Expanding conceptualizations of harm reduction: results from a qualitative community-based participatory research study with people who inject drugs.

BACKGROUND: The perspectives of people who use drugs are critical in understanding why people choose to reduce harm in relation to drug use, what practices are considered or preferred in conceptualizations of harm reduction, and which environmental factors interfere with or support the use of harm reduction strategies. This study explores how people who inject drugs (PWID) think about harm reduction and considers the critical imperative of equity in health and social services delivery for this community. METHODS: This community-based participatory research study was conducted in a Canadian urban centre. Using a peer-based recruitment and interviewing strategy, semi-structured qualitative interviews were conducted by and with PWID. The Vidaview Life Story Board, an innovative tool where interviewers and participant co-construct a visual "life-scape" using a board, markers, and customized picture magnets, was used to facilitate the interviews. The topics explored included injection drug use and harm reduction histories, facilitators and barriers to using harm reduction strategies, and suggestions for improving services and supports. RESULTS: Twenty-three interviews with PWID (14 men and 9 women) were analysed, with a median age of 50. Results highlighted an expanded conceptualization of harm reduction from the perspectives of PWID, including motivations for adopting harm reduction strategies and a description of harm reduction practices that went beyond conventional health-focused concerns. The most common personal practices that PWID used included working toward moderation, employing various cognitive strategies, and engaging in community activities. The importance of social or peer support and improving self-efficacy was also evident. Further, there was a call for less rigid eligibility criteria and procedures in health and social services, and the need to more adequately address the stigmatization of drug users. CONCLUSIONS: These findings demonstrated that PWID incorporate many personal harm reduction practices in their daily lives to improve their well-being, and these practices highlight the importance of agency, self-care, and community building. Health and social services are needed to better support these practices because the many socio-structural barriers this community faces often interfere with harm reduction efforts. Finally, "one size does not fit all" when it comes to harm reduction, and more personalized or de-medicalized conceptualizations are recommended.

Ecological analyses of the associations between injury risk and socioeconomic status, geography and Aboriginal ethnicity in British Columbia, Canada.

BACKGROUND: The current study examines what factors contribute to higher injury risk among Aboriginal peoples, compared to the total British Columbia (BC) population. We explore socioeconomic, geographic, and cultural factors, and combinations of these factors, that contribute to increased injury risk for Aboriginal peoples. This follows from our previously reported findings of improvements in injury risk over time for both the total and Aboriginal populations. DATA AND METHODS: We use provincial population-based linked health care databases of hospital discharge records. We identify three population groups: total BC population, and Aboriginal populations living off-reserve, or on-reserve. For each group we calculate age and gender-standardized relative risks (SRR) of injury-related hospitalization, relative to the total population of BC, for two 5-year time periods (1999-2003, and 2004-2008). We use custom data from the 2001 and 2006 long-form Censuses that described income, education, employment, housing conditions, proportion of urban dwellers, proportion of rural dwellers, and prevalence of Aboriginal ethnicity. We use multivariable linear regression to examine the associations between the census characteristics and SRR of injury. RESULTS: The best-fitting model was an excellent fit (R(2) = 0.905, p < 0.001) among the three population groups within Health Service Delivery Areas of BC. We find indicators in all three categories (socioeconomic, geographic, and cultural) are associated with disparity in injury risk. While the socioeconomic indicators (income, education, housing, employment) were shown to be highly correlated, only living in housing that needs major repair and occupational hazardousness, along with rural residence and Aboriginal ethnicity, remained in the final model. Our data show that cultural density is not associated with injury risk for Aboriginal peoples, and that living off-reserve is associated with reduced injury by improving socioeconomic and geographic conditions (compared to living on-reserve). Finally, our analyses show that Aboriginal status itself is associated with injury risk. CONCLUSIONS: Our findings confirm previous research indicating that geographical differences differentiate injury risk, including for Aboriginal populations, and that socioeconomic determinants are associated with health risks. Our analyses showing that Aboriginal status itself contributes to injury risk is new, but we can only speculate about pathway, and whether the causes are direct or indirect.

