Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded.

Monoplace hyperbaric chamber use of U.S. Navy Table 6: a 20-year experience.

We report a 20-year experience at LDS Hospital, Salt Lake City, UT using the U.S. Navy Treatment Table 6 (TT6) in an oxygen-filled monoplace hyperbaric chamber (1985-2004). Air breathing was provided via a demand regulator fitted with a SCUBA mouthpiece while the patient wore a nose clip. Intubated patients were mechanically ventilated with a Sechrist 500A ventilator, with a modified circuit providing air, when specified. We treated 90 patients: 72 divers (decompression sickness [DCS] = 67, arterial gas embolism [AGE] = 5), 10 hospital-associated AGE, and 8 miscellaneous conditions. They received a total of 118 TT6 (9 TT6 in intubated patients). Ninety-four percent of the TT6 schedules were tolerated and completed. The intolerance rate from two surveyed multiplace chambers was zero and 3% of 100 TT6 schedules each. Failure to complete the TT6 was due to oxygen toxicity (4) and claustrophobia (3). The U.S. Navy TT6 was well tolerated by patients with DCS or AGE treated in monoplace hyperbaric chambers, but tolerance may not be as high as when treated in the multiplace chamber.

Hypoxemia with air breathing periods in U.S. NAVY Treatment Table 6.

Air breathing is used to lessen hyperbaric oxygen (HBO2) toxicity. Hypoxemia could occur during hyperbaric air breathing in patients with lung dysfunction, although this has not been previously reported. We report two cases of hypoxemia during air breathing with two patients treated with the US Navy Table 6. Patient 1 was an 11-year-old male with cerebral gas embolism (during cardiac transplantation), patient 2 was a 66-year-old female with cerebral gas embolism from a central venous catheter accident. Both were mechanically ventilated. We monitored arterial blood gas (ABG) during therapy. In both patients, ABG measurements showed hypoxia during the first air breathing period at 1.9 atm abs (192.5 kPa). If patients require > or = 40% inspired oxygen before HBO2 therapy, oxygenation monitoring is advisable during air breathing periods, especially at lower chamber pressures (< or = 2.0 atm abs).

Vitamin A and preterm infants: what we know, what we don't know, and what we need to know.

Vitamin A is essential for optimal growth and development. In the developing world, vitamin A supplementation of the newborn infant reduces mortality. In the developed world, extremely preterm infants are born with low body stores of vitamin A and are at high risk of vitamin A deficiency. Optimal vitamin A supplementation for this population is not clearly defined, however, and, despite evidence of benefit, early vitamin A supplementation of extremely preterm infants is not uniformly practised in the United Kingdom. There is an urgent need for studies in preterm infants that include quantification of hepatic stores and functional assessment of vitamin A status as well as long term outcome.

Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial.

AIM: To test the hypothesis that maternal docosahexaenoic acid (DHA) supplementation during pregnancy enhances maturation of the visual evoked potential (VEP) in healthy term infants. METHODS: One hundred women were supplemented with either fish oil capsules rich in DHA (n = 50) or placebo capsules (n = 50) from week 15 of pregnancy until delivery. Total fatty acids in red blood cells and plasma were measured at weeks 15, 28, and 40 of pregnancy and at delivery in umbilical cord blood. Infant visual pathway development was assessed using VEPs recorded to flash stimuli shortly after birth and to both flash and pattern-reversal stimuli at 50 and 66 weeks post-conceptional age (PCA). RESULTS: Maternal supplementation did not significantly elevate the level of DHA in umbilical cord blood. Moreover, there were no significant differences in any of the VEP measures observed between supplementation groups. However, maturity of the pattern-reversal VEP at 50 and 66 weeks PCA was associated with DHA status of the infants at birth. Infants with higher DHA status, both as a concentration and as a percentage of total fatty acids, showed shorter P100 peak latencies of the pattern-reversal VEP than those with lower DHA status. CONCLUSIONS: Maternal DHA supplementation during pregnancy did not enhance VEP maturation in healthy term infants. However, these results show an association between the DHA status of infants at term and early postnatal development of the pattern-reversal VEP, suggesting that DHA status itself may influence maturation of the central visual pathways.

