Intrathecal formation of anticardiolipin antibodies in a patient with SLE-related relapsing longitudinal myelitis: a possible pathogenic connection.

BACKGROUND: Nontraumatic acute transverse myelitis (ATM) can occur in response to infectious, inflammatory and vascular triggers; 1% of patients with systemic lupus erythematosus (SLE) develop ATM, but the mechanism remains unknown. OBJECTIVE: The objective of this case report is to describe a case of intrathecal formation of anticardiolipin antibodies (aCL) during SLE-related ATM. METHODS: A single patient analysis was conducted. RESULTS: A 26-year-old housewife was diagnosed with SLE at age 19. Circulating aCL antibodies were positive at diagnosis. At age 21, she developed an episode of severe sepsis. At 23 years of age she developed an episode of ATM that left her paraplegic with a D10 sensory level, from which she recovered partially. Three years later, she developed a clinical relapse of ATM. During that second episode, serum levels of aCL were within normal limits, while cerebrospinal fluid levels were increased, suggesting intrathecal production of aCL. CONCLUSION: Here, we present a case of a woman who developed relapsing SLE-related longitudinally extensive ATM in whom intrathecal formation of aCL was demonstrated, suggesting that local production and cross-recognition of nervous tissue by those autoantibodies may be myelopathic.

Natural history of longitudinally extensive transverse myelitis in 35 Hispanic patients with systemic lupus erythematosus: good short-term functional outcome and paradoxical increase in long-term mortality.

Background and objective Acute transverse myelitis (TM) is an infrequent neurological complication of systemic lupus erythematosus (SLE). Short-term outcome varies widely between cohorts. Little is known about the epidemiology and long-term functional outcome of TM associated to SLE. Methods Patients with SLE and acute TM were identified during hospital admission, visits to the Emergency Room or the Neurology Outpatient Clinic. We evaluated ambispectively those patients with SLE presenting with clinical myelopathy and corroborated with spinal MRI. Cases were divided as partial (non-paralyzing) or complete (paralyzing). We determined long-term functional outcome as well as mortality in those patients with follow-up periods of at least five years. Results We identified 35 patients (partial, n = 15; complete, n = 20) in which complete clinical and imaging data were available (26 with follow-up ≥ 5 years). Patients with complete TM were significantly older than those with partial forms. Positive antiphospholipid antibodies were observed in 80% of patients, suggesting a possible mechanistical role. Surprisingly, functional recovery at one year was in general good; however, we observed a five-year mortality of 31% because of sepsis (in 10 cases) or pulmonary embolism (in one case). Conclusions Short-term outcome of SLE-related TM is generally good, and recurrence rate is low. However, we observed a long-term fatality rate of 31% for reasons unrelated to TM, suggesting that TM is a manifestation of severe immune dysregulation and a predictor of severity and mortality in patients with SLE.

[Usefulness of copeptin in discarding non-ST elevation acute myocardial infarction in patients with acute chest pain and negative first troponin I]. / Valor de la copeptina para la exclusión del infarto agudo de miocardio sin elevación del segmento ST en pacientes con dolor torácico y primera troponina negativa.

AIM: To evaluate the usefulness of copeptin as a rapid and reliable marker for discarding non-ST elevation acute myocardial infarction (NSTEMI) in patients attended in an Emergency Care Department due to acute chest pain with a normal or non-diagnostic electrocardiogram and a negative first troponin I result. DESIGN: A prospective observational study was carried out. SETTING: The Emergency Care Department of a university hospital. PATIENTS: The study comprised a total of 97 patients attended in the Emergency Care Department due to chest pain suggestive of acute coronary syndrome with an evolution of under 12h, a non-diagnostic electrocardiogram and a negative first troponin I result. INTERVENTIONS: None. VARIABLES OF INTEREST: Patient demographic data and baseline characteristics, copeptin upon admission, troponin I upon admission and after 6h, and final diagnosis. RESULTS: The final diagnosis was NSTEMI in 14 patients (14.4%) -no significant differences in copeptin concentration being observed between the 2 groups, though a tendency towards higher values was recorded in the NSTEMI group (median: 24.6pmol/l [interquartile range: 42.0] vs. 12.0pmol/l [16.1]; P=.06). The AUC ROC for copeptin upon admission was 0.657 (95%CI: 0.504-0.810), with a negative predictive value of 92% for a cutoff point of 14pmol/l. CONCLUSIONS: Copeptin determination upon admission to the Emergency Care Department in patients with chest pain for ≤12h, suggestive of acute coronary syndrome, with a non-diagnostic electrocardiogram and a negative first troponin I determination does not allow rapid and reliable exclusion of the presence of NSTEMI. Serial troponin I measurements are needed in this respect.