Prescription of methylphenidate to children and youth, 1990-1996.

BACKGROUND: There are concerns about the frequency and appropriateness of psychostimulant drug prescription to children. In order to identify unusual or unexpected patterns of use or prescribing, we reviewed prescription of methylphenidate (Ritalin) to children and adolescents aged 19 years or less in British Columbia between 1990 and 1996. METHODS: We obtained information about patients, physicians and prescriptions from British Columbia's Triplicate Prescription Program database for controlled drugs. Prescription data were available for the period Jan. 1, 1990, to Dec. 31, 1996. Linkage with the BC Linked Health Dataset provided additional demographic and health information. RESULTS: In 1990, 1715 children received at least 1 prescription for methylphenidate (1.9 per 1000 children). By 1996, the number had increased to 10,881 children (11.0 per 1000). Because some children were prescribed methylphenidate in more than 1 year, we also calculated the frequency with which the drug was prescribed to children who had never received it before. This rate increased from 1.0 per 1000 children in 1990 to 4.7 per 1000 in 1995; the rate fell in 1996 to 3.5 per 1000. The number of children receiving methylphenidate varied across health regions of the province, from 12.0 to 35.4 per 1000. Use also varied by socioeconomic status quintile: in the 2 lowest (least privileged) quintiles, 21.6 per 1000 children received methylphenidate, compared with 18.4 per 1000 in the 3 highest quintiles (relative risk 1.2, 95% confidence interval 1.1-1.2). Pediatricians and psychiatrists wrote 23% and 21% of all prescriptions respectively. General practitioners accounted for 56% of all prescriptions and 41% of initial methylphenidate prescriptions. A claim for prior specialist consultation was found in 30% of such cases. Many of the children who received more than 10 prescriptions had seen 4 or more physicians. The average daily dosage prescribed differed little among general practitioners, pediatricians and psychiatrists, unlike the mean interval between successive prescriptions: 89.9 (standard deviation [SD] 68.2), 99.8 (SD 64.1) and 75.9 (SD 70.2) days respectively. Persistence with therapy was more likely when a psychiatrist provided the initial prescription, or with involvement of more than one specialty. INTERPRETATION: Many trends and practices in the prescription of methylphenidate to children in British Columbia are consistent with other settings and accepted standards. Some aspects warrant closer investigation, including regional and socio-economic discrepancies in the distribution of patients, the relative involvement of primary and specialist care providers, continuity of care issues and time intervals between prescriptions.

Right to left hemispheric shift in occipital electroencephalographic responses to repeated Kimura figures.

Gordon and Carmon (1976) reported that repeated presentations of an initially novel stimulus were associated with a transfer of cerebral dominance over time (trials) from the right to the left hemisphere. To test the generalizability of these results the proportions of alpha rhythms over the left and right occipital and parietal lobes were measured following the presentation of recurring and nonrecurring complex visual patterns (the Kimura Figures) to the upper or lower, left or right peripheral visual fields. Analysis showed increased electrical activation (as inferred by attenuated proportions of alpha rhythms) of the left occipital lobe but decreased activation of the right occipital lobe. This shift occurred during repeated presentations of the same stimuli but not during single presentations of different novel stimuli. There was no significant shift in this activity over the parietal lobes. These results are consistent with the reports of other researchers who have found a shift of dominant neuroelectrical activity from the right to the left hemisphere as the novelty of a visuospatial stimulus decreases.

Modulation of the vascular smooth muscle angiotensin subtype 2 (AT2) receptor by angiotensin II.

