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[Role of allopurinol and rofecoxib in agranulocytosis and acute tubular necrosis].

OBJECTIVE: To report the case of a patient who developed a life-threatening agranulocytosis and acute tubular necrosis after the administration of allopurinol and rofecoxib. CASE REPORT: After minor surgery, a 70-year-old male underwent a routine blood test which encountered: anemia, leucopenia, neutropenia, thrombopenia, and altered creatinine levels. Both marrow and renal biopsies were performed, yielding the following results: acute tubular necrosis and agranulocytosis in the recovery stage. One month and a half before the aforementioned surgery a routine blood test had been performed, which showed normal values. The patient had then received allopurinol 100 mg/day for around 2 months, and rofecoxib 2.5 mg/day for 14 days. DISCUSSION: After ruling out other possible causes, a diagnosis of iatrogenically induced agranulocytosis and acute tubular necrosis was reached. We used a (modified) Karch-Lasagna algorithm with both drugs, and found the following imputability values: possible for rofecoxib and probable for allopurinol. In view of the widespread use of rofecoxib and COX-2 inhibitors, despite their recent availability, and of their potential role in the severe adverse effects discussed, healthcare professionals must be on the alert for the development of symptoms suggesting said or other adverse effects.

Aged↗

[A case of bacteria-associated hemophagocytic syndrome induced by nosocomial pneumonia].

This study reviews the case of a 67-year-old man who initially presented with high fever and dyspnea. He was subsequently admitted for treatment of pneumonia. On admission, severe leucopenia and thrombopenia were observed in the peripheral blood, with significant phagocytosis of hematopoietic cells including erythroblasts and leukocytes by macrophages in the bone marrow. Following the administration of antibiotic therapy, an improvement in pneumonia and cytopenia symptoms was noted. Clinically, we diagnosed this case as bacteria-associated hemophagocytic syndrome (BAHS) with community-acquired pneumonia. In general BAHS is seen following severe hematologic disease or pneumonia, and so the treatment of BAHS is quite difficult. This particular case had no additional hematologic disorder, and all presenting symptoms of BAHS were resolved immediately following the improvement in pneumonia with post-antibiotic therapy.

Aged↗

[Importance of thrombocytopenia for the management of HELLP syndrome: a report of 104 cases].

OBJECTIVES: To evaluate the importance of thrombocytopenia in the management of HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count). MATERIALS AND METHODS: This retrospective study included all patients with HELLP syndrome treated in the three departments of the Pellegrin Maternity Hospital in Bordeaux, between January 1993 and December 2001. One hundred and four patients were included and were divided into two groups according to the severity of thrombopenia: group 1 (platelet count<50000/mm(3)) and group 2 (50000<platelet count/mm(3)<100000). RESULTS: In group 1 complications occurred in 79% of cases and thrombocytopenia put patients at-risk for serious or life-threatening bleeding complications mainly in this group. CONCLUSION: It is crucial to class patients according to severity of thrombocytopenia, on admission. Termination of pregnancy should be considered for patients included in group 1. The other patients are best managed conservatively (depending on gestational age).

Adult↗

[A patient with an extremely severe immunohaemolytic anemia due to diclofenac].

A 77-year-old male was diagnosed with immunohaemolytic anaemia. He presented with fever, jaundice and oliguric renal insufficiency. He had been taking diclofenac for three days. Additional examinations and tests revealed a Coombs-positive haemolytic anaemia and thrombopenia. The micro-card gel-agglutination test demonstrated antibodies against diclofenac metabolites. After discontinuation of diclofenac and short-term treatment with prednisone and haemodialysis for two days, the patient made an almost full recovery. Haemolytic anaemia caused by diclofenac is rare. It can be caused by autoantibodies against erythrocytes and complement-fixing antibodies that bind to erythrocytes only in the presence of diclofenac or its metabolites. A timely diagnosis-supported by the appropriate laboratory tests--is of critical importance in this rare but extremely serious complication of the use of diclofenac. The treatment consists of withdrawal of diclofenac and supportive measures, possibly in combination with immunosuppressants.

Aged↗

Clinical experience with tamoxifen in peritoneal fibrosing syndromes.

