Membrane differentiation in the golgi apparatus of mammalian urinary bladder epithelium

The endomembrane system in superficial and intermediate epithelial cells of mammalian urinary bladder was studied by cytochemistry, thin-section and freeze-fracture electron microscopy to determine the sites where special forms of membrane differentiation first appear. Glutaraldehyde-resistant NADH-ferricyanide reductase, distinctive 11–12 nm intramembrane particles (IMP), and asymmetry of membrane leaflets served as markers of membrane maturation. The three markers were specifically associated with the maturing face of Golgi apparatus and were absent from the remainder of the endomembrane system. Activity of this enzyme was associated with the lateral regions of the maturing face, fusiform vesicles, and the plasmalemma. Asymmetric unit membrane (AUM) plaques were not observed in the Golgi apparatus per se but were present in immature fusiform vesicles that had not detached from the maturing face. When freeze-fracture replicas and thin sections were compared, randomly arranged 11–12 nm IMP first appeared in maturing face membranes that were adjacent to clusters of “free” polyribosomes in the Golgi apparatus region. The proximity of these polyribosomes suggests that they may be related to the coincident appearance of the 11–12 nm IMP in the maturing face membrane. Our observations support the hypothesis that membranes undergo differentiation during “flow” through compartments of the endomembrane system. The lateral regions of the maturing face of the Golgi apparatus appear to be a critical location for the morphogenesis of plasma membranes in urinary bladder.     

Controlled clinical comparison of BACTEC plus anaerobic/F to standard anaerobic/F as the anaerobic companion bottle to plus aerobic/F medium for culturing blood from adults

To determine the optimal anaerobic companion bottle to pair with BACTEC Plus Aerobic/F medium for recovery of pathogenic microorganisms from adult patients with bacteremia and fungemia, we compared Plus Anaerobic/F bottles with Standard Anaerobic/F bottles, each of which was filled with 4 to 6 ml of blood. The two bottles were paired with a Plus Aerobic/F bottle filled with 8 to 12 ml of blood. A total of 14,011 blood culture sets were obtained. Of these, 11,583 sets were received with all three bottles filled adequately and 12,257 were received with both anaerobic bottles filled adequately. Of 818 clinically important isolates detected in one or both adequately filled anaerobic bottles, significantly more staphylococci (P < 0.001), streptococci (P < 0.005), Escherichia coli isolates (P < 0.02), Klebsiella pneumoniae isolates (P < 0.005), and all microorganisms combined (P < 0.001) were detected in Plus Anaerobic/F bottles. In contrast, significantly more anaerobic gram-negative bacilli were detected in Standard Anaerobic/F bottles (P < 0.05). Of 397 unimicrobial episodes of septicemia, 354 were detected with both pairs, 30 were detected with Plus Aerobic/F-Plus Anaerobic/F pairs only, and 13 were detected with Plus Aerobic/F-Standard Anaerobic/F pairs only (P < 0.05). Significantly more episodes of bacteremia caused by members of the family Enterobacteriaceae (P < 0.05) and aerobic and facultative gram-positive bacteria (P < 0.025) were detected with Plus Anaerobic/F bottles only. In a paired-bottle analysis, 810 of 950 isolates were recovered from both pairs, 90 were recovered from Plus Aerobic/F-Plus Anaerobic/F pairs only, and 50 were recovered from Plus Aerobic/F-Standard Anaerobic/F pairs only (P < 0.001). Paired Plus Aerobic/F-Plus Anaerobic/F bottles yielded significantly more staphylococci (P < 0.001), streptococci (P < 0.05), and members of the family Enterobacteriaceae (P <0.001). We conclude that Plus Anaerobic/F bottles detect more microorganisms and episodes of bacteremia and fungemia than Standard Anaerobic/F bottles as companion bottles to Plus Aerobic/F bottles in the BACTEC 9240 blood culture system.     

