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.

[Intermittent hemodialysis, irreplaceable in specific cases of severe poisoning]. / L'hémodiayse intermittente, irremplaçable dans certains cas d'intoxications sévères.

The medical practitioner is in general well aware of the indications for hemodialysis in severe, acute or chronic renal insufficiency. Apart from the traditional indications for renal replacement therapy, there are some cases such as metfomin and ethylene glycol poisoning, lithium intoxication severe hypercalcemia and tumor lysis syndrome, in which intermittent hemodialysis is the most effective treatment, or sometimes the only effective one. Although these situations remain infrequent, it is crucial to recognize them as quickly as possible.

[What to expect from dialysis in the future?]. / Que peut-on attendre de la dialyse dans le futur?

The number of people with end stage kidney failure is increasing worldwide, mainly due to aging of the population. Hence the need for renal replacement therapy is continually expanding. Kidney transplantation, haemodialysis and peritoneal dialysis are currently the gold standard of renal replacement therapy. These three techniques have all their specific advantages and shortcomings. Facing the high complication rate of actual techniques, an increasingly migrant population and the growing desire to respect the environment, alternatives are needed. New techniques that might improve some of these points are in development and will be reviewed in this article.

[Contrast-induced nephropathy]. / Néphropathie au produit de contraste.

Iodine and gadolinium-based contrast induced nephropathy is the third leading cause of hospital-acquired acute kidney injury. It is essentially observed in patients with defined risk factors and is associated with increased morbidity and mortality. The prevention of contrast induced nephropathy consists in volume expansion through intravenous sodium chloride 0.9% or sodium bicarbonate 1.4%. Comparative randomized controlled trials appear to show a benefit in favor of sodium bicarbonate over saline fluids. According to last evidence, N-acetylcysteine does not provide additional benefit over intravenous fluids.

[What reasonable applications for regional citrate anticoagulation in renal replacement therapy?]. / Quelles applications raisonnables pour l'anticoagulation régionale au citrate en épuration extrarénale?

Regional citrate anticoagulation of the extracorporeal circuits (CRA) experienced considerable growth over the past decade. This development is partly explained by the significant progresses made in the field of bioengineering. These allow a secure administration of citrate, while an increasing availability of ionized calcium measurement at the bedside allows reactivity in monitoring the treatment. An increasing severity of the medical condition of patients requiring blood purification treatment gives more contrast to the profile of patient who may benefit from a CRA. If some methods of renal replacement therapy are well suited to this mode of anticoagulation, others are, to date, only at the stage of development and are applied under close medical supervision.

The three biological gaps and hyperoxaluria in ethylene glycol poisoning: case presentation and review.

Ethylene glycol is a toxic alcohol which may induce significant toxicity when ingested accidentally or intentionally. The main clinical complications of EG poisoning include central nervous system depression, cardiorespiratory instability and renal failure, which may be lethal if improperly treated. Although the demonstration of high plasma levels of ethylene glycol confirms the intoxication, such measurements are generally not obtained in the acute setting and can be misleading due to the rapid metabolism of EG. This implies the need for alternative, indirect, diagnostic methods, which reflect the metabolic fate of EG. These include an early and transient osmolar gap, followed by an anion gap metabolic acidosis and hyperoxaluria. Another frequent finding is a lactate gap between various methods of lactate measurements. An appropriate knowledge of these laboratory findings is essential for the diagnosis of EG poisoning, and for the initiation of antidote therapy (fomepizole) and hemodialysis in selected cases. These features are illustrated by the presentation of a prototypical case of EG poisoning, in which an incomplete diagnostic workup on hospital admission resulted in an unnecessary laparotomy and a significant delay in the management of the intoxication.

[Intermittent hemodialysis in the intensive care setting]. / L'hémodialyse intermittente aux soins intensifs.

Acute renal failure is a frequent and potentially lethal disease in intensive care units. Renal replacement therapy (RRT) is often required. Either intermittent or continuous methods of RRT can be used. When to start a RRT and which method to use is not always clearly defined and a global evaluation of the clinical situation is required. The choice of the modality of RRT will be up to the general clinical context, hemodynamic stability, the type of molecules to be cleared and the haemorrhagic risk as much as habits and available resources. No study currently showed a superiority of either continuous or intermittent renal replacement therapy. The collaboration between intensive care specialists and nephrologists allows an optimized choice for a given patient and allow better move from one technic to another if required.

[Previous and new concepts in the management of symptomatic hyponatraemia]. / Anciens et nouveaux concepts dans le traitement de l'hyponatrémie symptomatique.

Hyponatraemia is an electrolytic disorder whose danger is often underestimated. The treatment of symptomatic hyponatraemia has been a subject of controversy for a long time. This disorder needs to be treated aggressively and cautiously because of the associated risk of definitive neurological lesions. Recently, a number growing of studies recognised the high incidence of a concurrent condition that has to be diagnosed and treated: hypoxia.

Dinuclear zinc catalysts with unprecedented activities for the copolymerization of cyclohexene oxide and CO2.