Peritoneal sclerosis is one of the most important complications of peritoneal dialysis (PD) treatment. Encapsulating peritoneal sclerosis (EPS) represents the most advanced stage of that disease and has a high mortality. No therapy of choice has been established for sclerosing peritonitis, although many have been proposed, with variable results. Tamoxifen has been successfully used in the treatment of patients with fibrosing diseases, mainly retroperitoneal fibrosis. Our purpose in the present study was to investigate whether treatment with tamoxifen in PD patients with peritoneal sclerosis has a beneficial effect. Among more than 450 patients treated in our program since 1980, 23 were diagnosed with peritoneal sclerosis. Of those 23.9 were treated with tamoxifen [20 mg every 12 hours: tamoxifen group (TG)] for a mean period of 14.5 +/- 7 months (range: 6-30 months). The other 14 patients received no treatment and were considered the control group (CG). Both groups were similar in demography and peritoneal antecedents. Follow-up was longer in CG than in TG (mean: 47 months vs. 29 months), but the difference did not reach statistical significance. Mild thrombopenia in 1 patient was the only toxic effect observed with the use of tamoxifen. In CG, 4 patients developed EPS and died--3 of them during the first 6 months after diagnosis. No patient treated with tamoxifen developed EPS. Overall mortality was significantly higher in CG (71% vs. 22%, p = 0.03). Although follow-up was longer in CG, half the patients in that group died during the first 2 years after diagnosis. Our experience suggests that treatment with tamoxifen of patients diagnosed with peritoneal sclerosis diminishes the related complications and significantly reduces mortality, at least in the short- to mid-term. However, a prospective therapeutic trial is required to confirm our results.

Adult↗

[Method for improving results of local operations for pyo-necrotic disease of the foot associated with diabetes mellitus].

Under study was the influence of antimetabolite 5-fluoracil with the preferential influence on the lymphocytic link upon the outcomes of local operations in patients with diabetic foot syndrome. The investigation was performed in 95 diabetes mellitus patients who had undergone local operations for pyo-necrotic diseases of the foot. The group of investigation included 55 patients additionally given 5-fluoracil (5 mg/kg) during local operation. The injection of the drug was followed by moderate lympho- and thrombopenia arrested by the 7th day after a single injection, reduced content of the acute phase reactants and a dramatic drop of the content of circulating immune complexes. Clinically it was followed by a rapid disappearance of the inflammation signs in the wound. In the group of patients given 5-fluoracil there were reliably less reamputations, greater number of wounds healing by primary intention after the first local operation and of those successfully closed with the help of plastic operations. No general toxic effects of the used doses of the drug were noted.

Adult↗

[An unusual case of HELLP syndrome].

The Hellp's syndrome is a complication of gravidic hypertension which associates the microangiopathic hemolysis, the cytolytic hepatic anomalies and a thrombocytopenia. There are resemblences between the biologic and histologic forms of the thrombotic microangiopathy and Hellp's syndrome. In this publishing, we report one case of Hellp's syndrome which the particular character is that the hepatic and hemolytic biologic anomalies are still very discrete, where as the thrombopenia is deep; this led us to rediscuss about the authencity of Hellp's syndrome. A neurologic complication, particulary gravissim, is noticed in one case, it concerns the intracerebral hematoma with left deficiency syndrome.

Adult↗

Hepatic artery infusion using oxaliplatin in combination with 5-fluorouracil, folinic acid and mitomycin C: oxaliplatin pharmacokinetics and feasibility.

