Profound hypoxemia during treatment of low cardiac output after cardiopulmonary bypass

PURPOSE: To illustrate the multiple causes of hypoxemia to be considered following cardiopulmonary bypass and how therapy given to improve oxygen delivery may have contributed to a decrease in arterial oxygen saturation to life-threatening levels. CLINICAL FEATURES: A 61 yr old man with severe mitral regurgitation and chronic obstructive lung disease underwent surgery for mitral valve repair. A pulmonary artery catheter with the capacity to measure cardiac output and mixed venous oxygen saturation (SvO2) continuously was used. Two unsuccessful attempts were made to repair the valve which was finally replaced, requiring cardiopulmonary bypass of 317 min. Dobutamine 5 micrograms.kg-1.min-1 and sodium nitroprusside 1 microgram.kg-1.min-1 were used to increase cardiac output. Soon after, the SvO2 decreased progressively from 55 to 39%. The patient became cyanotic with a PaO2 of 39 mmHg. Sodium nitroprusside was stopped and amrinone 100 mg bolus followed by 10 micrograms.kg-1.min-1 was given in addition to adding PEEP to the ventilation. With these measures PaO2 could be maintained of safe levels but PEEP and high inspired oxygen concentrations were needed postoperatively until the trachea could be extubated on the third postoperative day. CONCLUSION: The profound hypoxemia in this case was likely due to a combination of intra- and extrapulmonary shunt, both augmented by sodium nitroprusside. The desaturation of mixed venous blood amplified the effect of these shunts in decreasing arterial oxygen saturation. The interaction of these factors are analyzed in this report.     

Laparoscopic management of suspicious adnexal masses

OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative laparoscopy in the management of adnexal masses that do not meet the standard serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One hundred thirty-eight patients underwent operative laparoscopy for removal of suspicious adnexal masses. The CA 125 level was >35 mIU/ml in 39 of 138 (28%) patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses were >10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures were converted to laparotomy, six because of inability to dissect the mass laparoscopically and five for staging or debulking of carcinoma. Operative times ranged from 25 to 210 minutes, with a mean of 86. Three major complications were encountered-an enterotomy and a lacerated vena cava, both of which were repaired laparoscopically, and a small bowel herniation through a lateral port site that required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of 1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of suspicious adnexal masses is technically feasible, with a low rate of morbidity and a short hospital stay. Adnexal carcinomas can be identified and managed appropriately with staging and complete resection as indicated. (Am J Obstet Gynecol 1996;175:1451-9.)     

Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Purpose

To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED₉₅) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass.

Methods

In a prospective non randomized study, ten patients received doxacurium 0.05 mg·kg^?1 (Group 1) and ten others received 0.075 mg · kg^?1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T₁) had recovered to 25% of control.

Results

The onset time (time to maximal T₁ depression) of doxacurium was 390 ± 148 sec in Group 1 and 370 ± 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T₁ recovery) was 165 ± 90 min in Group 1 and 258 ± 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T₁ was 57 ± 23% in Group 1 and 24 ± 21% in Group 2(P = 0.003); the mean T₄/T₁ ratio was 0.25 ± 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches.

Conclusion

In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED₉₅. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.     

Behavioral studies of stimulus deprivation amblyopia in monkeys

Contrast sensitivity and increment-threshold functions were studied for three rhesus monkeys with stimulus deprivation amblyopia. The monkeys' right eyelids were sutured closed before the age of 1 month for periods of two weeks, 19 months and 23 months. Contrast sensitivity measurements for all three monkeys showed greatly reduced visual function in the deprived eye with a high spatial frequency cut-off 6 octaves lower in the deprived than the nondeprived eyes. The increment-threshold data collected for the two long-term lid-sutured monkeys showed both photopic and scotopic abnormalities in the deprived eyes. For example, with complete dark adaptation although the spectral sensitivity data for both the deprived and nondeprived eyes were well fit by the scotopic luminosity function, the sensitivity for the deprived eye was approximately 4 log units lower than the nondeprived eye. In addition, the spectral sensitivity data for the deprived eyes showed scotopic luminosity functions for achromatic adapting field luminances of 188, 750 and 3000 td whereas the nondeprived eye showed normal photopic function for all light adapted conditions. Even when the spectral sensitivity measurements were made in the presence of intense blue backgrounds, the data obtained for the deprived eyes were best described as showing scotopic function over the short wavelengths and photopic function only at the longer wavelengths. The increment-threshold functions for achromatic stimuli showed normal rod-cone interactions in the nondeprived eyes, but the functions were monotonic for the deprived eyes over a 9 log unit range of background luminances. Therefore, the results of these experiments show that stimulus deprivation causes profound defects for visual resolution, rod saturation and the rate of change of sensitivity with light adaptation.     

