Synthesis of N-succinyl-L,L-diaminopimelic acid mimetics via selective protection.

The search for potential inhibitors that target so far unexplored bacterial enzyme mono-N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) has stimulated a development of methodology for quick and efficient preparation of mono-N-acylated 2,6-diaminopimelic acid (DAP) derivatives bearing the different carboxyl groups or lipophilic moieties on their amino group.

Inhibitors of N(alpha)-acetyl-L-ornithine deacetylase: synthesis, characterization and analysis of their inhibitory potency.

A series of N (alpha)-acyl (alkyl)- and N (alpha)-alkoxycarbonyl-derivatives of L- and D-ornithine were prepared, characterized, and analyzed for their potency toward the bacterial enzyme N (alpha)-acetyl-L-ornithine deacetylase (ArgE). ArgE catalyzes the conversion of N (alpha)-acetyl-L-ornithine to L-ornithine in the fifth step of the biosynthetic pathway for arginine, a necessary step for bacterial growth. Most of the compounds tested provided IC(50) values in the muM range toward ArgE, indicating that they are moderately strong inhibitors. N (alpha)-chloroacetyl-L-ornithine (1g) was the best inhibitor tested toward ArgE providing an IC(50) value of 85 microM while N (alpha)-trifluoroacetyl-L-ornithine (1f), N (alpha)-ethoxycarbonyl-L-ornithine (2b), and N (alpha)-acetyl-D-ornithine (1a) weakly inhibited ArgE activity providing IC(50) values between 200 and 410 microM. Weak inhibitory potency toward Bacillus subtilis-168 for N (alpha)-acetyl-D-ornithine (1a) and N (alpha)-fluoro- (1f), N (alpha)-chloro- (1g), N (alpha)-dichloro- (1h), and N (alpha)-trichloroacetyl-ornithine (1i) was also observed. These data correlate well with the IC(50) values determined for ArgE, suggesting that these compounds might be capable of getting across the cell membrane and that ArgE is likely the bacterial enzymatic target.

Evaluation of the size 4 i-gel airway in one hundred non-paralysed patients.

We studied the i-gel in 100 elective, anaesthetised patients (55:45 male:female, median age 53 years) assessing: ease of use, airway quality, positioning, seal and complications. First insertion attempt was successful in 86 patients, second attempt in 11 patients, and third attempt in three patients. Fifty three manipulations were required in 26 patients (median 1) to achieve a clear airway. Median insertion time was 15 s. During ventilation, expired tidal volume of 7 ml x kg(-1) was achieved in 96 (96%) patients. Median airway leak pressure was 24 cmH(2)O. On fibreoptic examination via the device, vocal cords were visible in 87 patients (91%). During maintenance, six patients (6%) required 12 airway manipulations. There was one episode of regurgitation, without aspiration. Other complications and patient side-effects were mild and few. The i-gel is easily and rapidly inserted, providing a reliable airway in over 90% of cases. Further studies are indicated to assess safety and performance compared to other supraglottic airway devices.

Meta-analysis of effectiveness of intermittent pneumatic compression devices with a comparison of thigh-high to knee-high sleeves.

This meta-analysis used all original articles from 1966 to June 1996 that fit the preset inclusion criteria to examine the clinical effectiveness of intermittent pneumatic compression (IPC) devices in preventing deep vein thrombosis (DVT) and pulmonary embolism and to compare the results of knee-high sleeves to thigh-high sleeves. IPC devices decreased the relative risk of DVT by 62 per cent when compared with placebo, 47 per cent compared with graduated compression stockings, and 48 per cent compared with mini-dose heparin. IPC devices significantly decreased the relative risk of DVT compared with placebo in high-risk patients such as neurosurgery and major orthopedic surgery patients and in modest risk patients such as general surgery patients. In major orthopedic surgery patients, the incidence of DVT was similar for IPC- and warfarin-treated patients; however, IPC was significantly better than warfarin at decreasing the incidence of calf only DVT, whereas warfarin seemed to be better at decreasing proximal DVT. IPC devices are effective in decreasing the incidence of DVT in patients at moderate to high risk and are probably more efficacious than graduated compression stockings or mini-dose heparin; however, IPC devices are not protective against pulmonary embolism. The data directly comparing the various methods of compression (knee-high versus thigh-high sleeves and graded-sequential versus uniform compression) are sparse and conflicting.

