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Background: Posterior hip and buttock pain can arise from several overlapping but distinct etiologies. Ischiofemoral impingement, sciatic neuropathy, and proximal hamstring tendinopathy, occurring alone or in combination, have been implicated as precipitants. However, diagnosis and management of underlying pathology can be challenging, as few diagnostic modalities reliably differentiate between these etiologies and surgeon decision-making may be complicated by uncertainty over which pathology to address. Indications: Posterior hip and buttock pain which occurs in a sciatic nerve distribution and is refractory to conservative measures (eg, physical therapy, analgesics, and activity modification) raises suspicion for 1 or several of the above pathologies. A combined procedure to address all 3—ischiofemoral decompression, sciatic neurolysis, and proximal hamstring repair—is described here. Technique Description: The patient is placed prone on a radiolucent table. An incision is made, and dissection is taken down through the superficial layers of the buttock, gluteal fascia, and fascia overlying the proximal hamstring tendons. The sciatic nerve is identified, mobilized, and lysed using blunt dissection. The fascia overlying the ischium is incised and the tendinous insertion decorticated with rongeur. Two anchors are placed, and sutures are passed through the proximal hamstring tendon in mattress fashion. An incision is made in line with the external rotators and dissection is taken down to the lesser trochanter. The lesser trochanter is identified, and osteotomy performed, with mobilization and removal of the resected fragment. The interval in the external rotators is closed with interrupted suture. Results: This is an uncommon procedure with little data on patient outcomes. Nonetheless, it is effective for relief of symptoms related to the pathologies enumerated above. Keys to success include careful diagnosis and comfort with surgical technique. Conclusion: The COMBIS procedure simultaneously addresses 3 common etiologies of posterior hip and buttock pain. Although it is important to conduct a thorough diagnostic evaluation to rule out imitators, patients with symptoms due to ischiofemoral impingement, sciatic neuropathy, proximal hamstring tendinopathy, or combination thereof may experience good relief of symptoms with appropriate application of this technique. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Recurrentlateral patellar dislocation is a devastating condition associated with different pathologies, including medial patellofemoral ligament (MPFL) injury, increased tibial tubercle to trochlear groove (TT-TG) distance, and trochlear dysplasia. This video aims to provide an overview of isolated MPFL reconstruction in a patient with recurrent patellar dislocation and chronic MPFL injury. Indications: Isolated MPFL reconstruction is indicated for patients with recurrent lateral patellar instability following an initial trial of nonoperative management, in the absence of other contributing anatomic factors. Candidates for isolated MPFL reconstruction should have a TT-TG distance of

Objectives:. Our objective was to compare outcomes following combined versus isolated resections for metastatic colorectal cancer and/or liver metastases using a large, contemporary national database. Background:. Controversy persists regarding optimal timing of resections in patients with synchronous colorectal liver metastases. Methods:. We analyzed 11,814 patients with disseminated colorectal cancer and/or liver metastases who underwent isolated colon, rectal, or liver resections (CRs, RRs, or LRs) or combined colon/liver or rectal/liver resections (CCLRs or CRLRs) in the National Surgical Quality Improvement Program Participant Use File (2011–2015). We examined associations between resection type and outcomes using univariate/multivariate analyses and used propensity adjustment to account for nonrandom receipt of isolated versus combined resections. Results:. Two thousand four hundred thirty-seven (20.6%); 2108 (17.8%); and 6243 (52.8%) patients underwent isolated CR, RR, or LR; 557 (4.7%) and 469 (4.0%) underwent CCLR or CRLR. Three thousand three hundred ninety-five patients (28.7%) had serious complications (SCs). One hundred forty patients (1.2%) died, of which 113 (80.7%) were failure to rescue (FTR). One thousand three hundred eighty-six (11.7%) patients experienced unplanned readmission. After propensity adjustment and controlling for procedural complexity, wound class, and operation year, CCLR/CRLR was independently associated with increased risk of SC, as well as readmission (compared with LR). CCLR was also independently associated with increased risk of FTR and death (compared with LR). Conclusions:. Combined resection uniformly confers increased risk of SC and increased risk of mortality after CCLR; addition of colorectal to LR increases risk of readmission. Combined resections are less safe, and potentially more costly, than isolated resections. Effective strategies to prevent SC after combined resections are warranted.

