Weil's disease: an unusually fulminant presentation characterized by pulmonary hemorrhage and shock.

A case of fulminant leptospirosis is presented, manifesting as rapid progression from acute undifferentiated febrile illness to refractory shock, jaundice, renal failure and massive pulmonary hemorrhage. The patient received aggressive intensive care unit support including prolonged intubation and ventilation. This case emphasizes that acute leptospirosis may well not be characterized by the classic scenario of a biphasic illness, but rather by a fulminant, monophasic illness.

Weil's disease: an unusually fulminant presentation characterized by pulmonary hemorrhage and shock

A case of fulminant leptospirosis is presented, manifesting as rapid progression from acute undifferentiated febrile illness to refractory shock, jaundice, renal failure and massive pulmonary hemorrhage. The patient received aggressive intensive care unit support including prolonged intubation and ventilation. This case emphasizes that acute leptospirosis may well not be characterized by the classic scenario of a biphasic illness, but rather by a fulminant, monophasic illness.

The location of KIT and PDGFRA gene mutations in gastrointestinal stromal tumours is site and phenotype associated.

AIMS: To assess the relation between KIT and PDGFRA mutations and the site of origin, histological phenotype, and pathomorphologically determined risk assessment in gastrointestinal stromal tumours (GISTs). METHODS: A series of 83 clinicopathologically characterised GISTs from 79 patients was analysed for KIT and PDGFRA mutations by polymerase chain reaction amplification, single strand conformation polymorphism analysis, and direct DNA sequencing. RESULTS: KIT or PDGFRA mutations were found in 57 and 11 GISTs, respectively. Most KIT mutations involved exon 11 (46 cases), followed by exon 9 (10 cases). The PDGFRA mutations mostly affected exon 18 (eight cases), followed by exon 12 (three cases). There was a significant association between KIT exon 9 mutations and an intestinal origin of GISTs, and between PDGFRA mutations and gastric origin of the tumours. In addition, the presence of PDGFRA mutations was significantly associated with epithelioid/mixed histology, as was the absence of identified receptor tyrosine kinase mutations. Vice versa, KIT exon 11 mutations were almost exclusively found in spindle cell GISTs. Furthermore, the presence of any KIT and PDGFRA mutations and the presence of KIT mutations alone were significantly associated with high risk/malignant GISTs. CONCLUSIONS: The location of KIT and PDGFRA mutations in GISTs is associated with the site of origin and histological phenotype. Genotyping of GISTs may be a helpful additional parameter in determining the biological profile of these tumours.

Gallium-68 chelate imaging of human colon carcinoma xenografts pretargeted with bispecific anti-CD44V6/anti-gallium chelate antibodies.

UNLABELLED: Recently, we demonstrated the feasibility of combining improved tumor-to-tissue contrasts and PET imaging for immunoscintigraphic tumor localization using a multistep targeting technique that consists of the administration of an antitumor/antihapten bispecific monoclonal antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that are still present in the circulation, and a low molecular weight Ga chelate, labeled with positron emitter 68Ga, serving as the hapten. Due to this technique, the biodistribution of the radiolabeled hapten is governed mainly by the binding characteristics of both the antitumor and the antihapten part of the BS-MAb. For a future clinical implementation of the method, we investigated MAb VFF18, which is reactive with the adhesion molecule CD44V6, a tumor-associated antigen, and up-regulated in colon, squamous cell and pancreas carcinoma, and two anti-Ga chelate MAbs, which are highly selective for only one of the two enantiomers (optical isomers) of the inherently racemic Ga chelate. METHODS: From the VFF18 MAb and the anti-Ga chelate MAbs, two BS-MAbs containing the same antitumor parts, but different antihapten parts, were prepared and tested for multistep targeting in human colon carcinoma-bearing nude mice. RESULTS: Despite identical biodistributions of both BS-MAbs and their very similar affinities for the corresponding Ga chelate enantiomers, tumor uptake of the two enantiomers 1 hr postinjection was significantly different [8.7 +/- 1.9% versus 5.8% +/- 1.6% of the injected dose/g (%i.d./g)], with tumor-to-blood ratios being higher for the BS-MAb showing the lower tumor uptake (7.6 +/- 1.6 versus 4.7 +/- 0.6). From data obtained with each BS-MAb, a similar initial tumor binding of approximately 15.5%i.d./g, but different in vivo half-lives of the corresponding BS-MAb-enantiomer immune complexes, could be estimated. Pretargeting with a mixture of both BS-MAbs followed by the administration of the racemic Ga chelate resulted in the lowest tumor uptake (3.9% +/- 1.5%i.d./g). PET imaging of nude mice with the enantiomeric, as well as with the racemic, 68Ga chelate demonstrated a clear delineation of tumors against blood pool background. CONCLUSION: Multistep immunoscintigraphy with BS-MAbs markedly increases tumor-to-tissue ratios in nude mice and enables PET imaging. Using a BS-MAb containing MAb VFF18, a more sensitive localization of CD44V6-positive tumors in patients should also be obtained.

Sodium nitroprusside does not influence tissue oxygen extraction capabilities during a critical reduction in oxygen delivery.

By its regulating effects on blood vessel tone, nitric oxide (NO) may play an important role in the coupling of oxygen delivery (DO2) to metabolic rate. We reasoned that if endogenous NO synthesis is an important modulator of oxygen extraction ratio (O2ER), then administration of a NO donor will alter oxygen extraction capabilities during a fall in blood flow. We studied the effects of the NO donor, nitroprusside, on the relationship between DO2 and oxygen uptake (VO2) during an acute reduction in DO2 induced by cardiac tamponade. Twenty-one healthy, anaesthetised, mechanically ventilated dogs were randomly divided into 3 groups. Group 1 (n = 7) served as control; Groups 2 and 3 were given sodium nitroprusside at 1.0 microgram/kg.min (n = 7), and 2.5 micrograms/kg.min intravenously (n = 7), respectively. All animals were given normal saline i.v. at a rate of 20 ml/kg.h throughout the study. Cardiac tamponade was induced by bolus injections of normal saline into the pericardial space. In the control animals the critical DO2 (DO2crit) was found at 10.1 +/- 1.5 ml/kg.min and critical O2ER (O2ERcrit) at 63.3 +/- 10.9%. Nitroprusside at the lower dose decreased systemic vascular resistance but did not significantly influence arterial pressure, cardiac output, DO2 or VO2; neither DO2crit nor O2ERcrit was altered (9.3 +/- 2.9 ml/kg.min and 70.4 +/- 20.9%). Nitroprusside at the higher dose induced significant decreases in mean arterial pressure and systemic vascular resistance, but had no significant effect on cardiac output. DO2crit (9.2 +/- 2.0 ml/kg.min) and O2ERcrit (59.8 +/- 13.2%) were similar to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)