A variety of new dinuclear zinc catalysts was developed and tested for the copolymerization of cyclohexene oxide and carbon dioxide. Electron-withdrawing groups thereby led to unprecedented activities with turnover frequencies up to 155,000 h(-1). These are by far the highest polymerization rates ever reported for the copolymerization of cyclohexene oxide and CO2.

Treatment of alopecia areata in C3H/HeJ mice with the topical immunosuppressant FK506 (Tacrolimus).

Alopecia areata-like hair loss has been observed in C3H/HeJ mice and can be defined as a tissue-restricted T cell mediated disease of the hair follicle. Because FK506 has been described as suppressing T cell mediated autoimmune diseases, we addressed the question whether topical treatment of C3H/HeJ mice with FK506 has a beneficial effect on alopecia areata (AA). For this purpose six C3H/HeJ mice with AA were treated topically with 0.1% FK506 ointment, four mice received the vehicle only. Four of six FK506-treated mice showed complete hair regrowth, whereas 1/4 vehicle-treated mice regrew hair. Mice treated successfully with FK506 had reduced perifollicular infiltrates of CD4+ and CD8+ cells and a decreased expression of MHC class I and II and ICAM-1 on hair follicle epithelium, compared to control mice. We conclude that topical treatment with FK506 is able to induce hair regrowth in AA of C3H/HeJ mice, most likely by suppressing the T cell mediated immune response.

Interferon-gamma-deficient mice are resistant to the development of alopecia areata.

BACKGROUND: Alopecia areata (AA) is a T-cell mediated putative autoimmune disease of hair follicles, which can be transferred by CD4(+) T cells. However, whether T-helper (Th) 1 or Th2 cytokines are predominant has not yet been defined. OBJECTIVES: To elucidate the importance of Th1 cells in the pathogenesis of AA we investigated the functional role of interferon (IFN)-gamma in the experimental induction of AA. METHODS: AA was experimentally induced by grafting full-thickness skin from AA-affected C3H/HeJ mice on to C3H/HeJ mice with a targeted deletion of the Th1 cytokine IFN-gamma gene (IFNgamma(-/-)) and on to wild-type mice (IFNgamma(+/+)). RESULTS: While 90% of wild-type mice developed AA, none of the IFNgamma(-/-) mice exhibited hair loss. Immunohistochemistry of skin sections revealed a dense perifollicular and intrafollicular infiltrate of CD4(+) and CD8(+) T cells in controls, while in IFNgamma(-/-) mice skin-infiltrating CD8(+) T cells were absent and the number of CD4(+) cells was significantly reduced. Aberrant expression of major histocompatibility complex class I and II molecules in the putative immune-privileged infrainfundibular site of the hair follicle was found to be weaker in AA-resistant IFNgamma(-/-) mice than in control mice with AA. Flow cytometry revealed that leucocytes of IFNgamma(-/-) mice did not respond to the transfer of AA-affected skin. As distinct from IFNgamma(+/+) mice, neither T-cell activation markers nor Th1 cytokines were upregulated in draining lymph node cells or skin-infiltrating leucocytes of AA-resistant IFNgamma(-/-) mice. However, there was no evidence for a shift towards a Th2 cytokine profile, nor for upregulation of regulatory T cells in IFNgamma(-/-) mice. CONCLUSIONS: IFNgamma(-/-) mice fail to activate Th1 cells in response to the transplanted (auto)antigens, which suggests an essential requirement for IFN-gamma-mediated Th1 activation in the induction of AA.

[Lupus erythematosus and sarcoidosis--coexistence or association?]. / Lupus erythematodes und Sarkoidose--Koexistenz oder Assoziation?

There are not many reports on simultaneous occurrence of the two rare multiorgan disorders lupus erythematosus and sarcoidosis. Since etiopathogenesis in both diseases is not yet fully defined, speculations concerning common immunological pathomechanisms as well as discussions about chance coexistence versus real association remain unsolved. As exemplified by our two patients, diagnostic problems may arise from the broad spectrum of cutaneous manifestations in both diseases as well as the similarity of extracutaneous symptomatology.

[Sites, types of manifestations and micromanifestations of atopic dermatitis in young adults. A personal follow-up 20 years after diagnosis in childhood]. / Lokalisationen, Manifestationstypen sowie Mikromanifestationen der atopischen Dermatitis bei jungen Erwachsenen. Eine persönliche Nachkontrolle 20 Jahren nach Diagnosestellung im Kindesalter.

A follow-up study of 47 patients who had suffered from atopic dermatitis in infancy (< 2 years aged old) was conducted by means of a questionnaire and personal interview/examination at the mean age of 23 years. It was found that 72.3% of them were still suffering from atopic dermatitis. The atopic eczema was mostly localized on the fingers (67.6%), on the head, e.g. forehead, eyelids and scalp (32% each), neck (35%) and chest (32%). Different localizations from the juvenile and adolescence phase were observed. In 73.5% the lichenoid type of atopic eczema was seen, in 67.6% the eczematic form of reaction, and in 28.4% the follicular form, the latter having decreased significantly in frequency since the adolescent phase. The pruriginous form with prurigo papules was observed only in the 8.8% of the patients who had been suffering from a chronic form of the disease since childhood. Nummular reactions were not observed. In 66% of the patients micromanifestations were present, most frequently perlèches (40.4%), retroauricular intertrigo (34%), atopic eyelid eczema (21%) and 21.3% "pulpite sèche" (tylotic, rhagadiform fingerpad eczema) (21.3%). In 14.9% of all patients these minimal forms of atopic dermatitis were present exclusively.

