Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report.

BACKGROUND: Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. CASE PRESENTATION: A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. CONCLUSIONS: We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

Efficacy of an alpha-hydroxy acid (AHA)-based cream, even in monotherapy, in patients with mild-moderate acne.

AIM AND METHODS: The treatment of mild-moderate acne with topical drugs in association with appropriate cosmetics is currently the golden standard. The tolerability and efficacy of a cream formulated with a new mix of alpha-hydroxy acids (Hyseac AHA cream) in 248 patients with mild-moderate acne (comedonic, inflammatory, or mixed) have been investigated in a multicenter, non-randomized, open study by 10 dermatologists from different Italian areas during their routine practice. The medication with Hyseac AHA cream was prescribed at first consultation for 60 days, twice a day, either as a monotherapy (49.2% patients) or in association with a pharmacological treatment (50.2%). RESULTS: The tolerability was good to excellent in 92.3% patients, without significant differences between patients using AHA cream in monotherapy (90.0%) or associated with concomitant pharmacological treatment (97.6%). The efficacy was overall high in 64.2% patients, again without significant differences related to concomitant pharmacological treatment or not (64.8% vs. 63.3%) and/or the acne clinical type (comedonic vs. inflammatory vs. mixed: 69.2% vs. 66.7% vs. 58%). CONCLUSION: The results of this study, while confirming the high tolerability and efficacy of this AHA cream in the treatment of mild/moderate acne, reasonably suggest its possible use also in monotherapy. Furthermore, its use can be reasonably hypothesized as a maintenance treatment after specific pharmacological treatment even in more severe acne types.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery.

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin) when compared with 20 mg piroxicam alone (Feldene) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Effects of N-acetoxy-2-acetylaminofluorene and N'-nitro-N-nitrosoguanidine on nuclear DNA synthesis in rat liver.

A system for the study of DNA synthesis in isolated nuclei is described for sham and regenerating rat liver. The system has been characterized with respect to nuclear purity, conditions for optimum incorporation of [5-methyl-3H]thymidine triphosphate, time course of incorporation, product analysis by neutral and alkaline sucrose gradients, and the effect of exogenously added DNA. No difference in the basal level of activity was detected between nuclei prepared from normal or regenerating liver when isolated 24 hr after operation. However, exogenous activated DNA preferentially stimulated [5-methyl-3H]thymidine triphosphate incorporation in nuclei from regenerating liver. Activated DNA caused to react with the carcinogen N-acetoxy-2-acetylaminofluorene was a less effective primer-template in this system and decreased in a dose-dependent fashion the incorporation of [5-methyl-3H]thymidine triphosphate to below basal levels in nuclei from both normal and regenerating liver. The carcinogen N-methyl-N'-nitro-N-nitrosoguanidine had no inhibitory effect when assayed in this fashion.

Fish functional traits are affected by hydrodynamics at small spatial scale.

The Mediterranean damselfish Chromis chromis is a species with a broad distribution found both in the Mediterranean Sea and Eastern Atlantic as far south as the coast of Angola. We hypothesized that the species may have significant functional morphological plasticity to adapt along a gradient of environmental conditions. It is a non-migratory zooplanktivorous species and spends the daytime searching for food in the middle of the water column. Therefore, local hydrodynamics could be one of the environmental factors affecting traits of C. chromis with repercussions at the population level. We compared the body condition, individual growth and body shapes of damselfish collected under two different hydrodynamic conditions (low ∼10 cm s(-1) vs. high ∼20 cm s(-1)). Specimens showed higher body condition under high-hydrodynamics, where conditions offered greater amounts of food, which were able to support larger individuals. Individuals smaller than 60-mm were more abundant under low-hydrodynamics. Morphometric analysis revealed that high-hydrodynamics were favored by fish with a more fusiform body shape and body traits developed for propellant swimming.

[Proglumetacin: possible first choice in the treatment of orthopedic- traumatologic disorders]. / La proglumetacina: potenziale farmaco di prima scelta nella terapia dei disturbi ortopedico-traumatologici.

