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Biomedical subjects

R J Simon

Publications and source records attributed to R J Simon.

At least 37 records · Page 2Linked to original sources
PubMed1994

Discovery of nanomolar ligands for 7-transmembrane G-protein-coupled receptors from a diverse N-(substituted)glycine peptoid library.

Screening a diverse, combinatorial library of ca. 5000 synthetic dimer and trimer N-(substituted)glycine "peptides" yielded novel, high-affinity ligands for 7-transmembrane G-protein-coupled receptors. The peptoid library was efficiently assembled using readily available chemical building blocks. The choice of side chains was biased to resemble known ligands to 7-transmembrane G-protein-coupled receptors. All peptides were screened in solution-phase, competitive radioligand-binding assays. Peptoid trimer CHIR 2279 binds to the alpha 1-adrenergic receptor with a Ki of 5 nM, and trimer CHIR 4531 binds to the mu-opiate receptor with a Ki of 6 nM. This represents the first example of the discovery of high-affinity receptor ligands from a combinatorial library of non-natural chemical entities.

Amino Acid Sequence↗
PubMed1994

Selective celiotomy for missile wounds of the abdomen based on laparoscopy.

The role of laparoscopy in the selective management of gunshot wounds (GSW) of the abdomen was prospectively investigated in 38 patients. All the patients were hemodynamically stable and had equivocal evidence of intraabdominal penetration. Laparoscopy was performed in the operating room under anesthesia. The site of penetration was in the thoracoabdominal area in 13, epigastrium in 7, and lower quadrants in 18. Twenty-three (60.5%) had nonpenetration on laparoscopy and a laparotomy was avoided. The remaining patients had injuries to the liver (4 patients), spleen (two patients), diaphragm (3 patients), hemoperitoneum or retroperitoneal hematoma (6 patients), and hollow viscus injuries (5 patients). Laparoscopy was also helpful in determining the need for laparotomy vs thoracotomy in lower chest wounds. The negative laparoscopy group (no penetration) had a significantly lower hospital stay compared to hemodynamically stable patients who had negative laparotomy without laparoscopy for nonpenetrating GSW. There were no complications related to laparoscopy. Laparoscopy is a useful modality in the evaluation of hemodynamically stable patients with abdominal missile wounds.

Abdominal Injuries↗
PubMed1994

Synthesis, molecular modelling, and NMR structure determination of four cyclic peptide antagonists of endothelin.

A combined distance geometry and molecular mechanics/dynamics (MM/MD) protocol was unable to predict the active conformation of the cyclic pentapeptide inhibitor of endothelin-1 receptor, BQ-123, and two analogues. However, the MM/MD method alone is sufficient to predict the solution conformation of a third analogue. In that one case, the combination of proline at residue 3 and an N alpha-methyl substitution at residue 5 provides enough internal constraints to eliminate conformational flexibility seen in the other three analogues. For this constrained analogue, the 50 lowest energy conformations (out of a set of 500 DGEOM-generated, MM/MD minimized conformations) differ by no more than 3.9 kcal/mol. Thirty three of these 50 conformations have backbone atom RMSDs of less than 0.33 A, relative to the lowest energy conformation. The accuracy of this MM/MD model is verified by determining the solution structure of each of the four analogues with 2D NMR techniques. Each of the cyclic pentapeptides has a well defined solution conformation where a proline residue is clearly in a gamma-turn, leaving the remaining residues in a loose beta-turn. All four experimental NMR conformations agree closely with the MM/MD model.

3T3 Cells↗
PubMed1994

Hypercapnia: is there a cause for concern?

Concern that barotrauma may lead to further deterioration in pulmonary function in patients with ARDS has stimulated interest in developing methods of reducing it. These new modalities have had limited acceptance. The reasons for this include technical difficulties, associated complications, and the hypercapnia produced by the reduction in minute ventilation associated with diminished peak inspiratory pressure (PIP). Recent reports have shown that hypercapnia does not produce many of the adverse effects previously attributed to it. We studied the effects of moderate levels of hypercapnia produced by inverse ratio ventilation with low tidal volumes in patients with severe pulmonary dysfunction (Lung Injury Score > or = 2.5). The mean peak PaCO2 and PIP of the group were 63.3 +/- 15.7 mm Hg and 44.0 +/- 12.4 cm H2O, respectively. We found no adverse effects on cardiac function, oxygen utilization, or long-term neurologic function in patients after hypercapnia. We conclude that moderate levels of hypercapnia are safe, and may be permitted in the care of patients with severe pulmonary dysfunction.