BACKGROUND: Several studies have demonstrated the efficacy of systemic oxaliplatin (Oxa) in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of colorectal liver metastases (CRLM). However, nothing is presently known about the pharmacokinetics of Oxa administered via the hepatic artery and only very little about the feasibility and toxicity of Oxa used for hepatic artery infusion (HAI). PATIENTS AND METHODS: We designed a phase II trial using Oxa in combination with 5-FU/FA and mitomycin C (MMC) for HAI treatment of patients with isolated non-resectable CRLM. Oxa (130 mg/m2) was delivered on day (d) 1 as a 120-min infusion followed by FA (140 mg/m2) for 10 min and 5-FU (480 mg/m2) for 120 min from d1 to d5 and MMC (7 mg/m2) for 30 min on d5 every 35 days. For Oxa pharmacokinetics, peripheral venous blood was collected before, during and after arterial infusion. Oxaliplatin was determined by liquid chromatography with post-column derivatization in blood ultra filtrate. RESULTS: A total of 33 HAI cycles were administered to 5 patients with tolerable toxicity, which mainly consisted of grade I and II nausea, vomiting, leucopenia, thrombopenia and abdominal pain. During 4 cycles nausea/vomiting III degree occurred, during 3 cycles diarrhoea and abdominal pain III degree. No neurotoxicity > or = II degree and no catheter occlusion was observed. Staging showed 4 PR and 1 PD. Pharmacokinetic analysis revealed an AUC value of 85.3 micrograms x min/ml after HAI. Recalculating these values with the previously reported AUC value for systemic administration (161 micrograms x min/ml) revealed a liver extraction ratio of 0.47 for Oxa. CONCLUSION: We conclude from our results that Oxa in combination with 5-FU/FA and MMC may be a feasible protocol for HAI treatment without major toxicity, especially avoiding higher grade neurotoxicity. This is probably attributable to the low systemic bioavailability of Oxa.

Aged↗

[Replacement therapy with protein C for meningococcal sepsis and fulminant purpura in pediatric patients].

Disseminated intravascular coagulation as associated to sepsis contributes to the development of clinical multiple organ failure by extensive thrombosis in microcirculation vessels. This condition commonly manifests itself in severe meningococcal sepsis. On the skin, its clinical manifestation is extensive purpura with necrotic lesions that usually progress to serious distal ischemia and may call for amputation. A common denominator in these events regarding hemostasis is a depletion of so-called natural anticoagulant proteins, particularly protein C. According to clinical observations replacement therapy with human plasma-derived protein C concentrates has been associated with significantly improved clinical outcome in patients with meningococcal sepsis and fulminant purpura. This paper reports a case of acquired protein C deficiency in a girl with meningococcal sepsis, fulminant purpura, disseminated intravascular coagulation, and septic shock. Fresh plasma therapy was intended to increase consumption coagulopathy-depleted coagulation factors and to provide small amounts of protein C. The inability to restore protein C concentrations above 30%, and the presence of severe thrombopenia in the setting of disseminated intravascular coagulation led to the onset of replacement therapy using a human protein C concentrate (Ceprotin), which increased plasma protein C concentrations and contributed to revert the existing hypercoagulability status. Finally, evidence available in the literature regarding fulminant meningococcal sepsis management using human protein C concentrates and recombinant activated protein C is discussed.

Child↗

[An advanced case of squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to chemotherapy with TS-1].

We report a case of advanced squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to oral chemotherapy with TS-1. The patient was an 89-year-old female with severe dementia. We carried out chemotherapy with TS-1 50 mg/day, without surgical treatment. The tumor disappeared clinically at 4 months after 3 courses of the TS-1 administration. Adverse drug reactions, including vomiting, leukopenia and thrombopenia, forced a stop of the administration of TS-1. Although she finally died of in senescence 2 months from the cease of administration, there was no recurrence of the cancer at the time.

Aged↗

[Self-limited thrombotic microangiopathy associated with perianal abscess].

A 43-year-old female with Staphyloccocus-induced perianal abscess, was admitted to hospital because of a clinical picture of acute renal failure and thrombotic microangiopathy. Schistocytes, thrombopenia, a negative Coombs test and no detectable plasma haptoglobin were diagnostic for thrombotic microangiopathy. Antibiotics, surgical drainage, plasmapheresis and fresh frozen plasma were given with a favourable evolution. We review the prognostic factors determining recovery of renal function and hematological abnormalities.

Abscess↗

Phase II study of tetrahydropyranyl adriamycin (pirarubicin) in elderly patients with advanced breast cancer.

