Antimycobacterial compound of chitosan and ethambutol: ultrastructural biological evaluation in vitro against Mycobacterium tuberculosis.

Chitosan (CS) is a promising biopolymer and has been tested as a complement to the action and compensation of toxicity presented by anti-tuberculosis drugs. The present work studied the adjuvant effect of CS with the drug ethambutol (EMB) as a compound (CS-EMB), to explore its antimicrobial and cytotoxic activity, using transmission electron microscopy (TEM), to examine ultracellular changes that represent possible antimycobacterial action of CS on Mycobacterium tuberculosis (Mtb). Antimycobacterial activities were tested against reference strains Mtb ATCC® H37Rv and multidrug resistant (MDR). In vitro cytotoxicity tests were performed on Raw 264.7. For the studied compounds, morphological, ultrastructural, and physical-chemical analyses were performed. Drug-polymer interactions that occur through the H bridges were confirmed by physical-chemical analyses. The CS-EMB compound is stable at pHs of 6.5-7.5, allowing its release at physiological pH. The antibacterial activity (minimum inhibitory concentration) of the CS-EMB compound was 50% greater than that of the EMB in the H37Rv and MDR strains and the ultrastructural changes in the bacilli observed by TEM proved that the CS-EMB compound has a bactericidal action, allowing it to break down the Mtb cell wall. The cytotoxicity of CS-EMB was higher than that of isolated EMB, IC50 279, and 176 µg/mL, respectively. It is concluded that CS-EMB forms a promising composite against strains Mtb H37Rv and multidrug resistant (MDR-TB).Key points• Our study will be the first to observe ultrastructurally the effects of the CS-EMB compound on Mtb cells.• CS-EMB antimicrobial activity in a multidrug-resistant clinical strain.• The CS-EMB compound has promising potential for the development of a new drug to fight tuberculosis.

Computational engineering of cellulase Cel9A-68 functional motions through mutations in its linker region.

Microbial cellulosic degradation by cellulases has become a complementary approach for biofuel production. However, its efficiency is hindered by the recalcitrance of cellulose fibres. In this context, computational protein design methods may offer an efficient way to obtain variants with improved enzymatic activity. Cel9A-68 is a cellulase from Thermobifida fusca that is still active at high temperatures. In a previous work, we described a collective bending motion, which governs the overall cellulase dynamics. This movement promotes the approximation of its CBM and CD structural domains (that are connected by a flexible linker). We have identified two residues (G460 and P461) located at the linker that act as a hinge point. Herein, we applied a new level of protein design, focusing on the modulation of this collective motion to obtain cellulase variants with enhanced functional dynamics. We probed whether specific linker mutations would affect Cel9A-68 dynamics through computational simulations. We assumed that P461G and G460+ (with an extra glycine) constructs would present enhanced interdomain motions, while the G460P mutant would be rigid. From our results, the P461G mutation resulted in a broader exploration of the conformational space, as confirmed by clustering and free energy analyses. The WT enzyme was the most rigid system. However, G460P and P460+ explored distinct conformational states described by opposite directions of low-frequency normal modes; they sampled preferentially closed and open conformations, respectively. Overall, we highlight two significant findings: (i) all mutants explored larger conformational spaces than the WT; (ii) the selection of distinct conformational populations was intimately associated with the mutation considered. Thus, the engineering of Cel9A-68 motions through linker mutations may constitute an efficient way to improve cellulase activity, facilitating the disruption of cellulose fibres.

Comparison of three different extenders on Murrah buffaloes (Bubalus bubalis) semen freezability.

