Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia.

Clinical trials have demonstrated that glutamine (GLN) supplementation can decrease infectious morbidity and improve survival in a number of settings of critical illness. The mechanism of this protection remains unclear. The objective of this study was to evaluate the effect of GLN on cytokine release, organ injury, and survival from endotoxin-induced septic shock. Endotoxemia was induced in Male Sprague-Dawley rats by intravenous administration of 5 mg/kg Escherichia coli lipopolysaccharide (LPS). Concomitantly, animals were fluid resuscitated with a lactated ringers (LR) solution and given GLN (0.75 g/kg i.v.) or LR alone. Blood samples were obtained at multiple time points post-LPS injury for cytokine analysis. Survival rates were monitored for 72 h. Organ injury was evaluated in a separate set of animals via pathologic exam of tissues harvested 6 h post-LPS injury. A single dose of GLN significantly attenuated the release of TNF-alpha at 2 h (P < 0.005) and IL-1 beta at 4 h (P < 0.0001). This attenuation of cytokine release was associated with a significant decrease in mortality (P < 0.003). Pathologic exam demonstrated significant protection of both lung and small bowel tissue by GLN. Blood gas values 6-h post-LPS injury showed increased PaO2 and bicarbonate concentration in GLN treated animals. These data indicate that GLN can significantly attenuate pro-inflammatory cytokine release, protect against end-organ damage, and decrease mortality from endotoxemia. GLN confers protection even when administered at the onset of endotoxemia, rather then as pre-treatment. Thus, one explanation for the clinical benefits observed from GLN-supplementation may be related to the attenuation of pro-inflammatory cytokines.

Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control.

OBJECTIVE: To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients. Previous clinical studies in seriously ill patients suggest a beneficial effect of glutamine on infectious morbidity, but no trials have examined possible clinical benefits in severely burned patients. DESIGN: Prospective, double-blind, randomized trial. SETTING: Burn intensive care unit of a university hospital. PATIENTS: Twenty-six severe burn patients with total burn surface area of 25% to 90% and presence of full-thickness burns. Patients were evaluated for occurrence of bacteremia and antibiotic use during the first 30 days of their burn unit admission. Nutritional status and overall inflammation were also measured. INTERVENTION: Either intravenous glutamine or an isonitrogenous control amino acid solution was administered as a continuous infusion during burn intensive care unit stay. MEASUREMENTS AND MAIN RESULTS: The incidence of Gram-negative bacteremia was significantly reduced in the glutamine-supplemented group (8%) vs. control (43%; p <.04). No difference was seen in the incidence of Gram-positive bacteremia or fungemia. Average number of positive blood cultures, antibiotic usage, and mortality rates also were reduced but did not reach statistical significance. Significant improvements in serum transferrin and prealbumin were observed in glutamine-supplemented patients at 14 days after burn injury (p <.01 and.04, respectively). C-reactive protein was also significantly reduced at 14 days after burn injury in the glutamine group (p <.01). CONCLUSIONS: Significantly fewer bacteremic episodes with Gram-negative organisms occurred in the glutamine-supplemented patients. Glutamine supplementation improved measures of nutrition and decreased measures of overall inflammation. In addition, a trend toward lower mortality rate, decreased overall bacteremia incidence, and antibiotic usage in the glutamine group was observed. Glutamine's beneficial effects may be a result of improved gut integrity or immune function, but the precise mechanism of glutamine's protection is unknown.

Glutamine induces heat shock protein and protects against endotoxin shock in the rat.

Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models of septic shock. Induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. In this study, we demonstrate that a single dose of intravenous glutamine causes a rapid and significant increase in HSP25 and HSP72 expression in multiple organs of the unstressed Sprague-Dawley rat. With the utilization of a fluid-resuscitated rat model of endotoxemia, mortality was dramatically reduced by glutamine administration concomitant with the endotoxin injury. Endotoxin-treated animals given glutamine exhibited dramatic increases in tissue HSP expression and marked reduction of end-organ damage. These data suggest glutamine may protect against mortality and attenuate end-organ injury in endotoxemic shock via enhanced HSP expression. Furthermore, glutamine confers protection when administered at the initiation of sepsis, rather than as pretreatment. Thus glutamine appears to be a clinically viable enhancer of HSP expression and may prove beneficial in the therapy of sepsis and sepsis-induced organ injury.

Care of the clinician.

Effective services for trauma survivors rely on addressing the support and care needs of clinicians and administrators.

Spiritual dimensions of a mind-body group for people with severe mental illness.

