Prognostic value of blood lactate, base deficit, and oxygen-derived variables in an LD50 model of penetrating trauma

OBJECTIVE: To determine whether blood lactate, base deficit, or oxygen-derived hemodynamic variables correlate with morbidity and mortality rates in a clinically-relevant LD50 model of penetrating trauma. DESIGN: Prospective, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized, mechanically-ventilated mongrel pigs (30+/-2 kg, n = 29). INTERVENTIONS: A captive bolt gun delivered a penetrating injury to the thigh, followed immediately by a 40% to 60% hemorrhage. After 1 hr, shed blood and supplemental crystalloid were administered for resuscitation. MEASUREMENTS AND MAIN RESULTS: After penetrating injury, 50.7+/-0.3% hemorrhage (range 50% to 52.5%), and a 1-hr shock period, seven of 14 animals died, compared with six of six animals after 55% to 60% hemorrhage, and 0 of nine animals after < or =47.5% hemorrhage. Only two of 13 deaths occurred during fluid resuscitation. At the LD50 hemorrhage, peak lactate concentration and base deficit were 11.2+/-0.8 mM and 9.3+/-1.5 mmol/L, respectively, and minimum mixed venous oxygen saturation, systemic oxygen delivery, and systemic oxygen consumption were 33+/-5%, 380+/-83 mL/min/kg, and 177+/-35 mL/min/kg, respectively. For comparison, baseline preinjury values were 1.6+/-0.1 mM, -6.7+/-0.6 mmol/L, 71+/-3%, 2189+/-198 mL/min/kg, and 628+/-102 mL/min/kg, respectively. Of all the variables, only lactate was significantly related to blood loss before and after fluid resuscitation in the 16 survivors. However, r2 values were relatively low (.20 to .50), which indicates that only a small fraction of the hyperiactacidemia was directly related to tissue hypoperfusion. In the whole population of survivors and nonsurvivors, both lactate and base deficit (but none of the oxygen-derived variables) correlated with blood loss. CONCLUSIONS: Arterial lactate is a stronger index of blood loss after penetrating trauma than base deficit or oxygen-derived hemodynamic variables. The reliability of arterial lactate depends on several factors, such as the time after injury, the proportion of survivors and nonsurvivors in the study population, and on factors other than tissue hypoxia.     

Cerebrosides alter the lyotropic and thermotropic phase transitions of DOPE:DOPC and DOPE:DOPC:sterol mixtures

An infectious cDNA of a highly myocarditic coxsackievirus B3 (CVB3m; Nancy strain) was cloned. Sequence data revealed 43 extra non-viral nucleotides upstream of the initial 5' sequence. However, the authentic 5' end sequence was maintained during replication of viral RNA transfected into HeLa cells, suggesting the RNA synthesizing complex edits the picornaviral 5' terminus sequence. Nucleotide sequences of the 5' nontranslated region and the capsid protein gene sequence of CVB3m were compared with the published sequences of five other CVB3 Nancy strains and two main lineages were found. In comparative assays for cardiovirulence, three of four CVB3 tested were cardiovirulent in adolescent male CD-1 mice. Only one of the three available CVB3 strains was neutralized with several anti-CVB3m monoclonal antibodies, suggesting that mutations in the surface epitopes of the capsid polypeptides contribute to antigenic drift within the serotype, perhaps in part through immunoselective pressures. Thus, phenotypic diversity of CVB3 within the prototype Nancy strain is an example of RNA viruses adapting to changing environments (cells, mice and humans) through mutations and selective pressure.     

The production of macrophage inflammatory protein-1 alpha by human basophils

Macrophage inflammatory protein-1alpha (MIP-1alpha) has previously been shown to be produced by mononuclear cells, eosinophils, and neutrophils. Its production by basophils has not been investigated. The objective of this study was to investigate the production of MIP-1alpha by basophils. Peripheral blood basophils were separated by Percoll gradient centrifugation, cultured overnight, and processed for double immunocytochemistry using Abs against MIP-1alpha and FcepsilonRIalpha (alpha subunit of IgE receptor type 1). We demonstrated that basophils expressed immunoreactive MIP-1alpha upon stimulation with anti-IgE. Less than 5% of the basophils stained for MIP-1alpha without stimulation. The secretion of MIP-1alpha by basophils was studied by ELISA. In these experiments, basophils were further enriched to 65 to 99% (median, 86%) by a negative selection method. Basophils released MIP-1alpha when stimulated by Abs against IgE and FCepsilonRIalpha as well as IL-3 and the calcium ionophore, A23187. In parallel experiments, PBMC, eosinophils, and neutrophils did not produce MIP-1alpha in response to anti-IgE, but they did so in response to A23187. No MIP-1alpha release was detected in platelet preparations. Preincubation with IL-3 (15 min or 18 h) augmented anti-IgE-included basophil MIP-1alpha production. The secretion of MIP-1alpha by basophils was detectable shortly after stimulation and gradually increased over 24 h. Since MIP-1alpha has potent inflammatory and histamine-releasing activities, its production by basophils may indicate a positive feedback mechanism for allergic inflammation.     