The use of frozen semen for artificial insemination is the main approach utilised for the genetic improvement of most domesticated species. The advantages include lower transportation costs, continuous availability of semen, fewer occurrences of sexually transmitted diseases and the incorporation of desirable genes in a relatively short amount of time. Nevertheless, the use of frozen semen in buffalo herds remains limited due to the loss of sperm quality when buffalo semen is frozen. So, the goal of this study was to evaluate the pre- and post-cryopreservation quality of buffalo semen diluted in three distinct freezing media: Tris-egg yolk, Botu-bov® (BB) and ACP-111®. Thirty-two ejaculates from four bulls were analysed in terms of kinetics, morphology and sperm viability by epifluorescence microscope. Thawed samples were also evaluated for capacitation-like damage, DNA fragmentation and plasma and acrosomal membrane integrity using flow cytometry. The Tris-egg yolk and BB® extenders yielded better results than the ACP-111® extender for kinetics parameter (total motility, progressive motility and percentage of rapid cells). However, semen samples were similar for parameters evaluated by flow cytometry. Taken together, the data indicate that in comparison with Tris-egg yolk and BB extender, ACP-111® can also be used as an extender for buffalo semen cryopreservation.

Relapsing bullous amyloidosis of the oral mucosa and acquired cutis laxa in a patient with multiple myeloma: a rare triple association.

It is well known that primary systemic amyloidosis [light chain (AL) amyloidosis] is associated with hidden dyscrasia or multiple myeloma. Acquired cutis laxa (cutis laxa acquisita; CLA) has also been described in patients with plasma cell dyscrasias, including multiple myeloma. We report a case in which haemorrhagic oral bullae were the first sign of an undiagnosed primary systemic amyloidosis related to multiple myeloma IgG-λ and previously diagnosed CLA. There is only one report in literature of this rare triple association; however, in that case the patient did not have oral mucosal involvement or bullous amyloidosis.

Distribution pattern of arthropods and their ecological interactions on the leaf surfaces of Terminalia argentea saplings.

Terminalia argentea tree, native to Brazil, is widely used in landscaping, recovering degraded areas, its wood, coal production, and the bark or leaf extracts has medicinal use. Despite of its importance, the arthropod fauna associated to this plant and its interspecific relationships still needs further studies. The objectives of this study were to evaluate the arthropods, their ecological indices and the distribution in the leaf faces on T. argentea saplings. The numbers of phytophagous insects (e.g., Cephalocoema sp.), pollinators (e.g., Tetragonisca angustula), and natural enemies (e.g., Oxyopidae), and their ecological indices (e.g., species richness), were higher on the adaxial leaf faces on T. argentea saplings. Aggregated distribution of phytophagous insects (e.g., Aphis spiraecola), pollinators (e.g., Trigona spinipes), and natural enemies (e.g., Camponotus sp.) on T. argentea saplings was observed. Abundance, diversity, and species richness of natural enemies correlated, positively, with those of phytophagous and pollinators insects. Predators and tending ants followed their prey and sucking insects, respectively. Tending ants protected sucking insects against predators, and reduced chewing insects. The high number of Cephalocoema sp. on T. argentea saplings is a problem, because this insect can feed on leaves of this plant, but its preference for the adaxial leaf face favors its control. The aggregation behavior of arthropods on T. argentea saplings favors the control of potential pests of this plant. There seems to be competition between tending ants for space and food resources on T. argentea saplings.

How reliable are follow-up studies on odontogenic keratocysts?

Follow-up studies on odontogenic keratocysts have reported widely varying recurrence rates. This raises the question of how reliable these studies are and how the results should be interpreted. The aim of this study was to critically assess the information from all follow-up studies published since 2004 against a set of criteria to determine how thorough the study was. These criteria include the exclusion of the orthokeratinized variant, exclusion of cysts associated with nevoid basal cell carcinoma syndrome, and appropriate reporting of dropouts. A search of four electronic databases covering the years 2004-2022 was performed. Only studies with a sufficient follow-up period (covering a range of 1-8 years) were included. Studies with fewer than 40 cases were excluded. Fourteen relevant studies were identified in the literature search. The vast majority of these studies had considerable shortcomings, giving rise to serious doubts about the validity of their recurrence rate results. Of note, these studies have often been included in meta-analyses that report on the best treatment options to reduce the tendency of recurrences. The results of this review strongly suggest that multicentre studies with strict protocols should be performed to advance knowledge of the presentation of recurrences, both the timing and frequency.

