Efectividad de la simvastatina tópica e inyectable contra hidrocoloide en la epitelización de heridas de espesor parcial en un modelo animal / Topic and subdermic injection of simvastatin for wound reepithelialization versus hydrocolloid dressing in an animal model

Introducción y Objetivos. En la actualidad existen una gran cantidad de apósitos y coberturas para el tratamiento de las heridas de espesor parcial; la elección depende de la experiencia del cirujano y sobre todo de la disponibilidad y recursos existentes. Las estatinas (inhibidores de la Hidroxi-Metil-CoA reductasa) se usan en el tratamiento de la hipercolesterolemia, aunque recientemente se han encontrado propiedades antinflamatorias, estimulantes de la angiogénesis y linfangiogénesis, antifibróticas, y especialmente estimuladoras de los queratinocitos. Nos proponemos comparar la epitelización e inflamación de las heridas en un modelo animal con la aplicación de simvastatina tópica, inyectable y apósito de hidrocoloide. Material y Método. Empleamos 20 ratas Wistar en 4 grupos, cada uno con 5 ratas, a las que practicamos heridas de espesor parcial por dermoabrasión en el dorso. A cada grupo se le aplicó gasa de organza, apósito de hidrocoloide, simvastatina tópica y simvastatina inyectada, respectivamente. Descubrimos las heridas a los 7 días y sacrificamos a los animales. Tomamos biopsias de las heridas y comparamos el grado de epitelización de cada grupo. Resultados. Al comparar la simvastatina en preparación tópica con el grupo de gasa de organza y el grupo de apósito de hidrocoloide, encontramos un mayor porcentaje de epitelización en el grupo tratado con simvastatina tópica, con una diferencia estadísticamente significativa (p<0.05). Las heridas tratadas con simvastatina tópica demostraron menor inflamación, menor fibrosis, mayor epitelización (queratinocitos), mayor cantidad de fibroblastos y no presentaron costra, de forma estadísticamente significativa. Conclusiones. La cobertura de heridas de espesor parcial con simvastatina tópica es más efectiva en epitelización y efecto antinflamatorio, en comparación con la simvastatina inyectable, los apósitos de hidrocoloide y las gasas de organza (AU)

Background and Objective. There are various alternatives and dressings for split thickness skin wounds, the choice depends on the experience and training of each surgeon. Statins, which are normally used for the treatment of hypercholesterolemia, have proven to induce and antinflammatory effect on wound keratinocytes, which provokes a faster re-epithelialization on in vitro studies. Our aim was to compare epithelialization and anti-inflammatory properties in split thickness wounds of rats, using hydrocolloid dressings versus a simvastatin based emulsion or simvastatin injected. Methods. We used 20 Wistar rats divided in 4 groups in which split thickness wounds were induced in the dorsum by dermoabrasion. Each group was treated with organza gauze, hydrolloid dressings, simvastatin cream and injectable simvastatin in the wound, respectively. Seven days later, the wounds were exposed and the animals where sacrificed. The wounds were analyzed with digital photographs and biopsies where taken in order to compare the epithelization percentage in each group. Results. There was a statistically significant improvement (p<0.05) in wound rate epithelialization in the rats treated with topic simvastatin. The wounds treated with topic simvastatin had less inflammation, less fibrosis, no evidence of crusting and a higher number of fibroblast. Conclusions. Split thickness skin wounds coverage with topical simvastatin is most effective in epithelialization and antinflamatory effect compared with injectable simvastatin, organza gauze dressings and hydrocolloid dressings (AU)

Neurally mediated syncope and cardiac beta-adrenergic receptor function.

