Value of noninvasive studies in community-acquired pneumonia

Noninvasive diagnostic studies, i.e., sputum gram stain, sputum culture, blood culture and antigen detection assays will assist the clinician in the selection of initial antimicrobial therapy in some patients. These tests may be even more valuable in adjusting treatment regimens to prevent the use of broad spectrum antimicrobial agents as routine therapy.     

Evaluating DSM: can an engineer count on it? A short note papersummarizing a panel session at the July 1992 summer power meeting

There is an increasing interest in demand-side management (DSM) by utilities and regulators throughout the USA. With this interest, there is an increasing need for DSM evaluation. Regulators expect utility engineers to use least cost planning and integrated resource planning approaches to adjust their generation capacity plans to reflect DSM. Increasingly, utilities are considering DSM to affect their T&D capacity plans. However, major utility DSM programs are less than a decade old. This leaves many utility engineers uneasy. How do they know that DSM will be there when they really need it? To verify and improve the contribution of DSM programs, utility analysts have developed a set of methodologies and procedures for evaluating DSM. The purpose of this panel session was to review these state of the art evaluations and the lessons learned from them so far. The authors explore the differences inherent in evaluating DSM at the T&D level versus the generation level, and review DSM's persistence and reliability in the residential, commercial, and industrial sectors     

Clinical relevance of the baboon as a model for the study of endometriosis

OBJECTIVE: To review the value of the baboon as a model for the study of endometriosis. DATA IDENTIFICATION AND SELECTION: Studies performed at the Institute of Primate Research in Nairobi, Kenya (1990-1994), and published in peer-reviewed journals. RESULT(S): Spontaneous endometriosis was found in about 25% of the baboons, and its prevalence increased with the duration of captivity. The laparoscopic appearance, pelvic localization, and microscopic aspects of the disease were similar to endometriosis in women. Microscopic endometriosis in macroscopically normal peritoneum was rare. Sampson's hypothesis (i.e., retrograde menstruation causes endometriosis) was supported by the increased incidence of retrograde menstruation in baboons with spontaneous endometriosis, the observation that cervical occlusion could cause retrograde menstruation and endometriosis, and the finding that intrapelvic injection of menstrual endometrium caused experimental moderate to severe endometriosis similar to the spontaneous disease. During follow-up of more than 2 years, endometriosis in baboons appeared to be a progressive disease, with active remodeling between several types of lesions. Progression was stimulated by high-dose immunosuppression. Fertility was normal in baboons with minimal disease but was reduced in baboons with mild, moderate, or severe endometriosis, possibly related to an increased incidence and recurrence of the luteinized unruptured follicle syndrome. CONCLUSION(S): The baboon is a good model for the study of endometriosis.     

Effect of ifosfamide treatment on glutathione and glutathione conjugation activity in patients with advanced cancers

Several studies have suggested that the glutathione/glutathione S-transferase (GSH/GST) system is involved in resistance of tumors toward ifosfamide and other cytostatic agents. Besides, ifosfamide metabolites (in vitro) as well as ifosfamide treatment (in vivo) have been shown to decrease cellular GSH availability. In the present study, the in vivo effects of three different ifosfamide treatment schedules on the GSH/GST system were studied in patients with advanced cancers (n = 24): continuous i.v. infusions of 1300 mg/m2 daily for 10 days and 5000 mg/m2/day for 24 h, as well as a 4-h infusion of 3000 mg/m2 daily for 3 days. The GSH/GST system was characterized by administering bromisoval, a probe drug to assess GSH conjugation activity in vivo, as well as by daily monitoring of GSH concentrations in blood cells and plasma. Bromisoval pharmacokinetics was assessed before and at the end of the ifosfamide treatment. Blood cell GSH levels decreased significantly (P < 0.05) during the 3- and 10-day ifosfamide treatment schedules; the 24-h treatment had no effect. The ifosfamide treatment schedules had only minimal effects on bromisoval pharmacokinetics. Assuming that the kinetics of the probe drug provide an accurate reflection of enzyme activity, this suggests that GST activity remains unchanged. Because GSH conjugation of bromisoval enantiomers requires both GST activity and GSH availability, these results also indicate that, despite the 35% decrease in GSH in blood cells of two patient groups, the GSH availability of the cancer patients was not rate-limiting for GSH conjugation of bromisoval enantiomers. If GSH levels in blood cells reflect those in tumors/other tissues, the present results indicate that ifosfamide may be used clinically to decrease GSH levels. However, whether a 35% decrease is sufficient to increase tumor sensitivity toward (other) cytostatics remains uncertain.