Deterministic modeling of single-channel and whole-cell currents.

As a complement to the experimental work, mathematical models are extensively used to study the functional properties of ionic channels. Even though it is generally assumed that the gating of ionic channels is a Markovian phenomenon, reports based on non-traditional analyses of experimental recordings suggest that non-Markovian processes might be also present. While the stochastic Markov models are by far the most adopted approach for the modeling of ionic channels, a model based on the idea of a deterministic process underlying the gating of ionic channels was proposed by Liebovitch and Toth (Liebovitch, L.S. and Toth, T.I., 1991. Journal of Theoretical Biology, 148(2), pp.243-267.) Here, by using a voltage-dependent K+ channel as a first approximation, we propose a modified version of the deterministic model of Liebovitch and Toth that, in addition to reproducing the single-channel currents simulated by a two-states Markov model, it is capable of reproducing the whole-cell currents produced by a population of K+ channels.

Trauma cardiaco cerrado / Blunt cardiac trauma

El trauma cardiaco constituye una de las primeras causas de mortalidad en la población general. Requiere alto índice de sospecha en trauma cerrado severo, mecanismo de desaceleración y en presencia de signos indirectos como: equimosis, huella del volante o del cinturón en el tórax anterior. Las lesiones incluyen: conmoción cardiaca, ruptura cardiaca, lesión cardiaca indirecta como la trombosis coronaria aguda, lesión aórtica, lesión del pericardio y herniación cardiaca. Entre las manifestaciones clínicas están: la angina refractaria a nitratos, el dolor pleurítico, la hipotensión arterial, la taquicardia, la ingurgitación yugular que aumenta con la inspiración, el galope por tercer ruido, el frote pericárdico, los soplos de reciente aparición, los estertores crepitantes por edema pulmonar. El electrocardiograma es el primer eslabón en el algoritmo diagnóstico con hallazgos como: la taquicardia sinusal, los complejos ventriculares prematuros, la fibrilación auricular, el bloqueo de rama derecha y los bloqueos auriculoventriculares. La radiografía de tórax ayuda a descartar lesiones adicionales óseas y pulmonares. La troponina I tiene un valor predictivo negativo del 93% para el trauma cardiaco, otras enzimas como la creatina quinasa total y la creatina quinasa fracción MB son menos específicas. El ecocardiograma está indicado en caso de hipotensión persistente, electrocardiograma con alteraciones o falla cardiaca aguda. El tratamiento incluye la estabilización inicial y un manejo específico de las lesiones. Entre las complicaciones se incluyen: el taponamiento cardiaco, la contusión miocárdica, el síndrome coronario agudo, las arritmias cardíacas y la lesión aórtica. El pronóstico se determina en mayor medida por los signos vitales al ingreso y la presencia de paro cardiaco durante el abordaje inicial.

Cardiac trauma is one of the primary causes of death amongst general population. It requires a high degree of suspicion of severe blunt trauma, deceleration mechanism and presence of indirect signs, such as ecchymosis and steering wheel or seatbelt marks in the anterior chest wall. Injuries include: cardiac concussion, heart rupture, indirect cardiac injury, such as acute coronary thrombosis, aortic injury, pericardial injury and cardiac herniation. The clinical signs and symptoms include: angina refractory to nitrates, pleuritic pain, hypotension, tachycardia, jugular venous distention that increases on inspiration, S3 gallop, pericardial rub, new murmur or crepitant rales due to pulmonary edema. The electrocardiogram is the first link in the diagnostic algorithm leading to findings such as sinus tachycardia, premature ventricular complexes, atrial fibrillation, right bundle branch block and atrioventricular block. Chest X-rays help to rule out other pulmonary or bone injuries. Troponin I has a negative predictive value of 93% for cardiac trauma; other less specific cardiac enzymes are creatine kinase and creatine kinase-MB. Echocardiogram is indicated in presence of persistent hypotension, abnormal ECG results or acute heart failure. The treatment includes initial stabilization and specific management of the injuries. Some complications may include: cardiac tamponade, myocardial contusion, acute coronary syndrome, cardiac arrhythmias and aortic injury. The prognosis of the patient depends on the vital signs at the time of arrival at the emergency department and the presence of cardiac arrest during the initial approach.