The angiotensin subtype 2 (AT2) receptor is scarce in most adult vascular tissues except after injury. Since angiotensin II (AngII) is released upon injury, we examined the possibility that AngII governs AT2 receptor expression in smooth muscle cells (SMC). A polyclonal antiserum, raised to a peptide corresponding to the AT2 receptor C-terminus, recognized a approximately 45-kDa protein after transfection of cos-7 cells with AT2 receptor cDNA. Detection of a approximately 65-kDa band in extracts of SMC indicated that the AT2 receptor was glycosylated. Treatment of SMCs with AngII increased AT2 receptor levels fourfold over 24 h. This response was abrogated by losartan, but not by PD123319, indicating AT1 receptor involvement. AngII-dependent increases in AT2 receptor levels were also prevented by LY294002, an inhibitor of phosphatidyinositol 3-kinase, but not by rapamycin. These results indicate AngII influences AT2 receptor expression through the AT1 receptor via a signaling pathway that includes PI3K.

Repression of phosphoenolpyruvate carboxykinase gene activity by insulin is blocked by 3-aminobenzamide but not by PD128763, a selective inhibitor of poly(ADP-ribose) polymerase.

Expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene is induced by 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase. Synthesis of PEPCK mRNA is repressed by insulin, but remains detectable in H4IIE hepatoma cells exposed simultaneously to both 3-aminobenzamide and insulin. This capability of 3-aminobenzamide to block the inhibitory actions of insulin suggests that ADP-ribosylation is required for the regulation of PEPCK gene expression by insulin. Furthermore, neither changes in chromatin condensation nor cell growth status were linked to these events. The inability of 3,4-dihydro-5-methylisoquinolinone (PD128763), a selective inhibitor of poly(ADP-ribose) polymerase, to impede insulin-dependent repression of PEPCK gene expression, however, indicated that 3-aminobenzamide does not operate by inhibiting poly(ADP-ribosyl)ation. The potential involvement of mono(ADP-ribosyl)ation, a process that is also inhibited by 3-aminobenzamide, in the regulation of PEPCK gene activity was then evaluated. Analysis of poly(ADP-ribose) polymerase activity and poly(ADP-ribosyl)ation confirmed that there were no significant changes in response to insulin, while microsomal mono(ADP-ribosyl)transferase activity was elevated approximately fourfold. An increase in protein hydroxylamine-sensitive mono(ADP-ribosyl)ation was observed following insulin treatment. The sensitivity of the mono(ADP-ribosyl)transferase activity to 3-aminobenzamide but not PD128763 makes it plausible that mono(ADP-ribosyl)ation rather than poly(ADP-ribosyl)ation contributes to the regulation of PEPCK gene expression.

Energy charge potential and glutathione levels as predictors of outcome following burn injury complicated by endotoxemia.

We studied the effect of water-soluble antioxidants geared at restoring glutathione levels on oxygen consumption, cell energetics as measured by energy charge potential (ECP), glutathione levels, and mortality, in response to a 20% total body surface area (TBSA) third degree burn injury combined with endotoxemia, five days after burn in a rat model. The 20% TBSA third degree burn injury was not fatal for the six day study period. Oxygen consumption as well as red blood cell ECP remained unchanged from control values. Liver ECP was significantly reduced; however, liver glutathione was significantly increased. The 20% TBSA burn injury combined with endotoxemia produced a 60% mortality rate. Twenty-four hour survivors (40%) demonstrated a significant decrease in oxygen consumption, red blood cell ECP, and liver ECP. Liver glutathione was significantly decreased compared with burn but was not significantly decreased compared with control. Nonsurvivors of the burn injury combined with endotoxin (60%) demonstrated a significant reduction in liver glutathione levels compared with survivors. Oxygen consumption and ECP could not be measured in the nonsurvivors due to the rapid loss of ATP in the moribund state that occurred by 4 h postinjury. Antioxidants produced 100% survival, attenuated in the fall in liver ECP, and restored red blood cell ECP and liver glutathione levels to normal values. We conclude that a modest burn injury combined with endotoxemia produces a liver glutathione debt, oxygen debt, an energy deficit, and 60% mortality. The mechanism of injury is oxidant related as antioxidants prevented mortality restored liver glutathione levels, and prevented or attenuated the decrease in ECP. A decrease in ECP and glutathione levels appear to be more sensitive indicators of outcome than the presence of an oxygen debt. The survivors, in both burn plus endotoxin groups treated with or without antioxidants was comparable, indicating a critical value for oxygen consumption exists before death occurs.

