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Query: UMLS:C0012739 (disseminated intravascular coagulation)
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Phase II studies on ifosfamide and mesna in pancreatic cancer have mostly been inconclusive. In all of these studies ifosfamide was administered as an i.v. bolus or by short infusions. Since dose fractionation of ifosfamide over several days increases its therapeutic index, we chose to maximize the dose fractioning by selecting a continuous-infusion schedule (1.75 g/m2 on days 1-5 every 21-28 days, with mesna 60%-100% of the ifosfamide dose up to 12 h after ifosfamide). Since 1987 29 patients (performance status less than or equal to 2) with advanced inoperable adenocarcinoma of the pancreas were studied (8 women and 21 men; median age 58 years: 36-73 years). A total of 25 patients are evaluable for response (1 ineligible; 3 inevaluable: 2 early deaths due to disseminated intravascular coagulation, 1 refusal). One female patient with a complete response on computed tomography scan (after five cycles) but residual liver metastases on surgical exploration survived for 473 days. Three male patients with partial response survived for 205, 335 and 355 days. Six more patients with minor response (3) or no change (3) but significant decrease of tumour marker CA 19-9 had a median survival of 213 days (106-243). Responders seemed to benefit in terms of pain relief and general well-being. The median overall survival of all patients was 148 days (21-473). Haematotoxicity was rarely dose-limiting [median nadirs: white blood cells = 2.1 x 10(9)/l (0.45-6.4), Hb = 10.7 g/dl (7.5-13), platelets = 137 x 10(9)/l (21-411)]. Nausea and vomiting were mild with prophylactic oral metoclopramide. No central nervous system toxicity or urotoxicity was observed. Alopecia was seen in all patients who had received at least two cycles. Continuous infusion of ifosfamide was generally well tolerated and useful for palliation in 10 of 25 patients. A higher dose intensity is recommended.
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PMID:Continuous 5-day infusion of ifosfamide with mesna in inoperable pancreatic cancer patients: a phase II study. 179 2

After an accidental or intentional ingestion of lindane, clinical manifestations of poisoning may include rapid onset of nausea and vomiting, coma, seizures, respiratory failure, and death. While rhabdomyolysis, secondary renal failure, and aplastic anemia have also been reported, coagulopathies have not been observed following poisoning with this pesticide. In this case report we describe a 43-year-old female who intentionally ingested 8 oz of a 20% lindane solution. Her serum lindane concentration reached 1.3 mcg/ml and her clinical manifestations included seizures, coma, rhabdomyolysis, secondary renal failure, and disseminated intravascular coagulation. The coagulopathy presented early in her clinical course and resolved when serum lindane levels fell. The patient died 11 days after the ingestion.
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PMID:Disseminated intravascular coagulation in a case of fatal lindane poisoning. 245 26

We experienced 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders in a 16-year period. Ninety-five percent of the patients had hematologic malignancies such as acute leukemia. All but one patient received cytotoxic or immunosuppressive therapy at or prior to the onset of bacteremia. Seventy-seven percent of the episodes occurred during profound granulocytopenia of below 100/mm3. All the patients acquired their infection in the hospital, and 96% had received antibiotic therapy during the preceding two weeks. Periodontal, anorectal, lower respiratory tract, and urogenital infections were the sources of bacteremia in about three-quarters of the episodes. Periodontal infection tended to progress to cellulitis of the face or the floor of the mouth, often resulting in bacteremia of the unimicrobial type, while anorectal infection predisposed to abscess formation, frequently leading to bacteremia of the polymicrobial type. Cellulitis at onset was seen in 35% of the episodes. Most sites of infection did not become apparent until one to three days after the onset of fever, probably because of depressed inflammatory response associated with severe granulocytopenia. The majority of patients complained of gastrointestinal symptoms such as nausea and vomiting, abdominal pain, diarrhea, and abdominal fullness at the onset of bacteremia. Major complications included bacteremic shock (63%), impaired consciousness (25%), ecthyma gangrenosum or hemorrhagic gangrenous cellulitis (18%), and jaundice (12%). Furthermore, there were one case each of endocarditis and disseminated intravascular coagulation. It was thus suggested that the clinical picture of P. aeruginosa bacteremia complicating hematologic disorders is influenced by the predisposing conditions associated with the underlying diseases and their treatment.
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PMID:[Pseudomonas aeruginosa bacteremia associated with hematologic disorders [I]. Predisposing factors and clinical manifestations]. 250 86

