The biology of the glycosylphosphatidylinositol-specific phospholipase C of Trypanosoma brucei.
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Biomedical subjects
Publications and source records attributed to H Webb.
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To evaluate the use of selective decontamination of the digestive tract (SDD) (polymyxin, amphotericin, tobramycin, and intravenous cefotaxime) in a mixed intensive care unit, we performed a stratified, randomized, prospective study. The 331 patients were recruited over an 18-month period, with 256 patients remaining more than 48 hours. Stratification by acute physiology and chronic health evaluation (APACHE II) preceded randomization to control (standard antibiotic therapy) or treatment (SDD) groups. Nosocomial infection was significantly reduced in the SDD group (16.7%; 21 of 126 patients) compared with the control group (30.8%; 40 of 130 patients; p = 0.008). No difference was found in overall mortality rate or length of stay between the two groups. Those patients with admission APACHE II scores 10 to 19 demonstrated the most significant reduction in nosocomial infection (23 of 70 control vs 13 of 76 SDD; p = 0.03) and mortality (15 of 70 control vs 8 of 76 SDD; p = 0.07). Emergence of multiresistant microorganisms was not a clinical problem, but a definite change occurred in the ecology of environmental and colonizing bacteria. With the exception of cefotaxime, a reduction was noted in systemic antibiotic usage in the SDD group. We conclude that SDD is useful in selected patients in a mixed intensive care unit.
Using a specially designed incubation chamber, differential synthesis and the response to added arachidonic acid (25 mM) and L-alpha-phosphatidylcholine (LAP; 2 mM) was quantified in gallbladders from male and female dogs. Prostaglandin I2 (PGI2) was the predominant prostanoid synthesized, and tissues from females produced much more PGI2 under basal conditions than did gallbladders harvested from male dogs. Addition of arachidonic acid stimulated PGI2 synthesis by almost 100 per cent. Arachidonate-stimulated mucosal and serosal production of PGI2 were (mean(s.e.m.] comparable, 343(178) and 375(89) pg/cm2/min, respectively. Gallbladders from female animals synthesized significantly more PGI2 than did tissue from males. Indomethacin inhibited PGI2 synthesis in a dose-response manner; at 7 x 10(-5) M, prostanoid synthesis was inhibited by greater than 80 per cent. Arachidonic acid did not stimulate prostaglandin E2 (PGE2) production by gallbladder tissue. LAP similarly stimulated PGI2 biosynthesis, but in contrast to the effect of arachidonic acid, the effect was significantly greater in the serosa than the mucosa, 355(107) and 213(59) pg/cm2/min, respectively. LAP also stimulated PGE2 biosynthesis by the canine gallbladder in a pattern very similar to that of PGI2. Based on the differences in response to the two agents added, we conclude that arachidonic acid and L-alpha-phosphatidylcholine stimulate prostaglandin biosynthesis via independent pathways. We advocate the use of the incubation chamber for the assessment of prostanoid biosynthesis by the gallbladder in vitro.
To study selectively the dilutional aspects of severe blood loss on the serum complement system, we developed an animal model consisting of isovolumic phlebotomy and reinfusion of washed autologous erythrocytes. This model avoided hypoperfusion, ischemia, and transfusion of foreign antigen. We measured total serum protein, C3 antigen, total complement hemolytic activity, and alternative pathway hemolytic activity. Each of the first three parameters dropped to 55% of initial value (P less than 0.005) by the end of the phlebotomy/reinfusion procedure and returned to normal levels by Day 1 or 2. C3 antigen and total complement hemolytic activity then rose to 150% of normal by Day 4 and gradually returned to normal within 2 weeks. Alternative pathway activity, by contrast, fell by more than 80% (P less than 0.005) within the first 6 hr, recovered by Day 4, and gradually rose to about 140% of normal by Day 21. Trauma patients treated for heavy blood loss who suffer depletion of hemolytic complement during the first few hours may be at greater risk of infection due to immune deficiencies. The implication of the results presented here is that the alternative pathway may be particularly weakened during blood loss and transfusion by simple dilution in addition to the effects of processes omitted in this model. Knowledge of the kinetics of complement recovery, independent of other effects usually accompanying trauma, may be helpful in determining whether these patients might benefit from exogenous manipulation of the complement system.
We have described a patient with multiple hepatic abscesses caused by a perforated jejunal diverticulum with a presumed route of infection via the portal vein. Patients with hepatic abscesses and no known source of infection should be evaluated for a contained mesenteric perforation of the gastrointestinal tract. Finally, in patients who fail to respond promptly to percutaneous catheter drainage of a liver abscess, a continuing source of infection, such as perforation of a jejunal diverticulum, should be suspected.
