Perineal body anatomy seen by three-dimensional endovaginal ultrasound of asymptomatic nulliparae.

AIM: The perineal body (PB) plays an important role in supporting the pelvic floor and the posterior vaginal wall, but its attachments and relationships are still debated. This study aimed to assess the normal anatomy of the PB using high-resolution three-dimensional endovaginal ultrasound (3D-EVUS) in asymptomatic nulliparae. METHOD: To validate the identification of perineal structures, 3D-EVUS was initially performed on nulliparous cadavers. Fresh frozen pelves were prepared and echogenic structures thought to be the PB, the external anal sphincter, the superficial and deep transverse perineii, pubovaginalis, puboperinealis, puboanalis, puborectalis and iliococcygeus muscles were tagged with biopsy needles, and marked with indigo carmine dye for localization during dissection. In the second part of the study, consecutive asymptomatic nulliparae were prospectively imaged with the same ultrasound modality. Interrater reproducibility was assessed off-line from stored 3D US volumes using a standardized technique. RESULTS: Five fresh frozen pelves and 44 asymptomatic nulliparae were assessed with 3D-EVUS. The PB was seen as an ovoid structure of mixed echogenicity between the rectum and vagina. It appeared to be divided into a superficial level, in contact with the external anal sphincter, the bulbospongiousus and the superficial transverse perineii muscle and a deep level, in contact with puboperinealis and puboanalis muscles. Interobserver repeatability was excellent for the measurements of PB height [intraclass correlation coefficient (ICC) 0.927], PB depth (ICC 0.969) and PB width (ICC 0.932). CONCLUSION: The PB is divided into two levels with different anatomical relationships with the pelvic floor muscles. 3D-EVUS yields reproducible assessment of this complex structure.

Laparoscopic vs open approach for acute cholecystitis in octogenarians. A prospective multicenter observational nationwide study.

BACKGROUND: The world population is aging, with octogenarians expected to reach over 400 million by 2050. Acute cholecystitis is a serious complication in the elderly. Age is not a contraindication for emergency cholecystectomy, an option that can both save lives and preserve quality of life. METHODS: The present study aimed to compare open and laparoscopic surgical approaches. Over six months, 38 emergency surgery units enrolled all consecutive octogenarians with acute cholecystitis undergoing cholecystectomy. Postoperative outcomes were compared after propensity score matching analysis. RESULTS: The study included 212 patients (84 years [81-86], 47.2% women). The open approach was used in 32.1% of patients, and the laparoscopic approach in 67.9%. After propensity score matching, a decrease in hospital stays (open, 8 days [6-13]; laparoscopic, 5 days [4-8]; P < .001), 30-day morbidity (open, 48.5%; laparoscopic, 26.5%; P = .01), and 30-day mortality (open, 13.2%, laparoscopic, 1.5%; P = .02) was found. Among the specific postoperative complications, a decrease in septicemia (open, 14.7%; laparoscopic, 0%; P = .001) was observed. CONCLUSIONS: Laparoscopic approach was used in two out of three octogenarians. After propensity score matching, octogenarians undergoing laparoscopic approach had shorter length of hospital stay, fewer 30-day postoperative complications, fewer episodes of septicemia, and less 30-day mortality than octogenarians undergoing open approach. These findings suggest that the laparoscopic approach may be the preferred choice for octogenarians with acute cholecystitis undergoing cholecystectomy.

Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial.

INTRODUCTION: Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions. OBJECTIVES: The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity. PATIENTS AND METHODS: We performed a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis. The patients were randomized to receive, in addition to their standard treatment, Polypodium leucotomos extract or placebo (both in capsule form) for 6 months. The percentage of days on which topical corticosteroids and other atopic dermatitis treatments were used was calculated. RESULTS: Use of Polypodium leucotomos extract did not significantly reduce the mean (SD) percentage of days on which topical corticosteroids were used (11% [12%] vs 12% [11%] for placebo). A significant reduction was, however, observed for oral histamine use (median percentage of days, 4.5% in the Polypodium leucotomos group and 13.6% in the placebo group [P= .038]). The percentage of patients who used oral antihistamines was also lower in the Polypodium leucotomos group. CONCLUSION: Long-term treatment with Polypodium leucotomos extract has benefits for children and adolescents with atopic dermatitis who require pharmacologic treatment to reduce inflammation and relieve itching.