Molecular cloning of rat cardiac sarcolemmal Ca2+/Mg2+ ectoATPase (Myoglein).

Rat cardiac sarcolemmal Ca2+/Mg2+ ectoATPase (Myoglein), a membrane-bound enzyme requiring millimolar concentrations of Ca2+ or Mg2+ for maximal hydrolysis of ATP, has been purified to apparent homogeneity. Tryptic digestion and amino acid sequencing was used to design an oligonucleotide probe for screening a rat heart cDNA library; this produced a partial cDNA clone (pND2.1), and sequencing of a 400 base pair portion revealed a 100% homology to human platelet CD36. Northern blotting with pND2.1 detected a 3.1 kb transcript in rat heart but not in other tissues. Interspecies expression analysis (cardiac tissue total RNA blot probed with pND2.1) detected a approximately 2.0 kb transcript in canine, rabbit and porcine heart, whereas transcripts of a 4.1 kb, approximately 3.0 kb and 2.1 kb were observed in human cardiac tissue. A rat genomic DNA Southern blot, probed with pND2.1, indicated that there was a single copy of the gene in the rat genome. Expression of the pND2.1 cDNA in E. coli produced an 89 kDa polypeptide recognized by anti-human CD36 antibody but not by anti-rat Ca2+/Mg2+ ectoATPase antibody. It is concluded that rat cardiac Ca2+/Mg2+ ectoATPase is tightly associated with a protein highly homologous to the adhesion molecule CD36.

Plasma catalase and glutathione levels are decreased in response to inhalation injury.

We determined the effect of a severe smoke exposure on plasma oxidant and antioxidant activity. Adult sheep were given a smoke exposure while under anesthesia that produced a carboxyhemoglobin level of 45% +/- 3%. Twelve sheep were studied; six were given smoke alone and volume-resuscitated with sufficient lactated Ringer's solution to maintain baseline hemodynamics. This response was compared with six control sheep during a 6-hour period. The smoke inhalation injury produced a significant increase in plasma hydrogen peroxide and a significant decrease in plasma lipid peroxidation. Circulating lipid peroxidation did not correlate with tissue lipid peroxidation because lung and liver lipid peroxidation were significantly increased. The plasma antioxidants glutathione, catalase, and vitamin E were significantly reduced in response to the injury. Vitamin C remained unchanged from control. Circulatory failure is not a key element in this study, because lactate levels were controlled with volume resuscitation. The degree of smoke inhalation to the airway produced distant organ lipid peroxidation and a decrease in circulating antioxidants--without producing an increase in circulating lipid peroxidation. Maintaining circulating antioxidants may prevent distant organ lipid peroxidation and may be of clinical use in devising treatment strategies for smoke inhalation injury with the availability of antioxidants.

Excessive liver oxidant stress causes mortality in response to burn injury combined with endotoxin and is prevented with antioxidants.