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To investigate whether female sex hormones and pregnancy induce increased gallbladder synthesis of prostaglandin I2 (PGI2) and prostaglandin E (PGE), we used an in vitro incubation chamber to quantitate the effects of progesterone, estrogen, pregnancy, and pregnancy plus a 2%-cholesterol diet on mucosal and serosal PGI2 and PGE production by the rabbit gallbladder. Neither the female sex hormones nor pregnancy alone caused a significant increase in PGI2 or PGE synthesis. The gallbladders of cholesterol-fed, pregnant rabbits demonstrated significant increases only in serosal synthesis of PGI2. This increased production was equivalent to that noted for gallbladders from nonpregnant rabbits fed a high-cholesterol diet. There were no increases in mucosal synthesis of PGE or of PGI2. Thus, neither elevated levels of progesterone or estrogen nor pregnancy is directly responsible for the increased PGI2 activity in the female gallbladder; conversely, this effect seems to be mediated by the increased biliary concentrations of cholesterol.
Postpneumonic empyema (EMP) may develop in substance abuse patients, requiring prolonged hospitalization. An algorithm that provides quality care and a rational basis for timely surgical intervention would be advantageous. We report our five-year experience with EMP in substance abuse patients and present such a treatment plan. Sixty-one substance abuse patients were treated for EMP. Posteroanterior, lateral, and decubitus x-ray studies were obtained before treatment to assess fluid movement. Chest tubes were placed to drain frank pus and to obtain material for positive smears. X-ray studies and computed tomography were done 24 hours later to assess parenchymal pathology and to detect any multiple loculations. Thirty-three substance abuse patients recovered following initial tube thoracostomy and 7 after a second chest tube was introduced. Twenty-one had multiple loculations and underwent thoracotomy. Twenty of the 21 required extensive debridement or decortication, or both; 2 required lobectomy and 1 pneumonectomy. Chest tubes were removed on an average of 6 +/- 1.5 days. Average postoperative stay was 10.7 +/- 2 days. There were 2 early deaths and 1 late death and no recurrent EMP. Bacteriology findings were nonspecific and often polymicrobial. We conclude that early thoracotomy can be lifesaving in the presence of a benign clinical course.
We studied the effects of intraaortic balloon counterpulsation (IABCP) on prostacyclin (PGI2) and thromboxane (TXB2) levels in dogs during 24 hours of 1:1 IABCP or a sham procedure in which the balloon was positioned but left deflated. The arterial PGI2 levels in the IABCP group increased from control values of 95 +/- 20 pg/ml to 268 +/- 95 pg/ml at 1 hour, 429 +/- 95 pg/ml at 4 hours, and 1,884 +/- 532 pg/ml at 24 hours. The arterial PGI2 levels were consistently higher in the IABCP group. Although the TXB2 measurements revealed no significant differences between groups, the IABCP group consistently had a higher level than the sham group. The platelet count in the control group decreased to 45% of baseline levels versus 55% for the IABCP group. We conclude that prolonged IABCP results in either net production of PGI2 or decreased degradation. The correlation between TXB2 and platelet counts is unclear and remains to be defined.
The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitise the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted). The Bmax of benzodiazepine binding to unwashed cortical P2 synaptosomal membranes has been reported to increase twofold in adult Wistar rats at mid-dark. By contrast the Bmax of juvenile Wistar rats in this study increased only 17% (116 +/- 2.4 fmol/mg protein to 140 +/- 3 fmol/mg protein) between 2 and 5 h after darkness. In melatonin-treated animals the increase in Bmax of 3H-diazepam binding was blocked (124 +/- 5 fmol/mg protein at 2 h; 127 +/- 3 fmol/mg protein at 5 h) and the Kd reduced (4.5 +/- 0.5 to 4.0 +/- 0.2 nM).(ABSTRACT TRUNCATED AT 400 WORDS)
Mediastinal neuroblastomas, which are common malignancies of childhood, are extremely rare in adults. This article presents a case of mediastinal neuroblastoma in a 57-year-old man. To the authors' knowledge, this is only the second recorded case of such a tumor in an adult. The patient's clinical course is described and is compared with other cases (in children, except for one instance) cited in the literature. The authors discuss the early diagnosis and surgical management of these uncommon lesions, which tend to be quite extensive and rapidly fatal, and which should be suspected in adults who present with a mediastinal mass.
Eleven rabbits (five female, six male) were fed a high (2%) cholesterol diet for 2 weeks. Twelve control rabbits (six female, six male) were fed standard rabbit chow. As expected, the cholesterol feeding raised serum and bile cholesterol concentrations and increased the lithogenic indexes. The gallbladders were harvested, and the mucosa and serosa were separately exposed to arachidonic acid in an in vitro incubation chamber at 37 degrees C. Cholesterol feeding stimulated the rates of synthesis of PGI2, but this effect was limited to the serosa (and not the mucosa) of gallbladders from female (but not male) animals. In contrast, cholesterol did not induce any changes in PGE biosynthesis.