Effects of dibutyl phthalate in male rabbits following in utero, adolescent, or postpubertal exposure.

We evaluated sequelae in male rabbits following exposure to dibutyl phthalate (DBP) at a dose level known to adversely affect testicular function in rodents without causing systemic toxicity. Because rabbits have a relatively long phase of reproductive development simulating better than rodents the reproductive development of humans, and because the use of rabbits facilitates multiple evaluations of mating ability and seminal quality, we used this animal model. Rabbits were exposed to 0 or 400 mg DBP/kg/day in utero (gestation days [GD] 15-29) or during adolescence (postnatal weeks [PNW] 4-12), and male offspring were examined at 6, 12, and 25 weeks of age. Another group was exposed after puberty (for 12 weeks) and examined at the conclusion of exposure. The most pronounced reproductive effects were in male rabbits exposed in utero. Male offspring in this group exhibited reduction in numbers of ejaculated sperm (down 43%; p < 0.01), in weights of testes (at 12 weeks, down 23%; p < 0.05) and in accessory sex glands (at 12 and 25 weeks, down 36%; p < 0.01 and down 27%; p < 0.05, respectively). Serum testosterone levels were down (at 6 weeks, 32%; p < 0.05); a slight increase in histological alterations of the testis (p < 0.05) and a doubling in the percentage (from 16 to 30%, p < 0.01) of abnormal sperm; and 1/17 males manifesting hypospadias, hypoplastic prostate, and cryptorchid testes with carcinoma in situ-like cells. In the DBP group exposed during adolescence, basal serum testosterone levels were reduced at 6 weeks (p < 0.01) while at 12 weeks, testosterone production in vivo failed to respond normally to a GnRH challenge (p < 0.01). In addition, weight of accessory sex glands was reduced at 12 weeks but not at 25 weeks after a recovery period; there was a slight increase in the percentage of abnormal sperm in the ejaculate; and 1/11 males was unilaterally cryptorchid. In both of these DBP-treated groups, daily sperm production, epididymal sperm counts, mating ability, and weights of body and nonreproductive organs were unaffected. Thus, DBP induces lesions in the reproductive system of the rabbit, with the intrauterine period being the most sensitive stage of life.     

Free and esterified fatty acid and cholesterol synthesis in adult males and its effect on the doubly-labelled water method

The purpose of the present study was to estimate whole-body fatty acid and cholesterol synthesis in weight-stable adults and to determine the likely effect on the doubly-labelled water (DLW) method for measuring energy expenditure. Synthesis was measured by 2H incorporation over 14 d in six adult males in approximate energy balance following noradrenaline infusion to maximize mobilization of free fatty acid from adipose tissue. The inter-individual variation in synthesis rates was large and in one subject the proportion of free fatty acid synthesized was ten times that of the mean of the rest of the group; the fasting concentration of esterified fatty acid in this subject was five times that of the rest of the group indicating likely violation of the assumptions underlying the calculation of whole-body synthesis. After 14 d of labelling in the other five subjects, 0.9 (SEM 0.3)% of the circulating free fatty acid, 9.3 (SEM 3.0)% of the esterified fatty acid, 14.6 (SEM 2.4)% of the free cholesterol and 28.3 (SEM 3.7)% of esterified cholesterol had been synthesized de novo. A high rate of synthesis correlated with a low pre-dose 2H abundance both within and between lipid classes suggesting that natural 2H abundance variations in some lipid classes may be used to determine their metabolic origin. Whole-body synthetic rates were 8 g/d for fatty acid and 0.3-0.5 g/d for cholesterol. These values correspond to very small errors on DLW-derived estimates of CO2 production; -2.5 litres/d for fatty acid and -0.1 to -0.2 litres/d for cholesterol. These results, obtained in subjects typically consuming a diet with a lower fat and cholesterol content that the typical Western diet, suggest that the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis in subjects in energy balance consuming a typical Western diet.     