Estrogen use in postmenopausal women--costs, risks, and benefits

The cost effectiveness of estrogen use in postmenopausal women was analyzed with use of data from the medical and epidemiologic literature. Risks of endometrial cancer, uterine bleeding, and gallbladder disease were weighed against benefits associated with relief of menopausal symptoms and with prevention of osteoporosis and consequent fractures. Net effects on life expectancy are probably small in either direction, although they are likely to be positive in women with existing osteoporosis or prior hysterectomy. Treatment appears to be relatively cost effective in menopausal women with prior hysterectomy or osteoporosis but does not appear to be cost effective as a prophylactiv measure in asymptomatic women with intact uteri. For women with menopausal symptoms and intact uteri, the decision to prescribe estrogens for the individual patient and the cost effectiveness of estrogen use at the societal level depend critically on the subjective values assigned to symptomatic relief.     

Sustained release theophylline for the forgetful asthmatic

Several theophylline pharmacologic strategies were tested for the forgetful medication-dependent asthmatic who frequently initiates treatment from below the therapeutic range of 10 to 20 micrograms/mL. Theodur was found to give comparable if not higher levels (two, eight, and 24 hours) starting from 0 microgram/mL than Slophyllin Gyrocap during a multiple dose 28-hour study. In a single dose 12-hour study, Theodur 100-mg tablets gave higher levels during the first nine hours than Theodur 200-mg tablets. Theodur 100-mg tablets may be preferred for the forgetful asthmatic who can sustain pulmonary function despite greater fluctuation with theophylline levels.     

Blood flow dynamics in different layers of the somatosensory region of the cerebral cortex on the rat during mechanical stimulation of the vibrissae

The present work reports studies of the quantitative spatial and temporal characteristics of changes in local blood flow in different layers of the somatosensory cortex of rats during adequate mechanical stimulation of the vibrissae. Studies were performed using 34 Wistar rats. Skull trepanning was performed under urethane (1 g/kg) anesthesia. Television-guided microscopy was used to introduce a set of three platinum electrodes (100 μm in diameter, with tip diameters of 30–40 μm) into the somatosensory cortex projection zone of the vibrissae. The first and third electrodes were positioned in cortical layers I–III and IV–VI and the central electrode was used to generate hydrogen within the tissue. Electrode positions were confirmed histologically after experiments. Animals were placed on artificial ventilation and one or all vibrissae were stimulated at a frequency of 3 Hz for 60 sec, with interstimulus intervals of 3 min. Changes in the local blood flow were measured during stimulation and for 1 min afterwards, using the hydrogen clearance method, and brain tissue impedance was also measured. There was a small (up to 5–7%) reduction in blood flow in the first seconds of stimulation, which was followed 15–25 sec later by an increase and subsequent return to initial when stimulation stopped. The increases in blood flow during stimulation of all vibrissae were by 24.2±6.7% (n=36) in layers IV–VI and 24.5±5.6% (n=34) in layers I–III; increases in response to stimulation of single vibrissae were by 19.4±7.4% (n=28) and 17.8±6.4% (n=28) respectively. The dynamics of impedance changes corresponded to those of blood flow changes. Thus, heterogeneity was found in changes of local brain blood flow in different layers of the somatosensory cortex during increases in cortical functional activity. Laboratory for Comparative Circulatory Physiology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia. Department of Experimental Neurology and Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, USA. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 4, pp. 67–76, April, 1997.     

Controlled evaluation of 5 versus 10 milliliters of blood cultured in aerobic BacT/Alert blood culture bottles.