Acute liver failure: Management update and prognosis.

Acute liver failure is a rare but serious syndrome, with an incidence of approximately 2,000 to 3,000 cases per year in North America. Its pathophysiology and clinical course vary, depending on the cause of the primary liver injury, and can lead to high morbidity and mortality or the need for liver transplantation, despite available therapies. This syndrome involves excessive activation of the immune system, with damage in other organs, contributing to its high mortality rate. The most accepted definition includes liver injury with hepatic encephalopathy and coagulopathy within the past 26 weeks in a patient with no previous liver disease. The main causes are paracetamol poisoning, viral hepatitis, and drug-induced liver injury, among others. Identifying the cause is crucial, given that it influences prognosis and treatment. Survival has improved with supportive measures, intensive therapy, complication prevention, and the use of medications, such as N-acetylcysteine. Liver transplantation is a curative option for nonresponders to medical treatment, but adequate evaluation of transplantation timing is vital for improving results. Factors such as patient age, underlying cause, and severity of organ failure influence the post-transplant outcomes and survival.

Hepatitis C virus-positive donors in HCV-negative recipients in liver transplantation: Is it possible in Mexico?

Hepatitis C virus (HCV) infection is a worldwide public health problem associated with significant morbidity and mortality. In the context of liver transplantation, the demand for organs continues to exceed the supply, prompting the consideration of using organs from HCV-positive donors in HCV-negative recipients. The introduction of direct-acting antivirals (DAAs), which have demonstrated great efficacy in eradicating the virus, has made transplantation of organs from donors with HCV infection possible. The present article provides a brief review of the current evidence on the use of organs from HCV-infected patients.

Antibiotic resistance profile in eye infections in a reference centre in Floridablanca, Colombia. / Perfil de resistencia antibiótica en infecciones oculares en un centro de referencia en Floridablanca, Colombia.

BACKGROUND AND OBJECTIVE: In view of the increasing bacterial resistance to antibiotics, it is necessary to determine it locally in order to serve as a guide in clinical management. The purpose of this study was to characterise the pattern of antibiotic sensitivity in cases of eye infections in a third level ophthalmological institution in Floridablanca (Colombia). MATERIALS AND METHODS: An observational cross-sectional study in which an analysis was made of the culture and antibiogram reports of specimens taken from cases of conjunctivitis, infectious keratitis, and endophthalmitis between January 2013 and June 2016. RESULTS: A total of 833 specimens were positive for bacteria. Considering both gram-positive and gram-negative microorganisms gentamicin, tobramycin, and ciprofloxacin showed high resistance rates (64.4%, 40.3%, and 29.1%, respectively). Moxifloxacin, vancomycin, imipenem, and gatifloxacin showed low percentages of resistance: 2.6%, 2.1%, 0.6%, and 0.4%, respectively. When comparing the results with previous studies in our institution, there was a decrease in sensitivity to the fourth-generation quinolones and imipenem, especially within the gram-negative ones. CONCLUSION: Fourth generation quinolones, imipenem and vancomycin continue to have a low in vitro resistance to bacteria that cause eye infections. However, there was a tendency to an increase in the resistance of gram-negative bacteria. Measures should be taken to try to control this phenomenon, and consider possible antimicrobial therapy alternatives to infections caused by these microorganisms.

Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells.