Therapeutically targeting receptor tyrosine kinases has proven to be paramount to overcoming chemotherapy resistance in several cancer indications, improving patient outcomes. Insulin-Like Growth Factor Receptor 1 (IGF-1R) and Epidermal Growth Factor Receptor 3 (ErbB3) have been implicated as two such drivers of resistance, however their simultaneous role in ovarian cancer chemotherapy resistance remains poorly elucidated. The aim of this work is to determine the effects of dual IGF-1R/ErbB3 inhibition on ovarian cancer cell signaling, growth, and in vivo efficacy. Assessment of in vitro chemotherapy response across a panel of ovarian cancer cell lines revealed that increased IGF-1R cell surface expression correlates with decreased sensitivity to chemotherapy, and that growth induced by IGF-1R and ErbB3 ligands is blocked by the tetravalent bispecific antibody targeting IGF-1R and ErbB3, istiratumab. In vitro chemotherapy treatment increased ovarian cancer cell line capacity to activate prosurvival PI3K signaling in response to ligand, which could be prevented with istiratumab treatment. Furthermore, in vivo efficacy of standard of care chemotherapies using a xenograft model of ovarian cancer was potentiated with istiratumab. Our results suggest a role for IGF-1R and ErbB3 in driving chemotherapy resistance of ovarian cancer.

Purpose: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies. Experimental Design: Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and in vivo chemotherapy activity in pancreatic cancer xenograft models were determined. Results: Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG in vitro Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity in vivo Conclusions: Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. Clin Cancer Res; 24(12); 2873-85. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Heregulin-driven ERBB3 signaling has been implicated as a mechanism of resistance to cytotoxic and antiendocrine therapies in preclinical breast cancer models. In this study, we evaluated the effects of seribantumab (MM-121), a heregulin-blocking anti-ERBB3 monoclonal antibody, alone and in combination with the aromatase inhibitor letrozole, on cell signaling and tumor growth in a preclinical model of postmenopausal estrogen receptor-positive (ER(+)) breast cancer. In vitro, heregulin treatment induced estrogen receptor phosphorylation in MCF-7Ca cells, and long-term letrozole-treated (LTLT-Ca) cells had increased expression and activation levels of EGFR, HER2, and ERBB3. Treatment with seribantumab, but not letrozole, inhibited basal and heregulin-mediated ERBB receptor phosphorylation and downstream effector activation in letrozole-sensitive (MCF-7Ca) and -refractory (LTLT-Ca) cells. Notably, in MCF-7Ca-derived xenograft tumors, cotreatment with seribantumab and letrozole had increased antitumor activity compared with letrozole alone, which was accompanied by downregulated PI3K/MTOR signaling both prior to and after the development of resistance to letrozole. Moreover, the addition of an MTOR inhibitor to this treatment regimen did not improve antitumor activity and was not well tolerated. Our results demonstrate that heregulin-driven ERBB3 signaling mediates resistance to letrozole in a preclinical model of ER(+) breast cancer, suggesting that heregulin-expressing ER(+) breast cancer patients may benefit from the addition of seribantumab to antiendocrine therapy., (©2015 American Association for Cancer Research.)

Despite the fact that epithelial ovarian cancers are the leading cause of death from gynecological cancer, very little is known about the pathophysiology of the disease. Mutations in the WNT and PI3K pathways are frequently observed in the human ovarian endometrioid adenocarcinomas (OEAs). However, the role of WNT/β-catenin and PTEN/AKT signaling in the etiology and/or progression of this disease is currently unclear. In this report we show that mice with a gain-of-function mutation in β-catenin that leads to dysregulated nuclear accumulation of β-catenin expression in the ovarian surface epithelium (OSE) cells develop indolent, undifferentiated tumors with both mesenchymal and epithelial characteristics. Combining dysregulated β-catenin with homozygous deletion of PTEN in the OSE resulted in development of significantly more aggressive tumors, which was correlated with inhibition of p53 expression and cellular senescence. Induced expression of both mTOR kinase, a master regulator of proliferation, and phosphorylation of its downstream target, S6Kinase was also observed in both the indolent and aggressive mouse tumors, as well as in human OEA with nuclear β-catenin accumulation. Ectopic allotransplants of the mouse ovarian tumor cells with a gain-of-function mutation in β-catenin and PTEN deletion developed into tumors with OEA histology, the growth of which were significantly inhibited by oral rapamycin treatment. These studies demonstrate that rapamycin might be an effective therapeutic for human ovarian endometrioid patients with dysregulated Wnt/β-catenin and Pten/PI3K signaling.