The synergy of microplastics with the heavy metal zinc has resulted in reducing the toxic effects of zinc on lentil (Lens culinaris) seed germination and seedling growth.

There is growing recognition of the impact of the rising presence of microplastics (MPs) on terrestrial plant growth and, in general, the terrestrial ecosystem. Simultaneously, there is growing heavy metal accumulation in agricultural lands at an astonishing rate owing to the overwhelming use of chemical fertilizers, herbicides, and weedicides. Thus, there is a need to investigate the synergetic effect of MPs along with heavy metals on the inducing combined toxicity. This study investigates effects at smaller exposure periods of a few hours using a novel optical imaging technique, Biospeckle Coherence Tomography. Biospeckle Optical Coherence Tomography (bOCT) is a novel optical imaging technique that we successfully demonstrated earlier in visualizing the internal activity of plants. Previous studies of authors using the bOCT technique have demonstrated its potential in the independent application of polyethylene microplastic (PEMPs) as well as zinc within 6 h after their treatments. The strong inhibitory effect of 100 mg L-1, Zn, and PEMPs alone on the germination of Lens culinaris could be visualized with bOCT. The current study demonstrated that against expectation, combined effects of Zn toxicity were reduced when combined with MPs. This is suggested due to the significant reduction of Zn uptake by the seedlings through the interaction of Zn and MPs in an aqueous solution. Mass-spectrometry results also indicate a reduced intake of Zn. Our findings suggest that PEMPs could be able to reduce the over-availability of Zn, thus mitigating the Zn toxicity on lentils.

Communication between the temporomandibular joint articular space and the extradural space in patients with temporal bone pneumatization: implications for temporomandibular joint surgery.

The pneumatization of the articular portion of the temporal bone is an anatomical variant that can modify the barrier between the articular space and the middle cranial fossa. Thus, this study aimed to identify the presence and degree of pneumatization, as well as the existence of pneumatic cell dehiscence towards the extradural or articular space determining whether it could lead to direct communication between the articular and extradural spaces. Hence, One-hundred skull computed tomography images were selected. The presence and extension of pneumatization were classified according to scores 0, 1, 2, and 3. Dehiscence towards extradural and articular spaces was recorded. In total, 200 TMJ from 100 patients were assessed and 40.5% of pneumatization cases were observed. The most prevalent score was 0 (restricted to the mastoid process), while the least prevalent score was 3 (extending beyond the crest of articular eminence). Dehiscence of the pneumatic cells towards the extradural space is more common than towards the articular space. One complete communication between the extradural and articular spaces was observed. Considering the results, it was concluded that to avoid neurological and ontological complications, awareness of the potential anatomical communications between articular and extradural spaces, particularly in patients with extensive pneumatisation, is necessary.

Prediction of early stroke recurrence in transient ischemic attack patients from the PROMAPA study: a comparison of prognostic risk scores.

