Fusobacterium nucleatum prosthetic hip infection in an adult with sickle cell-beta thalassemia.

Fusobacterium nucleatum is an anaerobic Gram-negative bacillus commensal to the human oropharynx and gastrointestinal tract which causes an array of human infection, yet it has never been associated with infection of prosthetic joints. We report the first case of prosthetic hip infection caused by F. nucleatum in a man with sickle cell-beta thalassemia.

[Fatigue and icterus in a 27-year-old patient with diabetes mellitus type I]. / Abgeschlagenheit und Ikterus bei 27-jähriger Diabetes-mellitus-Typ-1-Patientin.

We report about a 27-year-old female with type I diabetes who was admitted with progressive fatigue and a sudden onset of icterus. As the underlying cause, we found pernicious anemia with hemolytic activity as part of polyglandular autoimmune syndrome (PAS) type II. Under vitamin B(12) substitution we saw a quick rise in hemoglobin and improvement of complaints. Type I diabetes is the most frequent component of PAS II, whereas pernicious anemia is a rather rare component; however, a latent form is seen in about 12% of patients with type I diabetes. Therapy for pernicious anemia consists of parenteral vitamin B(12) substitution. Because of an increased incidence of gastric cancer in chronic atrophic gastritis, endoscopic follow-ups of the chronic atrophic autoimmune gastritis seem to be recommended. Due to the diverse characteristic of PAS II, with development of additional components after years of latency, regular follow-up clinical examinations and lab work are mandatory to detect further need of hormone and vitamin replacement that may sometimes be substantial for survival.

Quantitative atomic-scale analysis of interface structures: transmission electron microscopy and local density functional theory.

Transmission electron microscopy (TEM) and local density functional theory (LDFT) are combined to analyze the microscopic structure of the rhombohedral twin interface in alpha-Al2O3. LDFT provides interfacial energetics and atomic and electronic structures for three competing models. With high-resolution TEM the atomic structure at the interface is imaged quantitatively along two orthogonal zone axes. Electron energy loss spectroscopy in TEM with nanoscale spatial resolution yields the interfacial electronic structure. Both experiments confirm the theoretically preferred model quantitatively.

Does increased cement pressure produce superior femoral component fixation?

A new system of femoral cement pressurization is presented that attempts to produce sustained and elevated cement pressure. Five paired cadaver femora were pressurized with Simplex cement, and PFC femoral components were inserted. One of each pair was pressurized with the new system, and 1 was pressurized with an existing device. Pressure was recorded at the proximal and distal levels. After curing, all 10 specimens were sectioned at similar levels and subjected to push-out testing to failure. Specimens that achieved higher pressures and longer duration of pressures tended to show higher levels of failure (not statistically proven on 10 specimens). Cementing techniques that use higher pressurization of cement are recommended. It is mandatory, however, that the femur be thoroughly cleaned of fat before the application of these techniques to avoid a fat embolism syndrome.

Dissolution of gallbladder stones with methyl tert-butyl ether and stone recurrence: a European survey.

Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.

In vivo effects of a novel thromboxane A2/prostaglandin H2 (TXA2/PGH2) partial agonist, (+)5(Z)-7-[3-endo-phenylsulfonylamino[2.2.1]- bicyclohept-2-exo-yl]-heptenoic acid [(+)-S-145], on vascular, platelet and cardiac function.

A novel thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor ligand, (+)5(Z)-7-[3-endo-phenylsulfonylamino[2.2.1]-bicyclohept-2-e xo- yl]-heptenoic acid [(+)-S-145], was evaluated in guinea pigs to assess the in vivo pharmacodynamic profile of this compound at vascular, cardiac and platelet TXA2/PGH2 receptors. Comparison was made to the TXA2/PGH2 receptor antagonist SQ29548. Upon i.v. injection, (+)-S-145, but not SQ29548, elicited transient (approximately 1 min) increases in mean arterial blood pressure (ED50 +/- 95% confidence limit = 6.1 + 4.0, -2.2 micrograms/kg). The potency of i.v. (+)-S-145 (ID50 = 6.3 + 2.3, -2.3 micrograms/kg) against the pressor response to subsequent i.v. TXA2/PGH2 mimetic, U44069, was 9.5-fold greater than that of SQ29548 (ID50 = 59.1 + 52.9, - 52.9 micrograms/kg). Intravenous (+)-S-145 inhibited U44069-induced decreases in circulating platelet count (ID50 = 4.2 + 4.1, - 2.0 micrograms/kg). In thoracotomized guinea pigs, i.v. (+)-S-145 (31.6 micrograms/kg) and increasing i.v. doses of U44069 increased mean arterial blood pressure, total peripheral resistance, left ventricular end-diastolic pressure and left ventricular peak positive dP/dt (LV + dP/dt) and depressed cardiac output (P < .05). Pretreatment with i.v. (+)-S-145 (31.6 micrograms/kg) abolished these U44069-induced effects. In thoracotomized guinea pigs in which left ventricular end-diastolic pressure and HR were held constant, U44069 again increased LV + dP/dt (P < .05), but (+)-S-145 decreased LV + dP/dt (P < .05), which indicates the lack of an (+)-S-145 direct inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of thromboxane A2/prostaglandin H2 binding sites in guinea pig cardiac membrane preparations.

Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) induce platelet aggregation and are potent vasoconstrictors, and they have been implicated in coronary vasospasm and myocardial infarction. The TXA2 mimetic [1S-(1 alpha, 2 beta (5Z), 3 alpha (1E,3S*), 4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-h eptenoic acid (IBOP) was used to characterize binding to microsomal membrane preparations from saline-perfused guinea pig atria (GPA) and ventricles (GPV). [125I]IBOP bound to GPA and GPV in a protein-dependent and saturable manner, although total binding was two-fold greater and non-specific binding was proportionately less in GPA compared to GPV. Analysis of equilibrium binding data indicated one class of binding sites in both GPA and GPV with Kd values of 333 +/- 117 and 645 +/- 187 pM, respectively, which were in close agreement with kinetically determined Kd values of 226 and 882 pM, respectively. Bmax values of GPA and GPV of 57 +/- 5.6 and 24 +/- 4.3 fmol/mg protein were significantly different (P < 0.01). Ki values (from IC50s) were determined for various TXA2/PGH2 analogues and prostaglandins in competition binding assays with [125I]IBOP. The rank order for ability to inhibit binding in GPA was U46619 = SQ29548 > I-PTA-OH > PGF2 alpha = PGE2. In GPV, the rank order was U46619 = SQ29548 > PGF2 alpha = I-PTA-OH = PGE2. [125I]IBOP binding to GPA and GPV was completely displaced by the TXA2/PGH2 agonist U46619 and by the TXA2/PGH2 antagonist SQ29548.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole directly inhibits vascular smooth muscle cell proliferation in vitro and in vivo: implications in the treatment of restenosis after angioplasty.

OBJECTIVES: The effect of dipyridamole on smooth muscle cell proliferation and prevention of intimal thickening after arterial injury was investigated. BACKGROUND: In addition to antiplatelet activity, dipyridamole also inhibits cell proliferation. We examined whether the antiproliferative action of dipyridamole on smooth muscle cells, as demonstrated here, has a direct effect on intimal thickening after vascular injury. METHODS: Cell proliferation was determined by measuring deoxyribonucleic acid (DNA) synthesis and by cell counting. The in vivo effect of locally delivered dipyridamole was determined in a rabbit model with carotid or femoral artery injury. RESULTS: Dipyridamole produced a dose-dependent inhibition of smooth muscle cell proliferation, producing 50% inhibition at 7 micrograms/ml. Structural analogues SH-869 and mopamidol were 10 to 100 times less effective than dipyridamole, suggesting that cell growth inhibition may be unrelated to the antiplatelet activity of dipyridamole. Inhibition of cell proliferation by dipyridamole was attenuated by increasing the serum concentration in the culture medium. Bypassing serum by local delivery of dipyridamole at the periadventitial site produced 63% inhibition (p < 0.05) of cell replication in balloon-injured arteries. Locally delivered dipyridamole also inhibited intimal thickening (20%, p < 0.05) after balloon injury. CONCLUSIONS: Dipyridamole inhibited smooth muscle cell proliferation in vitro. This activity was attenuated by serum proteins. Locally delivered dipyridamole inhibited cell replication in arteries and intimal thickening after balloon injury. These results suggest that although systemic treatment with dipyridamole may not be efficacious because of inadequate serum levels, its antiproliferative action on smooth muscle cells may reduce restenosis when the drug is delivered locally after coronary angioplasty.

In vitro characterization of a novel TXA2/PGH2 receptor ligand (S-145) in platelets and vascular and airway smooth muscle.

