Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression

Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.     

MR gated subtraction angiography: evaluation of lower extremities

We report the first clinical experience with a new method for projective imaging of blood vessels (angiography) using magnetic resonance. Vascular contrast is produced noninvasively by the phase response of moving protons. Diastolic and systolic gated images produce, respectively, flow signal and flow void; the difference image is a map of the pulsatile flow: an arteriogram. Preliminary studies are presented of the lower extremities of one healthy volunteer and four patients (one each with occlusive disease, soft-tissue tumor, arteriovenous malformation, and venous femoral-popliteal graft). Patient data are compared with accompanying conventional arteriograms, and the new method is discussed.     

CONTINUOUS SUBCUTANEOUS PUMP INFUSION OF SOMATOSTATIN ANALOGUE SMS 201-995 VERSUS SUBCUTANEOUS INJECTION SCHEDULE IN ACROMEGALIC PATIENTS

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 μg/24 h. Subcutaneous injections (33 μg) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 rig/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 ± 129 (mean ± SD) to 385 ± 100 ng/ml ( P < 0 003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 ± 76 ng/ml).     

EFFECT OF EXTRADURAL ANALGESIA ON GLUCOSE METABOLISM AND GLUCONEOGENESIS: Studies in Association with Upper Abdominal Surgery

Concentrations of glucose and gluconeogenic substrates acrossthe splanchnic circulation were studied in 20 patients undergoingcholecystectomy with general anaesthesia. In 10 patients, generalanaesthesia was administered alone, and in 10 general anaesthesiawas combined with thoracic extradural analgesia. All patientsreceived a constant i.v. infusion of glucose. Blood glucoseconcentration increased markedly in the general anaesthesiagroup in contrast to a moderate and shortlived increase in thepatients given extradural analgesia, in whom the splanchnicrelease of glucose tended to be lower. The splanchnic uptakeof glycerol was lower in the patients given extradural analgesia,while the uptake of lactate and the increase in alanine uptakewas similar in both groups. Plasma catecholamine and serum cortisolconcentrations were higher in the group receiving general anaesthesiaalone, while serum growth hormone concentration was higher aftersurgery in the extradural group. The addition of extraduralblockade to general anaesthesia suppresses the increase in bloodglucose concentration-and this may be related to a reduced splanchnicrelease of glucose combined with an increased peripheral uptake.     

Noninvasive Measurement of Blood Pressure in Conscious Cynomolgus Monkeys

Systolic (SP), diastolic (DP), and mean arterial blood pressures(MAP) and pulse rate (PR) were recorded on treated and untreatedconscious cynomolgus monkeys by the oscillometric method (Dinamap1846SX/P). Each monkey was placed in a restraining tube withthe cuff placed on the base on the shaved tail. Measurementswere taken on untreated animals once or twice a day for 4 weeks.The mean and standard deviations for SP, DP, MAP, and PR wereapproximately 121 ± 17, 60 ± 14, and 84 ±17 mm Hg and 193 ± 18 pulses/min, respectively. One maleand one female cynomolgus monkey were treated with isoproterenol,norepinephrine, and nitropmsside. Blood pressure was measuredindirectly with the cuff on the tail and directly with an indwellingcatheter in the descending thoracic aorta. Although the oscillometricmethod was not as sensitive as the catheter, the oscillometricmethod detected a change in the same direction of SP, DP, MAP,and PR compared with the direct method for all drugs administered.The monitor was reliable and sufficiently accurate to concludethat it may be useful in toxicology studies for evaluation ofblood pressure parameters in Conscious Cynomolgus monkeys.     

Indications for breast imaging in women under age 35 years

To determine appropriate indications for breast imaging in young women, the authors correlated patient histories with mammographic and/or sonographic findings and biopsy or follow-up results for 625 patients aged 13-34 years. The only important indications were a palpable mass and suspicion of an abscess. Of the 335 studies performed for evaluation of a palpable mass, 184 (55%) were normal, 28 (8%) were compatible with benign disease, and 123 (37%) were suggestive of malignancy. Biopsies were performed in 73 patients; the findings were benign in 67 cases, and carcinoma was found in six. Imaging studies were considered helpful in four of the 15 cases of suspected abscess, in that the studies established the presence and extent of an abscess. Studies in 275 women were performed for a variety of other indications. The findings were normal in 239 (87%) studies, benign in 21 (8%), and suggestive of malignancy in 15 (5%); there were no known carcinomas in any of the patients. Women with the "low-yield" indications identified in this study should be followed up clinically rather than referred for imaging studies.     

Increased resistance to plasmic degradation of fibrin with highly crosslinked alpha-polymer chains formed at high factor XIII concentrations

We have previously demonstrated that increasing factor XIII concentrations above that present in plasma (1 U/mL) results in the formation of very high molecular weight alpha fate polyacrylamide and agarose gel electrophoresis (SDS-PAGE). In this report, we have examined the effect of such crosslinking on plasmic susceptibility of fibrin prepared from purified fibrinogen and from plasma in the presence of factor XIII concentrations between 0 and 10 U/mL. The crosslinking achieved with purified fibrinogen at 1 U/mL factor XIII increased resistance to plasmic degradation by 32% as measured in a radiolabeled clot lysis system. However, further increases in plasmic resistance occurred at factor XIII concentrations of 2 and 10 U/mL, the latter decreasing the lysis rate to 45% of that which occurred in the absence of factor XIII. To achieve the same rate of clot lysis with fibrin formed using 10 U/mL rather than 1 U/mL of factor XIII, an increase in plasmin concentration of up to 4.2-fold was required. Similar results were obtained using clots prepared from plasma in the presence of factor XIII concentrations greater than 1 U/mL. Since the alpha 2-plasmin inhibitor content was the same for fibrin at 1 or 10 U/mL factor XIII, the increasing plasmic resistance could not be attributed to increased binding of the inhibitor. We conclude that fibrin prepared in the presence of factor XIII at concentrations exceeding that in plasma shows increased resistance to plasmic degradation, which is likely explained by the formation of very high molecular weight alpha polymer chains.