BACKGROUND: Several clinical scales have been developed for predicting stroke recurrence. These clinical scores could be extremely useful to guide triage decisions. Our goal was to compare the very early predictive accuracy of the most relevant clinical scores [age, blood pressure, clinical features and duration of symptoms (ABCD) score, ABCD and diabetes (ABCD2) score, ABCD and brain infarction on imaging score, ABCD2 and brain infarction on imaging score, ABCD and prior TIA within 1 week of the index event (ABCD3) score, California Risk Score, Essen Stroke Risk Score and Stroke Prognosis Instrument II] in consecutive transient ischemic attack (TIA) patients. METHODS: Between April 2008 and December 2009, we included 1,255 consecutive TIA patients from 30 Spanish stroke centers (PROMAPA study). A neurologist treated all patients within the first 48 h after symptom onset. The duration and typology of clinical symptoms, vascular risk factors and etiological work-ups were prospectively recorded in a case report form in order to calculate established prognostic scores. We determined the early short-term risk of stroke (at 7 and 90 days). To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. Cox proportional hazards multivariate analyses determining independent predictors of stroke recurrence using the different components of all clinical scores were calculated. RESULTS: We calculated clinical scales for 1,137 patients (90.6%). Seven-day and 90-day stroke risks were 2.6 and 3.8%, respectively. Large-artery atherosclerosis (LAA) was observed in 190 patients (16.7%). We could confirm the predictive value of the ABCD3 score for stroke recurrence at the 7-day follow-up [0.66, 95% confidence interval (CI) 0.54-0.77] and 90-day follow-up (0.61, 95% CI 0.52-0.70), which improved when we added vascular imaging information and derived ABCD3V scores by assigning 2 points for at least 50% symptomatic stenosis on carotid or intracranial imaging (0.69, 95% CI 0.57-0.81, and 0.63, 95% CI 0.51-0.69, respectively). When we evaluated each component of all clinical scores using Cox regression analyses, we observed that prior TIA and LAA were independent predictors of stroke recurrence at the 7-day follow-up [hazard ratio (HR) 3.97, 95% CI 1.91-8.26, p < 0.001, and HR 3.11, 95% CI 1.47-6.58, p = 0.003, respectively] and 90-day follow-up (HR 2.35, 95% CI 1.28-4.31, p = 0.006, and HR 2.20, 95% CI 1.15-4.21, p = 0.018, respectively). CONCLUSION: All published scores that do not take into account vascular imaging or prior TIA when identifying stroke risk after TIA failed to predict risk when applied by neurologists. Clinical scores were not able to replace extensive emergent diagnostic evaluations such as vascular imaging, and they should take into account unstable patients with recent prior transient episodes.

Phage therapy to control multidrug-resistant Pseudomonas aeruginosa skin infections: in vitro and ex vivo experiments.

The main goal of this study was to evaluate the efficiency of phage therapy against one of the most common multidrug-resistant (MDR) agents of skin infections, Pseudomonas aeruginosa. A phage suspension [10(8) plaque-forming units (PFU) mL(-1)] was obtained using the clinical strain P. aeruginosa 709 as the host. The ability of the phage to inactivate P. aeruginosa was evaluated in vitro and ex vivo (human skin), using a multiplicity of infection (MOI) of 0.5 to 50. In the presence of the phage, the density of P. aeruginosa 709 [10(5) colony-forming units (CFU) mL(-1)] in the human skin decreased by 4 logs after 2 h of incubation. The application of a second dose of phage did not increase the efficiency of the therapy. This study indicates that the topical application of phage PA709 efficiently inactivates MDR P. aeruginosa 709. The high efficiency in the inactivation of MDR P. aeruginosa 709, its considerable host range (infection of 30 % of the P. aeruginosa isolates) and its high stability in buffer and ex vivo human skin make this phage very promising for the treatment of P. aeruginosa skin infections. The phage-bacteria interactions were examined in vitro and in ex vivo in order to provide a basis for the selection of the most suitable protocol for subsequent in vivo experiments.

Effects of microplastics on lentil (Lens culinaris) seed germination and seedling growth.

Widespread use of plastics and mishandling has resulted in severe environmental issues affecting seed germination and seedling growth. This study investigates the effect of polyethylene microplastics (740-4990 nm PEMPs) on lentil (Lens culinaris) seed germination and seedling growth using Biospeckle Optical Coherence Tomography (bOCT), a technique that we successfully demonstrated earlier in visualizing the internal activity of plants. Lentil seeds were exposed to PEMPs bioassay for seven days with 10, 50, and 100 mg L-1 concentrations. The average speckle contrast was calculated after 0 h, 6 h, 12 h, and 24 h of exposure, and statistically significant differences were observed just after 6 h of exposure under all the treatments. However, with conventional parameters, germination viability, germination rate, root and shoot lengths, fresh and dry seedling weights, and antioxidative enzymes, no significant effect was observed until 2 d of exposure. The results revealed that the presence of PEMPs significantly reduced the internal activity at the initial stages that could be visualized only by the use of bOCT, which has never been observed till now. Our results demonstrated for the first time the effect that microplastics indeed could hinder the internal activity during germination of the seeds, possibly resulting from the physical blockage of pores leading to stunted growth at later stages.