Pulmonary edema associated with hyperbaric oxygen therapy.

We report three cases of pulmonary edema associated with hyperbaric oxygen therapy, including one fatality. All three patients had cardiac disease and reduced left ventricular (LV) ejection fractions (EFs). Two patients had diabetes, and one patient had severe aortic stenosis. Hyperbaric oxygen therapy may contribute to pulmonary edema by increasing LV afterload, increasing LV filling pressures, increasing oxidative myocardial stress, decreasing LV compliance by oxygen radical-mediated reduction in nitric oxide, altering cardiac output between the right and left hearts, inducing bradycardia with concomitant LV dysfunction, increasing pulmonary capillary permeability, or by causing pulmonary oxygen toxicity. We advise caution in the use of hyperbaric oxygen therapy in patients with heart failure or in patients with reduced cardiac EFs.

Fatty acid status of women of reproductive age.

OBJECTIVE: Healthy foetal and infant development is dependent on an adequate maternal supply of essential and polyunsaturated fatty acids (PUFA). While there are published data on the fatty acid status of pregnant women, there are few on the status of non-pregnant women of reproductive age. The aims of this study were to test the hypotheses that the fatty acid status of non-pregnant women is affected by socio-economic status and anthropometric, behavioural and obstetric factors. DESIGN: Observational study METHODS: One-hundred and thirty-five women of child-bearing age (mean 29.8 y, s.d. 6.92) were invited to provide a blood sample and to answer a questionnaire, of whom 114 were included in the study. Plasma and red cell total fatty acids were measured as their methyl esters by gas chromatography mass spectrometry. RESULTS: On multivariate analyses, use of hormonal contraception was independently associated with lower plasma polyunsaturated fatty acids (difference between means -2.76, 95% confidence interval (-4.64, -0.88), P=0.0034), whereas cigarette smoking was associated with higher red cell oleic acid (0.74 (0.18, 1.29), P=0.0094). Fish intake was associated with higher red cell total n-3 fatty acids (0.62 (0.27, 0.85), P=0.0014). CONCLUSIONS: We have reported data on the range of the fatty acids of plasma and red blood cells (RBC) total lipids of 114 healthy women of reproductive age. These data provide further information on how socio-economic, anthropometric, behavioural and obstetric factors may be relevant to female and nutrition and health. SPONSORSHIP: University of Glasgow.

Carbon monoxide poisoning: interpretation of randomized clinical trials and unresolved treatment issues.

Since hyperbaric oxygen therapy (HBO2) appeared as a treatment for CO poisoning in 1960, whether and when to use it for CO poisoning have often been debated. HBO2 has been advocated to treat severe CO poisoning to limit delayed and permanent neurologic sequelae. Initially, inferences about efficacy were based on clinical experience and uncontrolled studies, but since1989, six prospective clinical trials have been reported comparing HBO2 and normobaric O2 administration to treat patients with acute CO poisoning. Of the six trials, four found better clinical outcomes among patients receiving HBO2 while two have shown no treatment effect. The most recent and best-designed randomized controlled clinical trial, performed in Salt Lake City, supports the efficacy of HBO2 in severe acute CO poisoning in accordance with scientific rationale and clinical experience. However, a number of important issues remain for future investigation, which could be addressed in a large multi-center trial. Such a trial should attempt to determine the optimal number of HBO2 treatments and the maximum treatment delay from CO poisoning for HBO2 to provide efficacy in patients with specific risk factors for a poor outcome.

Performance of the Baxter Flo-Gard 6201 volumetric infusion pump for monoplace chamber applications.