The stereoisomers of S-145, a novel thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor ligand, were compared to TXA2/PGH2 receptor antagonists, SQ29548 and BM13505 in guinea pig platelets, aortas and trachea. Equilibrium binding assays in platelets yielded Kd values (nanomolar) for (+)-S-145 (0.57 +/- 0.04), (-)-S-145 (9.2 +/- 1.3), SQ29548 (11.1 +/- 0.70) and BM13505 (118 +/- 16). In aortas, the corresponding Kb values (nanomolar) were (0.014 +/- 0.002), (1.90 +/- 0.31), (16.8 +/- 3.3) and (142 +/- 29), respectively, whereas in trachea, the Kd values (nanomolar) were (0.019 +/- 0.004), (1.12 +/- 0.18), (1.94 +/- 0.30) and (18.99 +/- 2.59), respectively. S-145 stereoisomers elicited platelet shape change stereoselectively that was characterized by EC50 values 8 to 16-fold higher than the EC50 values for these ligands to block aggregation induced by TXA2/PGH2 mimetic, U44069. S-145 (+)- and (-)-isomers stereoselectively induced transient aortic contraction at concentrations 214,000- and 16,000-fold higher, respectively, than the corresponding Kb values in this tissue. S-145-induced platelet shape change and aortic contraction were inhibitable by low concentrations of SQ29548. We postulate that S-145 may elicit partial agonist activity in platelets and aorta via lower affinity for the active than inactive state of the TXA2/PGH2 receptor in those tissues. S-145 had no agonist activity in isolated trachea possibly indicating different TXA2/PGH2 recognition sites in aorta and trachea or a smaller preligand ratio of active to inactive TXA2/PGH2 receptors in trachea than in aorta.

[Role of bile acids in the development of peptic lesions. Studies on the bile acid-binding capacity of a new kind of antacid]. / Der Stellenwert der Gallensäuren für die Entstehung peptischer Läsionen. Untersuchungen zum Gallensäurenbindungsvermögen eines neuartigen Antazidums.

Bile acids are a factor in the pathogenesis of peptic lesions of the mucosa. The introduction in the literature of the term type C gastritis reflects the recognition of this fact. It is possible that antacids develop their effect not merely via the neutralization of hydrochloric acid, but, to an appreciable extent, through the adsorption of toxic substances. Since antacids often elevate the gastric pH only slightly, we investigated bile acid binding not only as a function of dose, but also at low pH values. The aim of the study was, in a follow-on to previous studies of a layer-lattice antacid to describe the characteristics of an antacid of the mixed type (aluminium-magnesium hydroxide + smectite). Already at neutral pH, Gelofalk manifests a high level of bile acid absorption, which increases further at low pH values. The high bile acid absorption capacity of Gelofalk shows no correlation with decreasing bile acid polarity; the dose-dependency is lower at high than at low pH levels. This indicates that bile acid absorption by Gelofalk must, at least in part, involve other mechanisms than those operative in the case of pure layer-lattice antacids.

[The effect of pH and amount of antacids on bile acid binding in a quasi-natural reflux milieu]. / Einfluss von pH und Antazidummenge auf die Gallensäurenbindung in quasinatürlichem Refluxmilieu.

Bile acid adsorption may be one therapeutical mechanism of antacids. Little is known about the effect of pH and amount of antacid on bile acid adsorption. Therefore we carried out the following investigations using a lattice [correction of lettuce] layer antacid as a model substance. 5 ml of "quasi-natural reflux milieu" were mixed with 0.5, 1 or 2 ml of hydrotalcite and adjusted to pH 3, 5 or 7. The highest total bile acid adsorption was found at pH 3, the degree of bile acid adsorption correlated with bile acid lipophilicity, i.e. the most lipophilic and toxic bile acids are adsorbed best. High adsorption of lipophilic and particularly toxic bile acids even at low gastric pH may help to explain the good therapeutic effect of low-dose antacids in gastric ulcer.

[Endoscopy, shockwave lithotripsy and local lysis in complicated pigmentary calculi of extra- and intrahepatic bile ducts]. / Endoskopie, Stosswellenlithotripsie und lokale Lyse bei komplizierten Pigmentsteinen der extra- und intrahepatischen Gallengänge.

Endoscopy, extracorporeal shockwave lithotripsy (ESWL) and local lysis with alkaline solution of EDTA and bile salts in water were applied in combination in four patients with extra- and intrahepatic pigment stones as well as calcium bilirubinate covered concrements of the biliary tract. In the first patient (a man aged 80 years) a giant concrement of the bile duct was broken up after ESWL by three weeks of local chemical lysis and the fragments were removed by endoscopy. In the second case (man, aged 72), a nonextractable pigment stone was at first reduced in size by four-day local lysis and then removed endoscopically. Intrahepatic pigment stones were completely removed in the other two patients (boy of 12, man of 62) by local lysis only in 3 and 15 weeks, respectively. Even long-term use of the alkaline solution may not cause any serious side effects. Breaking up of stones after size reduction with ESWL of giant stones, size reduction of intact stones and contact lysis of intrahepatic stones are three important indications for chemical dissolution of biliary tract stones, respectively.