Extrafacial lentigo maligna melanoma: analysis of 71 cases and comparison with lentigo maligna melanoma of the head and neck

We report a retrospective analysis of extrafacial lentigo maligna melanoma (LMM), and a comparison with patients with LMM of the head and neck. Seventy-one patients (22 men, 49 women) with extrafacial LMM were identified from the Scottish Melanoma Group database for January 1979-March 1996. Their mean age (63 years) was significantly less than that of 335 patients with head and neck LMM (mean 72 years, P < 0.001), with a significantly greater difference among women than men. Extrafacial sites comprised 17.5% of LMMs. There was a marked body site distribution difference between the sexes (P = 0. 001): 68% of extrafacial LMMs in men were on the trunk while 80% in women were on the limbs, particularly the lower leg. Extrafacial LMMs were thinner at presentation than head and neck LMMs (P < 0.05) in both sexes, but this was not simply explained by the younger age of these patients as there was no significant correlation between age and tumour thickness at either extrafacial or at head and neck sites. Although the female lower leg is a site of chronic solar exposure in older women, the other extrafacial sites are habitually covered in the temperate Scottish climate. The significantly younger age group of patients with LMM at extrafacial compared with head and neck sites therefore suggests that the relationship between LMM and sunlight is not simply related to cumulative solar exposure. The demonstration that head and neck LMMs were thicker at presentation compared with extrafacial sites, despite being at a more routinely visible part of the body, suggests that there are still opportunities for targeted pigmented lesion public education.     

Chemotherapy for spinal cord astrocytoma

A combined retrospective and prospective study of 129 beta-thalassaemia major patients seen between 1965 and 1995 in Sabah Hospital, Kuwait has been carried out. The age range at diagnosis was 2 to 84 months, median 9 months. In approximately 80 per cent, the patients were outcomes of first- or second-cousin marriages. Nine (7 per cent) of the patients were HBsAg positive, while 42 (33 per cent) were hepatitis C seropositive. Eleven (9 per cent) patients had had bone marrow transplantation (BMT). There was no BMT-related mortality, but there were three graft rejections and two cases of chronic graft-versus-host disease (GVHD).     

AKT2, a member of the protein kinase B family, is activated by growth factors, v-Ha-ras, and v-src through phosphatidylinositol 3-kinase in human ovarian epithelial cancer cells

Three members have been identified in the protein kinase B (PKB) family, i.e., Akt/PKB alpha, AKT2/PKB beta, and AKT3/PKB gamma. Previous studies have demonstrated that only AKT2 is predominantly involved in human malignancies and has oncogenic activity. However, the mechanism of transforming activity of AKT2 is still not well understood. Here, we demonstrate the activation of AKT2 with several growth factors, including epidermal growth factor, insulin-like growth factor 1, insulin-like growth factor II, basic fibroblast growth factor, platelet-derived growth factor, and insulin, in human ovarian epithelial cancer cells. The kinase activity and the phosphorylation of AKT2 were induced by the growth factors and blocked by the phosphatidylinositol (PI) 3-kinase inhibitor, wortmannin, and dominant-negative Ras (N17Ras). Moreover, the activated Ras and v-Src, two proteins that transduce growth factor-generated signals, also activated AKT2, and this activation was not significantly enhanced by growth factor stimulation but was abrogated by wortmannin. These results indicate that AKT2 is a downstream target of PI 3-kinase and that Ras and Src function upstream of PI 3-kinase and mediate the activation of AKT2 by growth factors. The findings also provide further evidence that AKT2, in cooperation with Ras and Src, is important in the development of some human malignancies.     