Background: Recent evidence links aberrant activation of Hedgehog (Hh) signaling with the pathogenesis of several cancers including medulloblastoma, basal cell, small cell lung, pancreatic, prostate and ovarian. This investigation was designed to determine if inhibition of this pathway could inhibit serous ovarian cancer growth., Methodology: We utilized an in vivo pre-clinical model of serous ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous ovarian tumor tissue was used to generate tumor xenografts in mice that were subsequently treated with cyclopamine or IPI-926., Principal Findings: Both compounds demonstrated significant anti-tumor activity as single agents. When IPI-926 was used in combination with paclitaxel and carboplatinum (T/C), no synergistic effect was observed, though sustained treatment with IPI-926 after cessation of T/C continued to suppress tumor growth. Hh pathway activity was analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however, inhibited Hh signaling in both mouse stromal and human tumor cells. Expression data from the micro-dissected stroma in human serous ovarian tumors confirmed the presence of Gli1 transcript and a significant association between elevated Gli1 transcript levels and worsened survival., Conclusions/significance: IPI-926 treatment inhibits serous tumor growth suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may hold promise as a novel therapeutic target, especially in the maintenance setting.

Ovarian cancer represents the most lethal gynecologic malignancy, primarily due to a lack of early detection, which results in most patients being diagnosed at an advanced stage of disease. Though the ovarian surface epithelium is thought to provide the primary site of tumorigenesis, the exact etiology of the various tumor types associated with this disease remain undefined. Recent evidence suggests that ovarian tumors, like other solid tumors, contain distinct populations of cells that are responsible for tumor initiation, maintenance and growth. These specialized cells, termed cancer stem cells, display some of the hallmarks of normal stem cells and are thought to evade current chemotherapeutic strategies, resulting in an increased risk of recurrence. Here we review evidence for the existence of cancer stem cells in ovarian malignancies and their contribution to the pathology of this disease, critically evaluate the methods used for ovarian cancer stem cell definition and isolation, and discuss their clinical relevance.

Background: Recent data provide significant evidence to support the hypothesis that there are sub-populations of cells within solid tumors that have an increased tumor initiating potential relative to the total tumor population. CD133, a cell surface marker expressed on primitive cells of neural, hematopoietic, endothelial and epithelial lineages has been identified as a marker for tumor initiating cells in solid tumors of the brain, colon, pancreas, ovary and endometrium. Our objectives were to assess the relative level of CD133 expressing cells in primary human endometrial tumors, confirm their tumorigenic potential, and determine whether CD133 expression was epigenetically modified., Methods: We assessed CD133 expression in primary human endometrial tumors by flow cytometry and analyzed the relative tumorigenicity of CD133+ and CD133- cells in an in vivo NOD/SCID mouse model. We assessed potential changes in CD133 expression over the course of serial transplantation by immunofluorescence and flow cytometry. We further examined CD133 promoter methylation and expression in normal endometrium and malignant tumors., Results: As determined by flow cytometric analysis, the percentage of CD133+ cells in primary human endometrial cancer samples ranged from 5.7% to 27.4%. In addition, we confirmed the tumor initiating potential of CD133+ and CD133- cell fractions in NOD/SCID mice. Interestingly, the percentage of CD133+ cells in human endometrial tumor xenografts, as evidenced by immunofluorescence, increased with serial transplantation although this trend was not consistently detected by flow cytometry. We also determined that the relative levels of CD133 increased in endometrial cancer cell lines following treatment with 5-aza-2'-deoxycytidine suggesting a role for methylation in the regulation of CD133. To support this finding, we demonstrated that regions of the CD133 promoter were hypomethylated in malignant endometrial tissue relative to benign control endometrial tissue. Lastly, we determined that methylation of the CD133 promoter decreases over serial transplantation of an endometrial tumor xenograft., Conclusions: These findings support the hypotheses that CD133 expression in endometrial cancer may be epigenetically regulated and that cell fractions enriched for CD133+ cells may well contribute to endometrial cancer tumorigenicity, pathology and recurrence.

