Expressive suppression and cognitive reappraisal in veterans with PTSD: Results from the mind your heart study.

OBJECTIVE: This study examined whether expressive suppression (ES), a maladaptive regulation strategy, was more strongly associated with PTSD diagnosis and symptom clusters in veterans than cognitive reappraisal (CR), an adaptive regulation strategy. METHOD: In a cohort study, 746 participants recruited from VHA facilities completed Clinician Administered PTSD Scale-IV, Emotion Regulation Questionnaire, and Patient Health Questionnaire. Participants were categorized into groups: Current, Remitted/Lifetime, and Never PTSD. RESULTS: One-way ANOVA revealed significant differences between Current PTSD and both Remitted and Never PTSD for ES, but not CR. The Remitted and Never PTSD groups did not vary significantly from each other and were collapsed into one group for regressions. Adjusting for sex, race, employment, and comorbid depression, binary logistic regression showed ES, but not CR, was associated with increased likelihood of Current PTSD (p < .001, OR: 1.43). ES was also significantly associated with increased odds of meeting criteria for all symptom clusters (ps < 0.001). CR was not significantly associated with meeting criteria for Current PTSD or any symptom cluster. LIMITATIONS: Cross-sectional design and use of self-report limit causality inferences that can be drawn. CONCLUSIONS: ES is associated with increased odds of Current PTSD diagnosis and symptom clusters. Veterans in the Remitted and Never PTSD groups did not differ significantly. Greater suppression of emotional expression is more strongly linked with PTSD criteria in veterans than decreased cognitive reappraisal.

Suppression, but not reappraisal, is associated with inflammation in trauma-exposed veterans.

BACKGROUND: Emotion dysregulation can elicit inflammatory activity. The current study examined whether specific maladaptive and adaptive emotion regulation strategies were associated with inflammatory markers in trauma-exposed veterans, above and beyond PTSD. METHODS: In a cohort study, 606 participants exposed to a Criterion A trauma and recruited from Veteran Health Administration facilities completed fasting blood draws, the Emotion Regulation Questionnaire, and the Clinician Administered PTSD Scale-IV. Inflammation was assessed with high sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen levels. An inflammation index was created by summing standardized log-transformed levels of the three biomarkers. Our primary linear regression models were adjusted for sex, age, race, education, income, creatinine, and PTSD. RESULTS: Suppression, but not cognitive reappraisal, was significantly associated with higher levels of the inflammatory index (ß = 0.14, p = 0.001). Parallel analyses for the individual inflammatory markers also showed suppression, but not reappraisal, was significantly associated with higher hsCRP (ß = 0.11, p = 0.01), WBC (ß = 0.11, p = 0.01), and fibrinogen (ß = 0.10, p = 0.02). CONCLUSIONS: Emotional suppression is related to elevated systemic inflammation independent of PTSD. Cognitive reappraisal is unrelated to inflammation. Findings suggest over-utilization of maladaptive, rather than under-utilization of adaptive, emotion regulation strategies may be associated with systemic inflammation in trauma-exposed veterans.

Boom boom pow: Shock-facilitated aqueous alteration and evidence for two shock events in the Martian nakhlite meteorites.

Nakhlite meteorites are ~1.4 to 1.3 Ga old igneous rocks, aqueously altered on Mars ~630 Ma ago. We test the theory that water-rock interaction was impact driven. Electron backscatter diffraction demonstrates that the meteorites Miller Range 03346 and Lafayette were heterogeneously deformed, leading to localized regions of brecciation, plastic deformation, and mechanical twinning of augite. Numerical modeling shows that the pattern of deformation is consistent with shock-generated compressive and tensile stresses. Mesostasis within shocked areas was aqueously altered to phyllosilicates, carbonates, and oxides, suggesting a genetic link between the two processes. We propose that an impact ~630 Ma ago simultaneously deformed the nakhlite parent rocks and generated liquid water by melting of permafrost. Ensuing water-rock interaction focused on shocked mesostasis with a high density of reactive sites. The nakhlite source location must have two spatially correlated craters, one ~630 Ma old and another, ejecting the meteorites, ~11 Ma ago.

New bioactive motifs and their use in functionalized self-assembling peptides for NSC differentiation and neural tissue engineering.

Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the discovery of novel functional motifs fostering transplanted stem cell engraftment and nervous fiber regeneration. Using phage display technology we have discovered new peptide sequences that bind to murine neural stem cell (NSC)-derived neural precursor cells (NPCs), and promote their viability and differentiation in vitro when linked to LDLK12 self-assembling peptide (SAPeptide). We characterized the newly functionalized LDLK12 SAPeptides via atomic force microscopy, circular dichroism and rheology, obtaining nanostructured hydrogels that support human and murine NSC proliferation and differentiation in vitro. One functionalized SAPeptide (Ac-FAQ), showing the highest stem cell viability and neural differentiation in vitro, was finally tested in acute contusive spinal cord injury in rats, where it fostered nervous tissue regrowth and improved locomotor recovery. Interestingly, animals treated with the non-functionalized LDLK12 had an axon sprouting/regeneration intermediate between Ac-FAQ-treated animals and controls. These results suggest that hydrogels functionalized with phage-derived peptides may constitute promising biomimetic scaffolds for in vitro NSC differentiation, as well as regenerative therapy of the injured nervous system. Moreover, this multi-disciplinary approach can be used to customize SAPeptides for other specific tissue engineering applications.

Outcome after fixation of ankle fractures with an injury to the syndesmosis: the effect of the syndesmosis screw.

The purpose of this study was to compare the clinical and radiological outcome of patients with intact, broken and removed syndesmosis screws after Weber B or C ankle fracture with an associated injury to the syndesmosis. We hypothesised that there would be no difference. Of a possible 142 patients who fulfilled our inclusion criteria, 52 returned for clinical and radiological assessment at least one year after surgery. Of these, 27 had intact syndesmosis screws, ten had broken screws, and 15 had undergone elective removal of the screw. The mean American Orthopaedic Foot and Ankle Society ankle/hindfoot score was 83.07 (sd 13.59) in the intact screw group, 92.40 (sd 12.69) in the broken screw group, and 85.80 (sd 11.33) in the removed screw group (p = 0.0466). There was no difference in clinical outcome of patients with intact or removed syndesmotic screws. Paradoxically, patients with a broken syndesmosis screw had the best clinical outcome. Our data do not support the removal of intact or broken syndesmosis screws, and we caution against attributing post-operative ankle pain to breakage of the syndesmosis screw.

Simultaneous bilateral breast reconstruction using latissimus dorsi myocutaneous flaps: a retrospective review of an institutional experience.

A single institution's experience in the simultaneous reconstruction of both breasts using bilateral latissimus dorsi myocutaneous flaps is presented. The procedure was performed on 24 patients by the attending staff of the department of plastic surgery at St. Joseph Hospital in Houston, Texas, between 1979 and 1999. Of the 24 patients reviewed, six had immediate reconstructions, 13 had delayed primary reconstructions, and five had secondary reconstructions of failed or unsatisfactory primary procedures. In the group with delayed reconstructions, the average time between mastectomy and reconstruction was 46.4 months, with a range from 7 days to 21 years. The operative method, results, and outcomes of our experience in these patients is presented.

Subtalar arthrodesis for treatment of posterior tibial tendon insufficiency.

Subtalar arthrodesis is an effective treatment of the planovalgus deformity of posterior tibial tendon insufficiency that provides stable and reliable results with minimal complications. Disadvantages include the risk of symptomatic adjacent joint arthrosis at long-term follow-up and less clinical and radiographic correction of the deformity as compared with other reconstructive options, which may make the joint-preserving procedures more attractive for the primary treatment of patients with a flexible pes planovalgus deformity without subtalar pain.

Associated injuries found in chronic lateral ankle instability.

