Heterogeneous Nucleation of an n-Alkane on Tetrahedrally Coordinated Crystals.

Heterogeneous nucleation refers to the propensity for phase transformations to initiate preferentially on foreign surfaces, such as vessel walls, dust particles, or formulation additives. In crystallization, the form of the initial nucleus has ramifications for the crystallographic form, morphology, and properties of the resulting solid. Nevertheless, the discovery and design of nucleating agents remains a matter of trial and error because of the very small spatiotemporal scales over which the critical nucleus is formed and the extreme difficulty of examining such events empirically. Using molecular dynamics simulations, we demonstrate a method for the rapid screening of entire families of materials for activity as nucleating agents and for characterizing their mechanism of action. The method is applied to the crystallization of n-pentacontane, a model surrogate for polyethylene, on the family of tetrahedrally coordinated crystals, including diamond and silicon. A systematic variation of parameters in the interaction potential permits a comprehensive, physically based screening of nucleating agents in this class of materials, including both real and hypothetical candidates. The induction time for heterogeneous nucleation is shown to depend strongly on crystallographic registry between the nucleating agent and the critical nucleus, indicative of an epitaxial mechanism in this class of materials. Importantly, the severity of this registry requirement weakens with decreasing rigidity of the substrate and increasing strength of attraction to the surface of the nucleating agent. Employing this method, a high-throughput computational screening of nucleating agents becomes possible, facilitating the discovery of novel nucleating agents within a broad "materials genome" of possible additives.

Characterization of DNA conformation inside bacterial viruses.

In this study we develop a formalism to describe the organization of DNA inside bacteriophage capsids during genome packaging. We have previously shown that DNA inside bacteriophage phi29 (phi29) is organized into folded toroids [A. S. Petrov and S. C. Harvey, Structure 15, 21 (2007)], whereas epsilon15 (epsilon15) reveals the coaxial organization of the genetic material [A. S. Petrov, K. Lim-Hing, and S. C. Harvey, Structure 15, 807 (2007)]. We now show that each system undergoes two consecutive transitions. The first transition corresponds to the formation of global conformations and is analogous to a disorder-order conformational transition. The second transition is characterized by a significant loss of DNA mobility at the local level leading to glasslike dynamic behavior. Packing genetic material inside bacteriophages can be used as a general model to study the behavior of semiflexible chains inside confined spaces, and the proposed formalism developed here can be used to study other systems of linear polymer chains confined to closed spaces.

DNA organization and thermodynamics during viral packing.

An elastic DNA molecular mechanics model is used to compare DNA structures and packing thermodynamics in two bacteriophage systems, T7 and phi29. A discrete packing protocol allows for multiple molecular dynamics simulations of the entire packing event. In T7, the DNA is coaxially spooled around the cylindrical core protein, whereas the phi29 system, which lacks a core protein, organizes the DNA concentrically, but not coaxially. Two-dimensional projections of the packed structures from T7 simulations are consistent with cryo-electron micrographs of T7 phage DNA. The functional form of the force required to package the phi29 DNA is similar to forces determined experimentally, although the total free energy change is only 40% of the experimental value. Since electrostatics are not included in the simulations, this suggests that electrostatic repulsions are responsible for approximately 60% of the free energy required for packaging. The entropic penalty from DNA confinement has not been computed in previous studies, but it is often assumed to make a negligible contribution to the total work done in packing the DNA. Conformational entropy can be measured in our approach, and it accounts for 70-80% of the total work done in packing the elastic model DNA in both phages. For phi29, this corresponds to an entropic penalty of approximately 35% of the total work observed experimentally.

Folding behavior of model proteins with weak energetic frustration.

The native structure of fast-folding proteins, albeit a deep local free-energy minimum, may involve a relatively small energetic penalty due to nonoptimal, though favorable, contacts between amino acid residues. The weak energetic frustration that such contacts represent varies among different proteins and may account for folding behavior not seen in unfrustrated models. Minimalist model proteins with heterogeneous contacts--as represented by lattice heteropolymers consisting of three types of monomers--also give rise to weak energetic frustration in their corresponding native structures, and the present study of their equilibrium and nonequilibrium properties reveals some of the breadth in their behavior. In order to capture this range within a detailed study of only a few proteins, four candidate protein structures (with their cognate sequences) have been selected according to a figure of merit called the winding index--a characteristic of the number of turns the protein winds about an axis. The temperature-dependent heat capacities reveal a high-temperature collapse transition, and an infrequently observed low-temperature rearrangement transition that arises because of the presence of weak energetic frustration. Simulation results motivate the definition of a new measure of folding affinity as a sequence-dependent free energy--a function of both a reduced stability gap and high accessibility to non-native structures--that correlates strongly with folding rates.