Kaempferol is a natural flavonoid widely found in fruits, vegetables, and tea. Kaempferol possesses beneficial biological properties such as anti-inflammatory and antioxidant activities. Positive energy balance during obesity correlates with a pro-inflammatory chronic state. In this context, we hypothesized that kaempferol might promote anti-obesity effects by modulating adipogenesis and lipolytic pathways. Adipocyte viability at 24, 48, and 72 h was measured by an ATP-based assay. Pre-adipocytes (day 0) or mature adipocytes (day 12) were treated with 60 µM kaempferol until day 21 to evaluate its potential anti-adipogenic and lipolytic effect, respectively. Total lipid accumulation was assessed using Oil Red O staining assay. Gene expression was measured by RT-qPCR to evaluate the effect of kaempferol on adipogenesis and lipolysis gene expression. Our results showed a dose-dependent effect of kaempferol treatment on cell viability promoting cell death at higher than 60 µM concentration. Pre-adipocytes stimulation by 60 µM kaempferol resulted in 62% adipogenesis inhibition whereas in mature adipocytes, it reduced 39% intracellular lipid accumulation. Also, 60 µM kaempferol treatment decreased Cebpa mRNA expression when compared to control cells. In contrast, Pnpla2 and Lipe gene expression were upregulated in 3T3-L1 cells incubated with 60 µM kaempferol. In summary, our results showed that kaempferol modulates adipogenic differentiation in 3T3-L1 cells by promoting downregulation of Cebpa gene expression and decreasing lipid accumulation in mature adipocytes by its positive effects on Pnpla2 and Lipe mRNA levels. Kaempferol might display an anti-obesity effect.

Enhancement of recombinant hemoglobin production in Escherichia coli BL21(DE3) containing the Plesiomonas shigelloides heme transport system.

To produce recombinant hemoglobin in Escherichia coli, sufficient intracellular heme must be present, or the protein folds improperly and is degraded. In this study, coexpression of human hemoglobin genes and Plesiomonas shigelloides heme transport genes enhanced recombinant hemoglobin production in E. coli BL21(DE3) grown in medium containing heme.

Mycotic keratitis caused by Scedosporium apiospermum in an immunocompetent patient. / Queratitis micótica causada por Scedosporium apiospermum en paciente inmunocompetente.

CLINICAL CASE: A 51 year-old immunocompetent male was referred due to presenting with a large corneal ulcer with hypopyon in the right eye. Topical amphotericin B, fluconazole and moxifloxacin, as well as oral itraconazole were initially indicated. Following the report of mycotic structures on staining, topical natamycin was started. The result of the culture was reported two weeks later as, Scedosporium apiospermum (S. apiospermum), and topical voriconazole was then added. The response to treatment was very slow, and took five weeks after receiving triple therapy (natamycin, voriconazole and fluconazole) and one dose of intrastromal voriconazole, for the hypopyon to disappear. The final outcome was successful, achieving healing of the ulcer. The patient is waiting for a corneal transplant. DISCUSSION: A microbiological study is essential in patients in whom fungal keratitis is suspected. The treatment of choice against S. apiospermum is with voriconazole, but the combination of various antifungal agents may be required.

Comparative survival after permanent ventricular and dual chamber pacing for patients with chronic high degree atrioventricular block with and without preexistent congestive heart failure.

To determine whether survival after permanent ventricular demand (VVI) pacing differs from survival after permanent dual chamber (DVI or DDD) pacing in patients with chronic high degree atrioventricular (AV) block (Mobitz type II or trifascicular block), 132 patients who received a VVI pacemaker (Group 1) and 48 patients who received a DVI or DDD pacemaker (Group 2) were followed up for 1 to 5 years. There was no significant difference in sex distribution, mean age or incidence of coronary heart disease, hypertension, valvular heart disease, diabetes mellitus, stroke or renal failure between Groups 1 and 2. Overall, the predicted cumulative survival rate at 1, 3 and 5 years was 89, 76 and 73%, respectively, for Group 1 and 95, 82 and 70%, respectively, for Group 2. In patients with preexistent congestive heart failure, the predicted cumulative survival rate at 1, 3 and 5 years was 85, 66 and 47%, respectively, for Group 1 (n = 53) and 94, 81 and 69%, respectively, for Group 2 (n = 20). The 5 year predicted cumulative survival rate was significantly lower in Group 1 patients with preexistent congestive heart failure than in Group 2 patients with the same condition (p less than 0.02). There was no significant difference in 5 year cumulative survival rate between Groups 1 and 2 for patients without preexistent congestive heart failure. The results suggest that permanent dual chamber pacing enhances survival to a greater extent than does permanent ventricular demand pacing in patients with high degree AV block and preexistent congestive heart failure.