To evaluate the mechanism of neurally mediated syncope (NMS), we investigated basal autonomic nerve function using a conventional pharmacological method and [123I]-metaiodobenzyl-guanidine (MIBG) single photon emission computed tomography (SPECT). Nine patients with NMS, whose syncope was induced by head-up tilt test with or without isoproterenol, underwent [123I]-MIBG SPECT. Eight of nine NMS patients showed reduced myocardial uptake (two patients, diffuse; four patients, anteroseptal and inferior; one patient, anteroseptal; one patient, inferior). In the study of pharmacological autonomic nervous function test, atropine sulfate (atr.) (0.04 mg/kg), isoproterenol (isp.) (5 x 10(-3) microg/kg/min), propranolol (prop.) (0.2 mg/kg), phenylephrine (phenyl.) (0.4 microg/kg/min), and phentolamine (phent.) (0.2 mg/kg) were successively administered to patients with NMS (n = 5) and control subjects (n = 5). The heart rate (HR) after atr. and prop., and systolic blood pressure (SBP) after phent. were defined as intrinsic HR (IHR) and intrinsic SBP (ISBP). Parasympathetic activity (increase in HR by atr.), beta-sympathetic tone (HR after atr. minus IHR), beta-sensitivity (change in HR by 1 microg isp./kg/min), beta-secretion (beta-tone/beta-sensitivity), alpha-sympathetic tone (SBP before phenyl. minus ISBP), alpha-sensitivity (change in SBP by 1 microg phenyl./kg/min) and alpha-secretion (alpha-tone/alpha-sensitivity) were also calculated. The beta-secretion was decreased (0.0027+/-0.0008 versus 0.0060+/-0.0004 microg/kg/min/isp.; p < 0.05), while the beta-sensitivity was increased (5850+/-947 versus 3150+/-292 beats/microg/kg/min isp.; p < 0.05) in NMS compared with control subjects. In the other indexes, there were no significant differences between two groups. The results of the present study suggest that increased beta-sensitivity may contribute hypercontraction of left ventricles, which might partially explain the mechanism of NMS.

Operative management of abdominal aortic aneurysm with left-sided inferior vena cava.

Abdominal aortic aneurysm with left-sided inferior vena cava (IVC) is rare. In preoperative examination, it is important to conduct roentgenologic studies and determine any venous anomalies. Proximal anastomosis is technically difficult because the IVC crosses to the right on the aneurysmal neck. In this case of a 71-year-old Japanese man, proximal anastomosis was conducted safely under wide vena cava mobilization and contraction in the superior direction. In vein resection, vessels should be reconstructed because vein communication is not methodical.

Closure of calcified patent ductus arteriosus.

Patent ductus arteriosus (PDA) in adults is occasionally associated with calcification and pulmonary hypertension, for which an anterior approach through a median sternotomy with cardiopulmonary bypass is often used. Sutures are placed without circulatory arrest by using a transpulmonary balloon catheter as an occluder. To secure the suture tie, we used Nélaton's catheters as tourniquets.

Oral administration of fluoroquinolones in the treatment of typhoid fever and paratyphoid fever in Japan.

OBJECTIVE: To study the adverse reactions and therapeutic effects of fluoroquinolones to investigate whether they can be used for the treatment of patients with typhoid fever and paratyphoid fever. METHODS: The adverse reactions and therapeutic effects of fluoroquinolones were studied retrospectively in patients with typhoid fever and paratyphoid fever. PATIENTS: 58 patients (54 Japanese) with typhoid fever, 42 patients (41 Japanese) with paratyphoid fever, and 1 Japanese patient with both typhoid fever and paratyphoid fever, who were admitted in hospitals in Tokyo, Kawasaki, Yokohama, Kyoto, and Osaka from 1995 to 1998 and treated with fluoroquinolones. RESULTS: Almost 80% of the patients were treated with tosufloxacin (TFLX) and the remaining 20 % were treated with norfloxacin, ciprofloxacin, levofloxacin, or sparofloxacin. Side effects (nausea, urticaria, aphthous stomatitis) and elevation of serum amylase were found in 3.6% and 8.3 % of patients treated with TFLX, respectively, but these adverse reactions disappeared in all of these cases either with or without a change in the drug used. No adverse reactions were found in patients treated with the other fluoroquinolones. The clinical and bacteriological effects of these drugs were adequate. CONCLUSION: Though further studies still need to be performed on the fluoroquinolones other than TFLX, we can preliminarily conclude that fluoroquinolones are safe drugs and they can be recommended for the initial therapy of patients with typhoid fever and paratyphoid fever.