Adult↗
PubMed1994

A prospective reappraisal of primary repair of penetrating duodenal injuries.

Based on a retrospective analysis of 100 penetrating duodenal injuries, the role of primary repair or resection and anastomosis was assessed prospectively in 66 patients (1986-1992). Duodenal exclusion was reserved for extensive combined pancreato-duodenal injuries. Seven of the 66 patients died from extensive abdominal trauma (mean Abdominal Trauma Index, ATI 70) within 48 hours of admission. Fifty-six patients had primary repair, while pyloric exclusion was performed for three patients with extensive pancreatico-duodenal injuries. Three patients (5.1%) developed duodenal fistula, two being in the primary repair group (3.6%). All three patients had associated injury to the head of the pancreas. Four of the 59 patients died, one attributed to the duodenal repair, for a duodenal mortality of 1.7 per cent. Of the anatomic (ATI, duodenal, vascular, and pancreatic injury scores) and physiologic variables (shock, transfusions) analyzed, the ATI, the Duodenal Injury Score, and the Colon Injury Score were significantly higher in the fistula group. We conclude that the vast majority of penetrating duodenal injuries should be managed by primary repair or resection and anastomosis. Complex duodenal decompression or diverticulization rarely are necessary. Complex procedures should be considered for patients with ATI > 40, Duodenal Injury Score > 12, and the presence of injury to the head of the pancreas.

Abdomen↗
PubMed1993

A critical evaluation of laparoscopy in penetrating abdominal trauma.

One hundred hemodynamically stable patients with penetrating abdominal trauma (65, stab wounds, 35, gunshot wounds) were evaluated with laparoscopy. Sixty percent of the patients had wounds in the thoracoabdominal area or the upper abdominal quadrants and 25% had injuries located in the lower abdomen and flanks. Fifteen percent had epigastric wounds. Twenty-two stabs and 21 gunshots had not penetrated the peritoneum (negative laparoscopic results). Fifty-seven patients had peritoneal penetration and were noted to have hemoperitoneum only (n = 14), hemoperitoneum and solid organ injuries (n = 23), diaphragmatic lacerations (n = 17), and hollow viscus injuries (n = 2) on laparoscopic examination. Three of the 57 patients, one with omental herniation only and two with low grade nonbleeding lacerations of the liver, were managed uneventfully without laparotomy. The remaining 54 patients underwent laparotomy with confirmation of the laparoscopic findings. Seven patients (three with stab wounds and four with gunshots) had additional GI tract injuries seen at laparotomy. The diagnostic accuracy of laparoscopy was excellent for hemoperitoneum, solid organ injuries, diaphragmatic lacerations, and retroperitoneal hematomas. For GI injuries, laparoscopy was found to have a 100% specificity but only a 18% sensitivity. The majority of these discordant findings occurred in epigastric SWs and flank and lower quadrant GSWs, all in patients with undetected hollow viscus injuries. The major role of laparoscopy in penetrating abdominal trauma is in avoiding unnecessary laparotomy in tangential SWs and GSWs. It is excellent for evaluating the diaphragm in thoracoabdominal wounds. Caution is urged in excluding hollow viscus injuries based on laparoscopy.

Abdominal Injuries↗
PubMed1993

Candiduria as an early marker of disseminated infection in critically ill surgical patients: the role of fluconazole therapy.

The significance of candiduria in critically ill patients remains unclear. It may represent harmless colonization or a potentially life-threatening infection. We analyzed 47 patients in the surgical intensive care unit (SICU) (trauma: 20, general surgery: 15, neurosurgery: 12) who had candiduria, defined by a colony count greater than 100,000/mL. Twenty-seven of these patients were studied retrospectively. Twenty were evaluated prospectively. All patients were receiving broad-spectrum antibiotics for bacterial infections. Retrospective group: ten patients (group A) did not develop disseminated candidiasis, whereas 17 patients (group B) did. Group B had higher APACHE II scores on admission (13.4 +/- 7.8) and at the time of candiduria (13.7 +/- 4.4) when compared with group A [admission: 5.0 +/- 4.6; candiduria: 6.7 +/- 3.6 (p < 0.02)]. In group B, disseminated candidiasis was not diagnosed and treated until 9.9 +/- 4.4 days after development of candiduria. Prospective group: twenty patients with candiduria were treated with systemic fluconazole (group C) at the time of candiduria. The APACHE II scores of group C on admission (12.8 +/- 3.9) and at the time of candiduria (10.5 +/- 4.0) were comparable with those of group B. No patient in Group C developed disseminated candidiasis. The septic mortality rates of groups A, B, and C were 0%, 53%, and 5%, respectively (p < 0.05-0.0001). In patients exhibiting ongoing sepsis and organ failure (high APACHE scores), candiduria may be an early indicator of systemic infection. Diagnosis of disseminated infection and its treatment may be delayed if conventional criteria for candidiasis (positive blood cultures, multiple site isolation) are awaited.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The spleen at risk after penetrating trauma.