Prediction of peritoneal soiling in acute appendicitis with simple clinical and laboratory data. Prospective, multicenter, cohort study of 2,645 adult patients nationwide.

BACKGROUND AND AIMS: In order to facilitate the preoperative prediction of complicated appendicitis, we propose a complementary approach by selecting an endpoint defined by the intraoperative finding of peritoneal soiling (PS). METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending emergency general surgery patients on a 24-h, 7-days a week basis, enrolled consecutive adult patients requiring appendectomy. Patients were stratified according to the absence or the finding of PS during the surgical procedure. RESULTS: A total of 2645 patients were included; median age (IQR) was 35 (22-51) years, 44.3% were female. The laparoscopic approach was used in 70.8% of appendectomies. In a third of patients (31.7%), there was PS with pus around the appendix, or bowel contents, free pus, or blood in the peritoneal cavity. To develop the prediction model, 1764 patients were randomly selected for the derivation cohort and the remaining 881 patients were assigned to the validation cohort. On multivariable logistic regression analysis of all patients, two clinical variables (age, and pulse) and three laboratory variables (serum urea, serum sodium, and white blood cell count) were individually associated (P < .05) with a greater probability of having PS (Hosmer-Lemeshow chi, 1.63; P = .99; C-statistic, 0.7). Based on the multivariable regression model, both static and dynamic nomograms were developed for the prediction of PS in patients with acute appendicitis. CONCLUSIONS: The entry of simple clinical and laboratory variables in the dynamic nomogram may be useful in guiding the initial management of patients with acute appendicitis in resource-limited settings.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Ketanserin potentiates morphine-induced antinociception mediated by kappa-receptor activation.

How can we treat patients with reduced morphine doses without loosing the pain killing effect or morphine antinociceptive effects (MAE)? To address this question, we hypothesized that serotonin (5-HT2) receptor antagonism could enhance MAE mediated by kappa-opioid receptors. We pretreated mice with ketanserin, a 5-HT2 receptor antagonist, and measured the morphine dose required to observe analgesia. The morphine dose effective in 50% of animals (ED(50)) was reduced from 4.7 to 1.3mg/kg, and the morphine dose effective in 100% of animals (ED(max)) from 13.7 to 2.5mg/kg. Ketanserin has a similar enhancer effect when morphine, which has a dual role via mu and kappa receptors, was substituted by the antinociceptive spiradoline, a selective κ-opioid agonist. At a morphine dose of 3.5mg/kg, 30% of the mice showed antinociceptive behaviour, rising to 100% when ketanserin was co-administered and then reduced to 20% in the presence of nor-binaltorphimine, a kappa-opioid receptor antagonist. Our data strongly suggests a serotonergic inhibition of the kappa-opioid component of MAE and the possibility that this serotonergic inhibition could be reversed through 5-HT2 receptor antagonism.

Update of the Atlanta Classification of severity of acute pancreatitis: should a moderate category be included?

BACKGROUND: Persistent and multiple organ failure (POF and MOF) are predictive of death in acute pancreatitis (AP). Local complications without organ failure are associated with morbidity but a low risk of mortality. AIM: To design a three-category classification of AP severity and to compare it with the Atlanta Classification (AC) in terms of morbidity and mortality. METHOD: Severe AP was defined as death, POF (>48 h) or MOF. Moderate AP was defined as the presence of acute collections and/or pancreatic necrosis. Mild AP was defined by exclusion. We compared this classification with AC in 144 episodes of AP. RESULTS: In the three-category classification, severe AP was associated with significantly more frequent intensive care unit admission, invasive treatment and mortality than moderate and mild AP (p < 0.01). Severe AP patients required longer hospital stay and more nutritional support than mild AP patients (p < 0.01). Patients with moderate AP had significantly longer hospital stay and more need for nutritional support than patients with mild AP (p < 0.01). Five patients died, all of them with MOF and/or POF. CONCLUSIONS: A three-category classification distinguishes three homogeneous groups of severity.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

OBJECTIVE: to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. MATERIAL AND METHODS: prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. RESULTS: median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). CONCLUSION: MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

[A cost-effectiveness study of hepatic venous pressure gradient measurement in the secondary prevention of variceal bleeding]. / Estudio coste-efectividad sobre la medición del gradiente de presión venosa hepática en la profilaxis secundaria de la hemorragia digestiva varicosa.