The significance of recurrent odontogenic keratocysts in bone grafts.

A comprehensive literature review identified 10 reported cases of recurrent odontogenic keratocysts (OKCs) in bone grafts. Seven of them were sufficiently documented for further analysis. All except one of the patients had a long history of repeated recurrences. They were all approached via an extraoral route, avoiding a mucosal perforation, when the bone graft was placed after a segmental resection. In three cases, this was also true for the primary treatment. The origin of the recurrences is considered to be the oral mucosa, almost certainly involving the proliferation of epithelial islands or microcysts that were close to the original OKC. A plea is made to avoid segmental or marginal resections for this lesion and to pay attention to possible epithelial islands/microcysts in the overlying attached mucosa in the case where marsupialization is preferred.

Hepatitis E infection is an infrequent cause of acute hepatitis in the metropolitan area of Buenos Aires.

Background Argentina is considered a region of low seroprevalence of hepatitis E virus (HEV), however; no studies have evaluated its burden among acute hepatitis cases. OBJECTIVES: We aimed to estimate the proportion of acute HEV and outcome in a cohort of patients with acute hepatitis from 6 liver units in the Metropolitan area of Buenos Aires (MABA). STUDY DESIGN: We performed a prospective cohort study including patients ≥18 years with acute hepatitis (increase in transaminases x 5 ULN) fromJuly 2016 to May 2018. Severe hepatitis was defined as acute hepatitis + INR> 1.5 and acute liver failure as severe hepatitis + encephalopathy. In patients in whom other etiologies were excluded, HEV tests were performed: anti-HEV IgM/G and HEV-RNA in serum and feces. RESULTS: Overall, 268 patients with acute hepatitis were included in the study. The most frequent etiologies of acute hepatitis were hepatitis B (67patients, 25 %), hepatotoxicity (65, 24 %) and autoimmune hepatitis (26, 10 %). Acute HEV infection was confirmed in 8 (2.98 %; 95 %CI 1.25-5.63) patients who tested positive for anti-HEV IgM. A total of 63 (23.5 %) patients were hospitalized and 9 (3.3 %) patients died. Overall, 48 (18 %) patients developed severe hepatitis, 6 (2.2 %) have acute liver failure, 6 (1.9 %) underwent liver transplantation and 9 (3.4 %) patients died. CONCLUSIONS: the proportion of acute HEV in MABA was low during the period studied. We believe our findings will aid physicians prioritize other etiologies of acute hepatitis over HEV in order to optimize diagnostic resources and offer better care to their patients.

Does semen quality change after local treatment of seminal vesiculitis in stallions?

Inflammation of the seminal vesicle interferes with fertility and is a persistent problem that is difficult to treat. The aim of this study was to evaluate the semen quality of 5 stallions with seminal vesiculitis before and after local treatment. All stallions were endoscopically treated for seminal vesiculitis during 10 consecutive days. The glandular lumen was accessed and flushed with a Ringer Lactate solution prior to antibiotic infusion. The antibiotic was selected based on the antibiogram from bacterial culture of samples previously collected from the seminal vesicles. The kinetic parameters (total motility - TM; progressive motility - PM; and rapid sperm - RAP), plasma membrane integrity (PMI), percentage of leukocyte (LEUK) and colony forming units (CFU) of fresh semen samples were evaluated. Additionally, nitric oxide (NO) content in seminal plasma was measured. All parameters were assessed before (T0), one week after treatment (T1) and one month after therapy (T2). The sperm kinetics and plasma membrane integrity showed an improvement in T1 that didn't last until T2. Percentage of leukocytes and CFU decreased on fresh semen and NO decreased on seminal plasma at T1 but were similar between T0 and T2. The results demonstrate that one week (T1) of local treatment leads to an improvement in sperm quality. However, this was not maintained one month (T2) after therapy, as seminal parameters at this time are similar to the pre-treatment values (T0), indicating the recurrence of the disease one month after therapy.