[A case of AIDS complicated with liver tuberculosis].

We experienced a double infection of tuberculosis and amebiasis of the liver. A 28 year old male with AIDS was admitted to our hospital because of severe diarrhea and liver abscess by Entamoeba histolytica. In spite of improvement of the diarrhea and liver abscess by the therapy against E. historicica, serum levels of gamma-GTP and ALP remained high and hepatosplenomegaly gradually increased. A liver biopsy was performed. Pathology showed a granulomatous lesion with Langhans' giant cells. From this specimen, IS6110 gene, a specific DNA for Mycobacterium tuberculosis was detected by PCR method. After anti-tuberculosis treatment was given for 6 months the increased serum gamma-GTP, ALP decreased and hepatosplenomegaly diminished.

Effects of phosphodiesterase inhibitors after coronary artery bypass grafting.

The aim of this study was to estimate the postoperative effects of phosphodiesterase (PDE) inhibitors (milrinone and olprinone) after coronary artery bypass grafting (CABG). To prevent hypotension caused by the PDE inhibitors, low dose of catecholamines were used concomitantly. A total of 34 elective CABG cases were tested. In 12 cases, 0.25 microg kg(-1) min(-1) of milrinone, 3 microg kg(-1) min(-1) of dobutamine (DOB) and dopamine (DOA) were used concomitantly (Group-M). In another 10 patients, 0.1 microg kg(-1) min(-1) of olprinone and the same doses of the catecholamines were infused (Group-O). As a control, the same doses of DOA and DOB only were administered in 12 patients (Group-C). When the pump flow of the cardiopulmonary bypass (CPB) decreased to half, these drugs were given in all groups. Hemodynamics were recorded before CPB, just after the operation, and 3, 6, 12, 24, 48 and 72 h after the operation. Both milrinone and olprinone increased the cardiac index and decreased systemic vascular resistance to almost the same degree. Olprinone decreased mean aortic and pulmonary artery pressures, and also significantly reduced the preload of both right and left heart compared with milrinone. Significant hypotension was not detected due to the concomitant usage of low-dose catecholamines. This concomitant usage of PDE inhibitors and catecholamines allowed easy weaning from CPB, demonstrating excellent hemodynamics after CABG. Good oxygen demand and supply balance were maintained in peripheral tissue. These results suggest that these new PDE inhibitors may be effective not only for weaning from CPB but also for post-cardiotomy cardiogenic shock.

[A case of bacillary dysentery caused by new quinolone-resistant Shigella flexneri 2a].

A 73-year-old male was admitted to our hospital because of detection of Shigella flexneri 2a from his stool. Antimicrobial treatment with levofloxacin (LVFX) was started, but could not eliminate the organism in the stool. In the examination of drug susceptibility, this strain was highly resistant to all new quinolones. The minimal inhibitory concentration of norfloxacin, ofloxacin and ciprofloxacin to this strain was 12.5 micrograms/ml, 6.25 micrograms/ml and 6.25 micrograms/ml, respectively. The dual mutations were detected in the codon 83 and 87 of the gyrA gene by sequencing the quinolone-resistance determining region (QRDR). There was, however, no significant difference between the intracellular uptake of ciprofloxacin in this strain and in the ciprofloxacin-sensitive strain. The amount of ciprofloxacin in this strain unchanged when carbonyl cyanide m-chlorophenyl hydrazone (CCCP) was added. These results suggest that the advanced resistance in Shigella flexneri against new quinolones could be acquired by only this dual mutations without the change of the active efflux mechanism.