To augment the antitumor effect of high-dose melphalan and determine pharmacokinetics we conducted a phase I trial of escalating doses of high-dose IV melphalan with the chemosensitizer misonidazole for patients with advanced colorectal carcinoma. Fourteen patients with modified Dukes D adenocarcinoma of the colorectum were treated with a single course of melphalan (40-60 mg/m2 i.v. bolus q.d. X 3 days) and misonidazole (1-3 g/m2 p.o. q.d. X 3 days) followed by autologous bone marrow transplantation. Toxicity consisted of severe myelosuppression, moderate nausea and vomiting, and mild mucositis and diarrhea. One patient developed unexplained renal tubular acidosis, and a diffuse encephalopathy occurred in another patient. Three patients died within the first 30 days after the start of treatment, two due to tumor progression and one due to sepsis and disseminated intravascular coagulation-induced intracerebral hemorrhage. Six of 14 patients achieved a partial response, and the median response duration was 4 months (range 3-10 months). Analysis of misonidazole serum concentrations showed similar pharmacokinetics to those previously reported, suggesting no significant drug interaction with intravenous melphalan. Mean peak serum concentrations ranged from 81.8 micrograms/ml to 115.2 micrograms/ml at the second and third misonidazole dose levels, which approximate those known to provide effective chemosensitization with melphalan in animal models. In this phase I study, we showed that maximally tolerated doses of intravenous melphalan can safely be combined with oral misonidazole. In view of the large volumes of oral misonidazole required at the highest dose level, subsequent studies to determine the maximally tolerated dose of misonidazole should employ the intravenous form.
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PMID:High-dose melphalan, misonidazole, and autologous bone marrow transplantation for the treatment of metastatic colorectal carcinoma. A phase I study. 265 May 27

A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.
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PMID:Phase I study of recombinant human tumor necrosis factor. 331 81

Between January 1990 and December 1991, physicians used either intra-amniotic 20% hypertonic saline (HSI) solution (no more than 200 ml) or 3 mg intracervical prostaglandin E2 gel (PGE2) to induce mid-trimester abortion in 149 women at Ramathibodi Hospital in Bangkok, Thailand. 125 women were in the HSI group and 24 were in the PGE2 group. The mean induction to abortion time was 28.4 hours for the PGE2 group and 31.7 hours for the HSI group. The longest induction to abortion time was 73 hours for the HSI group and 127.2 hours for the PGE2 group. Nausea and vomiting only occurred in women in the PGE2 group (16.7%). Only 4 (3.3%) HSI cases developed fever. One of these cases had disseminated intravascular coagulation (DIC) defect which was likely caused by contamination during instillation of HSI. This case lost more than 500 ml of blood. One HSI case experienced increased electrolytes during HSI instillation, which was likely caused by leakage of sodium chloride into the vascular system. Even though many HSI cases (63.3%) experienced a retained placenta, hemorrhaging occurred in only 1 (0.8%) HSI case, the one with DIC. The women in the PGE2 group were less likely to experience a retained placenta (25%). The average length of stay in 70% of cases in both groups was 2 days. Provided clinicians use aseptic techniques and closely observe HSI patients, HSI termination of midtrimester pregnancy is effective and safe. HSI is less expensive than PGE2 and is available in most developing countries. PGE2 can be used as an alternative method instead of hysterotomy.
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PMID:Mid-trimester abortion using hypertonic saline or prostaglandin E2 gel: an analysis of efficacy and complications. 779 49

The etiology and pathogenesis of the HELLP syndrome, a multisystem disease occurring only in pregnancy, are still unclear. Curiously, very few authors have investigated whether inherited factors may be involved. We report two cases of HELLP syndrome in two unrelated women whose fetuses were relatives (first cousins). The first case concerned a woman aged 32 with a normal course pregnancy who was admitted to the hospital for fever, nausea and vomiting, low platelets, hemolysis and increased liver enzymes. Abruptio placentae with fetal death and severe disseminated intravascular coagulation with hemorrhages ensued within a few hours. Hysterectomy was then performed. After treatment with transfusions and drugs the patient slowly improved; 28 days later she left the hospital in good condition. The second case involved a woman aged 31 with a normal course pregnancy who was admitted to the hospital for epigastric pain, nausea, low platelets, hemolysis and increased liver enzymes. The patient underwent an immediate cesarean section and delivered a live infant; no bleeding occurred during or after delivery. The patient's condition rapidly improved and she left the hospital after 13 days. Until now, no author has proved that inherited fetal factors are at work in the HELLP syndrome. Our observations suggest a role for genetic factors, and this needs to be investigated in prospective studies.
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PMID:Is the HELLP syndrome due to inherited factors? Report of two cases. 806 66