Sixty-one patients underwent a primary ankle lateral ligament reconstruction for chronic instability between 1989 and 1996. In addition to the ligament reconstruction, all patients had evaluation of the peroneal retinaculum, peroneal tendon inspection by routine opening of the tendon sheath, and ankle joint inspection by arthrotomy. A retrospective review of the clinical history, physical exam, MRI examination, and intraoperative findings was conducted on these 61 patients. The purpose was to determine the type and frequency of associated injuries found at surgery and during the preoperative evaluation. At surgery no patients were found to have isolated lateral ligament injury. Fifteen different associated injuries were noted. The injuries found most often by direct inspection included: peroneal tenosynovitis, 47/61 patients (77%); anterolateral impingement lesion, 41/61 (67%); attenuated peroneal retinaculum, 33/61 (54%); and ankle synovitis, 30/61 (49%). Other less common but significant associated injuries included: intra-articular loose body, 16/61 (26%); peroneus brevis tear, 15/61 (25%); talus osteochondral lesion, 14/61 (23%); medial ankle tendon tenosynovitis, 3/61 (5%). The findings of this study indicate there is a high frequency of associated injuries in patients with chronic lateral ankle instability. Peroneal tendon and retinacular pathology, as well as anterolateral impingement lesions, occur most often. A high index of suspicion for possible associated injuries may result in more consistent outcomes with nonoperative and operative treatment of patients with chronic lateral ankle instability.

Subtalar arthrodesis with flexor digitorum longus transfer and spring ligament repair for treatment of posterior tibial tendon insufficiency.

The surgical treatment of flexible pes planovalgus deformities resulting from Stage 2 posterior tibial tendon insufficiency is controversial and many techniques have been proposed. We retrospectively reviewed the results of subtalar arthrodesis combined with spring ligament repair/reefing and flexor digitorum longus (FDL) transfer to the navicular. There were sixteen patients (seventeen feet) with an average follow-up of 27 months (9-52). All deformities were passively correctable. The average age was 56 yrs (39-78). All patients had failed conservative management, 88% had previously been treated with orthotics, and 53% had lateral pain from subfibular impingement. Two patients were noted to have degenerative changes of the subtalar joint. Successful subtalar joint fusion occurred in all patients with an average time to radiographic union of 10.1 weeks (5-24). The average AOFAS hindfoot score and Maryland foot score postoperatively was 82 and 86 respectively. Standing radiographic analysis demonstrated an average improvement in the AP talo-1st metatarsal angle of 6 degrees (24 degrees preoperative, 18 degrees postoperative). The talonavicular coverage angle improved an average of 17 degrees (34 degrees preoperative, 17 degrees postoperative). The lateral talo-1st metatarsal angle improved an average of 10 degrees (18 degrees preoperative, 8 degrees postoperative). The lateral talocalcaneal angle decreased an average of 21o (55 degrees preoperative, 34 degrees postoperative). The distance of the medial cuneiform to the floor on the lateral radiograph averaged 12mm preoperatively and 18mm postoperatively (avg. improvement 6mm). The combination of the flexor digitorum longus tendon transfer and spring ligament repair with subtalar arthrodesis is an effective and reliable procedure which provides excellent correction of hindfoot valgus as well as forefoot abduction and restoration of the height of the longitudinal arch. These results compare favorably with flexor transfer combined with either calcaneal osteotomy or lateral column lengthening.

Functional analysis and molecular modeling of a cloned urate transporter/channel.

Recombinant protein, designated UAT, prepared from a cloned rat renal cDNA library functions as a selective voltage-sensitive urate transporter/channel when fused with lipid bilayers. Since we previously suggested that UAT may represent the mammalian electrogenic urate transporter, UAT has been functionally characterized in the presence and absence of potential channel blockers, several of which are known to block mammalian electrogenic urate transport. Two substrates, oxonate (a competitive uricase inhibitor) and pyrazinoate, that inhibit renal electrogenic urate transport also block UAT activity. Of note, oxonate selectively blocks from the cytoplasmic side of the channel while pyrazinoate only blocks from the channel's extracellular face. Like oxonate, anti-uricase (an electrogenic transport inhibitor) also selectively blocks channel activity from the cytoplasmic side. Adenosine blocks from the extracellular side exclusively while xanthine blocks from both sides. These effects are consistent with newly identified regions of homology to uricase and the adenosine A1/A3 receptor in UAT and localize these homologous regions to the cytoplasmic and extracellular faces of UAT, respectively. Additionally, computer analyses identified four putative alpha-helical transmembrane domains, two beta sheets, and blocks of homology to the E and B loops of aquaporin-1 within UAT. The experimental observations substantiate our proposal that UAT is the molecular representation of the renal electrogenic urate transporter and, in conjunction with computer algorithms, suggest a possible molecular structure for this unique channel.

Millisecond Laue structures of an enzyme-product complex using photocaged substrate analogs.