Bottles developed for use in the BacT/Alert automated blood culture system (Organon Teknika Corp., Durham, N.C.) can accept up to 10 ml of blood without falling below a 1:5 ratio of blood to broth. We compared the yield and speed of detection of microorganisms in 13,128 adequately filled, paired, aerobic bottles inoculated with 5 versus 10 ml of blood at three university hospitals. A total of 798 microorganisms causing sepsis grew in one or both bottles. The overall recovery of microorganisms from 10-ml samples exceeded that from 5-ml samples (P < 0.001); the increased yield attributed to the additional 5 ml in the samples was 7.2%. The increased yield from 10-ml inocula was most marked for Escherichia coli (P < 0.01) and other members of the family Enterobacteriaceae (P < 0.001). Ten-milliliter samples did not yield more gram-positive bacteria, nonfermentative gram-negative rods, or yeasts. When both bottles were positive, the bottles inoculated with 10 ml of blood showed growth sooner (P < 0.001). Earlier detection with 10-ml inocula was especially notable for coagulase-negative staphylococci (P < 0.001), streptococci (P < 0.001), E. coli (P < 0.025), and other members of the family Enterobacteriaceae (P < 0.025). We conclude that an increase in the volume of blood inoculated into BacT/Alert aerobic blood culture bottles from 5 to 10 ml will increase the overall yield and the speed of detection of clinically important blood pathogens.     

Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease.

To determine if a normal antibody response can develop after therapy for Hodgkin's disease, we immunized 53 patients and 10 normal controls with dodecavalent pneumococcal vaccine. Antibody concentrations three weeks after immunization (geometric mean of 11 serotypes) were 1566 ng of protein nitrogen per milliliter in controls, 963 ng per milliliter after subtotal radiation (P less than 0.05 compared to controls), 658 ng per milliliter after chemotherapy (P less than 0.05), 377 ng per milliliter after subtotal radiation plus chemotherapy (P less than 0.01) and 283 ng per milliliter after total nodal radiation plus chemotherapy (P less 0.001). Low levels of antibody before immunization correlated with a poor response (r = +0.73, P less than 0.001). The ability to respond to immunization improved significantly but did not return to normal as long as four years after combined therapy. The antibody response to pneumococcal vaccine is profoundly impaired in patients who have received intensive treatment for Hodgkin's disease: the ability of this vaccine to protect them from overwhelming postsplenectomy infections remains in doubt.     

Demonstration of two types of fatigue in subjects with chronic liver disease using factor analysis

Purpose

The purpose of this investigation was to determine if it was possible to separate fatigue self-reports into two distinct types of fatigue symptom clusters in research subjects with chronic liver disease (CLD). It was hypothesized that when items from the Medical Outcomes Study Short-Form (SF-36v2) are combined with items from the Fatigue Severity Scale (FSS), these distinct factors will emerge.

Methods

Confirmatory and exploratory factor analyses from data collected in a prospective, natural history study of CLD patients were conducted. Items were selected from the SF-36v2 and the FSS for entry into the factor analyses. In order to establish convergent and discriminant validity, derived factor scores were correlated with subscale scores of the Human Activity Profile (HAP), Mental Component Score (MCS) from the SF-36v2, and the Emotional Functioning Subscale of the Chronic Liver Disease Questionnaire (CLDQ-EF).

Results

106 participants with CLD were included (50% female; age: 51?±?10). Two factors were identified. The factors included one that clustered around questions addressing fatigue related to physical activity (peripheral fatigue) and the other to the questions addressing generalized fatigue that did not require physical tasks to produce the fatigue (central fatigue). The standardized factor loadings of all items were greater than 0.6 on their underlying constructs. Moreover, all factor loadings are significant at p?<?0.01. Peripheral fatigue was related to HAP (r?=?0.26, r?=?0.24, p?<?0.01), as was central fatigue (r?=??0.34, r?=??0.33, p?<?0.01). Central fatigue was related to MCS and CLDQ-EF (r?=??0.60; r?=??0.63, p?<?0.01), whereas peripheral fatigue was not (r?=?0.07, p?>?0.40). We then tested the original scales to determine if the newly created factors correlated better with the validity measures. The full FSS did not correlate as well as the newly created central fatigue scale, while the original peripheral fatigue scale (the SF-36v2 physical functioning) was more related to HAP than the newly created scale.

Conclusions

In individuals with CLD, two separate factors pertaining to fatigue were identified. This recognition of the multifaceted nature of fatigue may help increase the specificity of self-reports of fatigue and lead to treatments that can specifically address the underlying factors contributing to fatigue.