UNLABELLED: In contrast to blunt splenic trauma where nonsurgical management is an option, splenorrhaphy is the current preferred approach for penetrating trauma. Splenectomy, however, may be required because of hemodynamic instability, the extent of the trauma, or when a pancreatic injury requires distal pancreatectomy. We evaluated our attempts at splenic preservation in 69 patients (1988-1992) in whom the spleen was at risk for removal. Fifty-seven patients had penetrating injury to the spleen and 12 patients had distal pancreatectomy. Splenic Trauma (n = 57): 6 patients (mean Abdominal Trauma Index 45) died within 24 hours of extensive injuries. All had splenectomy. Thirty-seven of the remaining 51 (72.5%) had successful splenorrhaphy, 85% with stab wounds (SWs) and 65.5% with gunshot wounds (GSWs). Splenic salvage was 100%, 100%, 92%, 37%, and 0%, respectively, for grades I-V injuries. Absorbable mesh splenorrhaphy improved splenic salvage in grade III and IV injuries from 67% and 0% in previous years (1983-1987) to 92% and 37% in recent years (1988-1992), p < 0.01. The use of the mesh did not increase septic complications, even in the presence of enteric perforation. Distal Pancreatectomy (n = 12): 1 died intraoperatively. The spleen was not injured in 6 and was preserved in all 6. The overall 54.5% splenic salvage rate was achieved without increasing morbidity or the number of transfusions. CONCLUSIONS: (1) Splenorrhaphy should be possible in the great majority of stable patients after penetrating trauma. (2) Absorbable mesh is a valuable adjunct that may facilitate the repair of more severe grades of splenic trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Early management of civilian gunshot wounds to the face.

We analyzed 54 civilian patients (1988-1992) with gunshot wounds (GSWs) of the face to review the management principles and results. Urgent airway control was needed in 18 cases (33%): by orotracheal intubation in 13, cricothyroidotomy in two, tracheostomy in two, and nasotracheal intubation in one. Central nervous system injury was seen in 12 (22%): 40% with orbital, 38% with mid-face, and 0% with lower face injuries. Two patients died of intracranial injuries (mortality, 4%). Vascular injury was present in five patients (9%), all detected by angiography. The local complication rate was 39% in the presence of intra-oral injury and 0% without intra-oral injury (p < 0.001). The maxilla was the most commonly fractured facial bone (41%) followed by the mandible in 28%. All maxillary, orbital, and zygomatic fractures were treated without reduction. One of the seven nasal fractures required open reduction for deformity. Six of the 15 mandible fractures were treated without reduction. Of eight patients treated with closed reduction, one developed nonunion. One patient treated with immediate open reduction developed osteomyelitis of the mandible and nonunion. Five patients (9%) had palate injuries. Two of them later developed intraoral fistulas following conservative treatment. The airway needs immediate attention in GSWs of the face. Computed tomographic scanning of the head or spine should be done when the bullet trajectory is above the lower face (the level of the mandible). Angiography is indicated when the trajectory of the bullet is suggestive. A conservative approach that effectively reduces the fractures is the procedure of choice. Open reductions should not be performed in the initial treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Definitive treatment of colon injuries: a prospective study.