Families' perception of the value of timed daily "family rounds" in a trauma ICU.

Daily communications between the ICU trauma patients' families and the trauma team are often limited due to the unpredictable nature of subsequent patient admissions and operative procedures. In order to improve the lines of family-physician communication and educate residents regarding family communication, our level I trauma center instituted daily "Family Rounds" (FR). FR occur at the same time every day, in the patient's ICU room. The purpose of this study was to determine whether families valued the scheduled daily FR, to establish whether FR improved the family-physician relationship, and to delineate strengths and weaknesses of the present structure of our FR. We mailed surveys to family members of trauma patients hospitalized in the trauma ICU for > or = 3 days. A total of 55 (22%) families responded. Combining "excellent" and "good" responses, 86.5 per cent of families looked forward to having a specific time of day to meet with the trauma team, and 90 per cent liked having rounds in the ICU room with the patient. However, 36 per cent did not like having only scheduled time for FR. The majority, 75 per cent, believed that all concerns were addressed during FR, and 84.9 per cent rated their overall experience as either excellent or good. Scheduled FR appear to improve communication between trauma surgeons and patients' families, enhance the family-physician relationship, and strengthen our surgical residency teaching program.

Effect of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease.

To assess the effects of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease, we performed radionuclide ventriculography on eight patients with normal right ventricular ejection fraction (RVEF greater than or equal to 35%) and 14 patients with mild to moderate right ventricular dysfunction (RVEF less than 35%) at rest. All patients had chronic stable angina pectoris, and nine patients had prior myocardial infarction. Radionuclide ventriculography was performed on placebo and during clinical beta-blockade (heart rate, 50 to 60 beats per minute and less than or equal to 20% increase in heart rate over baseline during stage I treadmill exercise, Bruce protocol) with the oral, cardioselective beta-blocking agent, betaxolol. The resting RVEF (mean +/- 1 SD) was 33% +/- 7% on placebo and 34% +/- 7% during clinical beta-blockade. Mean exercise RVEF was 40% +/- 8% on placebo and 39% +/- 8% during clinical beta-blockade. These differences were not statistically significant. Resting left ventricular ejection fraction ranged from 22% to 60% (mean, 42% +/- 8%). On placebo, one of eight patients with a resting RVEF greater than or equal to 35% had a normal exercise RVEF response (greater than or equal to 5% increment) whereas nine of 14 patients with resting RVEF less than 35% had normal exercise response. The discordant relationship between baseline RVEF and exercise response on placebo became less marked during clinical beta-blockade. We conclude that beta-blockade does not produce significant deterioration of right ventricular systolic function or right ventricular reserve either in patients with normal or in those with mild to moderately impaired resting right ventricular systolic function.

Pressure-dependent renin release during chronic blockade of nitric oxide synthase.

We evaluated pressure-dependent stimulation of renin release in rats with sustained hypertension induced by chronic blockade of nitric oxide synthase with N omega-nitro-L-arginine methyl ester (L-NAME) for 5 to 7 days. Rats were anesthetized and catheters were inserted into the carotid artery and abdominal aorta for measurement of arterial pressures. An adjustable snare was placed around the suprarenal aorta, and this snare was tightened to reduce renal perfusion pressure. Pressure-dependent renin release was evaluated in hypertensive rats by reducing renal perfusion pressure to 125, 85, and 65 mm Hg. Renin release was also evaluated in normotensive control rats at these same pressures. Basal systemic arterial pressures averaged 159 +/- 3 and 124 +/- 4 mm Hg (P < .001), respectively, in the L-NAME-treated (n = 22) and normotensive control (n = 18) rats. Basal plasma renin activity was lower in L-NAME than control rats (5.0 +/- 0.3 versus 9.5 +/- 1.3 U, P < .01), and plasma renin activity was markedly attenuated at all comparable levels of renal perfusion pressure. Maximal plasma renin activity levels were achieved at perfusion pressures reduced to 65 mm Hg, and plasma renin activity averaged 14 +/- 2 and 34 +/- 7 U (P < .01) in L-NAME hypertensive and control rats, respectively. However, infusion of the nitric oxide donor sodium nitroprusside similarly stimulated plasma renin activity levels to 39 +/- 3 and 45 +/- 3 U (P > .05), in the hypertensive and normal control groups, respectively. Overall, these findings are consistent with the hypothesis that prolonged L-NAME administration attenuates pressure-dependent renin release by inhibiting nitric oxide formation, which may function as a paracrine mechanism inversely linking renal perfusion pressure with the stimulation of renin release.