For non-hyperbaric purposes, the Baxter Flo-Gard 6201 volumetric pump is capable of infusing multiple types of fluids at rates of 1-1,999 ml x h(-1). We designed a study to determine flow accuracy of this pump at variable rates, fluid viscosities, and volumes over a range of chamber pressures. For hyperbaric use, the pump pressure sensor was adjusted. Sodium chloride solution 0.9% (NS), enteral formula, and packed red blood cells (PRBC) were infused at varying rates from 86.1 to 304 kPa (0.85 to 3.0 atm abs). For NS, measured compared to set flow rates ranged from 12.5% to -7.5% at settings of 1 and 5 ml x h(-1) from 86.1 to 304 kPa (0.85 to 3.0 atm abs) pressures, respectively. For NS infusions at a set rate of 100 ml x h(-1), the measured flow was identical to the set rate at all pressures. At flow settings of 1,999 ml x h(-1), the measured flow varied from the set flow by +/-4.9% Enteral infusion at 100 ml x h(-1) showed approximately a 3% increase in the measured vs. set flow rate. PRBC measured flow rates ranged from -0.4 to 6% of the set rate. During chamber compression and decompression, with set flow rates from 1 to 10 ml x h(-1), the measured flow was considerably less than expected during compression and more than expected during decompression. In conclusion, the Baxter Flo-Gard 6201 infusion pump demonstrated acceptable performance for infusing saline, enteral formula, and PRBC at low and high infusion rates into the pressurized monoplace hyperbaric chamber up to 304 kPa (3 atm abs), with the exception of low rates during compression and decompression.

Operational use and patient care in the monoplace hyperbaric chamber.

The author has made an attempt to describe presently available monoplace chambers, provide codes for their appropriate use in hospitals, and emphasize chamber safety. If appropriate safety precautions are not strictly adhered to, catastrophic accidents may occur, and have occurred. Critically ill patients may have indications for HBO and, indeed, can be treated with HBO in the monoplace chamber. This requires strict attention to detail and an understanding of critical care medicine as well as hyperbaric medicine. To facilitate care of these patients within the monoplace chamber several modifications have been implemented. Complete pulmonary and arterial hemodynamic monitoring, transcutaneous and laser Doppler monitoring, as well as vasopressors, sedation, paralysis, and mechanical ventilation can be supplied to patients treated with HBO within a monoplace chamber (Fig. 19). Suction within the monoplace chamber can be accomplished by adapting existing hospital equipment. Likewise, air breaks can be provided to all patients in the monoplace chamber, including those who are intubated and mechanically ventilated. These modifications have been presented here. Hemodynamic and intravenous access to the critically ill patient is important. Physiologic pressures, ECG, and typical intravenous setups have been described. Several techniques that the author has have personally found helpful have also been provided. The final section of this article presents clinical observations in a few critically ill patients. These anecdotes were only included to try to stimulate thought and hopefully an interchange of ideas that may help us deal more effectively with the management of these patients. This article also raises the question of what is the optimal arterial partial pressure of oxygen as opposed to merely treating the HBO patient with a standard protocol, particularly if the patient has a significant right-to-left shunt (anatomic or physiologic). It is hoped that further discussion, thought, and research can help elucidate answers to these questions.

A comparison of the expression patterns of several senescence-associated genes in response to stress and hormone treatment.

The expression of several Arabidopsis thaliana senescence-associated genes (SAGs) in attached and/or detached leaves was compared in response to age, dehydration, darkness, abscisic acid, cytokinin, and ethylene treatments. Most of the SAGs responded to most of the treatments in a similar fashion. Detachment in darkness and ethylene were the strongest inducers of both SAGs and visible yellowing. Detachment in light was also a strong inducer of SAGs, but not of visible yellowing. The other treatments varied more in their effects on individual SAGs. Responses were examined in both older and younger leaves, and generally were much stronger in the older ones. Individual SAGs differed from the norms in different ways, however, suggesting that their gene products play a role in overlapping but not identical circumstances. Some SAGs responded quickly to treatments, which may indicate a direct response. Others responded more slowly, which may indicate an indirect response via treatment-induced senescence. Four new SAGs were isolated as part of this work, one of which shows strong similarity to late embryogenesis-abundant (Lea) genes.

Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial .

OBJECTIVE: To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system. DESIGN: 5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3 MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control). SETTING: Rural Gambia. SUBJECTS: Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths. MAIN OUTCOME MEASURES: Birth weight; prevalence of low birth weight (< 2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality. RESULTS: Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P < 0.001) in the hungry season, by 94 g (P < 0.01) in the harvest season (November to May), and by 136 g (P < 0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P < 0.001). Head circumference was significantly increased (P < 0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P < 0.05) for stillbirths and 0.54 (0.35 to 0.85, P < 0.01) for all deaths in first week of life. Mortality after 7 days was unaffected. CONCLUSION: Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system.

Neuropsychologic and functional recovery from severe carbon monoxide poisoning without hyperbaric oxygen therapy.

STUDY OBJECTIVE: To test the hypothesis that neuropsychologic test results and functional outcome will be abnormal if hyperbaric oxygen (HBO) is not used in patients with severe carbon monoxide (CO) poisoning. METHODS: For a 1-year interval, we retrospectively identified all CO-poisoned patients who were comatose on presentation at a large, urban tertiary hospital and did not receive HBO therapy. Prospectively, 6 and 12 months after CO poisoning, we administered standardized questionnaires to assess functional outcome. At 6 months, we performed extensive neuropsychologic testing. RESULTS: All four patients exhibited normal performance on a neuropsychologic test battery at 6 months. The Folstein Mini-Mental Status Examination was normal in all patients. All patients had normal functional outcomes. CONCLUSION: Normal neuropsychologic and functional outcomes are possible after severe CO poisoning without the use of HBO therapy.

Characterization of the cDNA and gene coding for the biotin synthase of Arabidopsis thaliana.

Biotin, an essential cofactor, is synthesized de novo only by plants and some microbes. An Arabidopsis thaliana expressed sequence tag that shows sequence similarity to the carboxyl end of biotin synthase from Escherichia coli was used to isolate a near-full-length cDNA. This cDNA was shown to code for the Arabidopsis biotin synthase by its ability to complement a bioB mutant of E. coli. Site-specific mutagenesis indicates that residue threonine-173, which is highly conserved in biotin synthases, is important for catalytic competence of the enzyme. The primary sequence of the Arabidopsis biotin synthase is most similar to biotin synthases from E. coli, Serratia marcescens, and Saccharomyces cerevisiae (about 50% sequence identity) and more distantly related to the Bacillus sphaericus enzyme (33% sequence identity). The primary sequence of the amino terminus of the Arabidopsis biotin synthase may represent an organelle-targeting transit peptide. The single Arabidopsis gene coding for biotin synthase, BIO2, was isolated and sequenced. The biotin synthase coding sequence is interrupted by five introns. The gene sequence upstream of the translation start site has several unusual features, including imperfect palindromes and polypyrimidine sequences, which may function in the transcriptional regulation of the BIO2 gene.

The visual appearance and somatic cell count of mammary secretions collected from primigravid heifers during gestation and early postpartum.

Mammary secretions, obtained before and after calving, were examined for visual appearance, SCC, and bacteriology as part of a larger study determining the prevalence of IMI in 1588 primigravid heifers. Appearance of secretions was categorized into five groups: thin and watery, honey-like, serumy, milky, or thickened colostrum. Precalving secretions were further characterized as low viscosity (thin and watery, serumy, or milky) or high viscosity (honey-like and thickened colostrum). Postcalving secretions were further characterized as normal (milky, thickened colostrum) or abnormal (thin and watery, serumy, or honey-like). Infected precalving quarters (81%) had low viscosity secretions. Quarters that were uninfected precalving (75%) had high viscosity secretions. Greater than 90% of all postcalving milk samples appeared to be normal, regardless of geographic location, season, or bacterial infection status. Only 77% of the samples from quarters infected with contagious and noncontagious mastitis pathogens had normal appearance. Precalving SCC from bacteriologically negative quarters were lower than SCC from infected quarters. Similarly, postcalving SCC were lower from the bacteriologically negative quarters than from the infected quarters. Infected quarters had higher mean SCC than the uninfected quarters during both pre- and postcalving periods.