[Follow-up of atopic dermatitis after early childhood]. / Verlauf der atopischen Dermatitis nach dem Kleinkindalter.

A total of 106 patients, 57 women and 49 men, had had atopic dermatitis even in infancy and were monitored by means of questionnaires at a mean age of 23.5 years. Items of interest were the course of the dermatosis, influences on its course and the frequency of respiratory allergic manifestations. The persistence rate of atopic dermatitis was 60.4%. It was possible to identify ten different courses of atopic dermatitis. Only 11.3% of these patients had suffered from the eczema exclusively during infancy. In 27.4% of cases the patients were free of manifestations for an average of 9 years, after which they had a new attack of the illness. Almost one third of the patients showed a continuous type of development of their atopic dermatitis, which had persisted since infancy. The most common localizations were the antecubal fossa (48.4%), the fingers (45.3%) and the face (37.5%). The course of atopic dermatitis was influenced by the seasons in 71% of these patients, and 59.4% observed a connection between psychic stress and the exacerbation of skin conditions or a new attack of the dermatosis. As adults, 59.4% of all patients suffered from one or more respiratory allergic manifestation: 41.5% had pollinosis, 24.5% allergic rhinitis, and 25.5% bronchial asthma. Respiratory allergies disappeared in 24 cases (19.8%), bronchial asthma at a mean age of 13 years, and pollinosis at 15.3 years and perennial rhinitis at 16 years on average.

[Liver abscess: a practical approach]. / Abcès hépatiques: prise en charge pratique.

The management of a liver abscess suspected on the basis of clinical and radiological findings is radically different depending on its amoebic or pyogenic etiology. Medical management is usually enough to treat amoebic abscess, the prognosis of which is excellent while percutaneous aspiration puncture, drainage and antibiotics is the rule in pyogenic abscess, the prognosis of which depends on the quickness of diagnosis and risk factors associated. This article first relates a case of liver abscess we had in our service and then propose, on the basis of a literature review, a synthesis of the different characteristics, diagnostic and therapeutic approaches and follow-up of amoebic and pyogenic liver abscesses.

[Clinical aspects and etiology of erythroderma: an analysis of 64 cases]. / Klinik und Atiologie der Erythrodermie: Eine Analyse von 64 Fällen.

The difficulty of exfoliative dermatitis lies in the finding of underlying causes. In the present study the profile of 64 patients with erythroderma diagnosed between 1.1.1990 and 31.12.1999 were analysed. Clinical, histological and laboratory findings and their relationship to the aetiology were investigated. A masculine:feminine ratio of 2.6:1 was found. Among these patients the most common causative factors were pre-existing dermatoses (58%) and drugs (16%). In about eleven percent of the patients exfoliative dermatitis was associated with malignancy. Six out of seven malignancies were found in males, five of them suffering from pre-existing dermatosis. In 16 percent of the patients no aetiology of erythroderma could be found. No laboratory or clinical findings were indicative for an underlying malignant condition. Since we demonstrated underlying neoplastic disorders in seven (11%) of the cases, five of them also suffering from pre-existing dermatosis, we consider it absolutely necessary to screen for such diseases in the presence of the diagnosis exfoliative dermatitis.

[Headache, general malaise and left-side ptosis]. / Kopfschmerz, AZ-Verschlechterung und linksseitige Ptose.

A 82-year-old female was admitted to hospital because of deteriorated general condition, severe diffuse headache and complete left-sided ptosis. A computed tomography scan of the head revealed no subarachnoid haemorrhage. Based on the hypothesis that the symptoms resulted from an infarction in the brain stem, the previous medication with Aspirin was continued. After repeated vomitus hypotensive dehydration developed and was adequately treated. Because of confusion, elevated white blood counts and signs of meningism, a spinal puncture was performed. Only the serology for Borrelia-IgG was positive, therefore the patient received Rocephin. During treatment only the ptosis persisted, therefore the substitution with sodium and the medication with Prednisone were stopped. Afterwards the symptoms reappeared and the laboratory results showed insufficiency of the pituitary. A magnetic resonance scan showed a microadenoma of the pituitary with local bleeding. Nine months after pituitary apoplexy, with hormonal substitution only a divergent strabism on the left side persisted. Clinical findings, course and therapy of pituitary apoplexy are discussed.

17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.

For topical treatment of androgenetic alopecia (AGA) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present it is not precisely known how estrogens mediate their beneficial effect on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone, while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of AGA, we addressed the question whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of AGA.

Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice.

Alopecia areata (AA) is a complex, multi-factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy-derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically experience white hair regrowth from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen-dependent mechanisms and/or inflammatory activity to modify AA susceptibility.