Sodium and volume depletion activates neurogenic mechanisms in renal hypertensive dogs.

The acute response to ganglionic blockade (hexamethonium bromide, 30 mg/kg, i.v.) was used to evaluate the neurogenic contributions to mean arterial pressure maintenance in the conscious one-kidney, one clip hypertensive dog. Approximately 2 hours (112 minutes) after ganglionic blockade, captopril (10 mg/kg, i.v.) was given to block the renin-angiotensin system. Hypertensive animals were studied 3 days after clipping (group 2) or 2 to 4 weeks after clipping (groups 3 and 4). Groups 2 and 3 were fed a regular sodium diet, but group 4 animals were sodium and volume depleted. Normotensive control animals (group 1) were fed a regular sodium diet. On the day of the acute experiment the baseline blood pressures measured in group 2 (151 +/- 10 mm Hg, n = 5), group 3 (154 +/- 5 mm Hg, n = 7), and group 4 (160 +/- 8 mm Hg, n = 7) were not different (p greater than 0.05) from each other, but all were elevated (p less than 0.05) compared with the group 1 animals (106 +/- 3 mm Hg, n = 8). Also, there were no significant differences (p greater than 0.05) in the baseline plasma catecholamine levels among the three hypertensive groups. Ganglionic blockade produced a greater fall in blood pressure (p less than 0.05) in the sodium/volume-depleted dogs of group 4 (-35 mm Hg) than in group 1 (-10 mm Hg), group 2 (-3 mm Hg), or group 3 (-12 mm Hg) animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal mechanisms for suppression of renin secretion by atrial natriuretic factor.

The effects of synthetic atrial natriuretic factor on renin secretion were examined in anesthetized dogs with either a single filtering kidney or a single denervated nonfiltering kidney. In dogs with a single filtering kidney (Series 1, n = 6), a priming dose of atrial natriuretic factor (2 micrograms/kg, i.v.) followed by sustained intravenous infusions at doses of 200 and 400 ng/kg/min for 20 minutes each produced striking decrements (p less than 0.05) in renin secretion, from 1083 +/- 322 to 205 +/- 120 and 286 +/- 168 ng of angiotensin I per minute. This fall in renin secretion was associated with significant increases (p less than 0.05) in creatinine clearance, urine flow, sodium excretion, and the filtered load of sodium. Renal blood flow increased only transiently. In dogs with a single denervated nonfiltering kidney (Series 2, n = 6), infusion of atrial natriuretic factor at these doses also produced marked inhibition (p less than 0.05) of renin secretion, from 311 +/- 98 to 72 +/- 22 and 91 +/- 37 ng of angiotensin I per minute. Renal blood flow remained significantly elevated (p less than 0.05) throughout the infusion, in contrast to renal blood flow in Series I. Similar results were obtained in a third series of dogs (n = 6) with a single denervated nonfiltering kidney, during sustained intrarenal arterial infusions of atrial natriuretic factor. These results suggest that an increase in the sodium load delivered to the macula suppression of renin secretion by atrial natriuretic factor is mediated through its interactions with the two intrarenal receptor mechanisms, the renal vascular receptor and the macula densa.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intrarenal infusion of calcium entry blockers in anesthetized dogs.