Patency of vein grafts may be influenced by the medium in which they are stored temporarily. We compared saline solution vs blood on prostanoid production and maintenance of endothelium in canine veins after 1 hour of storage at 23 degrees C with 0.2 mg/ml of papaverine. Spontaneous and arachidonate-stimulated prostaglandin levels were measured by radioimmunoassay. Endothelial integrity was analyzed by light and electron microscopy. Prostaglandin production in blood vs that in saline solution was 1821 +/- 1264 and 1259 +/- 719 pg/cm2/min at control and 6705 +/- 3702 vs 6264 +/- 3409 pg/cm2/min, respectively, after stimulation. There were no statistically significant differences between the groups at any time point. Thromboxane levels were also indistinguishable between groups. Microscopy revealed 70% endothelial loss in blood vs 95% for saline solution. We conclude that endothelial preservation is enhanced by blood storage, that the medial layer produces substantial amounts of prostacyclin, and that additional storage solutions need to be investigated.
The purpose of this study was to investigate the effect of bright artificial light exposure on the rhythms of 6-sulphatoxy melatonin and cortisol excretion in urine. Six healthy males were exposed to light (greater than 3,000 lux) from 1900 to 0200 h (sunset 1928 h) on one occasion. The artificial light delayed the onset of 6-sulphatoxy melatonin excretion. On the next evening the onset of 6-sulphatoxy melatonin excretion in normal light/darkness was delayed by 1 h. The timing of the peak excretion of cortisol was not affected by the light treatment; however, cortisol excretion rate was maintained at a significantly higher rate in the morning and afternoon after the treatment. These results demonstrate the inhibitory action of high intensity light in humans and suggest that one 6-h period of extra light in the evening can phase delay the melatonin onset.
Surgical repair of complex thoracic aneurysms requiring aortic valve replacement and coronary revascularization is occasionally complicated by significant bleeding despite the experience of the surgeon. While bleeding from the mediastinal tissues and the anterior suture line is usually easily controlled, posterior bleeding may require dismantling the repair and a second bypass run. The synergism of a second bypass run and continued bleeding may result in increased mortality and/or morbidity. We recently encountered bleeding in a patient who developed ventricular dysfunction after bypass and opted to interpose a Gore-tex graft between the aneurysm wall and the right atrium with immediate hemostasis and a benign course. Subsequently we used four different shunts successfully in 9 of 33 patients. The average bleeding rate 30 minutes after protamine was 221 +/- 60 ml/minute with a range of 190 to 350 ml/minute. The initial two hour chest tube drainage averaged 880 +/- 285 ml with a range of 490 to 1300 ml. There were no re-explorations for bleeding. The shunt in the first patient has remained open without cardiac decompensation. The last patient developed heart failure and required elective repair of a leak at the descending end of an arch replacement. Our experience suggests that these shunts can be effective, particularly if posterior suture line bleeding is encountered.
The timing of surgical treatment of empyema remains controversial. Traditionally, thoracotomy is performed either within three weeks of diagnosis or delayed until presumed pleurodesis occurs. Often, these patients are moribund and the duration of illness impossible to determine. We report our surgical results in seven patients with a deteriorating clinical course and multiple loculations which persisted after tube thoracostomy and would not have responded to multiple thoracostomies. Five patients required decortication. One required lobectomy for an abscess which developed on the contralateral side six weeks after discharge. There were no deaths or recurrences of empyema. Average times from surgery to tube removal and to discharge were six to 12 days, respectively. We conclude that one can safely and cost-effectively treat these patients surgically even when the duration of illness and presence of pleurodesis are unknown, and that the postoperative course will be uncomplicated.
Iliac artery aneurysms are rare and the usual symptoms, pelvic pain and urological complaints, are nonspecific. We describe a patient with pelvic pain, intermittent urinary retention, and lower extremity edema. A right common iliac artery aneurysm was discovered during surgery after rupture had occurred. Pathologic examination revealed a mycotic process. This case demonstrates the obscure and unreported clinical features of iliac artery aneurysms. When this lesion is suspected, an angiogram should be performed promptly in an effort to prevent the predictable catastrophic consequences.
One-stage surgery was successfully performed in a 44-year-old hypertensive man with uncontrolled angina, multiple coarctations of the thoracic and abdominal aorta, and a previous subtotal gastrectomy. There was a gradient of 120 mm Hg between the thoracic and abdominal aorta. A graft was placed retroperitoneally from the infrarenal aorta to the ascending aorta and was followed by a coronary artery bypass graft. Twenty-four months postoperatively, the patient was free of angina, and his hypertension was easily controlled.