Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers.

Pulse oximetry is a standard of care during anaesthesia in high-income countries. However, 70% of operating environments in low- and middle-income countries have no pulse oximeter. The 'Lifebox' oximetry project set out to bridge this gap with an inexpensive oximeter meeting CE (European Conformity) and ISO (International Organization for Standardization) standards. To date, there are no performance-specific accuracy data on this instrument. The aim of this study was to establish whether the Lifebox pulse oximeter provides clinically reliable haemoglobin oxygen saturation (Sp O2 ) readings meeting USA Food and Drug Administration 510(k) standards. Using healthy volunteers, inspired oxygen fraction was adjusted to produce arterial haemoglobin oxygen saturation (Sa O2 ) readings between 71% and 100% measured with a multi-wavelength oximeter. Lifebox accuracy was expressed using bias (Sp O2 - Sa O2 ), precision (SD of the bias) and the root mean square error (Arms). Simultaneous readings of Sa O2 and Sp O2 in 57 subjects showed a mean (SD) bias of -0.41% (2.28%) and Arms 2.31%. The Lifebox pulse oximeter meets current USA Food and Drug Administration standards for accuracy, thus representing an inexpensive solution for patient monitoring without compromising standards.

Distinct long-term neurocognitive outcomes after equipotent sevoflurane or isoflurane anaesthesia in immature rats.

BACKGROUND: Many anaesthetics when given to young animals cause cell death and learning deficits that persist until much later in life. Recent attempts to compare the relative safety or toxicity between different agents have not adequately controlled for the relative dose of anaesthetic given, thereby making direct comparisons difficult. METHODS: Isoflurane or sevoflurane were given at 1 minimum alveolar concentration (MAC) for 4 h to postnatal day 7 (P7) rat pups. Beginning at P75 these animals underwent fear conditioning and at P83 Morris water maze testing to assess working memory, short-term memory and early long-term memory using delays of 1 min, 1 h, and 4 h. RESULTS: No difference between groups was seen in fear conditioning experiments. Morris water maze learning was equivalent between groups, and no difference was seen in working memory. Sevoflurane-treated animals had a deficit in early long-term memory, and isoflurane-treated animals had a deficit in both short-term and early long-term memory. CONCLUSIONS: Both isoflurane and sevoflurane delivered at 1 MAC for 4 h to immature rats caused a deficit in long-term memory. Isoflurane also caused a deficit in short-term memory. Isoflurane might be more detrimental than sevoflurane in very young animals.

Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study.

PURPOSE: Somatostatin (SST) analogues have been used to treat proliferative diabetic retinopathy, pseudotumor cerebri, thyroid orbitopathy, and cystoid macular edema. There is a paucity of published data in regards to cell-specific distribution of SST receptors (SSTR) in normal human eye tissues. Gene expression for all five known SSTRs in normal human ciliary body/iris, retina, choroid, and cultured retinal pigment epithelial (RPE) cells were studied. METHODS: mRNA was isolated from human ocular tissues (iris/ciliary body, retina, and choroid) dissected from eight pairs of normal eyes (9-62 years) and from RPE cells grown in culture. RT-PCR was done for all five SSTRs in all analyzed tissues. Immunohistochemistry for SSTR1 and SSTR2 was performed on eight pairs of normal human eyes (28-74 years) imbedded in paraffin. RESULTS: SSTR1 to 5 genes are expressed in retina, SSTR1 and SSTR2 genes in cultured RPE cells, and SSTR1, 2, and 4 in ciliary body and choroid. SSTR1 and SSTR2 immunoreactivity (-ir) was observed on a variety of cells within all analyzed tissues including cornea, iris, trabecular meshwork, Schlemm's canal, ciliary processes, ciliary muscle, retina, choroid, cultured RPE cells, and optic nerve. CONCLUSIONS: SSTR genes are widely expressed in normal human eye tissues, with genes for SSTR1 and SSTR2 being the most widely expressed. Genes for all SSTRs are expressed in retina. SSTR1-ir and SSTR2-ir were observed in all analyzed ocular tissues. Detailed knowledge of SSTRs distribution and function in the human eye will result in a better understanding of their role in health and disease.

Neurally mediated hypotension in fatigued Gulf War veterans: a preliminary report.

BACKGROUND: Many patients with chronic fatigue syndrome (CFS) have neurally mediated hypotension when subjected to head-up tilt, suggesting autonomic nervous system dysfunction. Some Gulf War veterans have symptoms similar to CFS. Whether they also tend to have neurally mediated hypotension is unknown. METHODS: We performed 3-stage tilt-table testing on 14 Gulf War veterans with chronic fatigue, 13 unfatigued control Gulf War veterans, and 14 unfatigued control subjects who did not serve in the Gulf War. Isoproterenol was used in stages 2 and 3 of the tilt protocol. RESULTS: More fatigued Gulf War veterans than unfatigued control subjects had hypotensive responses to tilt (P < 0.036). A positive response to the drug-free stage 1 of the tilt was observed in 4 of 14 fatigued Gulf War veterans versus 1 of 27 unfatigued control subjects (P < 0.012). Heart rate and heart rate variation during stage 1 was significantly greater in the fatigued group (P < 0.05). CONCLUSION: We conclude that more fatigued Gulf War veterans have neurally mediated hypotension than unfatigued control subjects, similar to observations in CFS. Autonomic nervous system dysfunction may be present in some fatigued Gulf War veterans.