Renal function and renin release were studied in anesthetized, uninephrectomized dogs during intrarenal infusions of the calcium influx blockers, verapamil and nifedipine. Verapamil increased renal blood flow by 20% (p less than 0.05) but did not alter glomerular filtration rate. Verapamil produced five-to-seven fold increases in urine flow and the rates of excretion of sodium and chloride (p less than 0.01). Significant increases in the rates of excretion of potassium, calcium and magnesium were also observed. Despite its striking effects on renal function, verapamil, in nonhypotensive doses, failed to alter renin secretion. Intrarenal infusion of nifedipine had no consistent effect on renal blood flow or the rate of glomerular filtration but increased urine flow and the rates of excretion of sodium and chloride by more than three fold (p less than 0.01). Nonhypotensive doses of nifedipine had no significant effect on renin release. In dogs with a denervated nonfiltering kidney, an intrarenal verapamil or nifedipine infusion did not produce a significant change in renin release. This study demonstrates a striking effect of calcium entry blockers on the reabsorption of sodium, chloride, and water by the renal tubules in intact dogs but renin release did not increase unless hypotension occurred.

Renal prostaglandins and the control of renin release.

This study examines the hypothesis that the renal prostaglandins function as essential mediators in stimulus-secretion coupling for one or more of the basic receptor mechanisms in the control of renin release. Changes in plasma renin activity (PRA) were evaluated in response to suprarenal aortic constriction before and after indomethacin administration in conscious dogs with either a single denervated nonfiltering kidney or with intact filtering kidneys. Suprarenal aortic constriction was adjusted to reduce renal perfusion pressure below the autoregulatory range in both groups of dogs. Inhibition of cyclooxygenase with indomethacin significantly decreased urinary prostaglandin E2 (PGE2) excretion, but indomethacin failed to block or attenuate the increase in PRA in response to a decrease in renal perfusion pressure in either group of dogs. These results fail to support the hypothesis that the renal prostaglandins function as essential mediators of the intrarenal receptor mechanisms for renin release which are activated by a decrease in renal perfusion pressure below the autoregulatory range.

Nitric oxide donors improve gut function after prolonged hypothermic ischemia.

The objective of this study was to determine whether the nitric oxide (NO) donors, spermine NO and 3-morpholinosydonimine-N-ethyl-carbamide (SIN1), alter the mucosal and microvascular responses of the feline small intestine to 6 hr of hypothermic ischemia and 2 hr of normothermic reperfusion. Intestinal mucosal permeability was monitored using the blood-to-lumen clearance of 51Cr-EDTA. Lymph flow and lymphatic protein clearance estimates were used to assess intestinal microvascular fluid filtration and vascular protein leakage, respectively. Spermine NO (0.1 mmol/L) or SIN1 (0.5 mmol/L) was added to the luminal perfusate during the entire reperfusion period. Both NO donors were effective in attenuating the increased mucosal permeability to 51Cr-EDTA and the depressed net water absorption, relative to untreated intestinal preparations exposed to the same protocol. Intestinal lymph flow, lymphatic protein clearance, and capillary hydrostatic pressure were increased by a greater extent in preparations treated with spermine NO. These findings suggest that NO donors may improve mucosal function in intestinal allografts subjected to prolonged hypothermic ischemia. This protective effect on mucosal epithelium appears to be unrelated to an action of the NO donors on the microvasculature.

Aldosterone and antialdosterone therapy in congestive heart failure.

The pathophysiologic cycle that links myocardial failure with the appearance of congestive heart failure is not fully understood. It is clear, however, that an activation of several neurohormonal systems and the interplay between kidneys, adrenal glands, and heart contribute to abnormal sodium and water homeostasis. Aldosterone, the body's most potent mineralocorticoid hormone, contributes to intravascular and extravascular volume expansion, and thus to the appearance of symptomatic failure. Antialdosterone therapy in patients with secondary hyperaldosteronism due to heart failure must achieve one or more of the following goals: reduce or, preferably, normalize plasma aldosterone levels by limiting synthesis; antagonize the renal and systemic effects of aldosterone at its receptor sites; and eliminate or minimize the multiple stimuli to aldosterone secretion.