Technical aspects of harvesting the radial artery with the harmonic scalpel.

BACKGROUND: Harvesting the radial artery (RA) with ultrasonic dissection with the Harmonic Scalpel reduces spasm induced by surgical handling. Topical exposure to phentolamine methanesulphonate (Regitine) exerts an additional effect of vasodilatation. METHODS: Between January and December 2002, the RA was harvested as a pediculated vessel with the Harmonic Scalpel in 145 consecutive patients undergoing myocardial revascularization. A fasciotomy of the pedicle was performed after harvest ing. A composite graft with the reverse free RA on the in situ left internal thoracic artery (ITA) was prepared before the construction of distal coronary anastomoses. The RA was then placed in a syringe filled with Regitine (0.07 microg/mL) for 10 minutes. \par RESULTS: The mean number of grafts/patient was 3.0. The mean number of RA anastomoses was 2.0/patient. Left ITA free flow was 105 +/- 34 mL/min. Regitine increased the RA free flow from 60 +/- 35 mL/min to 82 +/- 30 mL/min (P <.05). Fourteen patients underwent postoperative coronary angiography. All RA anastomoses were patent. CONCLUSION: The compound effect of RA harvesting with the Harmonic Scalpel and topical treatment with the alpha- blocking agent Regitine increases the RA free flow and significantly decreases intraoperative spasticity.

Midterm results of routine bilateral internal thoracic artery grafting.

BACKGROUND: Skeletonized dissection of the internal thoracic artery (ITA) decreases the occurrence of sternal devascularization, thus decreasing the risk of postoperative sternal complications in patients undergoing bilateral ITA grafting. METHODS: From April 1996 to July 1999, 1000 consecutive patients underwent bilateral skeletonized ITA grafting. Of the 770 male and 230 female patients, 420 were older than 70 years, and 312 had diabetes. RESULTS: Operative mortality was 3.3%. Follow-up (40-78 months) revealed 79 late deaths, and the Kaplan-Meier 6-year survival rate was 88%. Cox regression analysis revealed increased overall mortality (early and late) in patients with preoperative congestive heart failure (risk ratio [RR], 2.13; 95% confidence interval [CI], 1.31-3.45), in patients with peripheral vascular disease (RR, 5.52; 95% CI, 3.31-9.19), and in patients older than 70 years (RR, 2.18; 95% CI, 1.37-3.47). Early postoperative morbidity included sternal infection (2.2%), cerebrovascular accident (1.6%), and perioperative myocardial infarction (1%). Multiple regression analysis showed repeat operation (odds ratio [OR], 7.5; 95% CI, 1.77-31.6) and chronic obstructive pulmonary disease (OR, 3.6; 95% CI, 1.27-10.75) to be independent predictors of sternal infection. During follow-up, angina returned in 95 patients, 24 of whom required reintervention (20 cases of percutaneous balloon angioplasty and 4 reoperations). Postoperative coronary angiography performed in 87 patients revealed an ITA patency rate of 91%. CONCLUSIONS: Bilateral skeletonized ITA grafting is associated with satisfactory early and midterm results. We do not recommend the use of this surgical technique in patients with chronic obstructive pulmonary disease.

Pretreatment with alpha-adrenergic blockers for prevention of radial artery spasm.

BACKGROUND: Radial artery (RA) conduits are prone to early vasospasm. Current intraoperative treatment with papaverine fails to inhibit postoperative RA constriction. Pretreatment with topical a-antagonist solutions can inhibit RA vasoconstriction and cause dilatation for a longer period than achieved with papaverine. METHODS: In 10 patients undergoing myocardial revascularization, the radial artery was harvested as a skeletonized vessel. A composite graft with reverse free RA on an in situ left internal thoracic artery was prepared before construction of distal coronary anastomoses. The RA pedicle was then put in a small syringe filled with Regitine (phentolamine methansulphonic, 0.07 mg/mL) ("Jacuzzi") and warmed by immersing the container in a warm saline bath for 8 to 15 minutes. The RA free flow was measured before and after topical treatment with Regitine. RESULTS: The mean number of grafts per patient was 2.9 (range 2 to 4). The mean number of radial anastomoses was 1.8 per patient. Left internal thoracic artery free flow was 110 +/- 29 mL/min. Regitine increased radial free flow from 49 +/- 35 to 77 +/- 30 mL/min (p < 0.01). Five patients underwent postoperative coronary angiography. All radial anastomoses were patent. CONCLUSIONS: Topical treatment of RA with Regitine increases RA free flow and is an effective intraoperative means of decreasing RA spasticity.