We studied the effect of the oral administration of a water-soluble antioxidant solution containing ascorbic acid, glutathione, and a precursor for glutathione synthesis, N-Acetyl-L-cysteine, on liver antioxidant activity, liver cell energetics, and mortality in rats in response to a 20% third-degree burn injury challenged 5 days later with an intraperitoneal injection of 30 mg/kg endotoxin. Rats with burns were fluid-resuscitated with subcutaneous Ringer's lactate solution according to the Parkland formula (4 cc/kg/%burn). Rats challenged with endotoxin 5 days after burn were given an additional 100 ml/kg of subcutaneous Ringer's lactate solution immediately after the injection of endotoxin. A group of rats with burns challenged with endotoxin 5 days after burn were given an oral antioxidant solution beginning after burn injury. Liver cell energetics were measured as tissue energy charge potential (ECP), adenosine triphosphate (ATP) content, and total adenine nucleotides. The levels of endogenous liver glutathione, catalase, vitamin C, and vitamin E were measured to monitor antioxidant status. We found that burn injury alone did not produce any mortality over the 6-day period despite a 35% decrease in liver energy charge potential resulting from a decrease in ATP, a 34% decrease in liver catalase activity, and a 20% decrease in liver vitamin C. It was interesting that glutathione increased and vitamin E remained unchanged. We found that endotoxin injury combined with burn injury produced a 61% mortality rate with a 63% decrease in liver energy charge potential, again resulting from a decrease in ATP, a 74% decrease in liver catalase activity, a 16% decrease in vitamin C, and a 29% decrease in vitamin E. Glutathione was significantly decreased compared with burn alone. We compared the liver antioxidant status of survivors with that of nonsurvivors who were killed when appearing moribund and found that glutathione was decreased by 51% and vitamin C by 73% in nonsurvivors over that in survivors, whereas catalase and vitamin E levels were comparable between the two groups. The oral administration of the antioxidants prevented mortality and the decrease in antioxidant activity and attenuated the decrease in energy charge potential. We conclude that a 20% burn produces a modest decrease in liver energy charge potential and antioxidant defenses without producing mortality. The addition of endotoxin further decreases liver antioxidant defenses, liver energy charge potential, and markedly increases mortality. Antioxidants, given post-burn, restored antioxidant defenses, attenuated the altered cell energetics, and prevented mortality, indicating oxidants to be the cause of mortality. This data also suggests that a critical value of decreases in antioxidant defenses and ATP exists, resulting in mortality.

Correlates of battering among 997 men: family history, adjustment, and attitudinal differences.

In order to identify the characteristics associated with physical abuse of female partners, a detailed questionnaire was administered to 997 men who were recruited from either a forensic out-patient clinic (780) or from a community based employment center (217). This questionnaire sampled family and personal history, criminal behavior, psychopathology, and attitudes towards violence. Based upon self-report, the sample was divided into 184 non-abusive men, 517 moderately abusive men, and 296 severely abusive men. The full sample (997) was randomly divided into two subsamples and then, using a cross-validation design, group differences were identified in both subsamples on 46 of the 93 variables examined in this study. All significant effects were linear, such that the average scores of the severely abusive men were worse than the scores of the abusive men who, in turn, scored worse than the non-abusive men. In general, both groups of abusive men reported high rates of violence during childhood (both as victims and perpetrators), antisocial personality disorder, subjective distress, marital maladjustment, attitudes tolerant of spouse assault, and a range of impulsive behaviors (impulsive violence, substance abuse, motor vehicle accidents). The factors that correlated with abuse in the total sample also correlated with abuse in the community sample.

Antioxidants prevent the cellular deficit produced in response to burn injury.

We studied the effect of water-soluble antioxidants on the cell energetics in multiple organs in rats in response to a 20% total body surface area third-degree burn injury. Liver, lung, and heart tissue were studied. Cell energetics were measured as tissue energy charge potential (ECP), adenosine triphosphate (ATP) content, and total adenine nucleotides. The enzymatic antioxidant catalase was used as a marker of endogenous cell antioxidant activity, especially to hydrogen peroxide. The water-soluble antioxidants glutathione, N-acetylcysteine, and vitamin C were given orally beginning at the time of burn injury and for the 6-day study period. All rats were fluid resuscitated according to the Parkland formula. The mortality rate was 0% for this size burn. The ECP in lung, liver, and heart, was normal on day 1 after the burn injury. However, the ECP was significantly decreased from the controls in the liver by day 3, with a peak decrease at day 6 as inflammation increased. A decrease in the heart ECP occurred between day 3 and day 6. Total adenine nucleotides did not decrease, indicating the decrease in ECP to be the result of a decrease in ATP. ECP remained normal in the lung. Catalase was also decreased in the liver and the heart and remained at normal levels in the lung. The decrease in the liver and heart ECP and ATP was eliminated with the oral antioxidant administration after the burn injury. We conclude that a modest burn injury decreases cellular energy charge in the heart and liver not immediately after burn but 3 to 6 days later. The decrease in antioxidant activity precedes the decrease in ECP. The lung appears to be protected. Water-soluble antioxidants, given after burn injury, prevent the altered cell energetics-strongly suggesting a cause-and-effect relationship between increased oxidant release with inflammation, decreased antioxidant activity, and altered cell energetics.