Introduction: CO2 accumulation may limit crew survival in a disabled submarine. Reversible sedation using diazepam and flumazenil was proposed to reduce CO2 production., Methods: Two groups of three resting subjects were studied during a 48-h placebo phase with diazepam and flumazenil placebos, followed by a 48-h drug phase with oral diazepam to induce sedation and intranasal flumazenil to reverse it. CO2 exchange was measured every 2.5 h; twice a day, cognitive testing and meals were preceded by placebo or flumazenil. Return to sedated state was produced with either placebo or diazepam. In the drug phase, initial diazepam doses (10 to 40 mg) were followed by maintenance doses to achieve sedation corresponding to Alertness Scores of 3 or 4., Results: In the drug phase, subjects received a total of 360-495 mg of diazepam (with doses of 5-40 mg), average alertness score was 3.75, and mean Vco2 was 14% less than in the placebo phase (0.212 vs. 0.248 L x min(-)). Subjects were 21-36% less active when sedated with diazepam. The mean flumazenil dose to restore full alertness was 0.36 mg, with subjects being conversant and oriented within 5 min, performing cognitive tasks at 86-97% of their baseline. Subjects could follow instructions and ambulate independently, though unsteadily 6 h after final flumazenil dose; at 72 h they exhibited normal cognitive and physical functions., Discussion: Reversible sedation to lower crew metabolism in a disabled submarine may be effective, safe, and practical.

Evidence is accumulating that solid tumors contain a rare phenotypically distinct population of cells, termed cancer stem cells (CSC), which give rise to and maintain the bulk of the tumor. These CSC are thought to be resistant to current chemotherapeutic strategies due to their intrinsic stem-like properties and thus may provide the principal driving force behind recurrent tumor growth. Given the high frequency of recurrent metastasis associated with human ovarian cancer, we sought to determine whether primary human ovarian tumors contain populations of cells with enhanced tumor-initiating capacity, a characteristic of CSC. Using an in vivo serial transplantation model, we show that primary uncultured human ovarian tumors can be reliably propagated in NOD/SCID mice, generating heterogeneous tumors that maintain the histological integrity of the parental tumor. The observed frequency of tumor engraftment suggests only certain subpopulations of ovarian tumor cells have the capacity to recapitulate tumor growth. Further profiling of human ovarian tumors for expression of candidate CSC surface markers indicated consistent expression of CD133. To determine whether CD133 expression could define a tumor-initiating cell population in primary human ovarian tumors, fluorescence-activated cell sorting (FACS) methods were employed. Injection of sorted CD133(+) and CD133(-) cell populations into NOD/SCID mice established that tumor-derived CD133(+) cells have an increased tumorigenic capacity and are capable of recapitulating the original heterogeneous tumor. Our data indicate that CD133 expression defines a NOD/SCID tumor initiating subpopulation of cells in human ovarian cancer that may be an important target for new chemotherapeutic strategies aimed at eliminating ovarian cancer.

Introduction: Psychophysical measures of wet-suit hood sound attenuation are needed to provide the diving community with guidance on protection from underwater sound., Methods: Underwater hearing thresholds were obtained from 15 male and 5 female recreational divers with and without a 3-mm thick wet-suit hood. Dives were conducted at a depth of 1 m in a large quiet anechoic pool. Thresholds were determined using a two-interval forced-choice procedure with a 0.71 probability of positive response at convergence. A 1-s pure tone was presented with a 20-ms rise and fall time at 100, 200, 250, 300, 400, and 500 Hz., Results: Without a wet-suit hood, mean thresholds decreased from 99 dB re 1 microPa at 100 Hz to 85 dB at 500 Hz. Thresholds were statistically similar at 100 to 300 Hz with and without the wet-suit hood, but were significantly increased at 400 and 500 Hz with the hood (p < 0.001)., Conclusions: In conclusion, at shallow depths, a 3-mm neoprene wet-suit hood attenuates underwater sound by approximately 10 dB for frequencies between 400 Hz and 500 Hz. At frequencies below 400 Hz, a 3-mm neoprene wet-suit hood offers no sound protection.

