome.

This report reviews the use of trimethoprim-sulfamethoxazole (TMP-SMZ) in individuals with Pneumocystis carinii pneumonitis (PCP) and the acquired immunodeficiency syndrome (AIDS). Before AIDS, TMP-SMZ was at least as effective as pentamidine in pediatric and adult populations and was notably less toxic. In a study prospectively comparing TMP-SMZ with pentamidine in patients with AIDS, the toxicity associated with either therapy was very high, a problem suggesting a need for the development of additional types of therapy. There was no difference in the clinical responses to the different therapeutic regimens; the majority of patients showed some improvement. The rates of both major and minor toxic reactions were similar in the two groups, although the reactions differed qualitatively. In patients with AIDS rash was frequently associated with TMP-SMZ therapy and was almost never associated with pentamidine therapy. Neutropenia was common with both drugs. Pentamidine may produce hypoglycemia, which, though infrequent, may be life threatening. Neutropenia and rash are two adverse effects of TMP-SMZ therapy being described with great frequency in patients with AIDS. Mild neutropenia is common in patients with AIDS, even when therapy is not being administered. The high rate of toxic reactions limits the usefulness of TMP-SMZ for routine prophylaxis.

Acquired Immunodeficiency Syndrome↗