Fluid resuscitation with deferoxamine hetastarch complex attenuates the lung and systemic response to smoke inhalation.

BACKGROUND: We determined the effect of infusing the iron chelator deferoxamine complexed to hetastarch on the degree of lung dysfunction and systemic abnormalities produced by a severe smoke exposure. METHODS: Adult sheep were given a smoke exposure under anesthesia that produced a peak carboxyhemoglobin between 40% and 45%. Twenty-eight sheep were studied; eight were given smoke alone and resuscitated with sufficient lactated Ringer's solution to maintain baseline hemodynamics. Seven sheep were given a bolus plus 1 ml/kg/hr of a 10% deferoxamine-hetastarch solution for resuscitation; five were given hetastarch alone. The response was compared with eight controls during a period of 24 hours. RESULTS: Smoke alone and smoke with hetastarch resulted in a shunt fraction of greater than 25% and a 50% decrease in compliance, severe airway inflammation, mucosal slough, atelectasis, and some alveolar edema. Increased lipid peroxides measured as malondialdehyde were present in airway fluid. In addition, oxygen consumption increased by 100% early after injury, net 24-hour positive fluid balance was almost 3 L, and a significant increase occurred in liver lipid peroxidation. The group given deferoxamine had a significantly attenuated lung response, with only modest airway damage lung dysfunction, and minimal systemic changes including a net positive fluid balance of just over 1L and no liver lipid peroxidation. CONCLUSIONS: An iron chelator deferoxamine complexed to hetastarch, given after a severe smoke exposure, significantly attenuates the airway and the systemic inflammatory (oxidant) injury, indicating free iron release and subsequent increased oxidant activity to be a major etiologic factor.

Early outcomes of laparoscopic-assisted vaginal hysterectomy versus laparoscopic supracervical hysterectomy.

STUDY OBJECTIVE: To compare two different laparoscopic techniques for hysterectomy: laparoscopic-assisted vaginal hysterectomy (LAVH) and laparoscopic supracervical hysterectomy (LSH). DESIGN: A retrospective review of office and hospital charts, and a postoperative questionnaire completed by patients. SETTING: A private gynecology practice and private hospital in Nashville, Tennessee. PATIENTS: Forty women requiring laparoscopic hysterectomy between January 1993 and December 1994. Interventions. Twenty patients underwent LAVH and 20 LSH. Minimum follow-up was 3 months (range 3-27 mo). MEASUREMENTS AND MAIN RESULTS: The chart review focused on operating times, blood loss, length of hospital stay, complications, and total hospital costs to the patients. The operating times were shorter and the blood loss was less in the LSH group than in the LAVH group, but the difference did not reach statistical significance. Hospital stay was shorter (p = 0.0005) and hospital costs were less (p = 0.01) in the LSH group. Of women who were sexually active, those in the LSH group resumed intercourse earlier than those in the LAVH group (3.5 vs 5.9 wks), and reported better overall improvement in sexual function and ability to achieve orgasm. CONCLUSION: In certain patients, LSH is effective and associated with few complications.

Attrition from a male batterer treatment program: client-treatment congruence and lifestyle instability.

Although patient compliance is a problem for almost all forms of therapy, treatment programs for male batterers face special concerns. Male batterers are often perceived as coming to therapy only because of the external pressures of courts or intimate partners. In the present study, we examined the rates at which male batterers failed to attend treatment following an initial assessment interview. Of the 526 men recommended for treatment, only 218 (41%) attended a single treatment session, and only 132 (25%) completed the brief (10-week) treatment program. The variables associated with attrition fell into two general categories: (a) those associated with lifestyle instability (e.g., moves, unemployment, youthfulness), and (b) those variables indicating a congruence between the clients' self-identified problems and the targets of treatment (e.g., self-admitted problems with spousal assault). Suggestions are provided as to how programs could reduce their attrition rates by attending to the issues of client-treatment congruence and lifestyle instability.