Protamine-induced cardiotoxicity is prevented by anti-TNF-alpha antibodies and heparin.

BACKGROUND: We investigated the role of tumor necrosis factor alpha (TNF-alpha) in protamine-induced cardiotoxicity and the possibility of preventing or decreasing this effect by anti TNF-alpha antibodies and heparin. METHODS: Isolated rat hearts were perfused for 60 min with Krebs-Henseleit solution (KH). The control group was perfused with KH alone, the KH > protamine > KH group was treated from the 20th to the 40th minute with protamine, and the KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF group was treated the same as the KH > protamine > KH group but with anti-TNF-alpha antibodies added throughout perfusion. The KH + heparin > protamine + heparin > KH + heparin group was treated the same as the KH > protamine > KH group but with heparin added to KH throughout perfusion. The KH > protamine > KH + heparin was perfused the same as the KH> protamine > KH group but with heparin added to KH for the last 20 min. Left ventricular (LV) function and coronary flow were measured every 10 min. TNF-alpha was measured in the coronary sinus effluent. Left ventricular TNF messenger RNA was determined in the control and KH > protamine > KH groups at baseline and after the 40-min perfusion. RESULTS: Protamine caused a significant decrease of peak systolic pressure and dP/dt (to 25% of baseline). Significant amounts of TNF-alpha in the effluent in the KH > protamine > KH group (102.3 +/- 15.5 pg/min) and TNF messenger RNA expression in left ventricular samples were detected. TNF-alpha was below detectable concentrations in the control, KH + anti-TNF > protamine + anti-TNF > KH + anti-TNF, and KH + heparin > protamine + heparin > KH + heparin groups. TNF-alpha concentrations correlated with depression of LV peak systolic pressure (r = 0.984; P = 0.01) and first derivate of the increase of LV pressure (r = 0.976; P = 0.001). Heparin improved LV recovery and decreased protamine-induced TNF-alpha release (KH > protamine > KH + heparin group). CONCLUSIONS: Anti-TNF-alpha antibodies and heparin prevent protamine-induced TNF-alpha release and depression of LV function. Heparin improves protamine-induced depression of cardiac function.

A minimalist model protein with multiple folding funnels.

Kinetic and structural studies of wild-type proteins such as prions and amyloidogenic proteins provide suggestive evidence that proteins may adopt multiple long-lived states in addition to the native state. All of these states differ structurally because they lie far apart in configuration space, but their stability is not necessarily caused by cooperative (nucleation) effects. In this study, a minimalist model protein is designed to exhibit multiple long-lived states to explore the dynamics of the corresponding wild-type proteins. The minimalist protein is modeled as a 27-monomer sequence confined to a cubic lattice with three different monomer types. An order parameter-the winding index-is introduced to characterize the extent of folding. The winding index has several advantages over other commonly used order parameters like the number of native contacts. It can distinguish between enantiomers, its calculation requires less computational time than the number of native contacts, and reduced-dimensional landscapes can be developed when the native state structure is not known a priori. The results for the designed model protein prove by existence that the rugged energy landscape picture of protein folding can be generalized to include protein "misfolding" into long-lived states.

Composite arterial grafting with double skeletonized internal thoracic arteries.