The structure of a rate-limited product complex formed during a single initial round of turnover by isocitrate dehydrogenase has been determined. Photolytic liberation of either caged substrate or caged cofactor and Laue X-ray data collection were used to visualize the complex, which has a minimum half-life of approximately 10 milliseconds. The experiment was conducted with three different photoreactive compounds, each possessing a unique mechanism leading to the formation of the enzyme-substrate (ES) complex. Photoreaction efficiency and subsequent substrate affinities and binding rates in the crystal are critical parameters for these experiments. The structure suggests that CO2 dissociation is a rapid event that may help drive product formation, and that small conformational changes may contribute to slow product release.

Normative values for the nearpoint of convergence of elementary schoolchildren.

BACKGROUND: Nearpoint of convergence (NPC) values of 8 to 10 cm are widely used to diagnose binocular dysfunctions such as convergence insufficiency. However, there are no published age-related normative values in the literature to substantiate these values. METHODS: Subjects were 297 schoolchildren in kindergarten, third grade, and sixth grade who had passed a school-based Modified Clinical Technique vision screening. Each child had the NPC break and recovery taken three times using a standardized protocol developed by the Convergence Insufficiency and Reading Study group. The examiners used an Astron International (ACR/21) Accommodative Rule with a movable column of 20/30 letters as the target. RESULTS: For each grade, the distribution of NPC break was right skewed, with a concentration of values between 1 and 6 cm. At least 85% of the subjects in each grade had an NPC break < or = 6 cm. NPC break values (mean +/- SD) were 3.3 +/- 2.6 cm for kindergartners, 4.1 +/- 2.4 cm for third graders, and 4.3 +/- 3.4 cm for sixth graders, and the means were found to be statistically different (analysis of variance, p = 0.031). NPC recoveries (mean +/- SD) for the three groups were 7.3 +/- 4.8 cm, 8.7 +/- 4.2 cm, and 7.2 +/- 3.9 cm, respectively, which were also significantly different (analysis of variance, p = 0.027). The recovery distributions were more symmetric and less skewed than those for break. For each grade level, there was a strong positive relationship between NPC recovery and NPC break, but the difference between NPC recovery and break had a low correlation with the NPC break. SUMMARY: Kindergartners had somewhat better NPC breaks than third or sixth graders, whereas no clear age trend was present for NPC recovery. A supporting study using a random sample of clinic patients (aged 10-12 years) suggests that patients with NPC breaks > 6 cm are more than twice as likely to be symptomatic than patients with NPC breaks < or = 6 cm. Based on these results and the NPC break distributions in this study, a clinical cutoff value of 6 cm is suggested for patients of elementary school age. A cutoff value in the 6- to 10-cm range is recommended for children of elementary school age in a screening context. The exact value within this range depends on the level of concern with identifying patients who have visual signs and symptoms associated with a receded NPC.

The imprint of intrathymic self-peptides on the mature T cell receptor repertoire.

The analysis of T cell receptor alpha (TCR alpha) chains in mice transgenic for a TCR beta chain has allowed us to demonstrate a central role for self-peptides in the positive intrathymic selection of major histocompatibility complex (MHC) class II-restricted T cells. Analysis of specific V alpha-J alpha joins in mature CD4+ TCRhigh thymocytes and in peripheral CD4+ T cells revealed a limitation in amino-acid sequences. By analysis of immature thymocytes, we could show that this limited repertoire was selected from a more diverse repertoire. By analysis of the same beta chain-transgenic mice bred to H-2Ma-deficient mice that express one or a very limited number of peptides, we could demonstrate that the V alpha-J alpha join repertoire was now altered and much more limited. Together, these data provide molecular and genetic evidence that the intrathymic positive selection of the TCR repertoire is critically affected by self-peptides presented by MHC class II molecules, most likely on thymic cortical epithelial cells.

Postoperative pain control after lumbar spine fusion. Patient-controlled analgesia versus continuous epidural analgesia.