Advanced laparoscopic procedures for pelvic pain and dysmenorrhoea.

The effective removal of endometriosis is the major aim of physicians treating patients with pelvic pain. This can now be accomplished long-term as effectively at laparoscopy as at laparotomy (Wheeler and Malinak, 1987; Redwine, 1991; Martin, 1994). All successful operative laparoscopists dealing with endometriosis-associated pain should be familiar with and consider offering their patients the operative procedures discussed in this chapter. Adhesiolysis is a well-accepted therapy but uterine suspension and the nerve separating techniques of LUNA and PSN are much more controversial. Pain, being subjective, is difficult to quantify and a poor end point to monitor scientifically. However, there is a significant body of published work to suggest that uterine suspension, LUNA and PSN, which have all been performed for decades, seem effective laparoscopically in reducing pelvic pain associated with endometriosis. Much more data are obviously needed to determine if endometriosis-associated pain can be effectively treated with laparoscopic procedures. Properly designed scientific prospective randomized studies to evaluate some of the laparoscopic operations discussed to treat endometriosis-associated pain have recently been reported (Sutton, 1994). Thoughtful gynaecologists dealing daily with patients with endometriosis should consider discussing with them the advantages and disadvantages of the techniques reviewed in this chapter. From our experience and that of others, it appears that adhesiolysis, uterine suspension, LUNA and PSN can all be safely and effectively accomplished by skilled laparoscopists and result in good patient outcomes. All gynaecologists involved in the care of patients with endometriosis and pain should consider learning and offering these operations to their patients with appropriate discussion of the potential risks and benefits.

Increased lipid peroxidation and decreased antioxidant activity correspond with death after smoke exposure in the rat.

Oxidants are released directly from smoke and also as a result of the airways inflammation that occurs after smoke injury. We determined the relation between the degree of tissue oxidant change with the use of malondialdehyde content to measure lipid peroxidation and the degree of lung and systemic organ damage and resulting damage mortality 24 hours after a controlled smoke exposure in a rat model. We also monitored changes in the key tissue antioxidant catalase. We found that the degree of lung lipid peroxidation and the decrease in catalase activity directly correlated with mortality caused by respiratory failure and with the degree of lung inflammation but that they did not correlate with the peak carboxyhemoglobin level, a marker of smoke gas phase exposure. The lung oxidant changes also directly correlated with increased systemic lipid peroxidation and decreased catalase in liver and kidney tissue. We conclude that the initial smoke insult causes lung and in turn systemic inflammation with resulting release of oxidants, which leads to tissue oxidant injury. The degree of lung oxidant change significantly correlates with the degree of lung tissue injury, respiratory failure, and mortality, and the major source of the oxidant changes is tissue inflammation rather than oxidants in the smoke itself.

Increased early postburn fluid requirements and oxygen demands are predictive of the degree of airways injury by smoke inhalation.

The combination of burn and smoke inhalation was studied to determine if early hemodynamic and metabolic abnormalities would correspond with the degree of subsequent smoke-induced airways injury. Adult sheep (n = 45) given an 18% total body surface third-degree burn alone or with smoke exposures of 12 breaths of 5, 10, or 20 mL/kg tidal volume were continuously monitored with airways assessed at 4 or 24 hours. With increased smoke exposure (20 mL/kg tidal volume), oxygen consumption (VO2) in the first several hours and net positive fluid balance, especially in the first 6 hours, increased by 100% and 300%, respectively, over that seen with burn alone. The degree of increase in fluid requirement, net fluid retention, and VO2 with smoke, compared with burn alone, correlated best with the degree of airways damage quantitated at 24 hours, r = 0.83, 0.85, and 0.89, respectively. Airways damage at 4 hours did not predict the damage seen at 24 hours. Systemic changes were not caused by gas-phase toxins, such as carbon monoxide, because smoke filtered of particles had the same blood carbon monoxide control as whole smoke, but the systemic response was equal to burn alone, and there was no airways injury. The cause of the systemic changes is likely the result of the intense airways inflammation.

