Adriamycin extravasation.

Adriamycin extravasation creates a severe tissue necrosis which is unusual, because it may not appear until several weeks later, and may continue to worsen for several months. As soon as the progressive nature of the tissue necrosis is established, we recommend that an early wide excision be performed in an attempt to remove the necrotic area and the surrounding tissues containing the extravasated drugs--before it has had an opportunity to diffuse even further. Adequate debridement requires removal of any adjacent tissue that is indurated, reddened, edematous, or pale. Skin grafts take poorly if there are small amounts of Adriamycin left in the tissue of the recipient site. Synergistic effects with radiotherapy, and continued systemic Adriamycin therapy, can aggravate or recall necrosis. The administration of more dilute solutions of Adriamycin may decrease the hazard of extravasation necrosis.     

Fibrinolytic activator activity in human neoplasms

The results of this study suggest that many malignant tumors contain low levels of fibrinolytic activator activity. Evidence is presented to suggest that this low activity may be due to the presence of an inhibitor of fibrinolysis. The presence or absence of measurable fibrinolytic activator activity, and/or inhibitor in neoplastic growths may enable one to predict the probability of viable metastases to a distant site.     

Effectiveness of pergolide mesylate in long term treatment of hyperprolactinaemia.

Twenty five patients with hyperprolactinaemia were treated with pergolide mesylate, a new dopamine receptor agonist. Twenty three received treatment for six to 20 months, and in all serum prolactin concentrations were considerably reduced. In most patients prolactin concentrations were maintained in the normal range by a low, once daily dose of pergolide and reversal of associated reproductive disorders was observed. Tumour volume as assessed by computed tomography decreased considerably during treatment in three out of four patients with a pituitary tumour. The drug was well tolerated. Side effects were similar to those of bromocriptine, but four out of eight patients who had been forced to stop taking bromocriptine because of untoward effects were subsequently able to tolerate treatment with pergolide. Pergolide mesylate promises to be a useful addition to the currently available long acting dopamine agonists in the management of hyperprolactinaemia.     

Role of siderophores in the biocontrol of Pseudomonas tolaasii by fluorescent pseudomonad antagonists

A number of pseudomonad bacteria were investigated for their in vitro antagonism on agar against Pseudomonas tolaasii , the causative agent of bacterial blotch of the cultivated mushroom. Addition of FeCl₃ to the culture medium suppressed the antagonism in 14 of the 20 bacteria tested and the production of a substance with an absorption peak at 400 nm by all antagonists was eliminated by the presence of Fe³⁺. Both observations indicated that siderophores could be involved in the mode of action of some antagonists. The addition of the iron chelators EDTA and bipyridyl to the medium used for culture of antagonists and pathogens did not generally prevent growth. Siderophore production is not essential for the in vivo activity of antagonists.     

Postneonatal mortality in children from abusing families.

The postneonatal death rate was studied for 332 infants from 160 families, ascertained through an abused proband. There were nine deaths compared with 2.9 expected from the legitimacy, social class, age, and parity distribution (p = 0.003). All but one of the babies died at home, and all were referred to a coroner or procurator fiscal. No adequate explanation of death could be found in four cases. Bonding problems probably existed in most of the nine families before death occurred.     

Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross

Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1, known to reduce survival in mice after STm infections, are located in the Chr 1 interval, and the Chr 7 association overlaps with a previously identified QTL peak called Ses2. We identified two new genetic regions on Chr 2 and 4 associated with susceptibility to STm infection. Our data reveal the diversity of responses to STm infection across a range of host genetics and identified new candidate regions for survival of STm infection.     

P2 pyridine N-oxide thrombin inhibitors: a novel peptidomimetic scaffold

In this study, we have demonstrated that the critical hydrogen bonding motif of the established 3-aminopyrazinone thrombin inhibitors can be effectively mimicked by a 2-aminopyridine N-oxide. As this peptidomimetic core is more resistant toward oxidative metabolism, it also overcomes the metabolic liability associated with the pyrazinones. An optimization study of the P(1) benzylamide delivered the potent thrombin inhibitor 21 (K(i) = 3.2 nM, 2xaPTT = 360 nM), which exhibited good plasma levels and half-life after oral dosing in the dog (C(max) = 2.6 microM, t(1/2) = 4.5 h).