Correlation of menstrual cycle at time of breast cancer surgery to disease-free and overall survival.

The timing of surgery during the menstrual cycle of premenopausal breast cancer patients was correlated with their disease-free survival (DFS) and overall survival (OS). The study included 150 premenopausal patients treated for breast cancer between 1977 and 1992. The data were analyzed using three different menstrual cycle phase categorization schemes: (1) days 0 to 6 and 21 to 32 vs 7 to 20; (2) days 0 to 2 and 13 to 32 vs 3 to 12; and (3) days 0 to 14 vs 14 to 32. Two different surgery dates used for analysis were biopsy date and definitive surgery date. There was no association of the timing of surgery with OS. Only one categorization scheme correlated with DFS (scheme No. 2), and this correlation was significant using either surgery or biopsy dates. Thus, premenopausal breast cancer patients who have biopsy and/or definitive surgery during their perimenstrual phase (days 0 to 2 or after day 13) of the menstrual cycle may have a longer DFS than patients operated on during their midcycle phase (days 3 to 13); however, this may not affect overall survival.

Assessment of physicians' ability to prescribe parenteral nutrition support in a community teaching hospital.

OBJECTIVE: To assess the knowledge and skill base of the physicians in our hospital in prescribing parenteral nutrition support. DESIGN: Physicians completed parenteral nutrition orders for three mock patients. A range of clinically appropriate responses was established before the survey by the hospital Nutrition Support Team. Each case was scored according to set criteria, and the three case scores were averaged to yield a total score of 0 to 100. SUBJECTS/SETTING: Forty-eight attending, resident, and student physicians in the departments of family practice, internal medicine, and general surgery in a community teaching hospital. STATISTICAL ANALYSIS: Student's t test was used to compare interval data between two groups, and analysis of variance was used to compare interval data among three or more groups. If Bartlett's test for homogeneity of variance showed differences between the groups, the Kruskal-Wallis one-way analysis of variance was used. If analysis of variance revealed a significant difference, the data were reanalyzed using three different multiple-comparison procedures (Tukey, Scheffe, and Bonferroni) to decrease the possibility of a type I error. RESULTS: The mean total score was 48.6 +/- 20.8. Total score differed according to the number of nutrition lectures attended during residency. Total score tended to differ by specialty and number of patients treated with parenteral nutrition; however, these differences did not reach statistical significance. APPLICATIONS/CONCLUSIONS: This tool can be adapted and used by other hospitals, medical schools, and residency programs to assess physicians' knowledge base, design educational programs, and improve the parenteral nutrition ordering process.

Hypersensitivity-like reactions related to insertion of aquavene-based midline and PICC catheters.

Catheter-related hypersensitivity-type adverse reactions have been associated with insertion of the LANDMARK Midline Catheter (Menlo Care Inc., Menlo Park, CA). The authors' retrospective study showed an incidence for these reactions of 0.3% (7/2169) as well as an incidence of 3.3% (2/61) with insertion of CENTERMARK PICC (Menlo Care Inc., Menlo Park, CA), another aquavene-based catheter. The mechanism causing these reactions remains unknown, but the authors think that there is a small but significant risk of potentially life-threatening adverse reactions associated with insertion of these catheters. The health care professional who uses these catheters should be aware of these hypersensitivity reactions and should report any cases that occur to the Food and Drug Administration's MedWatch immediately.

The formation of cocaethylene and clinical presentation of ED patients testing positive for the use of cocaine and ethanol.