Thirty elderly (over 70 years) women with measurable advanced breast cancer entered into this Phase II study. An initial dose of 30 mg/m2 of pirarubicin (THP) every 3 weeks was given intravenously. THP was escalated by levels of 10 mg/m2 according to the blood cell count done at day 14 and day 21 until a maximum dose per cycle of 70 mg/m2 was reached. The mean total cumulative dose of THP received was 204 mg/m2 (range 30-710 mg/m2). The mean number of cycles given was 5.5 (range 1-24). Of 28 evaluable patients, 1 achieved a complete response (CR), 6 had a partial response (PR) (CR + PR = 25%; 95% confidence interval 9-41%), 13 showed no change, and 5 had a progressive disease. The median time to progression was 3 months (range 0.5-18+ months). Of 28 patients evaluable for toxicity, the hematologic toxicity at day 15 was neutropenia grade 3 and 4 in 61% of the patients and thrombopenia grade 3 and 4, 0% of cycles. No cumulative hematologic toxicity was detected. Nonhematologic toxicities consisted of nausea and vomiting in 50% of patients (WHO grade 3 = 5%) and alopecia in 64% (WHO grade 2-3 = 36%). No stomatitis occurred. No cardiac toxicity was observed. The results of this study show that THP is an active drug in elderly patients with advanced breast cancer. Because of its safety, THP deserves further investigation in this application.

Adenocarcinoma↗

[Clinical study of modified M-VAC therapy with one 21-day cycle for advanced urothelial cancer].

Although M-VAC therapy is a standard chemotherapy for advanced transitional cell carcinoma, the treatment schedule has to be delayed or cancelled in many patients because of the toxicity. To reduce the toxicity we modified the treatment schedule of M-VAC treatment. The dosages of this simplified M-VAC therapy were 30 mg/m2 methotrexate (on day 1), 3 mg/m2 vinblastine (on day 2), 30 mg/m2 doxorubicin (on day 2) and 70 mg/m2 cisplatin (on day 2), with courses repeated every 21 days for four cycles as a principle. Seventeen patients with histologically proven advanced transitional cell carcinoma were treated with this simplified M-VAC therapy without dose modification or delay. The median number of cycles was 4. Neutropenia, anemia and thrombopenia (grade 4) was observed in 2, 1 and 2 patients respectively, but no drug-related deaths were observed. Complete response and partial response were achieved in 2 (12%) and 10 (59%) patients respectively. Of 2 complete responders one patient was alive without evidence of disease at 12 months and another patient died of the disease at 42 months. Of 10 partial responders 6 patients underwent the additional surgical resection of residual tumors. Of these 6 patients 3 patients are alive without evidence of disease at 6, 30 and 31 months. The remaining 3 developed recurrence and 2 died of the disease at 13 and 29 months. Five non-responders died of the disease at 5 months after the start of the therapy. Response rate of simplified M-VAC therapy was excellent and treatment duration was short. However, relapses were commonly observed as well as the original M-VAC treatment.

Aged↗

Severe systemic autoimmune disease associated with Epstein-Barr virus infection.

Infection with Epstein-Barr virus (EBV) has been associated with different autoimmune manifestations. The authors describe a girl who developed a severe systemic autoimmune disease with severe autoimmune hemolytic anemia, mild autoimmune thrombopenia, antineutrophil antibodies, and fatal autoimmune hepatitis after EBV infection. Despite immunosuppressive treatment and ultimately liver transplantation, this patient could not overcome her clinical condition and died. The etiopathogenesis of this complex disease and the association with EBV infection is discussed.

Anemia, Hemolytic↗

[The HELLP syndrome. 13 cases].

The Hellp syndrome is a complication of raised blood pressure in pregnancy, haemolysis, a rise in liver enzymes and thrombopenia. In this retrospective study we report 12 cases of Hellp syndrome which occurred in the University Hospital Centre of Poitiers between 1982 and 1990 and we discuss causes, the progress, the prognosis and the management. Six patients were helped by prophylactic Caesarean operation. Two patients had eclamptic fits. Fortunately there was no maternal death. There were seven cases of intrauterine growth retardation, two of in utero fetal death and one of early neonatal death. When clinical and biological parameters of the Hellp syndrome come right following delivery, the outlook for the mother is quickly favourable, but the syndrome can continue and sometimes become worse after delivery. Stopping the pregnancy is the basic treatment and conservative treatment has only a very limited success. Finally, the prognosis for the future is usually good and it is unlikely to recur.