PLA2 activity regulates Ca2+ storage-dependent cellular proliferation

The objective of this study is to determine the role of arachidonic acid (AA) in cell proliferation by inhibiting AA synthetic enzyme phospholipase A2 (PLA2) and to determine its involvement in the role of the second messenger intracellular calcium (Ca2+). Methods used to determine the effects on proliferation of cell cultures of primary meningioma and astrocytoma U373-MG included treatment with micromolar concentrations of PLA2 inhibitors 4-bromophenacylbromide and quinacrine. Effects of these drugs on proliferation were further investigated by the application of concentrations that inhibit growth by 50% while antagonizing these agents with AA replacement. Free cytosolic Ca2+ was measured with the use of fluorescent dye Fura-2 during PLA2 agonist/antagonist studies. These Ca2+ measurements were performed in the absence of extracellular Ca2+ to identify the contribution of intracellular Ca2+ sources. PLA2 inhibition resulted in decreased growth of cultured astrocytoma and meningioma cells in a dose-dependent manner in the micromolar range. This inhibitory effect was antagonized by the addition of AA. PLA2 inhibition caused an elevation of basal-cytosolic-free [Ca2+] while depleting internal Ca2+ stores. These Ca2+ changes were also antagonized by the addition of AA. In conclusion, these results demonstrate that AA, a PLA2 enzyme product, is involved in regulating the growth rate of these cell types. The PLA2 pathway also regulates the maintenance of the internal Ca2+ stores. Ca2+ is known to be a growth-related intracellular second messenger. These results suggest that the growth regulatory functions of AA are mediated by Ca2+-dependent mechanisms.     

Noniatrogenic esophageal trauma

Few guidelines are available with which to facilitate treatment in patients with noniatrogenic injuries of the esophagus. Early diagnosis and proper management are essential if a good outcome is to be expected. In an effort to define better the treatment of patients with penetrating and blunt injuries of the esophagus, we report our recent 5-year experience at an urban trauma center. From July 1988 to June 1993, nineteen patients with esophageal perforations from penetrating (18) and blunt (1) trauma were identified by our trauma registry. There was no mortality in this group of patients and morbidity was mostly due to associated injuries. Eleven cervical esophageal injuries were repaired. One cervical injury was treated by stopping oral intake and giving intravenous antibiotics. The neck was not drained in 10 of the surgical cases. In 1 patient a tracheoesophageal fistula developed, which later was repaired with a pectoralis muscle flap. Seven perforations were identified in the thoracic (2) and abdominal (5) portions of the esophagus. All were due to gunshot wounds. In 4 cases, a fundal wrap was used to reinforce the repairs. Postoperative contrast studies confirmed that all repairs were intact. We conclude that penetrating and blunt tears of the esophagus can be repaired safely with minimal mortality. Morbidity is usually from associated injuries such as to the spinal cord and trachea. When identified early, cervical esophageal injuries do not need to be drained routinely.     

Risk factors and clinical presentation of acute primary HIV infection in India

CONTEXT: Most previous studies of clinical presentation and risk factors in early human immunodeficiency virus (HIV) infection have relied on retrospective analyses and referred seroconverters, and thus were subject to possible bias. OBJECTIVES: To apply a method based on measurement of prevalent HIV-1 p24 antigenemia for identification of risk factors for newly acquired HIV infection and to describe the signs and symptoms of acute HIV infection. DESIGN AND SETTING: Nested case-control study in Pune, India. PARTICIPANTS: HIV antibody-negative persons attending 2 sexually transmitted disease (STD) clinics between May 1993 and June 1996. OUTCOME MEASURES: Prevalent p24 antigenemia, risk factors for HIV infection, and clinical symptoms of acute primary HIV infection. RESULTS: Of 3874 HIV antibody-negative persons tested, 58 (1.5%) were p24 antigen positive at initial presentation to the clinics. Unprotected sexual contact with a commercial sex worker (CSW) was reported by 39 (77%) of the 51 p24 antigenemic men, compared with 131 (51 %) of 255 control men (adjusted odds ratio [AOR], 3.4; 95% confidence interval [CI], 1.2-9.6; P=.02). The presence of an active genital ulcer at the time of screening was found in 46 (79%) of the 58 p24 antigenemic men and women, compared with 137 (47%) of the 290 control subjects (AOR, 4.2; 95% CI, 2.0-9.0; P<.001). Signs and symptoms independently associated with p24 antigenemia in HIV antibody-seronegative persons included fever, which was reported by 28 (48%) of the 58 p24 antigenemic subjects, but only 52 (18%) of the 290 control subjects (AOR, 4.7; 95% CI, 2.4-9.0; P<.001). Joint pain was reported by 10% of subjects recently HIV infected, compared with 2% of the control subjects (AOR, 6.5; 95% CI, 1.7-24.8; P=.006). Night sweats were reported by 9% of the p24 antigenemic, but only 1% of the control subjects (AOR, 9.1; 95% CI, 1.7-47.6; P=.009). Overall, fever, joint pain, and/or night sweats were reported in 27 (47%) of the 58 subjects with recent HIV infection. CONCLUSIONS: This systematic case-control study of p24 antigen screening in HIV-seronegative patients attending STD clinics in India identified unprotected sex with a CSW and a genital ulcer as independent risk factors associated with newly acquired HIV infection. In addition, p24 antigen positivity identified recent fever, night sweats, and arthralgias as symptoms that may be predictive of recent HIV infection. In a study of patients attending STD clinics in India, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective research method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection.