Computation of a probabilistic statistical shape model in a maximum-a-posteriori framework.

OBJECTIVES: When analyzing shapes and shape variabilities, the first step is bringing those shapes into correspondence. This is a fundamental problem even when solved by manually determining exact correspondences such as landmarks. We developed a method to represent a mean shape and a variability model for a training data set based on probabilistic correspondence computed between the observations. METHODS: First, the observations are matched on each other with an affine transformation found by the Expectation-Maximization Iterative-Closest-Points (EM-ICP) registration. We then propose a maximum-a-posteriori (MAP) framework in order to compute the statistical shape model (SSM) parameters which result in an optimal adaptation of the model to the observations. The optimization of the MAP explanation is realized with respect to the observation parameters and the generative model parameters in a global criterion and leads to very efficient and closed-form solutions for (almost) all parameters. RESULTS: We compared our probabilistic SSM to a SSM based on one-to-one correspondences and the PCA (classical SSM). Experiments on synthetic data served to test the performances on non-convex shapes (15 training shapes) which have proved difficult in terms of proper correspondence determination. We then computed the SSMs for real putamen data (21 training shapes). The evaluation was done by measuring the generalization ability as well as the specificity of both SSMs and showed that especially shape detail differences are better modeled by the probabilistic SSM (Hausdorff distance in generalization ability Re approximately 25% smaller). CONCLUSIONS: The experimental outcome shows the efficiency and advantages of the new approach as the probabilistic SSM performs better in modeling shape details and differences.

Ureteral repair with titanium staples: comparison with suture closure.

OBJECTIVES: Vascular closure staple (VCS) clips made of titanium were initially developed for microvascular anastomoses with little knowledge of their effectiveness in larger tubular tissue structures. This study compares VCS clips and sutures in the closure of longitudinal ureterotomy incisions. METHODS: In 9 pigs, 1-cm-long anterior, longitudinal ureterotomy incisions were randomly assigned to closure with either 4-0 interrupted polyglactin sutures or VCS clips. RESULTS: Clip closure was significantly faster (74+/-28 versus 534+/-182 seconds). All 18 ureters were patent and without signs of leakage, calculus formation, or stenoses after 3 months. Clip closure resulted in slightly but not statistically significantly less narrowing of the duct lumen, but there was no difference in wall thickness at the repair site. At histologic examination, all 18 incisions healed without signs of acute inflammation or marked fibrosis. CONCLUSIONS: Ureterotomy closure with VCS clips results in wound healing that is as effective as suture closure, with a comparable degree of narrowing. The time required for clip closure is only about 1/7 that required for suture closure.

Arterial reconstruction with vascular clips is safe and quicker than sutured repair.

BACKGROUND: Non-penetrating, arcuate-legged vascular-closure staple clips made of titanium were initially developed for microvascular anastomoses with little experience of their use in larger vessels. The purpose of this study was to compare vascular-closure staple clips to sutured anastomoses in common iliac arteries in a porcine model. METHODS: In an experimental study, transected iliac arteries on both sides of 11 pigs were randomly assigned to end-to-end anastomosis performed with vascular-closure staple clips or interrupted 6-0 polypropylene sutures. Angiographic, macroscopic and microscopic results were assessed after 2 months. RESULTS: There was no significant difference in the patency rate, tensile strength of the anastomoses, vessel diameter at the repair site, intimal thickness or wall thickness of the arteries after either method of closure. The mean (s.d.) clamp time was 19.8 (6.1) minutes for clip repair, and 36.0 (6.9) seconds for suture repair (P < 0.001). The times required for the reconstruction of the anastomoses were 17.4 (6.1) and 35.5 (7.1) minutes, respectively (P < 0.001). CONCLUSIONS: Arterial anastomoses performed with vascular-closure staple clips are faster than sutured anastomoses, and result in comparable wound healing when assessed for patency, tensile strength, degree of narrowing and intimal reaction.

Arterial and venous repair with vascular clips: comparison with suture closure.

PURPOSE: Nonpenetrating, arcuate-legged titanium vascular closure staple (VCS) clips were initially developed for microvascular anastomoses with little experience of their use in larger vessels. The purpose of this study was to compare the VCS clips with standard suture closure of arteriotomies and venotomies in common iliac vessels of pigs. METHODS: In nine pigs, longitudinal 1 cm iliac arterial and venous incisions were repaired with VCS clips on one side and continuous 6-0 polypropylene suture on the other, and the macroscopic and microscopic results were assessed after 3 months. RESULTS: The time required for vessel repair was significantly shorter with clips than with sutures both in arteries (51 +/- 9 vs 414 +/- 36 seconds) and in veins (100 +/- 32 vs 439 +/- 45 seconds). There was no significant difference in the inner diameter, intimal thickness, or intima-to-media height ratios of the arteries or veins after either method of closure. CONCLUSIONS: Repair of 1 cm incisions in small-diameter arteries and veins with VCS clips results in wound healing as good as that achieved with standard suture closure, when assessed for patency, leakage, degree of narrowing, and intimal reaction. The time required for clip closure is considerably shorter than for suture closure.

Common bile duct repair with titanium staples. Comparison with suture closure.

BACKGROUND: Vascular Closure Staple (VCS) clips made of titanium were initially developed for microvascular anastomoses with little experience of their use in larger tubular structures. This study compares VCS clips and sutures in the closure of supraduodenal choledochotomy. METHODS: In nine pigs, two longitudinal incisions of the common bile duct (CBD) were randomly assigned to closure with 4-0 interrupted polyglactin sutures or VCS clips. RESULTS: Clip closure was significantly faster (116 +/- 28 vs 581 +/- 88 s). All nine CBDs were patent and without signs of calculus formation after 3 months. Clip closure resulted in slightly less narrowing of the duct lumen and thinner scar at the repair site. At histological examination, all 18 incisions had healed without signs of fistula formation or marked fibrosis. CONCLUSIONS: Choledochotomy closure with VCS clips results in as good or better wound healing than suture closure, with a comparable degree of narrowing. The time required for clip closure is only about one-fifth that of suture closure.

A quick and simple method to close vascular, biliary, and urinary tract incisions using the new Vascular Closure Staples: a preliminary report.

Traditional suture reconstruction of tubular organs creates a perforating needle injury, leaves suture material on the endothelial or mucosal surfaces, and is cumbersome when done endoscopically. One alternative method of reconstruction of tubular organs could use the new nonpenetrating clip to create an everted closure. In five pigs, a longitudinal incision of the infrarenal aorta, inferior vena cava, left ureter, gallbladder, and the common bile duct (in two) was closed with Vascular Closure Staples (VCS-clips). Four weeks after surgery, all ten blood vessels remained patent with no thrombosis. There was a well-healed wound with continuous intimal layer. The ureteral, gallbladder, and common bile duct wounds healed without leakage or obstruction in all animals. There was complete mucosal bridging of the wound, although in some specimens one or two clips were exposed to the lumen. The VCS-clips are easily and quickly applied and are safe insofar as can be determined by short-term follow-up.

Fluid resuscitation in a model of uncontrolled hemorrhage: too much too early, or too little too late?

UNLABELLED: Early fluid resuscitation in hypotensive trauma patients is controversial due to the risk of increasing blood loss and mortality. We determined the effects of infusion rate and time of resuscitation on blood loss and mortality and compared the outcome to nonresuscitated animals in severe, uncontrolled hemorrhagic shock in a rat model. In anesthetized rats, piercing of the infrarenal aorta with a 25-G needle caused a fall of mean arterial pressure to <20 mm Hg and blood loss of about 20 ml/kg in 90% of the animals. Animals were assigned to the following treatment groups (n = 6): 60 ml/kg of lactated Ringer's solution (LR) infused at a rate of 1.5 ml/min and given at 2.5 min (Group I), 5 min (Group II), or 10 min (Group III) postinjury, or LR infused at a rate of 3.0 ml/min and given at 5 min (Group IV) or 10 min (Group V) postinjury. Another group (n = 9) was not resuscitated. The animals were followed for 3 hr. Total blood loss in Group I (30.5 +/- 2.6 ml/kg) was significantly (P < 0.05) higher when compared to nonresuscitated animals (22.1 +/- 0.8 ml/ kg) or Group III (22.7 +/- 1.0 ml/kg), and also significantly higher in Group IV (35.8 +/- 4.1 ml/kg) when compared to nonresuscitated animals or Group V (23.0 +/- 1.2 ml/kg). The mortality rate was 7/9 in nonresuscitated animals and 5/6 in Group IV, both were significantly higher than in Groups II, III, and V (0 or 1/6) and markedly higher than in Group I (2/6). CONCLUSIONS: In this model of uncontrolled hemorrhage, initially uncorrected severe shock resulted in a high mortality rate. The risk of increased blood loss and mortality associated with early fluid resuscitation could be diminished by avoiding too fast of infusion rates early after the injury.

Early resuscitation with low-volume PolyDCLHb is effective in the treatment of shock induced by penetrating vascular injury.

OBJECTIVE: To study the efficacy of an oxygen-carrying solution in early resuscitation of hemorrhagic shock induced by penetrating vascular injury. DESIGN: Experimental study with anesthetized rats. MATERIALS AND METHODS: Severe hemorrhagic shock was induced by a 25-gauge needle puncture to the infrarenal aorta. Forty animals were resuscitated 10 minutes after injury with either lactated Ringer's solution (LR; 60 mL/kg), 7.5% hypertonic saline (HTS; 5 mL/kg), or modified diaspirin cross-linked hemoglobin (PolyDCLHb; 5 or 20 mL/kg) or were not resuscitated (NR) and followed for 6 hours. RESULTS: Total blood loss was similar in all treatment groups. Mean arterial pressure was restored to baseline values, base deficit was corrected to base excess, and venous oxygen saturation improved with PolyDCLHb and more slowly with LR but persisted below baseline values with HTS and NR. The 6-hour mortality rates were zero of eight (low-dose PolyDCLHb), three of eight (high-dose PolyDCLHb), two of eight (LR), six of eight (HTS), and six of eight (NR). CONCLUSION: Early resuscitation with low-volume hemoglobin is effective in restoring tissue perfusion and improving survival in uncontrolled hemorrhagic shock.

Hypertonic saline resuscitation detrimentally affects renal function and survival in dehydrated rats.

The purpose of our studies was to determine whether hypertonic (7.5%) saline (HTS) resuscitation is effective in the setting of dehydration. We compared the effects of HTS (5 cc/kg) to those of Ringer's lactate (RL; 45 cc/kg) on renal function, following resuscitation from hypovolemia in hydrated (free access to food/water) vs. dehydrated (food/water restricted) rats (300-350 g). Renal failure was produced by hemorrhage (15 cc/kg) plus renal artery occlusion (25 min) followed by fluid resuscitation. Dehydration was confirmed by hemoconcentration and weight loss (8-10%). Renal function was assessed at 24 hr using 14C-inulin clearance (Cin) measurements. In hydrated animals, the Cin of RL-treated rats (625 +/- 54 microliters/min/100 g; n = 12) was no different from the Cin in HTS-treated rats (517 +/- 48 microliters/min/100 g; n = 13). Among dehydrated rats, Cin in HTS-treated rats (n = 6) was significantly lower (P < or = 0.05) than in RL-treated rats (n = 5) (117 +/- 33 microliters/min/100 g vs. 542 +/- 84 microliters/min/100 g, respectively). Cin in dehydrated RL-treated rats was not significantly different from that in hydrated RL-treated rats. Furthermore, in dehydrated animals, nine of nine resuscitated with RL survived, compared to six of 13 resuscitated with HTS. All hydrated animals survived. In summary, renal failure was ameliorated by RL and worsened by HTS resuscitation in dehydrated rats. Furthermore, mortality was increased in dehydrated animals resuscitated with HTS compared to RL.

[Lyme borreliosis in an endemic region in Europe. Prevalence of antibodies and clinical spectrum]. / Lyme-Borreliose in einem europäischen Endemiegebiet. Antikörperprävalenz und klinisches Spektrum.

A representative sample of the population of two villages located in an area of North Baden where borreliosis is endemic was studied to ascertain the prevalence of antibodies against Borrelia burgdorferi and of clinical abnormalities. The aim of the study was to determine what clinical symptoms and signs were correlated with positive antibody status. Out of the 2928 inhabitants 1228 were investigated, and 207 of these (16.9%) were seropositive. Certain clinical abnormalities showed highly significant statistical correlations with positive antibody status. Arthritis (defined in terms of heat, redness and effusion) was noted in 34.3% of the seropositive patients, but in only 9.3% of seronegative patients (P less than 0.0001). Complaints of arthralgia were noted in 23.4% of seropositive patients and 13.3% of seronegative patients (P less than 0.001). Motor neuropathies showed similar correlation with seropositive status (12.0% vs 4.0%; P less than 0.001), as did sensory neuropathies (25.4% vs 6.7%; P less than 0.001). Differences were also noted in the prevalence of cardiac arrhythmias (ventricular extrasystoles, conduction abnormalities and intermittent tachyarrhythmias), which were found in 19.8% of the seropositive as against 3.0% of the seronegative subjects (P less than 0.001). The findings are evidence of a causal link between the listed clinical abnormalities and the presence of antibodies against Borrelia burgdorferi.

Cefotaxime versus penicillin in the late stage of Lyme disease--prospective, randomized therapeutic study.

The low responsiveness of Lyme arthritis to high dose intravenous penicillin G therapy has evoked the demand for new drugs for the treatment of late stage borreliosis. As can be deduced from in vitro susceptibility data, third generation cephalosporins are far more effective on Borrelia burgdorferi spirochetes than penicillin G. The study presented here was designed to compare cefotaxime at a dosage of 2 x 3 g/day with penicillin G at a dosage of 2 x 10 megaunits/day, for ten days in a prospective randomized trial. A total of 135 patients were included in the study. They were diagnosed to suffer from late stage Lyme borreliosis on the basis of defined clinical symptoms compatible with stage three borreliosis manifestations of at least six months' duration and positive antibody titers against B. burgdorferi. Final outcomes were recorded after a 24 month post-treatment observation period with re-examination at three-month-intervals. Cefotaxime proved to be significantly superior to penicillin G with 87.9% versus 61.3% of treatments resulting in full or incomplete remission of symptoms (p = 0.002). Clinical remission was accompanied by declining antibody titers. Herxheimer-like reactions were observed in 20% of the patients of the penicillin group and in 40.5% of the patients of the cefotaxime group and may be interpreted as an indication of a response to therapy.

[The use of collagen fasciae and fibrin adhesive for supporting wound healing in skin defects with large surfaces]. / Einsatz von Kollagenfaszien und Fibrinkleber zur Unterstützung der Wundheilung bei grossflächigen Hautdefekten.

In 50 domestic pigeons, two circular pieces were removed from the skin to the right and left of the crista sterni, and the wounds were treated in different ways: A. with a collagen membrane dampened with a sodium chloride solution, B. with a fibrin glue, C. with a combination of A) and B). The wounds of group D were left untreated. Scab formation could be seen in all cases, also under the transparent membrane. The collagen membrane had no protective function in the experiment, however, it contributed to the acceleration of re-epithelialisation and the reduction of the wound diameter. The additional application of fibrin glue improved wound healing even further.

Expression of genes for platelet-derived growth factor in adult human venous endothelium. A possible non-platelet-dependent cause of intimal hyperplasia in vein grafts and perianastomotic areas of vascular prostheses.

Neointimal fibromuscular hyperplasia (NFH) in vein grafts and perianastomotic zones of vascular prostheses has been attributed to the effects of platelet-derived growth factor (PDGF) released by platelets interacting with bypass conduits. But inhibition of platelet aggregation often fails to prevent NFH, and recurrent growth of intact, platelet-free endothelium over perianastomotic areas where NFH occurs is inconsistent with the concept of sustained PDGF release from platelets causing NFH progression at late times after surgical procedures. Cultured bovine aortic endothelial cells (ECs) and human umbilical vein ECs have been shown to release a PDGF-like molecule. We report that confluent cultured fourth passage adult human saphenous vein ECs (AHSVECs) grown in the presence of heparin (100 micrograms/ml) and retina-derived growth factor (RDGF) studied by Northern blotting transcribed a messenger ribonucleic acid (mRNA) of 3.9 kb, strongly hybridizing to PDGF B chain probes, and two species of 2.0 and 2.6 kb hybridizing to PDGF A chain probes. Withdrawal of RDGF and heparin from these cultures for 48 hours before mRNA extraction amplified the scanning densitometric mRNA signal per cell by 8.0 +/- 7.6 fold (mean +/- SD) (N = 4 cultures) for B chain mRNA and 5.2 +/- 3.6 fold (N = 3 cultures) for A chain mRNA. In addition, AHSVEC cultures released a PDGF-like substance, because 50% vol/vol AHSVEC-conditioned serum-free medium increased tritiated thymidine uptake elevenfold in PDGF receptor-bearing 3T3 cells whereas an excess (50 micrograms/ml) of nonspecific goat anti-human-PDGF antibody significantly reduced this increase by a mean of 30% to 7.0 +/- 3.4 fold (N = 6 trials, p less than 0.001). Flow cytometry determined AHSVEC cultures to be proliferating with a mean of 6.2% +/- 1.9% (N = 3 culture lines) of ECs in S phase even at confluence when deprived of EC mitogens for 48 hours. Adult human ECs, which proliferate on bypass conduits and host vessels after perioperative injury, may play a role in causing NFH by stimulating proliferation of adjacent smooth muscle cells. Prevention of NFH may require not only antiplatelet agents but also ways to prevent EC release of smooth muscle cell mitogens in response to perioperative EC injury.

Platelet survival and serotonin content after placement of arterial prostheses in dogs: effects of neointimal coverage and high- and low-dose aspirin.

Because prosthetic neointima produces much less prostacyclin (PGI2) than arterial intima and may be more susceptible to cyclooxygenase inhibition, aspirin treatment might enhance surface thrombogenesis. To test this hypothesis, aortic prostheses were placed in eight dogs and measurements of platelet survival and platelet serotonin (5HT) were made under conditions of no treatment and treatment with low-dose (2mg/kg) and high-dose (30 mg/kg) aspirin. These doses equally suppressed platelet function. Measurements were performed preoperatively, 6 to 8 weeks postoperatively (when little neointima was present), and 28 to 32 weeks postoperatively (neointima fully developed). Platelet survival and 5HT levels were markedly reduced 6 to 8 weeks postoperatively and returned to normal at 28 to 32 weeks after implantation. At all times, low-dose aspirin improved platelet survival and this effect was most apparent 6 to 8 weeks postoperatively. Treatment with either aspirin dose decreased platelet 5HT levels at the 28 to 32 week postoperative period but not at other times. At recovery of prostheses, 90% of the luminal surface was covered with endothelialized neointima. Neointimal production of PGI2 was one half to one third that of aortic production. Despite this, low- and high-dose aspirin equally suppressed PGI2 production from both neointima and aorta. Furthermore, aspirin did not increase labeled platelet uptake on neointima. We conclude that (1) aspirin treatment does not render prosthetic neointima thrombogenic and (2) aspirin alters platelet survival and 5HT levels by mechanisms other than inhibition of platelet and neointima cyclooxygenase.

[Comparative studies of sudden and non-sudden death due to coronary disease]. / Vergleichende Untersuchungen zum akuten und nicht akuten Tod koronarer Genese.

A comparative study of patients dying acutely and non-acutely from coronary heart disease was performed. The average age of the acute death group was significantly lower than the non-acute death group. There is no difference between the average age at death of the latter and that of those persons who died from non-coronary causes. The majority of patients with chronic ischemic heart disease (CIHD) died a sudden death. This proportion is especially high among males under 50. Taking into account the different manifestations of chronic ischemic heart disease most males and females with sudden death died as a consequence of acute coronary insufficiency. In the group of non-acute coronary deaths, acute and recurrent myocardial infarction dominated as the cause of death. Coronary thrombosis was less frequent in the acute compared to the non-acute death group. There was no significant difference in the frequency of cardiac rupture between the two groups. Severe coronary arteriosclerosis was substantially more frequent in the acute group compared with the non-acute.

Platelet reactivity in vivo in dogs with arterial prostheses seeded with endothelial cells.