A multivariate approach to the treatment of peripheral nerve transection injury: the role of electromagnetic field therapy.

A multivariate approach to the treatment of peripheral nerve transection injury has been used in a rat model. A pilot study (48 animals, 8 groups) examined variables associated with the method and timing of surgical repair, the arrest of wallerian degeneration, and the role of pulsing electromagnetic field therapy (PEMF) in functional recovery. A second phase (90 animals, 6 groups) then studied the timing and duration of pulsing electromagnetic field therapy as the only variable in larger groups of animals. The pilot study revealed that a vein-graft conduit did not improve functional recovery compared with standard epineurial repair. Additionally, delayed repair compared favorably with immediate repair. The use of chlorpromazine to inhibit the toxic effects of calcium influx appeared to enhance early functional recovery, and the combination of delayed nerve repair and pulsing electromagnetic field therapy seemed to consistently improve function. The second phase of the study has demonstrated (for the first time) statistical improvement in ambulation in animals treated with delayed surgical repair and prolonged pulsing electromagnetic field therapy. We postulate that future treatment of nerve transection injuries will involve a combined treatment regimen consisting of the immediate arrest of wallerian degeneration, delayed surgery, and pulsing electromagnetic field therapy.

Characterization of a thromboxane A2/prostaglandin H2 receptor in guinea pig lung membranes using a radioiodinated thromboxane mimetic.

Thromboxane A2 (TXA2) and prostaglandin H2 (PGH2) are potent constrictors of airway smooth muscle and may mediate some of the pulmonary effects of leukotrienes. To date, the TXA2/PGH2 receptor in lung has not been well characterized. In this report, we describe the evaluation of the TXA2/PGH2 receptor in guinea pig lung membranes using the new radiolabeled TXA2 mimetic [1S(1 alpha,2 beta(5Z),3 alpha(1E,3S*),4 alpha)]-7-[3-(3-hydroxy-4-(4'- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptan-2-yl]-5-h eptenoic acid (IBOP). IBOP elicited a dose-dependent contraction of guinea pig lung parenchymal strips (EC50 = 3.03 +/- 0.97 nM, three experiments), which was blocked by the TXA2/PGH2 antagonists SQ29548 (pKB = 7.44 +/- 0.2, three experiments), BM13505 (pKB = 6.29 +/- 0.26, three experiments), and I-PTA-OH (pKB = 5.82 +/- 0.36, three experiments). In radioligand binding studies, the binding of [125I]IBOP to guinea pig lung membranes prepared from perfused lungs was saturable, displaceable, and dependent upon protein concentration. Binding was optimal at pH 6.5 and was enhanced by the addition of mono- and divalent cations. The standard assay buffer was 25 mM 3-(N-morpholino)propanesulfonic acid, pH 6.5, 100 mM NaCl, 5 mM MgCl2. Binding was inhibited by pretreatment with dithiothreitol, N-ethylmaleimide, or beta-mercaptoethanol. Binding was unaffected by the addition of guanine nucleotide analogs at concentrations up to 300 microM. Analysis of the time course of binding of [125]IBOP at 30 degrees yielded k-1 = 0.0447 min-1, k1 = 2.49 x 10(8) M-1 min-1, and Kd = k-1/k1 = 180 pM. Computer analysis of equilibrium binding studies using nonlinear methods (LUNDON-1) revealed a single class of noninteracting binding sites with a Kd of 86.9 +/- 11.9 pM and a Bmax of 81.8 +/- 7.7 fmol/mg of protein (three experiments). [125I]IBOP binding to guinea pig lung membranes was inhibited by a series of TXA2/PGH2 receptor agonists and antagonists, with a rank order different from that previously determined for washed guinea pig platelets (Spearman's r = 0.686, p greater than 0.05). [125I]IBOP binding to guinea pig lung membranes was also inhibited by the prostanoids prostaglandin D2, prostaglandin E2, prostaglandin F2 alpha, and 9 alpha,11 beta-prostaglandin F2, all of which have been proposed to act at the TXA2/PGH2 receptor in lung.