Effect of Duodenal-Jejunal Bypass Surgery on Glycemic Control in Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: To determine whether upper gastrointestinal tract (UGI) bypass itself has beneficial effects on the factors involved in regulating glucose homeostasis in patients with type 2 diabetes (T2D). METHODS: A 12-month randomized controlled trial was conducted in 17 overweight/obese subjects with T2D, who received standard medical care (SC, n = 7, BMI = 31.7 ± 3.5 kg/m(2) ) or duodenal-jejunal bypass surgery with minimal gastric resection (DJBm) (n = 10; BMI = 29.7 ± 1.9 kg/m(2)). A 5-h modified oral glucose tolerance test was performed at baseline and at 1, 6, and 12 months after surgery or starting SC. RESULTS: Body weight decreased progressively after DJBm (7.9 ± 4.1%, 9.6 ± 4.2%, and 10.2 ± 4.3% at 1, 6, and 12 months, respectively) but remained stable in the SC group (P < 0.001). DJBm, but not SC, improved: (1) oral glucose tolerance (decreased 2-h glucose concentration, P = 0.039), (2) insulin sensitivity (decreased homeostasis model assessment of insulin resistance, P = 0.013), (3) early insulin response to a glucose load (increased insulinogenic index, P = 0.022), and (4) overall glycemic control (reduction in HbA1c with fewer diabetes medications). CONCLUSIONS: DJBm causes moderate weight loss and improves metabolic function in T2D. However, our study cannot separate the benefits of moderate weight loss from the potential therapeutic effect of UGI tract bypass itself on the observed metabolic improvements.

Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes.

Gastric bypass surgery causes resolution of type 2 diabetes (T2DM), which has led to the hypothesis that upper gastrointestinal (UGI) tract diversion, itself, improves glycemic control. The purpose of this study was to determine whether UGI tract bypass without gastric exclusion has therapeutic effects in patients with T2DM. We performed a prospective trial to assess glucose and ß-cell response to an oral glucose load before and at 6, 9, and 12 months after duodenal-jejunal bypass (DJB) surgery. Thirty-five overweight or obese adults (BMI: 27.0 ± 4.0 kg/m(2)) with T2DM and 35 sex-, age-, race-, and BMI-matched subjects with normal glucose tolerance (NGT) were studied. Subjects lost weight after surgery, which was greatest at 3 months (6.9 ± 4.9%) with subsequent regain to 4.2 ± 5.3% weight loss at 12 months after surgery. Glycated hemoglobin (HbA(1c)) decreased from 9.3 ± 1.6% before to 7.7 ± 2.0% at 12 months after surgery (P < 0.001), in conjunction with a 20% decrease in the use of diabetes medications (P < 0.05); 7 (20%) subjects achieved remission of diabetes (no medications and HbA(1c) <6.5%). The area under the curve after glucose ingestion was ~20% lower for glucose but doubled for insulin and C-peptide at 12 months, compared with pre-surgery values (all P < 0.01). However, the ß-cell response was still 70% lower than subjects with NGT (P < 0.001). DJB surgery improves glycemic control and increases, but does not normalize the ß-cell response to glucose ingestion. These findings suggest that altering the intestinal site of delivery of ingested nutrients has moderate therapeutic effects by improving ß-cell function and glycemic control.

Long-long limb Roux-en-Y gastric bypass is more efficacious in treatment of type 2 diabetes and lipid disorders in super-obese patients.