Anemia, Hemolytic↗

[Role of an exclusive concomitant radio-chemotherapy treatment in non operable esophageal cancer: results of a 10-year experience in Antoine-Lacassagne Center].

Treatment of non operable esophageal cancer still remains debatable. To date, radio-chemotherapy treatment could be considered as a standard, offers to the patients real hope and a new area of management in this unfavourable cancer. The aim of the present study was to report retrospectively a 10 year experience in concomitant radio-chemotherapy primary treatment in non operable esophageal cancer patients in Antoine Lacassagne anti cancer Center. Between January 1989 and June 1997, 63 consecutive, previously untreated patients with squamous cell carcinoma of the esophagus and who were inoperable for various reasons were majoritably treated with cisplatin (70 mg/m2) at J1 plus 5-fluorouracil (800 mg/m2/d) from J1 to J5 every 3 weeks (78% of patients) concomitantly with external beam radiotherapy (2 types). Two other chemotherapy regimens has been also used. Seventy-five percent (47/63) of the patients received the stipuled concomitant radio-chemotherapy dose. Neutropenia in the form of WHO grade 3-4 : 27% (17/63) was observed, grade 3-4 anemia and thrombopenia in 16 (26 %) and in 9 (15%) patients, respectively, grade 3-4 emesis in 6 % (4/63), grade 3-4 mucositis in 10 % (6/63). On 47 patients with accessible responder status, 18 of them presented a complete response, 20 a partial response, 6 a stable disease and 3 a progressive disease. The median follow up was 7 years. The median overall survival was 9.6 months with 11% estimated to be alive after 5 years. Combined treatment with cisplatin 5-fluorouracil and radiotherapy for inoperable cancer of the esophageal is relatively well tolerated and reasonably efficacious in a very selected group of patients.

Adult↗

[Long-term follow-up study of 35 children with ADS treated with zidovudine (AZT)].

Thirty-five children diagnosed of AIDS were studied in order to evaluate toxicity and efficacy of oral Zidovudine treatment (AZT), as well as to analyze the clinical, biochemical, immunological and virological evolution of HIV infection throughout the treatment. Patients (19 males and 16 females) were studied from April 1988 to May 1990 with a mean follow-up time of 13.5 months (SD = 6.7 months). The mean age of the group was 4.68 years. The means of acquisition of this disease was 71.45 vertical and 28.6% via hemo-derivatives. Tolerance has been good with the main toxicity being hematological (28.5% anemia and/or neutropenia), 23% of which required blood supplements. The presence of neurological involvement and thrombopenia were observed in the incidence of greater toxicity. No influence on weight during AXT treatment was observed and hepatosplenomegalia and adenopathies were not modified. Bacterial and opportunistic infections were observed in 97.1% and 20% of patients, respectively. Neurological evolution was irregular and the improvement observed in some patients was mild and transitory. Three patients died during the follow-up from intercurrent infectious process. A progressive increase in MCV and a tendency towards leucopenia and lymphopenia (mainly in hemo-derivative infected patients) was observed. Neither significant immunological nor virological changes were observed during the treatment (except the tendency to diminish basal hypergammaglobulinemia). The results of this study were compared to other pediatric series treated with AZT.

Acquired Immunodeficiency Syndrome↗

[Visceral leishmaniasis: a study of 15 cases].

We report 15 cases of visceral leishmaniasis in adults, diagnosed by visualization of the parasite in 14 of them and in one case, based on clinic, serology and good response to treatment. Thirteen patients developed an acute clinical state and two patients, a subacute-chronic state. All of them had fever, half of them, a constitutional syndrome and 12, visceromegaly. Fifteen had anemia, 13, leukopenia and 10, thrombopenia. Serology was positive in 75% of cases. All patients were treated with meglumine antimoniate. No adverse effects were observed and in 14 patients, the treatment was successful. There were no recurrences. A patient died due to septic shock by Pneumococcus with DCI.

Age Factors↗