OBJECTIVES: Composite arterial grafting is a surgical technique for arterial myocardial revascularization, in which free arterial conduits are proximally anastomosed end-to-side to an intact internal thoracic artery (ITA). This report describes technical aspects and results of composite grafting using bilateral skeletonized ITAs. METHODS: From April 1996 to February 1999, 1057 patients underwent coronary artery bypass grafting (CABG) using bilateral skeletonized internal thoracic arteries. In 600 of them (57%), composite arterial grafting was performed. There were 452 men and 148 women. The mean age was 69 +/- 7 years. Two-hundred and six patients (34%) were diabetics, 84 (14%) had severe left ventricular dysfunction (ejection fraction of < 35%), and 26 (4.3%) underwent emergency operations. In 574 patients, the right ITA was used as a free graft connected to the in-situ left ITA. In 26, the free left ITA was attached to the in-situ right ITA, and in 38, mini-composite grafts (free distal left ITA on the left ITA, or free distal right ITA on the right ITA) were constructed. The average number of grafts was 3.0/patient (range, 2--6). RESULTS: The operative mortality was 2.8% (n = 17), and there were ten (1.7%), deep sternal wound infections. The mean follow-up was 25 months (range, 14--36 months). The 3-year survival was 92.5%. Ninety-seven percent of the surviving patients were angina-free. CONCLUSIONS: We currently perform this surgery routinely in most patients referred for CABG, and regard bilateral skeletonized internal thoracic arteries as the most appropriate arterial conduits for the composite technique.

Vasoactive response of different parts of human internal thoracic artery to isosorbide-dinitrate and nitroglycerin: an in-vitro study.

OBJECTIVE: The left internal thoracic artery (LITA) is the most important graft for coronary artery bypass grafting (CABG). Its distal region is, however, prone to vasospasm. The effect of nitroglycerin (NTG) and isosorbide-dinitrate (ISDN) on different segments of this region was studied. METHODS: Rings of three segments of the LITA were studied: 6-9 mm proximal to the bifurcation (part A); 1-3 mm proximal to the bifurcation (part B); and 3-6 mm distal to the bifurcation (part C). After baseline, maximal contraction of the rings was achieved using 60 mmol/l of KCl, they were exposed to increasing doses of ISDN and NTG (10-100 microg/ml), and dose-response curves were recorded. RESULTS: The contractile response of part A to KCl was significantly lower than that of parts B and C (1.87+/-0.25 versus 4.05+/-0.39 and 7.64+/-0.54 g, respectively; P<0.001). Both nitrates inhibited the contractile response in a concentration-dependent manner. The relaxing effects of both nitrates on part A was most pronounced (P<0.01), with the effect of ISDN being higher than that of NTG (P<0.01). CONCLUSIONS: The region 6-9 mm proximal to the LITA bifurcation is less prone to vasospasm, and has greater relaxation responses to ISDN and NTG than the more vasospastic distal parts of the LITA. We recommend avoiding the use of the very distal part of this artery during CABG, and to use high doses of ISDN rather than NTG as an anti-spastic measure.

Bilateral skeletonized internal thoracic artery grafting in 303 patients seventy years and older.

OBJECTIVES: Higher patency rates of the internal thoracic artery have led myocardial revascularization with bilateral internal thoracic arteries to be a procedure designated primarily for young patients. Fewer leg wound complications and sternal collateral flow preservation with the skeletonizing dissection technique can make bilateral internal thoracic artery grafting attractive also for elderly patients. METHODS: Between May 1996 and May 1998, 303 consecutive patients aged 70 years or older (mean age 75.5 years; range 70-92 years) underwent coronary artery bypass grafting with double skeletonized internal thoracic arteries. Forty-four (14.5%) patients were 80 years or older, and 89 (28%) had diabetes. The mean number of grafts was 3.1 per patient (2-6). RESULTS: Operative mortality was 2.6% (n = 8): it was higher for octogenarians (6.8%) than for younger patients (1.9%) (P =.06). The only significant preoperative predictors of early mortality were complicated percutaneous transluminal coronary angioplasty (P =.03) and preoperative use of intra-aortic balloon pumping (P =.03). Six patients (2%) had sternal wound infections for which chronic lung disease (P =.02) and emergency operation (P =.006) were the only significant predictors. Twenty-two (7.2%) late deaths occurred, and 1- and 3-year survivals were 93% and 90%, respectively. The 3-year survival of patients 80 years old or older was 92%. CONCLUSIONS: Bilateral grafting of the skeletonized internal thoracic artery carries relatively low morbidity and mortality in elderly patients and can be recommended for selected patients including octogenarians.

Emergency myocardial revascularization for acute myocardial infarction: survival benefits of avoiding cardiopulmonary bypass.

OBJECTIVE: Emergency coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI) is associated with increased operative mortality. It has been suggested that this mortality might be reduced by performing the operation without cardiopulmonary bypass (CPB). METHODS: Between January 1992 and April 1998, 77 patients underwent emergency CABG within 48 h of AMI. Thirty seven were operated on with CPB, and 40 without CPB. The two groups were similar regarding age, gender, left-ventricular ejection fraction (EF) and preoperative use of intra-aortic balloon pump (IABP; 50%). The mean number of grafts/patient was 3 in the CPB group, and 1.9 in the No-CPB group (P<0.0001). RESULTS: Operative mortality in the CPB group was 24% (nine of 37) compared to 5% (two of 40) without CPB (P=0.015). Follow-up ranged between 6 and 66 months. There were no late deaths in the CPB group compared to nine (22%) in the No-CPB group (P<0.0066). Patients operated on with CPB had lower rates of recurrent angina (0 versus 15%; P=0.04) and re-interventions (0 versus 15%; P=0.04). CONCLUSIONS: Our experience suggests that CABG without CPB is the preferred method of myocardial revascularization, due to the fact that it carries lower mortality than CABG with CPB. The trade-off includes increased rates of recurrent angina, re-interventions and late mortality.

Technical aspects of double-skeletonized internal mammary artery grafting.

BACKGROUND: Bilateral internal mammary artery (IMA) grafting is performed to provide complete arterial myocardial revascularization with the intention of decreasing postoperative return of angina and the need for reoperation. We present here technical views of double-skeletonized IMA grafting, and evaluate its clinical outcome. METHODS: Skeletonized IMA is harvested gently with scissors and silver clips, without use of cauterization, and embedded in a small syringe filled with papaverine. Three strategies for arterial revascularization were employed in 762 consecutive patients: (1) the cross arrangement (242 patients, 32%), where the in situ right internal mammary artery (RIMA) is used for the left anterior descending artery (LAD), in situ left internal mammary artery (LIMA) to circumflex marginal branches and the gastroepiploic artery for the right coronary artery (RCA); (2) the composite arrangement (476 patients, 62%), where free IMA is attached end-to-side to the other in situ IMA; and (3) the natural arrangement (44 patients, 6%), where the in situ RIMA is connected to the RCA and in situ LIMA to LAD. Mean age was 66 years (range 30 to 92). Two hundred ninety-two patients (38%) were older than 70, and 229 (30%) were diabetic. RESULTS: Operative mortality was 2.5% (n = 19). The mortality of urgent and elective cases was 1.2% (8 of 663), and that of emergency operation was 11% (11 of 99). There were 9 (1.2%) perioperative myocardial infarctions, and 10 patients (1.3%) sustained strokes. Sternal wound infection occurred in 14 (1.8%). CONCLUSIONS: The three strategies described here provide the surgeon with the versatility required for arterial revascularization with bilateral IMAs in most patients referred for coronary artery bypass grafting.

Protamine induces vasorelaxation of human internal thoracic artery by endothelial NO-synthase pathway.

BACKGROUND: Protamine is commonly used in cardiac surgery to reverse the anticoagulant effects of heparin. We investigated the role of different nitric oxide synthase pathways in the response of the human internal thoracic artery to protamine and evaluated whether heparin could prevent this effect. METHODS: A tension-recording method was used to obtain baseline measurements of contractions of human internal thoracic artery rings achieved with norepinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as control. The other contained a heparin or Nomega-Nitro-L-arginine (L-NAM, an inhibitor of both endothelial and inducible nitric oxide synthase) or a specific inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasing doses of protamine were added to both chambers and dose-response curves were obtained. RESULTS: Protamine was found to relax contracted internal thoracic arteries 56% +/- 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presence of aminoguanidine or heparin. CONCLUSIONS: Protamine induces nitric oxide-dependent relaxation of the internal thoracic artery by activation of endothelial nitric oxide synthase pathway. Heparin could not prevent this relaxing effect of protamine.

[Clinical characteristics of Crohn's disease in children and adults].

There are few reports contrasting the clinical characteristics of Crohn's disease in different age groups. We therefore compared retrospectively children and adults with Crohn's disease. 23 children (mean age: 12.8 +/- 2.5 years) and 66 adults (mean age: 27.0 +/- 4.0 years) were studied. Presenting symptoms of abdominal pain and diarrhea were significantly more common in adults, while in children anorexia and weight loss were more frequent. Children tended to present with extra-gastrointestinal tract symptoms as well, mainly anemia and joint involvement. Common symptoms during active disease did not differ between groups, except that weight loss, evident in all children, was found in only 70% of adults. Anemia was present during active disease in all pediatric cases but in only 62% of adults. There were no significant differences between groups regarding disease location, gastrointestinal complications and extra-intestinal manifestations. We conclude that in children Crohn's disease may differ significantly, mainly presenting with nonclassical symptoms, such as anemia and joint involvement. The primary care physician should be aware of these differences.