This study was designed to assess platelet activity in vivo with vascular prostheses seeded with endothelial cells to determine the time course for development of thromboresistance and to test the ability of prostheses to produce prostacyclin. Sixteen dogs were randomly allocated to receive seeded (experimental group) or unseeded (control group) velour Dacron aortic prostheses. Serial measurements of platelet survival were performed to assess platelet interaction with prostheses in vivo, and platelet serotonin was monitored as an index of platelet release in vivo. After placement of prostheses, dogs in the experimental group had rapid normalization of platelet survival, with most having normal platelet survival at 4 to 8 weeks after surgery. In contrast, most control animals had reduced platelet survival throughout the 12 week period of study. Significant differences between groups in mean platelet survival were noted at 8 weeks after surgery (p less than .005) and in mean platelet serotonin at 12 weeks after surgery (p less than .05). Luminal surface production of 6-keto-PGF1 alpha from seeded prostheses was similar to aortic production and significantly greater (p less than .05) than that of control prostheses. Gross thrombus was present on 6.0 +/- 3.4% of the prosthetic surface in experimental animals in comparison to 26.6 +/- 19.2% in controls (p less than .005). The results of these studies document accelerated nonreactivity with platelets of seeded prostheses due to rapid coverage with endothelium possessing a normal ability to produce prostacyclin.

Platelet changes after placement of aortic prostheses in dogs. II. Impaired surface-induced arterial thrombosis.

An experimental preparation was developed to assess changes in surface-induced arterial thrombosis in nine dogs with woven Dacron aortic prostheses. The preparation consisted in measuring the occlusion time of an A-V shunt with controlled flow rate (200 mg/min). This measurement depended on formation of an occlusive, platelet-rich thrombus on a diaphragm of polyester mesh. Two to 6 months after placement of thoracoabdominal aortic prostheses, all animals demonstrated striking prolongation of A-V shung occlusion time. This occurred in the presence and absence of heparin anticoagulation. No change in A-V shunt occlusion time was noted in dogs who had sham operations. These findings complement out studies showing biochemical and functional changes in circulating platelets in dogs with aortic prostheses, and together they are consistent with mild platelet damage sufficient to impair surface-induced thrombosis. They also support our contention than, in dogs, platelets interact reversibly with prosthetic surfaces.

Platelet changes after placement of aortic prostheses in dogs. I. Biochemical and functional alterations.

Changes in circulating platelets were observed after placement of woven Dacron aortic prostheses in dogs. Platelets had increased sensitivity to aggregating agents for up to 6 months postoperatively, during which period platelet survival was maximally shortened. Platelet survival gradually lengthened but remained less than preoperative values, even at 18 months. Platelet 5HT, consistently reduced after placement of aortic prostheses, closely paralleled changes in platelet survival. Studies with platelets labeled simultaneously with 14C-5HT and 51Cr suggested in vivo platelet release and reutilization of 5HT. In vitro platelet uptake of 14C-5HT, however, was depressed. Urinary excretion of 5HIAA increased slightly, but not significantly, after placement of aortic prostheses. These findings suggested that platelet interaction with the prosthetic surface led to partial release of platelet storage granule contents. Reutilization of released 5HT occurred but was limited because of impaired platelet uptake or storage of 5HT. Platelet damage was suggested by 51Cr-platelet cross-transfusion experiments. Platelets from normal dogs had normal recovery and reduced survival when cross-transfused into animals with aortic prostheses. When platelets from dogs with aortic prostheses were cross-transfused into normal animals, recovery was strikingly reduced and survival very short. Taken together, these studies suggest that, in dogs, platelet interaction in thrombosis on prosthetic surfaces is, in part, a reversible process, with platelets re-entering the circulation in an altered state.

Fecal intestinal alkaline phosphatase: a parameter for toxic damage of the small intestinal mucosa.

An immunoprecipitation procedure is presented for the measurement of rat intestinal alkaline phosphatase (I-AP) in feces. Controls exhibit a logarithmic normal distribution of fecal I-AP. Single administration of an agent toxic for small intestinal mucosa like bleomycin or triparanol induces an increase of fecal I-AP on the 1st day and a marked reduction of I-AP activity on the following 3 days. After the 5th day, abnormal high fecal I-AP activities were observed during regeneration. In parallel, morphometry and measurements of I-AP activity in the homogenate of small intestinal mucosa were performed. Rat fecal I-AP excretion proved to be a simple, non-invasive, sensitive marker for toxic damage of the small intestinal mucosa.