In a mind-body group designed to address issues of well-being for people with severe mental disorders, experiences with spiritual themes of optimal functioning and ultimate meaning emerged with surprising clarity.

The effect of air pollution on the integrity of chlorophyll, spectral reflectance response, and on concentrations of nickel, vanadium, and sulfur in the lichen Ramalina duriaei (De Not.) Bagl.

The following study was designed to determine the environmental impact of pollutants emitted by combustion of heavy fuel oil in Ashdod, in Southwestern Israel. For this purpose we measured concentrations of total S, V, and Ni in the local epiphytic fruticose lichen Ramalina duriaei, which grows in the peripheral region of the town, and compared these results with those obtained in thalli collected 100 km away, in the HaZorea Forest, northeastern Israel. We also transplanted thalli from the HaZorea Forest to the Ashdod region for a 10-month period. At the end of the experiment we measured the elemental content in all samples. In addition we measured chlorophyll degradation expressed as changes in the 435 nm/415 nm OD ratio, and changes in the spectral responses of the thalli. In several sites in the Ashdod region we found high concentrations of S, V, and Ni in transplanted thalli, which correlated with the NDVI values. These findings agree with other measurements of SO2 and V in the Ashdod area. We suggest that a high V/Ni ratio in lichens is a tracer for air pollution caused by the combustion of heavy fuel oil.

Endovaginal ultrasonographic measurement of early embryonic size as a means of assessing gestational age.

Crown-rump length has consistently been found to be the most accurate method of determining gestational age in the first trimester. The original regression curve established by Robinson in 1973 with static arm scanners remains the one most widely employed. New endovaginal ultrasonographic probes afford a degree of detail that allows embryonic structures to be seen as soon as they are distinct from the yolk sac. Previously, measurements of very early embryonic structures have mistakenly been labeled crown-rump lengths. There has been widespread use of nomograms constructed from regression curves, where the bulk of the data were derived from small fetuses and then such curves extrapolated back to embryos of very small size. The purpose of this study was to establish a nomogram for gestational age assessment by measuring early embryos prior to the development of a "crown" or "rump." This present study consisted of 143 patients. To be included they had to have had no history of any prior bleeding, and all were delivered of singleton infants within 2 weeks of their estimated delivery date by last menstrual period. All had a single early embryonic size measurement between 1 and 25 mm using high-frequency endovaginal probes. Regression analysis revealed a linear equation of Gestational age (days) = early embryonic size (mm) + 42 with a correlation coefficient r = 0.87; 95% confidence limit = +/- 3 days. We conclude that using high-frequency vaginal ultrasonographic probes and having a better understanding of embryonic anatomic stages allow for the construction of a nomogram of gestational age derived from measurements of early embryonic size prior to development of a crown-rump length.

Evidence for replication slippage in the evolution of Oenothera chloroplast DNA.

Evolutionary relationships of four plastid genomes (plastomes) from different Oenothera species have been assessed by sequence comparisons of two intergenic regions that separate the ribosomal protein genes rpl16, rpl14, and rps8. Sequence changes include base substitutions, the occurrence of a 29-base tandem duplication, and variation in the length of two poly-A stretches. Additions/deletions in chloroplast DNA may not be useful for evolutionary comparisons more distant than these, particularly if the sequences undergo divergence after the initial event, but the length mutations reported here allow a finer resolution of the phylogeny of the closely related Oenothera plastomes than would have been possible if only base substitutions had been considered. Comparisons with the orthogous sequence from tobacco chloroplast DNA indicate the direction of change at most of the sites. The results suggest that plastomes I and II are closely related to each other, as are plastomes III and IV. Replication slippage is proposed as a mechanism to explain the length mutations.

Postpartum rupture of a splenic artery.

Postpartum abdominal apoplexy is a rare obstetric complication that is associated with a very high maternal mortality rate. We report a patient with a low risk pregnancy and spontaneous vaginal delivery, who at 17 h post partum went into shock secondary to rupture of the splenic artery. She recovered following splenectomy and transfusion of 10 units of blood. This is the seventh documented case of splenic artery rupture in the postpartum period. Four of the seven patients survived. The cases are reviewed and the clinical presentation, pathogenesis and treatment are discussed.

Raman solitons in media with a Stark shift: soliton regeneration through self-phase modulation.

An internal phase-shift mechanism can lead to the amplification of Raman solitons even in the presence of coherence decay and detuning. We study here the case of a Raman medium with strong ac Stark shift by using both analytical and numerical methods. Our results also suggest the possibility of propagating stable transient Raman solitons in optical fibers.