Biochemical aspects of flight and flightlessness in Gryllus: flight fuels, enzyme activities and electrophoretic profiles of flight muscles from flight-capable and flightless morphs.

Female Gryllus assimilis subjected to 4.5-7.7h continuous tethered flight had significantly lower amounts of total lipid, triglyceride and total soluble carbohydrate compared with unflown controls. A much greater amount of total lipid (6.3mg) was used during flight compared with carbohydrate (0.14mg). Flown individuals also had substantially reduced amounts of injected, radiolabeled [(14)C]-oleic acid. Activities of lipid, carbohydrate and amino acid catabolizing enzymes in flight muscles of G. assimilis and its wing-polymorphic congener, G. firmus, were very similar to activities in insects which primarily utilize lipid to power flight. By contrast, enzyme activities were very different from those in insects which primarily or exclusively use carbohydrate or proline as a flight fuel. These results strongly implicate lipid as the major flight fuel in Gryllus. Previous studies have shown that lipid levels are higher in flight-capable (long-winged) G. firmus that have small ovaries compared with flightless (short-winged) females that have large ovaries. Results of the present and previous studies collectively indicate that elevated lipid in long-winged G. firmus represents an energetic cost of flight capability which reduces (trade-offs with) reproduction in Gryllus. In G. firmus, mass-specific activities of nearly all enzymes were considerably reduced in underdeveloped, and to a lesser degree in histolyzed muscle, compared with fully-developed flight muscle. An important exception was alanine aminotransferase, whose activity was the highest in histolyzed muscle, and which may be involved in the catabolism of amino acids derived from muscle degradation. Despite the dramatic differences in enzyme activity, electrophoretic profiles of soluble flight-muscle proteins differed only subtly between fully-developed and underdeveloped or histolyzed flight muscles.

Cellular and subcellular heterogeneity of glutathione metabolism and transport in rat kidney cells.

Selective permeabilization of plasma membranes with digitonin produced separation of cytosolic and mitochondrial compartments of proximal tubular (PT) and distal tubular (DT) cells from a rat kidney. Subcellular distributions of several intracellular glutathione (GSH)-dependent enzymes were similar in the two cell types but specific activities were significantly higher in PT cells, indicating that DT cells, particularly in their mitochondrial fraction, have a diminished capacity to detoxify reactive oxygen species. To enable isolation of suspensions of mitochondria, renal cells were treated with digitonin followed by the bacterial protease nagarse and were filtered through polycarbonate membranes. Activity distributions of enzymatic markers for subcellular fractions were quantitated and uptake of GSH was studied in suspensions of PT and DT cell mitochondria. While PT cell mitochondria catalyzed rapid uptake of GSH that was inhibited by malate, indicating involvement of dicarboxylate carriers, DT cell mitochondria exhibited limited capacity for GSH uptake that was not inhibited by substrates for the two dicarboxylate carriers. This report provides the first description of methodology for the preparation of mitochondria from renal cells derived from specific nephron cell types and shows that mitochondria from DT cells have a significantly lower capacity to use GSH for detoxification and regulation of redox status.

Flight-muscle polymorphism in the cricket Gryllus firmus: muscle characteristics and their influence on the evolution of flightlessness.

Flight muscles of the cricket Gryllus firmus are polymorphic, existing as pink or white phenotypes. White muscles are smaller in size, have reduced number and size of muscle fibers, and have reduced in vitro enzyme activities and respiration rates relative to pink muscles of newly molted, fully winged adults. G. firmus is also polymorphic for wing length. All newly molted long-winged adults exhibited the pink-muscle phenotype, while most newly molted short-winged adults exhibited the white-muscle phenotype, which resulted from arrested muscle growth. As long-winged adults aged, fully grown pink muscle was transformed into white muscle via histolysis. The substantially higher respiration rate of pink muscle likely contributes to the elevated whole-organism respiration rate of long-winged females, which has been documented previously and which is thought to divert nutrients from egg production. Histolyzed white flight muscle from long-winged crickets also exhibited significantly elevated respiration rate and enzyme activities compared with underdeveloped white muscle from short-winged adults, although these differences were not as great as those between pink and white muscles. Fecundity was much more elevated in females with white verus pink flight muscles than it was in females with short versus long wings. The fitness gain resulting from flightlessness has typically been estimated in previous studies by comparing enhanced egg production of short-winged and long-winged females, without considering the influence of flight-muscle variation. Our results suggest that the magnitude of this fitness gain has been substantially underestimated.