OBJECTIVE: variceal rebleeding is common following a first episode of hemorrhage in cirrhotic patients. The objective of this study was to determine the cost-effectiveness of monitoring hepatic venous pressure gradient (HVPG) to guide secondary prophylaxis. METHODS: we created a Markov decision model to calculate cost-effectiveness for two strategies: Group 1: HVPG monitoring to decide treatment -when portal pressure was reduced by at least 20 percent or HVPG was less than 12 mmHg after beta-blocker administration, patients received beta-blockers; when portal pressure did not meet these criteria therapy was endoscopic band ligation. Group 2: in this group there was no monitoring of HVPG. Patients with large varices received treatment with beta-blockers combined with EBL; patients with small varices received beta-blockers plus isosorbide mononitrate. RESULTS: there was no recurrent variceal bleeding in group 1 for good responders, and for 17% of poor responders. In group 2 a 25% rebleeding rate was detected in patients with small varices and 13% for those with big varices. Overall cost in group 1 was 14,100.49 euros, and 14,677.16 in group 2. CONCLUSIONS: HVPG measurement is cost-effective for the secondary prophylaxis of variceal bleeding.

Translocation of bacterial DNA from Gram-positive microorganisms is associated with a species-specific inflammatory response in serum and ascitic fluid of patients with cirrhosis.

Translocation of bacterial-DNA in patients with cirrhosis and ascites triggers an innate immune response. Identification of characteristics to which this response is sensitive is relevant from a clinical standpoint. The aim of this study has been to determine if the proinflammatory immune response established in vivo in cirrhotic patients with ascites as a consequence of bacterial-DNA translocation is related to the identified bacterial species and their frequency of cytosine-guanosine content in serum and ascitic fluid. Patients with advanced cirrhosis and ascites were included in the study and distributed into groups I and II according to the absence or presence of bacterial-DNA translocation, respectively. Serum and ascitic fluid levels of proinflammatory cytokines after normalization of bacterial-DNA concentration and the activated form of nuclear factor-kappa B in ascitic fluid pellets were measured by enzyme-linked immunosorbent assay techniques. Translocation of bacterial-DNA with higher cytosine-guanosine content induced the highest cytokine response, which was higher than that in patients without bacterial-DNA translocation. The activated form of nuclear factor-kappa B in ascitic fluid pellets of patients with bacterial-DNA translocation was greater in patients with higher bacterial-DNA cytosine-guanosine content, whereas the amount of total nuclear factor-kappa B remained unaltered. Bacterial-DNA translocation induces a marked immune reaction in vivo in patients with advanced cirrhosis and ascites which is related, among other factors, to the bacterial-DNA cytosine-guanosine content. Therefore, the host's immune response to bacterial-DNA translocation constitutes a species-specific phenomenon.

Functional status of beta-2-adrenoceptor in isolated membranes of mature erythrocytes from patients with cirrhosis and oesophageal varices.

Propranolol is a widely used drug for prophylaxis of variceal bleeding in patients with cirrhosis, but not all patients show an adequate clinical response. This variability may be in relation to beta adrenoceptor activity, but no information is available in this setting. Thirty-nine patients with advanced cirrhosis and presence of oesophageal varices were sequentially included. We studied the function of beta-2-adrenoceptor in isolated membranes of mature erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production before and after isoproterenol. Blood samples obtained from 11 healthy volunteers were used as control. Patients showed a six-fold increase in the mean basal cAMP production as compared to healthy volunteers. Isoproterenol produced a small, non-significantly and highly variable increase in the AC activity in patients compared with controls. cAMP values remain stable after three months of continuous treatment with oral beta-blockers in both groups. Patients without antecedent of variceal bleeding or with an active alcohol intake showed a significantly higher isoproterenol effect. In conclusion, beta-receptor function in human erythrocytes membranes is altered in patients with cirrhosis and oesophageal varices.

Cross-reactivity among amide-type local anesthetics in a case of allergy to mepivacaine.