Variation in copy number of a 24-base pair tandem repeat in the chloroplast DNA of Oenothera hookeri strain Johansen.

A highly variable region of chloroplast DNA has been analyzed from three isolates of Oenothera hookeri strain Johansen. The variability results from the presence of two, four or seven copies of a discrete 24-base pair tandem repeat in a segment of the chloroplast DNA within the inverted repeat. Alignment of this DNA region with the published tobacco cpDNA sequence shows that in Oenothera, the repeats are insertions within a large unidentified reading frame, with each repeat unit specifying an eight amino acid in-frame addition. A model to explain the frequent alterations in the copy number of this 24-bp unit is proposed: imprecise alignment and recombination between the two large inverted repeats followed by copy correction could result in an amplification or deletion of the 24-bp segments.

Computed tomography of the disarticulated incus.

Complete incus disarticulation may be a complication of trauma, chronic otitis, or prosthetic stapedectomy. Purposeful incus disarticulation (with incus interposition) is used as a method of ossicular reconstruction. CT has been a valuable diagnostic tool for preoperative location of the incus in the former disorders and for determination of the status of the ossiculoplasty in the latter.

Antenatal ultrasonography: the experience in a high risk perinatal center.

During a 52-month span, 14,324 ultrasonographic examinations were performed on 9,453 pregnant patients. One-hundred and fifty-one anatomical malformations were found in 122 fetuses (1.29%). Our analysis of patients referred to the perinatal center for ultrasonography indicates that the number of high risk patients has increased, and a parallel increase of neonatal surgical anomalies has resulted. An analysis of fetuses concluded that anomalies of the: gastrointestinal tract had improved care, deaths occurred due to associated anomalies or severe prematurity; genitourinary system received earlier diagnosis and treatment; central nervous system/musculoskeletal system/hydrops--no difference in management, treatment or outcome was noted; teratoma/cystic hygroma--did not effect treatment; cardiovascular system--inutero medical treatment by digitalization of the mother was possible. Paradoxically, an increase in the mortality of diaphragmatic hernia patients was noted and concluded to be secondary to the extremely early detection of this anomaly.

Delayed staple penetration of the heart: transthoracic migration with late tamponade.

Most foreign bodies in the chest do their damage at the time of injury. While needle-like objects may migrate (6), delayed intrathoracic injury is rare. Delayed transthoracic penetration of the heart by a staple is reported, and is felt to be unique because acute hemopericardium resulted 30 days after the time of initial injury. The principles of recognition of pericardial tamponade, initial stabilization with periocardiocentesis, and immediate exploration are emphasized.

Comparison of biparietal diameter and femur length in the third trimester: effects of gestational age and variation in fetal growth.

A multiple regression-based statistical model capable of quantitatively comparing two or more sonographic parameters for the effects of gestational age, variation in fetal growth and error in sonographic measurement is presented and then used to compare the biparietal diameter and femur length as estimators of gestational age in late pregnancy. A total of 311 patients were studied between 24 and 42 weeks' gestation. Variation in fetal growth was expressed as the birth weight percentile for gestational age. Biparietal diameter and femur length correlated equally well with gestational age. However, the biparietal diameter was more than twice as sensitive as the femur length to variation in fetal growth. Femur length had a larger error associated with its measurement. These results suggest that the biparietal diameter and femur length in late pregnancy are equal estimators of gestational age; that the femur length is a more stable estimator of gestational age when fetal growth deviates from normal; and that the femur length is technically more difficult to obtain.

Stapes prosthesis: evaluation with CT.

We used computed tomography (CT) to evaluate 44 patients who had undergone stapedectomy with insertion of a prosthesis. Several patients had poor surgical results, including recurrent conductive hearing loss, vertigo, and sensorineural hearing loss. Conductive hearing loss occurring immediately after the procedure was most often caused by anatomic limitations or surgical technique. Causes of delayed or recurrent conductive hearing loss included reparative granuloma formation, incus necrosis (at the attachment of the wire), prosthesis subluxation (most often posterior), and regrowth of otosclerosis, which occasionally is further complicated by incus dislocation. We found that CT is often diagnostic when these complications occur. Immediate sensorineural hearing loss or vertigo can be self-limited if caused by serous labyrinthitis. When delayed, these symptoms may be due to perilymph fistula. If caused by the latter, CT may not yield abnormal findings unless subluxation of the prosthesis into the vestibule has occurred.