The results of a prospective protocol for penetrating injuries of the colon in 252 patients are presented. The protocol emphasized definitive management of the injury by repair, resection and anastomosis or exteriorized repair. Colostomy was reserved for left colon injuries requiring resection or for delayed treatment. Two hundred nineteen patients (86.9%) had definitive treatment by repair (N = 159), resection and anastomosis (N = 26), or exteriorized repair. This was successful in 205 patients (93.6%). Three patients had anastomotic leak after repair or ileocolostomy. Eight of the 34 patients with exteriorized repair had suture-line breakdown and 26 (76.5%) patients avoided a colostomy. Injury severity indices (anatomic: Abdominal Trauma Index and Flint grading of colon injury) were higher in the exteriorized repair than in the repair group. Postoperative abdominal abscesses occurred in 43 patients (17.1%). A multiple regression analysis identified the Abdominal Trauma Index (P < 0.0001) and the presence of colostomy (P < 0.0004) as significant independent factors in association with this complication. Mortality from sepsis was 2.4 per cent (6 patients) and in only one patient was the death directly related to colon injury management. We conclude that the majority of colon injuries can be managed by repair or resection with anastomosis. End colostomy is unavoidable in Flint 3 injuries of the left colon. In other situations, ileocolic or colocolic anastomoses appear to be safe in hemodynamically stable patients. Loop colostomy has a role in delayed treatment, but can be replaced by an exteriorized repair in Grade 2 colon injuries that do not require resection.

Abscess↗
PubMed1992

Peptoids: a modular approach to drug discovery.

Peptoids, oligomers of N-substituted glycines, are described as a motif for the generation of chemically diverse libraries of novel molecules. Ramachandran-type plots were calculated and indicate a greater diversity of conformational states available for peptoids than for peptides. The monomers incorporate t-butyl-based side-chain and 9-fluorenylmethoxy-carbonyl alpha-amine protection. The controlled oligomerization of the peptoid monomers was performed manually and robotically with in situ activation by either benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate or bromotris(pyrrolidino)phosphonium hexaflurophosphate. Other steps were identical to peptide synthesis using alpha-(9-fluorenylmethoxycarbonyl)amino acids. A total of 15 monomers and 10 oligomers (peptoids) are described. Preliminary data are presented on the stability of a representative oligopeptoid to enzymatic hydrolysis. Peptoid versions of peptide ligands of three biological systems (bovine pancreatic alpha-amylase, hepatitis A virus 3C proteinase, and human immunodeficiency virus transactivator-responsive element RNA) were found with affinities comparable to those of the corresponding peptides. The potential use of libraries of these compounds in receptor- or enzyme-based assays is discussed.

Alkylation↗
PubMed1992

Central and regional hemodynamics determine optimal management of major venous injuries.

Controversy continues in the selection of optimal management of major venous injuries. We analyzed our experience with 191 major venous injuries in 163 patients (1986 to 1991). The mechanism of injury was gunshot (112), stab (44), blunt (six), and iatrogenic (one). Eighteen cervicothoracic, 51 caval, 30 iliac, 36 visceral, and 56 extremity veins were involved. Of the 191 injuries, 105 (54.9%) were repaired (lateral repair 76, end-to-end anastomosis 15, vein patch four, vein graft five, Gore-Tex graft four, and compilation one). Of the remaining venous injuries, 64 were ligated as a result of hemodynamic instability. Twenty-two injuries in 18 patients did not receive treatment because 16 of 18 patients died before vascular control or repair. The overall amputation rate was 1.2%, and the mortality rate was 28.2% (46/163). The highest mortality rate occurred in those patients who required resuscitative thoracotomy (100%, p < 0.00001), retrohepatic caval injuries (90%, p < 0.0004), and multiple venous injuries (81.8%, p < 0.00001). Seventeen patients underwent fasciotomies (15 prophylactic and two therapeutic). Clinical or measured venous hypertension by stump pressure assisted in deciding for venous repair in 20 patients. A significant decrease in venous stump pressure (p < 0.000001) was noted after venous reconstruction. Thus the decision to ligate or repair venous injuries correlated primarily with (1) hemodynamic stability, and in stable patients, with (2) extent and location of injury and (3) clinical and measured venous hypertension. Venous ligation in clinically stable patients did not increase the need for fasciotomy or amputation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Guaiac testing in the diagnosis of rectal trauma: what is its value?

Rectal examination with guaiac testing is a standard part of the emergency department evaluation of acutely traumatized patients. Its major role is in the recognition of occult bowel injury. We questioned its efficacy in detecting occult rectal injury in patients with penetrating trauma. We reviewed the charts of 19 patients with suspected rectal injury. Ten injuries were to the abdomen, nine to the buttock, and three to the thigh. Guaiac testing was 69% (11/16) sensitive and 33% (1/3) specific. Rigid sigmoidoscopy was 100% (12/12) sensitive and 67% (2/3) specific. Sensitivity was 100% (8/8) when the two were combined. Our findings suggest that guaiac testing is not accurate enough to rule out the presence of occult rectal injury. The result of guaiac testing must not influence the decision to further evaluate patients with high-risk injuries.