The Sorin Bicarbon valve: clinical evaluation in Israel.

BACKGROUND: Four collaborating centers pooled their results with the Sorin Bicarbon Bileaflet valve. MATERIAL AND METHODS: Between 6/91 and 11/95, 431 patients, 235 males and 196 females, underwent valve replacement using the new Sorin prosthesis; age range: 16-88, mean 61.4 yrs. OPERATIONS: AVR - 206, MVR - 177, TVR - 1, DVR - 47. Additional procedures - 139: CAB -117, valve repair - 22. AV sizes: 19-27, MV sizes: 21-33. RESULTS: Thirty day mortality was 4.3%. Early complications included: CVA - 1.4%, +ve blood culture - 2%, reop for bleeding - 5%. Late complications: infective endocarditis - 2.3%, valve thrombosis - 0.2%, thromboemboli - 2.5%, major bleeding - 1.6%, reoperation - 3%, late deaths (all causes) - 4.3%. No structural deterioration has been reported with this valve and acceptable gradients have been observed. Hemolysis is negligible. CONCLUSIONS: Based on this intermediate experience the Sorin Bicarbon prosthesis is well-designed with good hemodynamic properties, and an acceptably low incidence of complications.

Effects of an angiotensin II antagonist on ischemic and nonischemic isolated rat hearts.

BACKGROUND: Increasing evidence suggests that a locally integrated or intramyocardial renin-angiotensin system plays a significant role in ischemia-reperfusion injury. We evaluated the effects of losartan, an angiotensin II type 1 receptor blocking agent, on ischemic and nonischemic isolated rat hearts. METHODS: Using the modified Langendorff model, hearts were perfused with either low or high doses of losartan (18.2 mmol/L or 182.2 mmol/L, respectively) or with saline added to Krebs-Henseleit solution during phase I of the study. During phase II, hearts were exposed to a 60-minute period of global ischemia. Ischemic arrest was induced with warm cardioplegic solution (KCl, 16 mEq/L) containing either high-dose losartan (182.2 mmol/L) or Krebs-Henseleit solution only. RESULTS: During phase I of the study, no statistically significant differences were observed between the low-dose losartan group and the control group. However, hearts treated with high-dose losartan demonstrated an increase in peak systolic pressure, maximum first derivative of pressure, pressure-time integral, coronary flow, and oxygen consumption (p < 0.0001). During phase II, hearts treated with losartan showed a significantly better recovery on reperfusion, as reflected by better contractility (p < 0.001), higher oxygen consumption (p < 0.001), higher coronary flow (p < 0.0001), and lower creatine phosphokinase levels (41.1 +/- 1.7 versus 73.3 +/- 5.6 U/L; p < 0.001). CONCLUSIONS: High doses of losartan have a positive inotropic effect on normally perfused hearts. Given in cardioplegic solution, the drug has a significant protective effect on ischemic isolated rat hearts.

Epidemiology of Crohn's disease in southern Israel.

OBJECTIVES: Crohn's disease in Israel was described in the past as being of low incidence, more common in Europe-America-born Jews than other Jews, and of uncharacteristically low morbidity. However, recent experience has suggested that these premises are no longer correct. METHODS: The records of all hospital and outpatient cases of Crohn's disease in southern Israel for the period 1968-1992 were reviewed. Private family practitioners and specialists were contacted to assure complete case ascertainment. RESULTS: The prevalence rate of Crohn's disease among Jews on December 31, 1992, was 50.6/10(5) (Asia-Africa-born Jews 55.0/10(5), Europe-America-born Jews 58.7/10(5), and the rate was 8.2/10(5) among Bedouin Arabs. The annual incidence rate (1987-1992) was calculated as 4.2/10(5)/yr in Jews (Asia-Africa-born 4.6/10(5)/yr, Europe-America-born 3.9/10(5)/yr). The age of presentation declined progressively over the study period, was lower in Israel-born patients than immigrants, and was lower in ileocolonic versus other sites of disease. CONCLUSIONS: The data show that Crohn's disease has become more common in Jews in Israel, losing ethnic differences of frequency, and that it occurs at a younger age than before. In Arabs, the disease is more rare.