STUDY DESIGN: A prospective, randomized, double-blind clinical trial. OBJECTIVE: To compare the efficacy of postoperative continuous epidural analgesia versus patient-controlled analgesia in patients undergoing lumbar fusion. SUMMARY OF BACKGROUND DATA: Controversy remains regarding the optimal strategy for postoperative pain control. METHODS: Fifty-four patients were divided into two treatment groups. There was no difference between the groups with respect to age, levels fused, estimated blood loss, and use of spinal instrumentation. Patient-controlled analgesia or epidural analgesia was administered in a double-blind manner for a 3-day postoperative course. Each patient received both an epidural and a patient-controlled analgesia delivery system; 26 received the epidural active agent and 28 received patient-controlled analgesia. Postoperative time to liquids and solid food, ambulation, length of stay, and side effects was recorded. Pain was evaluated by a visual analog scale on postoperative days 1, 2, and 3. RESULTS: Results showed no difference between the groups with reference to diet, ambulation, length of stay, and visual analog scale scores. Minor side effects occurred in 71% of patients in both groups. No major complications occurred. Epidural catheter dislodgment occurred in 11% of patients. The total cost for epidural analgesia was approximately $550 more than that for patient-controlled analgesia for a 3-day postoperative course. CONCLUSIONS: These data suggest that there is no clinical advantage of epidural opiate/local anesthetic analgesia over systemic opiate by patient-controlled analgesia for spinal fusion patients. However, possible technical limitations (namely, the low dosage of bupivacaine and placement of the catheter tip) may have prevented adequate delivery of anesthetic to the involved segments. Although the incidence of side effects is similar, cost factors and a high incidence of epidural catheter dislodgment favor use of patient-controlled analgesia.

Caged NADP and NAD. Synthesis and characterization of functionally distinct caged compounds.

Two caged NADP compounds have been synthesized and characterized for use in the crystallographic study of isocitrate dehydrogenase (IDH), as well as for general use in cell biology, metabolism, and enzymology. One caged NADP compound has been designed to be "catalytically caged" so that it can bind to IDH prior to photolysis but is not catalytically active. A second NADP compound is "affinity caged" so that addition of the caging group inhibits binding of the compound to IDH prior to photolysis. The catalytically caged compound was synthesized in a two-step process, starting with the NADase-catalyzed exchange of a synthetic nicotinamide derivative onto NADP. X-ray structures of the NADP compounds with IDH show the catalytically caged NADP bound to the enzyme with its nicotinamide group improperly positioned to allow turnover, while the affinity caged NADP does not bind to the enzyme at concentrations up to 50 mM. Two analogous caged NAD compounds have also been synthesized. The NADP and NAD compounds were characterized in terms of kinetics, quantum yield, and product formation. The affinity caged NADP compound P2'-[1-(4,5-dimethoxy-2-nitrophenyl)ethyl] NADP (VIII) is photolyzed at a rate of 1.8 x 10(4) s-1 with a quantum yield of 0.19 at pH 7; the NAD analog P-[1-(4,5-dimethoxy-2-nitrophenyl)ethyl] NAD (IX) is photolyzed at at a rate of 1.7 x 10(4) s-1 with a quantum yield of 0.17.

Assessment and longevity of the silicone gel breast implant.

Many patients are now consulting plastic surgeons for evaluation of their silicone gel breast implants. This study assesses the accuracy of a clinician's ability to determine if a silicone gel breast implant has failed. In addition, it sheds light on the long-term integrity of the silicone gel breast implant. This study examined the condition of 350 silicone gel breast implants in a group of 159 of the authors' patients who previously had undergone augmentation mammaplasty or breast reconstruction. These women underwent secondary open procedures including capsulotomy or capsulectomy for fibrous capsule contractures, exchange of implants, or other revisional surgery. The condition of the implant was noted at the time of this secondary operation. The preoperative evaluation, which included the patient's history and physical examination and often mammography, was then matched against the operative findings to determine the pertinent factors that predict the integrity of a silicone gel breast implant. A history of trauma and/or a reported change in shape of a patient's breast correlated with implant failure. An analysis of implant failure as a function of implant age revealed that 63 percent of silicone gel breast implants in place 12 years or greater in this study population were not intact. A change in the patient's physical examination, including a softened breast consistency and/or the presence of a nodule or mass adjacent to an implant, also was suggestive of implant failure. Several different mammographic presentations of implants that were not intact were identified. This modality predicted implant failure in 89 percent of implants studied. It is hoped that this information will help clinicians to make a more accurate assessment of the condition of a patient's silicone gel breast implant. It should be noted that all women in our study underwent secondary procedures, as stated above. The results obtained apply to this patient group but may not specifically pertain to the general implant-bearing population.