Predicting Motor Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Predicting motor outcome following intracerebral hemorrhage is challenging. We tested whether the combination of clinical scores and DTI-based assessment of corticospinal tract damage within the first 12 hours of symptom onset after intracerebral hemorrhage predicts motor outcome at 3 months. MATERIALS AND METHODS: We prospectively studied patients with motor deficits secondary to primary intracerebral hemorrhage within the first 12 hours of symptom onset. Patients underwent multimodal MR imaging including DTI. We assessed intracerebral hemorrhage and perihematomal edema location and volume, and corticospinal tract involvement. The corticospinal tract was considered affected when the tractogram passed through the intracerebral hemorrhage or/and the perihematomal edema. We also calculated affected corticospinal tract-to-unaffected corticospinal tract ratios for fractional anisotropy, mean diffusivity, and axial and radial diffusivities. Motor impairment was graded by the motor subindex scores of the modified NIHSS. Motor outcome at 3 months was classified as good (modified NIHSS 0-3) or poor (modified NIHSS 4-8). RESULTS: Of 62 patients, 43 were included. At admission, the median NIHSS score was 13 (interquartile range = 8-17), and the median modified NIHSS score was 5 (interquartile range = 2-8). At 3 months, 13 (30.23%) had poor motor outcome. Significant independent predictors of motor outcome were NIHSS and modified NIHSS at admission, posterior limb of the internal capsule involvement by intracerebral hemorrhage at admission, intracerebral hemorrhage volume at admission, 72-hour NIHSS, and 72-hour modified NIHSS. The sensitivity, specificity, and positive and negative predictive values for poor motor outcome at 3 months by a combined modified NIHSS of >6 and posterior limb of the internal capsule involvement in the first 12 hours from symptom onset were 84%, 79%, 65%, and 92%, respectively (area under the curve = 0.89; 95% CI, 0.78-1). CONCLUSIONS: Combined assessment of motor function and posterior limb of the internal capsule damage during acute intracerebral hemorrhage accurately predicts motor outcome.

Biological screening of extracts from leaf and stem bark of Croton floribundus Spreng. (Euphorbiaceae).

This work describes the preliminary evaluation of cytotoxic, antimicrobial, molluscicidal, antioxidant and anticholinesterase activities from leaf (LECF) and stem bark alcoholic extracts (BECF) of the species Croton floribundus Spreng. (Euphorbiaceae), popularly known as capixingui or tapixingui. BECF presented significant toxicity (LC50 = 89.6 µg/ml) in the Artemia salina Leach, 1819 (Crustacea: Branchiopoda) bioassay, whereas LECF did not show activity (LC50 > 1000 µg/ml). From DPPH method, the values of IC50 for the LECF and BECF were 61.2 µg/ml and 62.2 µg/ml, respectively, showing that C. floribundus has an expressive antioxidant activity. Antimicrobial susceptibility was evaluated by microdilution technique and only BECF was active against Staphylococcus aureus (MIC = 39.6 µg/ml). The extracts did not present molluscicidal activity against snail Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Both extracts revealed the presence of several components with an inhibiting capacity of acetylcholinesterase enzyme on the bioautographic assay. C. floribundus showed to be a promising species considering that it exhibited good biological activity in the most assays performed.

Seasonal variation of bacterial communities in shellfish harvesting waters: preliminary study before applying phage therapy.