The purpose of this investigation was to document the clinical presentation of emergency department (ED) patients who tested positive for concurrent cocaine (COC) and ethanol (EtOH) use and the incidence of cocaethylene (CE) formation in this study population. Four study groups were evaluated: (1) drug-free, (2) EtOH-only, (3) COC-only, and (4) COC plus EtOH. CE was detected in plasma or urine specimens in 88% of the COC/EtOH-positive patients, and correlated directly with plasma COC and its metabolite benzoylecognine. Blood pressure and body temperature did not vary across study groups. COC/EtOH-positive patients displayed a significantly higher mean respiratory rate while the EtOH-only study group had an elevated mean heart rate. No significant differences were detected with respect to cardiac and neurological complaints between study groups. Trauma complaints in the drug-positive groups were more frequent than the incidence reported in the drug-free population. COC/EtOH-positive patients had the greatest percentage of trauma complaints (34.6%). Nearly half of the patients who tested positive for CE cited trauma as the primary reason for reporting to the ED. We conclude that ED patients who have concurrently used COC and EtOH are more closely associated with presentations related to traumatic injury than to those related to toxicologic complications.

Concurrent use of cocaine and alcohol by patients treated in the emergency department.

STUDY OBJECTIVE: To compare the demographics, presenting signs and symptoms, morbidity, and mortality of emergency department patients with drug screen results positive for benzoylecgonine ester (BE; a cocaine metabolite) and those positive for BE and alcohol. METHODS: We carried out a retrospective cohort study, in a university-affiliated community hospital, of 190 patients positive for BE alone and 125 patients positive for BE and alcohol. RESULTS: Patients positive for BE and alcohol were more often male and single. They were more likely to have been intubated, admitted to an ICU, and involved in violent trauma and to have demonstrated altered mental status than patients who tested positive for BE alone. These patients had higher mean heart rate and blood pressure values than patients positive for BE alone, and the two patients with myocardial infarction were positive for BE and alcohol. The incidence of rhabdomyolysis and the mean blood urea nitrogen value were lower in the patients positive for BE and alcohol. The two deaths in our study were patients in the BE-and-alcohol group, but these were due to trauma and not to the toxic effects of cocaine or alcohol. CONCLUSION: Cocaine use was associated with a low incidence of morbidity and mortality, but patients who combined it with alcohol had decreased mental status and required a higher intensity of care.

Results of laparoscopic versus open cholecystectomy in a community hospital.

In a retrospective study, the first 301 patients who had laparoscopic cholecystectomy (LC) in a university-affiliated community hospital were compared with a historical matched control group of patients who had open cholecystectomy. The patients who had LC had a shorter hospital stay, required less postoperative pain medication, resumed normal activities and returned to work sooner, and had a lower minor and total complication rate. The mean operating time was 45 minutes longer for LC. Major complications, common bile duct injuries, and mortality were similar in both patient groups. The learning curve, use of laser, and use of cholangiography were all analyzed. Our results with LC compared favorably with results reported in the medical literature.

The cost of laparoscopic versus open cholecystectomy in a community hospital.

This retrospective study reviewed the hospital and professional costs, charges, and reimbursements for laparoscopic cholecystectomy (lap chole) and open cholecystectomy (open chole) and compared the two procedures. There was no significant difference in hospital costs between lap and open chole procedures; however, there were marked differences in the categories of costs for each procedure. The mean total (hospital and professional) charge was 8% greater for lap chole. The mean total (hospital and professional) reimbursement for patients with private insurance was 23% greater for lap chole, but no significant difference was seen for patients on Medicare or Medicaid. Lap chole patients returned to work 11 days sooner than open chole patients; this can result in a 69% decrease in short-term disability costs to employers. The clinical variables that significantly affect total charges and reimbursement are discussed.

Serum potassium concentrations in trauma patients.

Hypokalemia occurs in 50% to 68% of trauma patients. To investigate the pathophysiology of these changes in serum potassium, we prospectively studied 133 trauma patients. Among the patients who had hypokalemia, the serum potassium usually decreased within 1 hour of trauma and returned to normal within 24 hours without significant potassium replacement. In bivariant analysis, age, admission systolic blood pressure, cardiac injury, and serum epinephrine level were associated with admission serum potassium value (K1), whereas sex, mechanism of injury, number of organ systems injured, blood glucose, serum alcohol, arterial pH, Injury Severity Score, trauma score, estimated blood loss, and urine potassium were not significantly related to K1. But in a multiple regression model, the only significant independent variables were age, arterial pH, and serum epinephrine level.

Reflex sympathetic dystrophy after modified radical mastectomy: a case report.

Despite the long history of descriptions of reflex sympathetic dystrophy (RSD), much confusion remains regarding its pathogenesis, diagnosis, and treatment. It most commonly occurs after trauma and is more frequent in women, white persons, and the elderly. The first case of RSD after mastectomy is reported and the proposed pathophysiology and management of RSD are reviewed.

Emergency room resuscitative thoracotomy: when is it indicated?

This study was designed to examine the results of emergency room resuscitative thoracotomy (ERRT) and to formulate cost-effective indications for this procedure. A retrospective study was performed of 28 patients who had ERRT at St. Elizabeth Hospital Medical Center, Youngstown, Ohio, during the 4 years from July 1985 through June 1989. The prognostic factors analyzed included mechanism and site of injury, signs of life (SOL), vital signs (VS), age, gender, and prehospital care. The overall survival rate of ERRT was 7% (2 of 28 patients). The survival rate was 18% (2 of 11 patients) with penetrating trauma, and 0% (none of 17 patients) with blunt trauma. The best survival rate was 66% in the subgroup of patients with penetrating trauma and SOL present at the scene and in the emergency room (ER), (two of three patients). Our observations were combined with those of 23 studies from the literature involving 2294 trauma patients who had ERRT. Using meta-analysis, the survival rate was 11% overall. Improved survival was noted for patients with penetrating trauma compared with patients with blunt trauma (14% vs. 2%, p < 0.01). There were no survivors in the group of patients with no SOL at the scene, and there were no neurologically intact survivors among blunt trauma patients with no SOL upon arrival at the ER. An algorithm based on mechanism of injury and presence or absence of SOL at the scene and in the ER is proposed. This algorithm would decrease the number of ERRTs performed by 41% without decreasing the number of neurologically intact survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary malignant melanoma of the small bowel: a case study.

Malignant melanoma involving the gastrointestinal (GI) tract is diagnosed premortem in only 4 per cent of patients with the disease, even though in autopsy series 60 per cent of patients who died of malignant melanoma have GI metastases. Usually, these GI lesions are metastatic. However, a few cases of primary GI malignant melanoma have been reported. Such a case is reported and discussed, including the clinical presentation, pathophysiology, treatment, and prognosis of this disease.

Delayed splenic rupture: real or imaginary?

Although splenic injury is the most frequent abdominal injury resulting from blunt trauma, delayed splenic rupture is a rare event. From 1981 to 1990, 75 patients treated at St. Elizabeth Hospital Medical Center (Youngstown, OH) had blunt splenic injury. Splenic rupture was delayed in six of these patients (8%). More severe trauma, such as occurs with motor vehicle accidents, is more likely to lead to immediate rupture. Lesser trauma resulting from minor falls or fights is more likely to lead to delayed rupture. Subcapsular hematoma is the most common etiology for delayed splenic rupture. Although there is no reliable symptom or sign during the latent period, abdominal pain occurs almost uniformly and Kehr's sign is quite common. Peritoneal lavage and abdominal computerized axial tomography scan are accurate in diagnosing splenic rupture. Unfortunately, they are not always reliable in predicting delayed rupture.