Effects of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass.

To estimate the effectiveness of concomitant usage of milrinone and catecholamine for weaning from cardiopulmonary bypass (CPB), a clinical study was made, in elective coronary artery bypass grafting (CABG) cases. 24 consecutive patients underwent elective CABG in our institute. In all cases, moderate hypothermia and cardioplegic(St. Thomas solution) cardiac arrest were performed. In 12 cases, continuous intravenous 0.25 microgram/kg/min of milrinone, 3 micrograms/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly as inotropic agents (Group-I). The same initial doses of catecholamine (DOB and DOA) as the Group-I were administered in another 12 patients (Group-II). When the pump flow of CPB decreased to a half, these drugs were administered in both groups. Hemodynamic data were measured before CPB, just after operation, 3, 6, 12, 24, 48, and 72 hours after operation. There were no significant differences in aortic and pulmonary artery pressure between both groups. However, cardiac index (CI) of the Group-I demonstrated significantly (p < 0.01) higher values than that of Group-II until 24 hours after surgery. Systemic vascular resistance index (SVRI) of the Group-I demonstrated significantly (p < 0.01) lower value than that of Group-II from 3 to 12 hours after operation. There were no significant differences in oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. These results suggested that concomitant usage of milrinone and low dose catecholamine increased CI and decreased SVRI, and made weaning from CPB very easy, demonstrating excellent hemodynamics. This high potential phosphodiesterase inhibitor may be suitable for not only weaning from CPB but also post-cardiotomy cardiogenic shock.

Inhibition of M-type K+ current by linopirdine, a neurotransmitter-release enhancer, in NG108-15 neuronal cells and rat cerebral neurons in culture.

The effect of linopirdine, a neurotransmitter-release enhancer, on the M-type K+-current, IK(M), was examined in NGPM1-27 cells, mouse neuroblastomaxrat glioma NG108-15 cells transformed to express m1-muscarinic acetylcholine (ACh) receptors, using the nystatin-perforated patch-recording mode under voltage-clamp conditions. The application of linopirdine induced the inward current associated with an inhibition of IK(M), which mimics an excitatory part of the ACh-induced responses in NGPM1-27 cells. The affinity of linopirdine for the inhibition of IK(M) was 24.7 microM in NGPM1-27 cells. In the presence of linopirdine, ACh failed to evoke a further inward current, but ACh still elicited an outward current, thus suggesting that the Ca2+-dependent K+ current is rather insensitive to linopirdine. Linopirdine also inhibited another voltage-gated potassium current (IK(V)) at the concentration of 72.3 microM. Finally, the inhibitory effect of linopirdine on IK(M) was confirmed in pyramidal neurons acutely dissociated from the rat cerebral cortex at 35.8 microM. The results suggest that linopirdine is thus considered to be an inhibitor of some type of K+ channels in both NGPM1-27 cells and the rat cerebral neurons.

[A case of coronary arterial fistula originating from both coronary artery and draining to the right atrium].

We encountered a case with bilateral fistulas of coronary arteries into the right atrium, a rare cardiac anomaly. The case was a 17-year-old woman, who visited our hospital at the age of 11 because of fever. At that time, the patient was diagnosed as having a left coronary artery-right atrial fistula through cardiac catheterization (CAG). When the patient developed staphylococcus infected endocarditis at the age of 16, a thick fistula of the coronary artery, directly running from the deformed left coronary arterial sinus, a fistula of the left circumflex branch, and also a fistula of the right coronary artery into the right atrium were detected by CAG. The outlets of these fistulas were closed from the inside of the right atrium under artificial cardiopulmonary circulation and cardiac arrest, and each fistula was ligated at the outside of cardiac chambers. At that time, we took particular care that any branch of the sinuatrial node was not injured. Although all fistulas were confirmed to be closed by postoperative CAG, and no evidence of ischemia was detected by myocardial scintigraphy, deformity of the left coronary arterial sinus remained, requiring further follow up.