The recurrent emergence of infections outbreaks associated with shellfish consumption is an important health problem, which results in substantial economic losses to the seafood industry. Even after depuration, shellfish is still involved in outbreaks caused by pathogenic bacteria, which increases the demand for new efficient strategies to control the shellfish infection transmission. Phage therapy during the shellfish depuration is a promising approach, but its success depends on a detailed understanding of the dynamics of bacterial communities in the harvesting waters. This study intends to evaluate the seasonal dynamics of the overall bacterial communities, disease-causing bacterial populations and bacterial sanitary quality indicators in two authorized harvesting-zones at Ria de Aveiro. During the hot season, the total bacterial community presented high complexity and new prevalent populations of the main shellfish pathogenic bacteria emerged. These results indicate that the spring/summer season is a critical period during which phage therapy should be applied.

Molecular signatures of brain injury after intracerebral hemorrhage.

BACKGROUND: The mechanisms of cellular death in the tissue surrounding an intracerebral hemorrhage (ICH) are not defined. OBJECTIVE: To investigate the relationship of markers of excitotoxicity and inflammation to brain injury after ICH. METHODS: A total of 124 consecutive patients with spontaneous ICH admitted within 24 hours of stroke onset were prospectively investigated. The volumes of the initial ICH, peripheral edema on days 3 to 4, and the residual cavity at 3 months were measured on CT scan. Glutamate, cytokines, and adhesion molecules were measured in blood samples obtained on admission. Stroke severity and neurologic outcome were evaluated with the Canadian Stroke Scale. RESULTS: Poor neurologic outcome at 3 months (Canadian Stroke Scale < 7) was observed in 53 patients (43%). Stroke severity and glutamate concentrations (by each increment of 10 micromol/L, odds ratio 1.23; 95% CI 1.09 to 1.41), but not the initial volume of ICH, were independent predictors of poor outcome. In the multiple linear regression analyses, tumor necrosis factor-alpha concentration was correlated (r = 0.83, p < 0.0001) with the volume of perihematoma edema, and glutamate concentrations were correlated (r = 0.78, p < 0.0001) with the volume of the residual cavity. These same results were observed when lobar (n = 58) and deep (n = 66) ICH were analyzed separately. CONCLUSIONS: High plasma levels of proinflammatory molecules within 24 hours of intracerebral hemorrhage onset are correlated with the magnitude of the subsequent perihematoma brain edema, whereas poor neurologic outcome and the volume of the residual cavity are related to increased plasma glutamate concentrations.

Exchange transfusion and major surgery in acute hepatic failure.

Of the many techniques available for short-term support of the failing liver, a closed "isovolemic" method of exchange transfusions remains simple and safe. We used this method to exchange 143 U. of blood in eight patients in Stage III/IV hepatic failure; four patients had no previous underlying liver disease. Significant improvements of biochemical and coagulation parameters resulted. Serum bilirubin, glutamic oxaloacetic transaminase and, lactic dehydrogenase levels fell from a mean, 24.7 mg. per 100 ml., 3,100 mU. per milliliter, 2,796 mU. per millilter, respectively, to 10.9 mg. per 100 ml., 122.9 mU. per milliliter, and 558.5 mU. per milliliter, respectively, 6 to 12 hours following transfusion. Prolongation of serum prothrombin and thrombin times (over controls) of 31.1 and 30.1 seconds (mean) were markedly decreased to 3.2 and 6.1 seconds 6 to 12 hours following transfusion; partial thromboplastin times were decreased from a mean 196.4 seconds to 87.8 seconds after the same period. Levels of Factors VII, IX, and X were increased transiently. Correlations of exchange transfusion to reversal of coma and improvements in electroencephalograms were poor. Two patients in coma were subjected to major surgery following exchange transfusion; one patient survived vagotomy and hemigastrectomy for stress bleeding and one withstood a temporary baboon liver heterotopic transplant which aided in recovery from coma. We recommend isovolemic exchange transfusion as specific treatment for coagulation abnormalities and as an over-all aid in lowering the mortality rate of patients in hepatic coma. Marked improvements in homeostasis make major surgery feasible.