Clinical indications for cervical spine radiographs in alert trauma patients.

Cervical spine fracture/dislocation is a potentially devastating injury that may be clinically difficult to diagnose. Therefore, a vast majority of trauma patients undergo cervical spine X rays when only a relatively small number of them will actually have a cervical spine injury. Because of the costly overuse of radiography, studies have been undertaken to define high yield criteria for evaluation of patients. This study examined the characteristics of acute cervical spine fracture/dislocation in alert trauma patients. Of 79 patients with this discharge diagnosis at St. Elizabeth Hospital Medical Center between 1982 and 1987, 47 met the criteria of Class I level of consciousness. All 47 patients complained of neck pain or demonstrated cervical tenderness to palpation. Other parameters (such as loss of consciousness, paresthesias, decreased sensation, weakness, cervical muscle spasm, decreased anal tone, and associated injuries) did not, individually or in combination with each other, consistently predict cervical spine injury. Although occult or painless cervical spine injuries have been reported in the literature, a careful review of these cases revealed that these injuries were not truly asymptomatic. Our study suggests that selected patients can be excluded from radiologic evaluation of the cervical spine. However, large prospective studies are needed to validate this finding.

Combining abdominal aortic aneurysmectomy with gastrointestinal or biliary surgery.

A retrospective study was undertaken to compare the morbidity and mortality of patients who had simultaneous abdominal aortic aneurysm (AAA) resection and gastrointestinal (GI) or biliary surgery with patients who had AAA resection alone. This series consisted of 89 patients who underwent surgery over a 6-year period (January, 1980 through December, 1985) at St. Elizabeth Hospital Medical Center. The patients were separated into three groups: group 1 had elective AAA resection; group 2 had AAA resection and a GI or biliary procedure simultaneously; and group 3 had resection of a ruptured AAA. The patients in groups 1 and 2 were similar with respect to sex, age, surgeons, estimated blood loss, operative time, preoperative risk factors and hospital stay. The patients in group 3 had shorter preoperative and longer postoperative hospital stays, were older, and had greater preoperative risk. The morbidity and mortality of the patients in group 2 were consistently the same or less than that of patients in group 1, even when individual surgeons and preoperative risk factors were compared. The patients in group 3 had a significantly higher morbidity and mortality. This article reviews the literature on management of patients with simultaneous AAA and other intraabdominal pathology and presents a suggested approach to treatment.

Isolated Crohn's disease of the appendix. Two case reports and a review of the literature.

Two patients were diagnosed and treated at St Elizabeth Hospital Medical Center, Youngstown, Ohio, for isolated Crohn's disease of the appendix. Including these two patients, 75 such patients have been described in the world literature from 1953 to July 1986, to our knowledge. Crohn's disease of the appendix should be considered in patients who are in their second and third decades of life, who have pain and tenderness in the right lower quadrant of the abdomen, and whose symptoms are protracted (longer than three days) and/or recurrent. Intraoperatively, if the appendiceal wall appears hypertrophic, thickened, and chronically inflamed, a frozen section may confirm the diagnosis. Crohn's disease of the appendix is a diagnosis of exclusion. Appendectomy may be performed safely and has a low morbidity and mortality. The incidence of enterocutaneous fistula and the recurrence rate are much lower than for Crohn's disease of the small and large bowel.

Comparison of right colon, left colon, and rectal carcinoma.

Three hundred fifteen cases of adenocarcinoma were analyzed for differences between lesions in the right colon, left colon, and rectum for the period 1978 to 1983. The right colon cancers accounted for 1/3 of the cases and were associated with a higher incidence of anemia. The incidence of obstruction was the same between the right and left colon but lower for the rectal lesions. Left colon and rectal cancers had a higher incidence of gross bleeding than right colon cancers, but all had a high rate of occult blood in the stool. The Duke stage of the lesions, which was similar throughout the colon and rectum, is a reliable prognostic indicator.