HELLP syndrome in the parturient (hemolysis, elevated liver enzymes, and low platelet count) is associated with poor maternal and fetal outcomes. Maternal mortality has been estimated to be as high as 24%. Patients with HELLP syndrome are also at greater risk of pulmonary edema, adult respiratory distress syndrome, abruptio placentae, disseminated intravascular coagulation, ruptured liver hematomas, and acute renal failure. Perinatal mortality is equally high, ranging from 79 to 367 per 1,000 live births, and neonatal complications correlate with the severity of maternal disease. Many clinicians view HELLP syndrome as an entity of preeclampsia, and because of varied symptomatology, the initial diagnosis may be obscured. Prodromal signs include: (1) weakness and fatigue, (2) nausea and vomiting, (3) right upper quadrant and/or epigastric pain, (4) headache, (5) changes in vision, (6) increased tendency to bleed from minor trauma, (7) jaundice, (8) diarrhea, and (9) shoulder or neck pain. Before delivery, aggressive obstetric management is directed toward stabilization of the affected organ systems, if possible, and timely interruption of the pregnancy in the early phase of the accelerated disease progression. Definitive therapy is delivery. Parturients with HELLP syndrome are often critically ill; their infants are frequently premature and their conditions are compromised. Management criteria should include a multidisciplinary approach in a tertiary care center. Obstetric anesthesia personnel should perform a thorough preanesthetic evaluation and be familiar with the pathophysiologic changes of this syndrome. Determining the anesthetic of choice depends on the patient's condition, fetal well-being, and the urgency of the situation. In the presence of severe coagulopathy, regional anesthesia is contraindicated.
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PMID:HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) pathophysiology and anesthetic considerations. 922 38

A patient with ABO blood group incompatibility who was treated by exchange transfusion is reported. A 63-year-old woman with blood group B type Rh (+) was accidentally transfused approximately 120 ml of A type Rh (+) packed red cells. She developed shock state, complaining chilliness, trepidation, nausea and vomiting just after the atypical blood transfusion. Fortunately, we could save her life without any complication by doing exchange transfusion in addition to anti-shock therapy and anticoagulant therapy preventing disseminated intravascular coagulation. The exchange transfusion was performed while monitoring central venous pressure. The total withdrawn blood reached 4300 ml, and 18 units of B type Rh (+) packed red cells, 10 units of AB type Rh (+) fresh frozen plasmas, 1250 ml of plasma protein fractions and 1750 ml of plasma expanders were infused with crystalloid fluid therapy. Although the amount of atypical blood transfusion to her was relatively small, it is considered that the exchange blood transfusion which seems to be only the fundamental therapy against atypical blood transfusion, took effect in saving her life without any complication.
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PMID:[A case of ABO blood group incompatibility treated by exchange transfusion]. 951 41

Sixty cases of P. falciparum and 165 cases of P. vivax were studied clinically along with species identification of parasite after examination of the blood slide by experts at Calcutta. It was observed that malaria had been changing its clinical profile. The classic paroxysm is evident only in 40% cases of P. falciparum and 47.27% of P. vivax malaria, but the difference between the two groups is not statistically significant. On the other hand continuous or remittent type of fever has been observed in 40% and 27.27% cases of P. falciparum and P. vivax respectively, while absence of classic paroxysms of fever, in association with splenomegaly when present, poses a diagnostic difficulty with enteric fever. Association of jaundice in 40% and 9.09% cases with P. falciparum and P. vivax respectively along with hepatomegaly in 80% and 63.63% in them in conjunction with nausea and/or vomiting leads to clinical mimicry with infective hepatitis. Splenomegaly which has been described as cardinal feature of malaria was observed in 40% cases with P. falciparum and only in 18.18% cases of P. vivax malaria and this is a clear deviation from earlier description and this difference between the two groups is highly significant at 99% level of confidence. Co-existent enteric fever was observed in 3.33% of falciparum and 2.6% of vivax malaria, though this difference is not statistically significant. Acute respiratory distress was observed in 6.6% of P. falciparum malaria only. Oliguria with impaired renal function was noted in 5% cases of P. falciparum malaria. The present study has also noted convulsion or coma in 8.33%, purpura with disseminated intravascular coagulation in 3.33% and black water fever in 3.33% cases in falciparum malaria which were not observed in cases with vivax malaria and these differences are statistically significant. However, stupor with bilateral extensor planter response was observed in two cases (1.3%) of vivax malaria.
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PMID:Changing scenario of malaria: a study at Calcutta. 1044 29


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