Among the various adverse reactions to local anesthetics, IgE-mediated reactions, particularly to the more commonly used amide group, are extremely rare. We report the case of a 39-year-old man who suffered itching and generalized urticaria with facial angioedema 15 minutes after administration of mepivacaine. Skin tests revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine, but negative reactions to bupivacaine and levobupivacaine. Furthermore, double-blind placebo-controlled subcutaneous challenge with bupivacaine and levobupivacaine was well tolerated. We conclude that an extensive allergologic study must be carried out in rare cases of true allergic reaction to amide-type local anesthetics in order to rule out cross reactivity.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in patients with cirrhosis and variceal bleeding significantly improves the control of the bleeding episode, and hemodynamic data have shown that a dosage of 500 mg/h allows a more marked reduction of portal pressure versus the usual dosage of 250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved outcome. METHODS: sixty-two patients with variceal bleeding were included in the study. Patients were randomized to receive the usual dosage of SMT (group I: 250 mg/h), or a double dosage (group II: 500 mg/h), together with emergency endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was similar in both groups of patients. Early rebleeding was less frequent in patients receiving double vs. single dosage of SMT (p = 0.06). When considering patients with advanced liver disease (Child-Pugh B or C) early rebleeding was significantly less frequent in patients receiving the 500 mg/h dose of SMT (39 vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h) in association with emergency sclerotherapy in patients with cirrhosis and esophageal hemorrhage significantly decreases the rate of early rebleeding in patients with more advanced stages of liver disease.

Variations of pharmacokinetics of drugs in patients with cirrhosis.

Liver cirrhosis is the end stage of many different chronic liver diseases and is becoming an important cause of mortality and morbidity across the world. In theory, the numerous physiopathological changes suffered by these patients warrant relevant pharmacokinetic changes in most drugs. However, the influence of these changes on the efficacy and toxicity responses of patients with cirrhosis have been evaluated by few clinical trials and observational studies. As a consequence, therapeutic decisions in these patients are usually complex and subject to uncertainties. In this article, we review the regulatory guidelines to study responses to drugs according to pharmacokinetic variability and the published information that is useful for guiding the dosage adjustment of frequently used drugs in patients with cirrhosis (antivirals, antibiotics, analgesics, etc.) to obtain the best risk-benefit ratio.

Norfloxacin decreases bacterial adherence of quinolone-resistant strains of Escherichia coli isolated from patients with cirrhosis.

BACKGROUND: Long-term administration of norfloxacin is recommended for secondary prophylaxis of spontaneous bacterial peritonitis in cirrhosis, but it may be associated with the development of quinolone-resistant bacteria in stools. However, these bacteria rarely cause infections. AIM: To assess bacterial adherence of either quinolone-sensitive or -resistant Escherichia coli obtained from stools of cirrhotic patients, as one of the main virulence factors, and its variations when sub-minimum inhibitory concentration of norfloxacin were added to the medium. METHODS: E. coli strains were co-cultured with oral epithelial cells obtained from patients in presence/absence of norfloxacin. Bacterial adherence was measured as percentage of cells exhibiting positive adherence and the number of bacteria attached to epithelial cells. RESULTS: 37 sensitive and 22 resistant E. coli strains were studied. Bacterial adherence was similar in both series (78% vs. 81%, P = N.S.), and these percentages were similarly and significantly reduced when subminimum inhibitory concentration of norfloxacin was added to the culture medium (P < 0.001). CONCLUSIONS: Bacterial adherence of E. coli obtained from patients with cirrhosis is unrelated to the sensitivity/resistance to quinolones, and is similarly reduced in both cases when subminimum inhibitory concentration of norfloxacin is added to the medium.

Treatment with pegylated interferon alpha-2b and ribavirin in patients unresponsive to previous treatments with standard interferon as monotherapy or combined with ribavirin.

BACKGROUND: Little information is available on the effect of pegylated interferon (PEG) and ribavirin (RBV) in patients with chronic hepatitis due to virus C (CHC) who were non-responders to previous treatment. OBJECTIVES: To evaluate response to treatment in patients who were non-responders to previous treatment. METHODS: One hundred and twenty-four patients who were non-responders to previous treatment were included. All patients were treated with PEG alpha 2b interferon (dose: 1.5 mg/kg body weight) and RBV (weight-dependent dosage). A qualitative PCR of virus C after six months was evaluated. In those in whom this was positive, treatment was discontinued; in those who were negative treatment was continued to the end of the year. RESULTS: Response following treatment (RFT) was 35.4% (44 patients), and sustained viral response (SVR) 29.8% (37 patients). No relation was observed between RFT, SVR and any previous treatment. RFT was dependent on low initial viremia and SVR was significantly and independently related to low serum hepatitis C RNA and a non-1 genotype. In general, treatment was well tolerated. Medication was discontinued in 5 patients, and doses reduced in 18. CONCLUSION: On retreatment with PEG and RBV a SVR of 29.8% was achieved in patients who had not responded to previous treatment, so its use in this group of patients is indicated.