Increasing use of active low-frequency sonar by submarines and ships raises the risk of accidental exposure of recreational divers to low-frequency underwater sound (LFS). This study aimed to characterize the subjective responses of recreational scuba divers to LFS to ascertain the extent to which LFS may impact their enjoyment, comfort, or time spent underwater. Seventeen male and nine female recreational scuba divers participated. Diving was conducted in an acoustically transparent tank located within a larger anechoic pool. Subjects wore scuba gear and were positioned I m below the surface in a prone position. The sound transducer was located 4 m directly below the diver's head. Sound exposures consisted of three signal types (pure tone, 30 Hz hyperbolic sweep up, and 30 Hz hyperbolic sweep down) each presented at six center frequencies from 100 to 500 Hz and six sound pressure levels(SPL) ranging from 130 to 157 dB re 1 microPa. The duration of each sound exposure was 7 s. Subjects responded via an underwater console to rate aversion to LFS on a category-ratio scale, and to indicate the presence or absence of vibration of any body part. Aversion to LFS and the percent incidence of vibration increased as the SPL increased. The percent incidence of vibration decreased linearly with increasing frequency. At the highest SPL the probability that an aversion rating would exceed Very Severe (7 on the category-ratio scale) was predicted to be 19%. There was no significant difference in aversion among signal types. The 100 Hz frequency was the most aversive frequency (P < 0.05). A plot of aversion vs. frequency showed a U-shaped function with minimum aversion at 250 Hz. In conclusion, diver aversion to LFS is dependent upon SPL and center frequency. The highest aversion rating was given for 100 Hz, this frequency corresponded with the greatest probability of detecting vibration. Factors other than vibration seem to account for aversion to the highest frequencies. Our data suggest that LFS exposures up to 145 dB re 1 microPa at frequencies between 100 and 500 Hz will have minimal impact on the recreational diver.

Performance and physiology of five operators of the one-atmosphere diving system JIM were assessed when diving JIM in mild (20 degrees C) and warm (30 degrees C) water. Each operator completed a minimum of 3 dives at each water temperature; during each dive 5 walks of 18 m and 3 step maneuvers were accomplished. At the conclusion of 40-min dives in water at 30 degrees C, operator heart rate averaged 151 beats/min, system interior temperature averaged 32.6 degrees C, and the mean respiration rate of operators was 28 breaths/min. Task completion times were faster in warm water. Thermal considerations in the deployment of the JIM system are discussed in relation to these data.

The behavioral toxicity of an organic tin compound under consideration for use in marine antifouling paint was assessed using a Sidman avoidance paradigm. The assessed compound, an organometallic polymer (tributyltin [methacrylic-CO-methylmethacrylate] ester), is from a group of alkyltin compounds of which triethyl and tributyltin are known to be toxic. Rats were tested under a free-operant avoidance procedure for 6 months while ingesting the polymer in their drinking water. At the beginning of the 5th month significant behavioral changes became evident, reflected in increases in shock rate, decreased responding, and a shifting of the interresponse time distribution. Performance improved upon withdrawal of the contaminant suggesting that limited exposure to the polymer may not result in permanent behavioral dysfunction.

The noise inside the U.S. Navy MK 12 SSDS helmet was measured and its effect on the hearing of divers assessed. Seven male divers completed 20 dives while breathing air at simulated depths ranging from 1.8 to 30.5 msw with dive durations ranging from 40 to 120 min. Microphones recorded sound pressure levels inside the helmet while the diver was in the water and exercising. Average corrected sound intensity levels in the helmet ranged from 90.5 dB(A) at 1.8 msw to 97.3 dB(A) at 30.5 msw. Diver hearing threshold level shifts were recorded as a function of helmet noise exposure; moderate threshold shifts were observed at depths of 9.1 msw or deeper after 120-min dives. The hearing of all divers completing dives up to 120 min returned to predive levels within 24 h after noise exposure. However, dive durations in excess of 120 min at 9.1 and 20.1 msw resulted in substantial auditory shifts in 1 diver, which required 2-3 d to recover to predive levels. These results suggest that the impact of helmet noise on diver hearing should be included in planning operations using the MK 12 SSDS.

The visual reaction time performance of divers experiencing CNS oxygen toxicity was assessed during the development of closed-circuit 100% oxygen breathing diving schedules at the U.S. Navy Experimental Diving Unit. Divers repeatedly performed the visual reaction time test of the Performance Measurement System (PMS) during multiple excursion dives. Each diver wore a Draeger LAR V UBA and performed moderate work on an underwater bicycle ergometer while engaged in the reaction time test. A single subject, repeated measures design was used. Six divers experienced 7 episodes of CNS oxygen toxicity while engaged in the visual reaction time test. Two episodes were preceded by a slowing and increase in variability of reaction time. Five episodes were not preceded by changes in reaction time performance. Other objective and subjective symptoms of toxicity experienced by the divers did not appear to be correlated with reaction time performance. Thus, the PMS visual reaction time test was not reliable method of detecting CNS oxygen toxicity in this study.