Assessing the need to update prevention guidelines: a comparison of two methods.

BACKGROUND: An important concern for developers of clinical practice guidelines is how best to determine when guidelines require updating to ensure they remain current and evidence based. Because of the high costs associated with updating guidelines, recent attention has focused on approaches that can reliably assess the extent of updating required. Recently, Shekelle and colleagues proposed a model of limited literature searches with modest expert involvement as a way to reduce the cost and time requirements for assessing whether a guideline needs updating. METHODS: The main objective of this study was to compare the Shekelle et al. assessment model (review approach) and a conventional process using typical systematic review methods (traditional approach) in terms of comprehensiveness and effort. We modeled the review approach on that by Shekelle and colleagues but refined it iteratively over three phases to achieve greater efficiency. Using both methods independently, we assessed the need to update six topics from the 1996 Guide to Clinical Preventive Services from the US Preventive Services Task Force. Main outcomes included completeness of study identification, importance of missed studies and the effort involved. RESULTS: Although the review approach identified fewer eligible studies than the traditional approach, none of the studies missed was rated as important by task force members acting as liaisons to the project with respect to whether the topic required an update. On average, the review approach produced substantially fewer citations to review than the traditional approach. The effort involved and potential time saving depended largely on the scope of the topic. CONCLUSIONS: The revised review approach provides an efficient and acceptable method for judging whether a guideline requires updating.     

Effect of L-ascorbic add supplementation on testicular oxidative stress and endocrine disorders in mature male rats exposed to intensive swimming exercise

In order to investigate the ameliorative potential of L-ascorbic acid on intensive swimming exercise induced testicular oxidative stress, 18 Wistar male rats (age: 3 months, weight: 127.5 ± 5.3 g) were randomly divided into the following groups: (i) control group (CG,n = 6); (ii) experimental group (EG,n = 6); and (iii) supplemented group (SG,n = 6). An exercise protocol of 3 h swimming per day, five days per week was followed for 6 weeks in EG and SG with no exercise in CG. In SG, L-ascorbic acid was supplied orally at a dose of 25-mg/kg of bodyweight each day for 6 weeks. A significant decrease (P < 0.05) was noted in paired testicular weights, epididymal sperm count, testicular Δ⁵, 3β-hydroxyseroid dehydrogenase, 17β-hydroxyseroid dehydrogenase, plasma levels of testosterone luteinizing hormone, follicle stimulating hormone, prolactin, the numbers of preleptotine spermatocytes, midpachytene spermatocytes and stage 7 spermatids of stage VII seminiferous epithelium cycle in EG when compared with CG. A significant elevation (P < 0.05) in plasma corticosterone and testicular content of malondialdehyde along with a significant reduction (P < 0.05) in glutathione, ascorbic acid, α-tocopherol, superoxide dismutase, catalase and glutathione-peroxidase, and glutathione-S-transferase were noted in testes of EG compared with CG. No significant change was noted in final bodyweight or numbers of spermatogonia-A among the groups. Furthermore, L-ascorbic acid supplementation restored the above parameters to the control level. Conclusion  It can be concluded that intensive swimming exercise induced oxidative stress causes dysfunctions in the male reproductive system, which can be protected by L-ascorbic acid.     

Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study.

PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy in women with primary or locally advanced breast cancer. PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases were randomly assigned to receive a maximum of six cycles of either doxorubicin (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV) every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3 weeks, followed by surgery on completion of chemotherapy. Results A total of 363 patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete clinical response was observed in 17% and 20% of patients treated with AC and AD, respectively (P = .42). Overall (complete and partial) clinical response rates for AC and AD were 61% and 70%, respectively (P = .06). There was no significant difference in either the pathologic complete response rates in the breast with AC (24%) and AD (21%; P = .61) or in the number of patients with positive axillary nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32 months, there is no significant difference between the two groups for the number of relapses. CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer, our data do not suggest a benefit for simultaneous AD over AC.