Ninety-seven patients (44 males and 53 females of mean age 42.6 +/- 12,9 years) with orthopedic-traumatologic disorders (osteoarthritis, 38; painful joints, 26; fibrositis, painful shoulder, 20; peri- and extra-articular disorders, 13) had been treated during 7 to 30 days with two suppositories (400 mg) or three capsules (450 mg) proglumetacin (Proxil Rorer). Most patients responded well to very well to the treatment with significant improvement of pain and inflammatory symptoms as well as restoring of limited function. Such a response resulted proportional to the dose (53% of good responders among those given the lower dose and 82% among those at the higher dose) and to the kind of pathology. The patients with acute disorders (7) responded all very well in 7 days; those with subacute disorders (57) responded well to very well in a proportion of 57% within 15 days; those with chronic disorders responded to a proportion of 48% within 30 days. Tolerance resulted very good anyway: in no case had the treatment to be withdrawn, nor allergic or C.S.N. reactions were observed, so that the overall tolerance was defined excellent to good in 90% of patients. Thirty-three patients complained of accessory symptoms, mainly epigastric pain and nausea, almost always mild and anyway transient. Proglumetacin can therefore be properly defined as a firstchoice treatment for the management, also ambulatory, of orthopedic-traumatologic disorders.

Relevance of hydration state of the fat free mass in estimating fat mass by body impedance analysis.

Body impedance analysis (BIA) is widely used to assess body composition, however, accurate estimates of fat mass (FM) are sometimes rendered impossible due to over- or dehydration states. In fact, BIA is accurate in total body water (TBW) estimates, and TBW can be converted into fat free mass (FFM) assuming 73% hydration; but, if there is an alteration in the hydration state, such a fixed value does not fit with the real content of fluids in the FFM compartment, thus causing wrong estimates of FFM and in turn of FM. For this reason, phase-sensitive bioelectric analyzers operating at a single frequency or at multiple frequencies have recently been under investigation in order to produce an equation that is also able to estimate the volume of extracellular water (ECW). Some authors, rather than trying to find the best equation or the best instrument approach, have tested the direct use of resistance, reactance and phase angle values derived from 50 kHz impedance measurements, assuming that normal bioelectrical values are associated with normal hydration states. Using a large series of data we have found strong correlations between BIA-derived FM and BMI, and our data show that screening the subjects with normal hydration states using the direct bioelectrical parameters (BIAGRAM) improves the predictivity of standard equations, since it avoids trying to estimate FM in overhydrated subjects.

Genetic testing of candidate genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare cardiac genetic disease characterized by the presence of structural alterations in the right ventricle which may cause ventricular arrhythmias and may induce sudden cardiac death. ARVC/D has been associated with mutations in genes encoding myocyte adhesion proteins. However, only 30%-50% of patients have mutations in these genes. Genetic testing is useful in obtaining a diagnosis, particularly in individuals who do not completely fulfill clinical criteria, thereby also enabling the undertaking of preventive strategies in family members. The main goal of this study was to identify mutations in candidate genes associated with intercalate disks that could be potentially involved in ARVC/D pathogenesis. We analyze a cohort of 14 Spanish unrelated patients clinically diagnosed with ARVC/D without any genetic alteration in all previously known responsible genes. Thus, a genetic screening has been performed in 7 additional potential candidate genes (ACTC1 -actin alpha cardiac muscle 1-, CDHN -cadherin 2 type 1 or N-cadherin-, CTNNA1 -catenin alpha 1-, Cx43 or GJA1 -gap junction protein alpha 1-, MVCL -Metavinculin-, MYL2 -myosin light chain 2- and MYL3 -myosin light chain 3-) by direct sequencing analysis. Our genetic analysis did not identify any disease-causing mutation. Thirty single nucleotides polymorphisms were found, six of them novel. In conclusion, our ARVC/D Spanish cohort has not shown any mutations in the analyzed candidate genes despite their involvement in formation and maintenance of the intercalated disk.

Visceral artery aneurysms.

Visceral artery aneurysms (VAA) frequently present as life-threatening emergencies. The purpose of this study was to review our experience with VAA treatment. Between 1988 and April 2002, 31 VAA were treated in 28 patients (14 males, 14 females) with average age of 55 +/- 15 years. The most common locations were the splenic artery (16) and the hepatic artery (7). Three patients underwent emergency surgery, 22 patients had elective open surgery, and 7 patients underwent endovascular treatment. In the surgical group the perioperative mortality rate was 3.6%. The perioperative morbidity rate was 7.1% (one case of respiratory distress manifested in the immediate postoperative period and one urgent case of bilious fistula). In the endovascular group none of the patients died; the perioperative morbidity rate was of 14.3% (one case of hepatic artery thrombosis after failure of gastroduodenal artery aneurysm embolization). Failure of the procedure was 42.9% (3 cases of aneurysm recanalization). In conclusion, we believe that an aggressive surgical approach is justified, even in the case of asymptomatic VAA, because of the low morbidity and mortality rates. Endovascular treatment should be reserved for selected cases.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin®) when compared with 20 mg piroxicam alone (Feldene®) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.