8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and delta F508 first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis is an autosomal recessive disorder affecting chloride transport in pancreas, lung, and other tissues, which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Certain alkyl xanthines such as CPX (8-cyclopentyl-1,3-dipropylxanthine) stimulate Cl- efflux from cells bearing the delta F508 genotype common to most cases of cystic fibrosis. We have hypothesized that the CFTR molecule itself might be the site for CPX action, perhaps in the region of the first nucleotide binding fold (NBF-1) domain. Therefore, to test this hypothesis directly we have used a rapid membrane filtration assay to measure the kinetics of association and dissociation of [3H]CPX to both recombinant NBF-1 and recombinant NBF-1 bearing the delta F508 mutation. We report that [3H]CPX binds with higher affinity to the delta F508-NBF-1 of CFTR (Kd = 1.0 nM) than to the wild-type NBF-1 of CFTR (Kd = 17.0 nM). These Kd values were calculated from direct measurements of the association and dissociation rate constants. The rate constants for the dissociation reaction of the wild-type NBF-1 and delta F508-NBF-1 of CFTR were not different from each other. However, the corresponding rate constants for the association reaction were k(+1) (NBF-1) = 4.7 +/- 0.9 x 10(4) M(-1) s(-1) and k(+1) (delta F508-NBF-1) = 1.6 +/- 0.3 x 10(5) M(-1) s(-1), respectively. These Kd values were corroborated by equilibrium-binding experiments, which gave very similar values. We have also measured the relative displacement of various xanthines from both wild-type NBF-1 and delta F508-NBF-1, in anticipation that the order of potencies for binding might parallel the action of the different xanthines on CF cells. For wild-type NBF-1, the rank order was DA-CPX > DAX > CPX > caffeine > adenosine >> IBMX > 2-thioCPX. For delta F508-NBF-1, the rank order was DAX > CPX > caffeine > DA-CPX > adenosine >> IBMX > 2-thioCPX. These relative potencies show close parallels with previously observed relative potencies of these drugs on CF cells, and thus lend strong support to the hypothesis that the mechanism of action on CF cells may involve direct interaction with the CFTR molecule itself.

Success of calcaneonavicular coalition resection in the adult population.

Twelve adult patients (13 feet), average age 33 years (range, 19-48 years), with calcaneonavicular coalitions remained symptomatic after a trial of conservative treatment. Surgical resections were performed. Before surgery, there was < 5 degrees of inversion/eversion in 11 patients, radiographic evidence of degenerative arthritis in 10 feet (77%), and talar beaking in 7 feet. At an average postoperative follow-up of 36 months, subjective relief of preoperative symptoms was achieved in all but two patients. Two patients required subsequent hindfoot arthrodesis. Resection of calcaneonavicular coalition in the adult can be successful and provides an option to arthrodesis after nonoperative methods have failed.

Amphotericin B kills unicellular leishmanias by forming aqueous pores permeable to small cations and anions.

The polyene antibiotic amphotericin B (AmB) is known to form two types of ionic channels across sterol-containing liposomes, depending on its concentration and time after mixing (Cohen, 1992). In the present study, it is shown that AmB only kills unicellular Leishmania promastigotes (LPs) when aqueous pores permeable to small cations and anions are formed. Changes of membrane potential across ergosterol-containing liposomes and LPs were followed by fluorescence changes of 3,3' dipropylthiadicarbocyanine (DiSC3(5)). In KCl-loaded liposomes suspended in an iso-osmotic sucrose solution, low AmB concentrations ( NO3 > Cl > I > Br > acetate (SO2-4 being impermeable). Cell killing by AmB was followed by fluorescence changes of the DNA-binding compound ethidium bromide (EB). At low concentrations (/=0.1 microM), a salt influx via the aqueous pores formed by the antibiotic was followed by osmotic changes leading to cell lysis. This last stage is supported by electron microscopy observations of the changes of parasite morphology immediately upon addition of AmB, which indicated that the typical elongated promastigote cell forms became rounded and the flagella swells and round up. The present work is the first demonstration of the in vitro sensitivity of Leishmania promastigotes to osmotic lysis by AmB.