Dual-specificity phosphatase 6 regulates CD4+ T-cell functions and restrains spontaneous colitis in IL-10-deficient mice.

Mitogen-activated protein kinase (MAPK) phosphatases are dual-specificity phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues within MAPKs. DUSP6 preferentially dephosphorylates extracellular signal-regulated kinases 1 and 2 (ERK1/2) rendering them inactive. Here, we study the role of DUSP6 in CD4(+) T-cell function, differentiation, and inflammatory profile in the colon. Upon T-cell receptor (TCR) stimulation, DUSP6 knockout (Dusp6(-/-)) CD4(+) T cells showed increased ERK1/2 activation, proliferation, T helper 1 differentiation, and interferon-γ production, as well as a marked decrease in survival, interleukin- 17A (IL-17A) secretion, and regulatory T-cell function. To analyze the role of DUSP6 in vivo, we employed the Il10(-/-) model of colitis and generated Il10(-/-)/Dusp6(-/-) double-knockout mice. Il10(-/-)/Dusp6(-/-) mice suffered from accelerated and exacerbated spontaneous colitis, which was prevented by ERK1/2 inhibition. ERK1/2 inhibition also augmented regulatory T-cell differentiation in vitro and in vivo in both C57Bl/6 and Dusp6(-/-) mice. In summary, DUSP6 regulates CD4(+) T-cell activation and differentiation by inhibiting the TCR-dependent ERK1/2 activation. DUSP6 might therefore be a potential intervention target for limiting aberrant T-cell responses in T-cell-mediated diseases, such as inflammatory bowel disease.

Tobramycin penetration into epithelial lining fluid of patients with pneumonia.

OBJECTIVE: To study the penetration of tobramycin in lung tissue evaluated as the concentration in epithelial lining fluid and to characterize the time course of the drug in the treatment of patients with pneumonia. METHODS: The subjects were 16 patients with pneumonia and taking tobramycin who had clinical indications for bronchoscopy. Bronchoscopy with bronchoalveolar lavage of the pneumonic area was performed once on each patient 1/2%, 2, 4, or 8 hours after the previous tobramycin dose. Urea was used as an endogenous marker for quantification of epithelial lining fluid obtained at bronchoalveolar lavage. Tobramycin concentrations in serum were measured for all patients at the aforementioned 4 time points. Tobramycin concentration was determined by means of fluorescent polarization immunoassay modified for bronchoalveolar samples. RESULTS: Levels of tobramycin in the fluid of the epithelial lining were 2.33+/-0.5 at 1/2 hour, 1.67+/-0.6 at 2 hours, 1.62+/-1.19 at 4 hours, and 0.77+/-0.38 microg/mL at 8 hours. The ratio of epithelial lining fluid to serum concentration of tobramycin was 0.30+/-0.03 at 1/2 hour, 0.42+/-0.16 at 2 hours, 0.64+/-0.37 at 4 hours, and 1.53+/-0.76 at 8 hours. The ratio at peak serum time was similar to that reported for tobramycin and netilmicin. CONCLUSIONS: High peak serum concentrations of tobramycin are necessary to obtain microbiologically active concentrations at the alveolar level. The fluid of the epithelial lining constitutes a deep compartment for aminoglycosides. The disappearance of tobramycin was slower than at the serum level.

Long-term management of homozygous protein C deficiency: replacement therapy with subcutaneous purified protein C concentrate.

We present the case of a full-term newborn in whom purpura fulminans developed shortly after birth. A diagnosis of homozygous protein C deficiency was established based upon undetectable plasma protein C activity and antigenemia in the newborn infant, and was later confirmed by protein C gene analysis. Specific replacement therapy with intravenous protein C concentrate was started 9 days after birth. This rapidly led to the complete regression of cutaneous lesions and consumption coagulopathy. After stabilization, oral anticoagulation was initiated in association with prophylactic treatment with intravenous protein C concentrate. However, oral anticoagulation was finally abandoned as the patient presented several thrombotic and hemorrhagic episodes clearly related to difficulties with anticoagulation. Due to the hazards related to prolonged venous access, we are currently using subcutaneous infusion of protein C concentrate for the long-term management of this condition, with satisfactory results.