Adult↗
PubMed1992

Laparoscopy in the evaluation of the intrathoracic abdomen after penetrating injury.

Penetrating trauma to the intrathoracic abdomen is a difficult clinical problem, especially with reference to the detection of diaphragmatic injuries. A retrospective analysis of 657 laparotomies for penetrating abdominal trauma at our institution revealed 78 laparotomies with negative results. The majority (44.8%) were for wounds in the lower chest and upper abdomen. The role of laparoscopy in evaluating these difficult areas was studied in 40 (34 stab wounds and 6 gunshot injuries) patients. Fifteen stab wounds and five gunshot wounds were nonpenetrating. Laparoscopy revealed eight clinically unsuspected diaphragmatic lacerations in seven patients. Twenty patients had hemoperitoneum. Five patients with omental bleeding and abdominal wall bleeding and four with nonbleeding liver lacerations underwent nontherapeutic laparotomies. One patient with a nonbleeding liver laceration was observed successfully without laparotomy. Ten of the 20 patients with hemoperitoneum had therapeutic laparotomies. The incidence of diaphragmatic lesions discovered by laparoscopy in this series was comparable with that reported after a mandatory laparotomy for thoracoabdominal wounds. It is concluded that laparoscopy is an excellent modality for the evaluation of the intrathoracic abdomen and the diaphragm.

Abdominal Injuries↗
PubMed1992

Analysis of organ procurement failure at an urban trauma center and the impact of HIV on organ procurement at a regional transplantation center.

A 42-month experience with 100 patients with fatal head injuries was analyzed to identify areas of organ procurement failure. Thirty-six patients were ineligible for organ donation. Reasons for exclusion included advanced age (7), sepsis (16), hepatitis (1), systemic illnesses (3), and HIV infection or risk (9). Resuscitation failure (17 patients) and late deaths from failed support (16 patients) left 31 potential donors. Of the 30 families asked to donate, 17 consented (56.7%). Annual consent rates were 25%, 71%, 75%, and 67%. Efforts to improve organ procurement should focus on resuscitation and physiologic support of potential donors. To assess the impact of HIV infection or risk on organ procurement, a 3-year experience of the regional transplantation center (RTP) was reviewed. Of 1,714 referrals to the RTP from 102 hospitals, 1,120 were from trauma centers. The incidence of rejection because of HIV risk or infection was significantly higher in the trauma center group than in the group from non-trauma centers, 17.2% versus 10.2% (p less than 0.004). A similar difference was noted between metropolitan and suburban hospitals (p less than 0.0001). Hepatitis risk was comparable, 3.9% vs. 3.2%. The risk of HIV infection is emerging as a factor limiting organ donation at urban trauma centers.

Adolescent↗
PubMed1987

Effect of supplemental vitamin A on colon anastomotic healing in rats given preoperative irradiation.

We studied the effect of dietary supplementation with vitamin A on the healing of colon anastomoses in irradiated bowel. Rats were divided into two groups. Those in the first group were fed a standard chow diet and those in the second group were fed the same diet supplemented with 150 IU vitamin A/g of chow. The rats were maintained on their respective diets throughout the experiment. After 7 days, half the rats in each group underwent abdominal irradiation (200 rads). Seven days later, all of the rats underwent distal colon division and anastomosis under pentobarbital anesthesia. All rats were killed 7 days postoperatively, the colons excised, and bursting strength and hydroxyproline determinations performed on both the anastomotic segment and a normal proximal segment of adjacent colon. There was a significant decrease in the bursting strength at the colon anastomosis (p less than 0.02) and in the collagen content (p less than 0.02) after preoperative irradiation. This effect was mitigated by dietary vitamin A supplementation.

Animals↗
PubMed1976

Pathways to the hospital for the geriatric psychiatric patient in New York and London.

This communication examines the pathways of geriatric psychiatric patients in New York and London from the time of onset of a psychiatric episode to hospitalization. Informants of 50 patients in each city were interviewed with a semi-structured interview covering the events and the patient's activities prior to hospitalization. The results show that the time from the onset of the episode to hospitalization is significantly shorter in London than it is in New York. The major portion of this difference is accounted for by the longer time spent London the doctor is significantly more involved in New York between episode onset and initial medical contact. In the decision to hospitalize. In New York the main reason for hospitalization is harmful behavior, while in London it is psychiatric symptoms.

Aged↗