BACKGROUND: Super-obese patients can achieve adequate weight loss with long limb Roux-en-Y gastric bypass (RYGB). These patients, however, might need longer intestinal limbs to control co-morbidities such as type 2 diabetes, lipid disorders, hypertension, sleep apnea, and gastroesophageal reflux disorder. METHODS: A total of 105 patients with a body mass index of > or =50 kg/m(2) were randomly divided into 2 similar groups regarding sex, age, and number of co-morbidities. All underwent laparoscopic Roux-en-Y gastric bypass. In group 1, the length of the biliary limb was 50 cm and the length of the Roux limb was 150 cm. In group 2, the length of the biliary limb was 100 cm and the length of the Roux limb was 250 cm. RESULTS: The follow-up for both group was 48 months. Diabetes was controlled in 58% of group 1 and in 93% of group 2 (P <0.05). Lipid disorders improved in 57% of group 1 and in 70% of group 2 (P <0.05). No statistical difference was found in the control or improvement of hypertension, sleep apnea, or gastroesophageal reflux disorder. The excess weight loss was faster in group 1 but was similar in both groups at 48 months (70% in group 1 and 74% in group 2), with no statistical difference. CONCLUSION: Patients with longer biliary and Roux limbs achieved greater type 2 diabetes control, greater lipid disorder improvement, and showed a trend toward faster excess weight loss.

Staple line reinforcement with new biomaterial increased burst strength pressure: an animal study.

BACKGROUND: Most bariatric operations rely on stapler devices. Although today staplers are extremely safe, efficient, and reliable, a potential risk exists for staple line failures, leading to three complications: leaks, fistulas, and bleeding. Porcine small intestinal submucosa strip applied over the staple line suture might help prevent these problems. METHODS: Forty animals (canine model developed at the University of São Paulo, São Paulo, Brazil) underwent general anesthesia and laparotomy. One nonreinforced staple line suture and one staple line suture reinforced with Surgisis SLR was created in each animal. The burst strength pressure of the 80 staple line sutures was obtained. Suture line bleeding and the ease of use of the membrane were also noted. The data were compared (Student's t test). The dogs were euthanized after the procedure. Two surgeons with experience in stapler devices performed all procedures. RESULTS: The mean +/- SD burst pressure was 209.26 +/- 76.41 mm Hg and 441.33 +/- 128.64 mm Hg for the stapler line without and with the biodegradable membrane, respectively. The difference was statistically significant (P = .002). No in vivo suture line bleeding occurred. The biodegradable membrane was easy to use. CONCLUSION: The biodegradable membrane was able to increase the burst strength pressure of the bowel segment staple line. It might help prevent some causes of staple line leaks.

Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m(2): a tailored approach.

BACKGROUND: Patients with a body mass index (BMI) < 35 kg/m(2) who are obese, have uncontrolled co-morbidities, and have tried to lose weight with no success do not meet the "traditional" criteria for obesity surgery, and no other treatment is being offered to them. METHODS: A total of 37 obese patients (30 women and 7 men) had been undergoing clinical treatment with no resolution or improvement of their life-threatening co-morbidities. The mean BMI was 32.5 kg/m(2). Their age ranged from 28 to 45 years. All patients had type 2 diabetes mellitus, hypertension, and lipid disorder. Gastroesophageal reflux disease was present in 7 patients and sleep apnea in 3. These patients underwent the same preoperative evaluation as other patients for gastric bypass. The patients were required to have approval from their primary care physician. All patients provided written informed consent. Laparoscopic Roux-en-Y gastric bypass was performed. After extensive explanation and documentation, the Brazilian insurance companies approved the procedure in 3 cases, and international (non-American) insurance companies approved the procedure in 4 cases. RESULTS: The follow-up range was 6-48 months. The mean excess weight loss was 81%. Thirty-six patients had total remission of their co-morbidities. One patient still had mild hypertension, but with a reduction in the number of antihypertensive drugs used. No surgery-related complications occurred. CONCLUSION: Obese patients with a BMI of <35 kg/m(2) and severe co-morbidities can benefit from laparoscopic Roux-en-Y gastric bypass. This treatment option should be offered to this group of patients.