[A case of brain abscess accompanied with sudden-onset hemiplegia as initial manifestation].

A 58-year-old male experienced a sudden stroke-like onset of right hemiplegia and numbness of his right upper limb while engaged in his desk-work on April 7, 1997. He had a past history of diabetes mellitus and hyperlipidemia. On admission, he had no fever and the blood pressure was 140/70 mmHg. General physical examination was unremarkable. Neurological examination showed 4/5 strength of his right unilateral extremities and numbness of his right upper limb. Clinical features and computed tomography (CT) without contrast medium at the onset of hemiplegia suggested a stroke. Seven days after admission, his consciousness worsened and body temperature fluctuated between 37 and 38 degrees C. Subsequent Gd-enhanced magnetic resonance (MR) which demonstrated an irregular shaped ring-enhancement lesion and lumbar puncture 9 days after admission was compatible with the diagnosis of brain abscess. Surgical drainage confirmed the presence of brain abscess due to alpha-streptococcus. It improved following surgical drainage and antibiotic therapy with PAPM.BP 2 g/day and PIPC 4 g/day. An afebrile patient of sudden stroke-like onset may be a rarity to be added to the differential diagnosis of brain abscess.

Post-operative effects of olprinone after coronary artery bypass grafting.

The aim of this study was to test the effects of olprinone after coronary artery bypass grafting (CABG). In order to prevent hypotension caused by olprinone, low doses of catecolamines were used concomitantly. Total 22 elective CABG cases were evaluated. In all cases, moderate hypothermia and cardioplegic cardiac arrest were performed. In 10 cases, continuous intravenous 0.1 microg/kg/min of olprinone, 3 microg/kg/min of dobutamine (DOB) and dopamine (DOA) as the initial doses, were used concomitantly (Group I). As a control, the same initial doses of catecolamine (DOB and DOA) of Group I were administered in another 12 patients (Group II). When the pump flow of cardiopulmonary bypass (CPB) was decreased to half, these drugs were administered in both groups. Hemodynamics were recorded before CPB, just after the operation and 3, 6, 12, 24, 48, and 72 hours after the operation. Three hours after the operation, both mean aortic pressure (AoP) and pulmonary artery pressures (PAP) of Group I demonstrated significantly lower values than those of Group II. Cardiac index (CI) of Group I showed significantly higher values than that of Group II until 6 hours after surgery. The systemic vascular resistance index (SVRI) of Group I indicated a significantly lower value than that of Group II until 24 hours after the operation. Pulmonary capillary wedge pressure (PCWP) of Group I demonstrated a significantly lower value than that of Group II. There were no significant differences in urine output, oxygen delivery (DO2) and oxygen consumption (VO2) between both groups. Olprinone increased CI and decreased SVRI, and it showed easy weaning from CPB, demonstrating excellent hemodynamics after CABG. These results suggested that this new phosphodiesterase inhibitor may be effective for not only weaning from CPB but also post-cardiotomy cardiogenic shock.

[Toxic shock-like syndrome after acupuncturation].

A 80-year-olkd male was admitted to our hospital because of severe pain and swelling on his left lower leg on January 23, 1996. He had received an acupuncture to both legs because of intermittent claudication once a week from July, 1995 to January 18, 1996. On the next day of the last acupuncture, pain and swelling on his left leg appeared. On admission, his left leg showed diffuse swelling and redness with blisters. We diagnosed this patient as toxic shock-like syndrome (TSLS), based on the rapid exacerbation of the skin changes, necrotizing superficial fasciitis, multiple organ failure with shock, and the detection of group A streptococcus from culture samples obtained from both skin blister and necrotic fascia. He recovered from the disease by amputation of the involved leg and antibiotic therapy. Acupuncture could have been the cause of streptococcal infection.