Alterations in CNS gene expression in a rodent model of moderate traumatic brain injury complicated by acute alcohol intoxication.

The combined effects of acute alcoholic intoxication and moderate traumatic brain injury (TBI) on zif/268, glial fibrillary acidic protein (GFAP), and preproenkephalin (PPE) mRNA expression were examined. Adult male Wistar rats received ip injections of a 5% alcohol solution (2.4 g/kg in a final volume of 20 ml isotonic saline) 10 min prior to fixed-head, mechanical injury. Using Northern analysis, a transient three- to fourfold induction of zif/268 mRNA levels was observed 45 min after injury in both TBI and alcohol-treated rats. This induction occurred in regions close to the impact site, namely, the olfactory bulb (OB) and frontal cortex (FTCTX) but not in the more distal piriform/amygdala cortex (P/A). No PPE mRNA changes were observed at 45 min for any experimental group. By 6 h, zif/268 transcript levels returned to or fell below basal levels in the OB and FTCTX while GFAP mRNA levels began to increase in TBI rats. At 24 h, GFAP mRNA levels were greatly increased in all three brain regions of TBI rats. However, alcohol inhibited the temporal induction of GFAP mRNA in the FTCTX and P/A triggered by TBI at 6 and 24 h. These results suggest that although acute alcohol intoxication prior to TBI does not influence gene expression patterns immediately after injury, it may minimize the transcriptional activation of astrocytes particularly in more distant brain regions that were influenced by the impact in nonintoxicated rats.

Histopathologic consequences of moderate concussion in an animal model: correlations with duration of unconsciousness.

Although duration of unconsciousness is commonly used as a prognostic index following traumatic brain injury (TBI), few controlled studies have statistically evaluated the relationship between unconsciousness and histologic pathology, particularly after moderate head injury. Using a pendulum-striker concussive device, a reproducible model of TBI in rats was developed. This model is uncomplicated by skull fractures, contusions, or experimenter-induced craniotomies. In the present study, the severity of the histopathology observed in this model of moderate closed-head injury at 48 h posttrauma is linearly related to the duration of unconsciousness (p < 0.0001). The pathology, assessed with a silver stain for neurodegeneration, is particularly striking if unconsciousness persists for 4 minutes or more. These data suggest that the initial period of unconsciousness may be a useful predictor of clinical brain histopathology associated with moderate closed-head injury, predicting either the degree of pathology and/or the rate it progresses if left untreated.

Cryosurgery in prostatic cancer: elimination of local lesion.

From 1969 through 1976, we performed cryosurgery in 229 cases of prostatic cancer. Most of these patients had bulky, locally extensive primary tumors, and one-half had disseminated disease. Through the open perineal approach, which gives exposure for an adequate freeze, cryosurgery has been well tolerated. The primary surgical goal has been to reduce or eliminate the local lesion to minimize subsequent cancer-related lower urinary tract problems and to cure those patients with truly localized disease. In every case cryosurgery produced dramatic shrinkage of the local lesion. After four to eight weeks a local recurrence was suspected in 13 per cent, and 41 per cent eventually had some evidence of a recurrent cancer nodule or persistent cancer in the bladder neck. In a series of statistical analyses we have related these recurrences to other clinical factors. Cryosurgery has been a safe, effective way to reduce or eliminate the primary prostatic cancer, even in patients with large local lesions.

Cryosurgery in prostatic cancer: survival.

From 1969 through 1976 we performed cryosurgery in 229 cases of prostatic cancer. This article presents survival in cryosurgery and other treatment groups. In every stage, despite a preponderance of large primary tumors and poor-risk patients, cryosurgery matched total prostatectomy and compared favorably to other modalities, including radiation therapy, at our center and elsewhere. According to previous authors, and in view of the present data, eradication of the local lesion is associated with better survival even in advanced cases. Cryosurgery provides a safe, effective method.

Cytologic effects of Thiotepa and Adriamycin on normal canine urothelium.

An experimental investigation was carried out to produce and observe controlled, sequential changes in normal bladder urothelium of female dogs caused by Thiotepa (triethylene thiophosphoramide) and Adriamycin (doxorubicin hydrochloride). Thiotepa (30 mg in 30 ml saline) was instilled for two hours into the bladders of five dogs at weekly intervals, and Adriamycin (1 ml/kg body weight) was given intravenously to five dogs at weekly intervals for a period of ten weeks. Control animals underwent only bladder irrigation with saline. Periodic catheterized urine and saline bladder irrigations and bladder biopsy specimens were obtained. After the tenth week all dogs were killed and autopsies conducted. Major observations in the experimental animals included cellular enlargement, bizarre cell shapes, cytoplasmic vacuolization, nuclear and nucleolar enlargement, multinucleation, pyknosis, karyorrhexis and infiltration by neutrophilic leukocytes. In some animals, reversion to a normal cytologic pattern occurred in the ten-week period. The application of these observations to human urinary cytopathology is discussed.