Alpha-tocopherol attenuates lung edema and lipid peroxidation caused by acute zymosan-induced peritonitis.

BACKGROUND: Inflammation-induced disease as seen with trauma and infection can lead to increased lung oxidant activity resulting in cell membrane lipid peroxidation. Acute zymosan-induced peritonitis in rats produces lung inflammation, edema, and lipid peroxidation. We determined whether administered alpha-tocopherol (vitamin E), the key antioxidant protection against cell membrane lipid peroxidation, would improve this process. METHODS: Male Wistar rats were given 0.75 mg/kg of intraperitoneal zymosan, volume resuscitated, monitored, and killed at 4 or 24 hours. Lung histologic changes and levels of conjugated dienes, a marker of lipid peroxidation, were used to monitor injury. The levels of vitamin E, vitamin C, and catalase were used to monitor antioxidant defenses. The effect of administering alpha-tocopherol (50 mg/kg) by gavage immediately after zymosan on the degree of the lung injury was then determined. RESULTS: Twenty-four hours after zymosan was administered, the vitamin E levels in plasma were significantly decreased, but lung tissue vitamin E levels were maintained, whereas tissue catalase and vitamin E levels decreased. Lung tissue-conjugated diene levels, alveolar edema, and neutrophil count were significantly increased. alpha-Tocopherol treatment increased the postzymosan plasma vitamin E levels by 50%. Lung tissue vitamin E levels did not increase; however, the degree of lung injury and lipid peroxidation was significantly attenuated. Tissue catalase levels were also maintained. CONCLUSIONS: We conclude that alpha-tocopherol given at the onset of a progressing inflammatory injury can protect the lung from oxidant damage and attenuate the degree of lung injury.

Effect of graded increases in smoke inhalation injury on the early systemic response to a body burn.

OBJECTIVE: To study the early (first 24 hrs) effect of increasing lung exposure to smoke on the hemodynamic response to a modest body burn. DESIGN: A prospective randomized study. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-two adult yearling female sheep. INTERVENTIONS: Adult sheep (n = 32) were given an 18% of body surface burn; 24 sheep were then exposed to cotton toweling smoke using 12 breaths of a tidal volume of 5, 10, or 20 mL/kg. Animals were awakened, resuscitated to baseline oxygen delivery, and then killed at 24 hrs. MEASUREMENTS AND MAIN RESULTS: Vascular pressure, cardiac output, and oxygen consumption and delivery were measured, as well as blood gases, lung and soft tissue lymph flow, and fluid balance. We found that a 5-mL/kg tidal volume smoke exposure x 12 breaths did not produce significant airway inflammation or alter the cardiopulmonary response to a burn alone. Oxygen consumption (VO2) remained at baseline and the net 24-hr positive fluid balance of 1.5 L was comparable to a burn alone. Increasing the smoke exposure to 10 mL/kg tidal volume, which produced a moderate airway injury, resulted in a significant increase in early fluid requirements, a 40% early increase in VO2, a doubling of positive fluid balance, as well as a marked increase in burn edema. However, gas exchange was not impaired. The 20-mL/kg tidal volume exposure resulted in an early 100% increase in VO2, a three-fold increase in fluid requirements at 1 to 4 hrs, compared with burn alone, in addition to a severe airway inflammation with mucosal slough and resulting impaired gas exchange. CONCLUSIONS: The addition of a smoke exposure which produces airway inflammation and injury significantly increases early post burn systemic metabolic demands and fluid requirements, as well as the degree of burn edema and positive fluid balance compared with a burn alone. The magnitude of the accentuated response appears to correspond with the degree of airway inflammation and not with alveolar dysfunction.