A battery of neuropsychologic tests was administered to individuals who had sustained CNS decompression sickness or arterial gas embolism. Testing was intended to assess the presence of residual cognitive impairment. Five clinical cases are presented in which information obtained through this testing played a determining role in the detection and treatment of residual cerebral dysfunction. Recovery of cerebral integrity was documented using the test battery. Even in the absence of clear signs from a standard neurologic examination, sufficient information was gathered by neuropsychologic testing to prompt recompression therapy. Temporary suppression of CNS symptoms by initial recompression was often observed, as documented by follow-up neurologic and neuropsychologic evaluations. Recovery of full cognitive functioning followed repeated hyperbaric treatments, suggesting that CNS insults may be more refractory to therapy than previously thought.

The cognitive performance of six male Marines undergoing a 10-d heat acclimatization regimen was assessed using repeated acquisition and time estimation tasks. Subjects performed controlled treadmill exercise in a heat acclimatization chamber at 33.3 degrees C dry bulb, 29.4 degrees C wet bulb temperature. Multiple performance assessments were conducted during each daily heat exposure of 155 min. On the first day of heat exposure, time estimates decreased from preacclimatization baseline values recorded at moderate temperatures while performance on the repeated acquisition tasks yielded slight decrements. By the 10th day of heat exposure, all subjects demonstrated significant heat acclimatization. However, mean performance on the repeated acquisition task was still impaired and time estimates were higher than during the first heat exposure. These results suggest that tasks requiring the acquisition of new behaviors may be difficult to perform in a hot environment, even by partially acclimatized individuals.

The neuropsychologic status of 25 male U.S. Navy saturation divers was assessed before and after saturation dives conducted at the Navy Experimental Diving Unit. Between 1982 and 1986, 5 dives to simulated depths of 198 to 335 msw were accomplished. Eighteen divers completed 1 dive, and 7 divers completed 2 saturation dives during this period. Dive durations ranged from 26 to 31 d, with helium-oxygen used as the breathing medium. On each dive the men engaged in strenuous, meaningful, in-water work on the bottom. Comparison of neuropsychologic assessment battery results pre- and postdives did not reveal permanent changes in neuropsychologic status. Transient alterations in affect, visual focusing, and physical activity level presented upon surfacing but resolved within 10 d.

The effectiveness of the U.S. Navy (USN) Diving Manual treatment algorithm in treating pain-only decompression sickness (DCS) was analyzed. Treatment logs from the Naval Diving and Salvage Training Center and the Navy Experimental Diving Unit during the decade 1976-1986 were examined. Two hundred and ninety-two cases diagnosed initially as pain-only DCS were identified. Using the treatment algorithm, 208 cases were completed on USN Treatment Table 5 (TT-5), and 84 cases completed on USN Treatment Table 6 (TT-6). Recurrence of symptoms was 4.3% after TT-5, and 3.6% following TT-6. Difference in rate of recurrence was not statistically significant between treatment tables. Overall, the success rate for following the USN treatment algorithm was 95.9%. These data support the use of the shorter TT-5 in accordance with the Navy treatment algorithm.

Morphine sulfate was tested under hyperbaric pressure to assess its effects on behavior. Four male hooded rats were trained to avoid brief electric shocks under a free-operant unsignalled avoidance procedure. Using an individual organism design, we injected each rat subcutaneously with morphine sulfate (2.0, 4.0, 6.0, 8.0 mg/kg body wt.) or saline (0.1 ml/100 g body wt.). Rats were tested at 1.0 and 7.1 atmospheres absolute (ATA) in a dry hyperbaric chamber while breathing a mixture of helium and oxygen. Each session lasted 60 min. Overall, the analgesic effects of morphine at 1.0 and 7.1 ATA were found to be similar. Shock avoidance by a rat was found to be a monotonic function of the drug dose; the fewest shocks were associated with the 2.0 mg/kg dose. Increased pressure did not significantly affect the number of shocks received by a rat across doses. Total responding remained stable throughout the study, but the temporal pattern of responding was differentially influenced by drug dose.