Pyoderma gangrenosum and pregnancy: an example of abnormal inflammation and challenging treatment.

Pyoderma gangrenosum (PG) is a neutrophil-predominant inflammatory disease that initially presents as a sterile pustule and may progress to ulcerations. Its root cause is unknown, but the presentation is commonly associated with systemic inflammatory conditions such as inflammatory bowel disease, arthritis and haematological abnormalities. On the other hand, pregnant women show a progressive neutrophilia during gestation, which culminates in a major inflammatory event to help drive labour. Although uncommonly, PG has been associated with pregnancy, which provides an additional link to systemic inflammation as an underlying cause of PG. We reviewed documented presentations of PG in gravid and post-partum patients, and have speculated on the possible pathogenesis based on their clinical presentations. Also, we summarize the reported treatments and their outcomes in these patients.

Catheter-associated masses in patients receiving intrathecal analgesic therapy.

UNLABELLED: A cohort of seven patients receiving intrathecal analgesic drug therapy for chronic intractable pain underwent radiocontrast myelography and computed tomography (CT) scanning to screen for catheter-associated intrathecal masses. Three of seven patients examined had intraspinal masses associated with the tip of the drug infusion catheter after a total of 118 mo of therapy. The index case presented with exacerbation of neuropathic pain and paralysis of the left lower extremity. The two additional cases detected by CT myelography were asymptomatic at the time the catheter-associated mass was assessed. The mean duration of therapy before diagnosis of the catheter-associated mass was 19.6 mo, with a range of 16-25 mo. An intergroup comparison of demographic and treatment variables between patients, with and without catheter-associated masses, demonstrated that patients with masses were younger and were receiving a larger morphine dose than patients without masses. The differences were statistically significant (P = 0.05). In one patient with an asymptomatic catheter-associated intrathecal mass, regression of the mass was observed after cessation of therapy. In a second asymptomatic patient, the mass remained stable over 1 yr of continued treatment after substitution of hydromorphone for morphine without interruption of therapy. Neither asymptomatic patient has subsequently developed additional neurologic findings or injury after detection of occult catheter-associated intrathecal masses and clinical intervention. We suggest that all patients receiving long-term intrathecal analgesia should undergo periodic radiographic surveillance to further define their risk of developing occult catheter-associated masses and to allow intervention before neurologic injury can develop. IMPLICATIONS: Catheter-associated intrathecal masses were detected in three of seven patients receiving long-term intrathecal analgesia. In the two asymptomatic patients, timely clinical intervention was associated with the avoidance of subsequent neurologic injury and spontaneous resolution of one of the occult masses.

Comparison of transvaginal ultrasound, hysteroscopy, and dilatation and curettage in the diagnosis of abnormal vaginal bleeding and intrauterine pathology in perimenopausal and postmenopausal women.

STUDY OBJECTIVE: To compare transvaginal ultrasound, hysteroscopy, and dilation and curettage (D&C) in the evaluation of women with perimenopausal and postmenopausal bleeding. DESIGN: Descriptive study (Canadian Task Force classification II-1). SETTING: Seven outpatient clinics. PATIENTS: One thousand two hundred eighty-six women. INTERVENTION: Transvaginal ultrasound, hysteroscopy, and D&C. MEASUREMENTS AND MAIN RESULTS: Of our patient population, 29 (2.26%) had a histologic diagnosis of endometrial carcinoma; in 2 of them (7.14%) endometrial thickness was 5 mm or less. In 10 women (34.5%), endometrial carcinoma was missed by hysteroscopy (sensitivity 65.52%, specificity 99.92%). Complication rate of D&C was 1.4%. CONCLUSION: In women with perimenopausal and postmenopausal bleeding neither transvaginal ultrasound nor hysteroscopy as a single diagnostic tool is suitable to rule out endometrial cancer.

NMR spectroscopic investigations of mixed aggregates underlying highly enantioselective 1,2-additions of lithium cyclopropylacetylide to quinazolinones.

The solution structures of mixed aggregates derived from lithium alkoxides and lithium acetylides were investigated as part of a program to develop practical syntheses of quinazolinone-based nonnucleoside reverse transcriptase inhibitors. Low-temperature (6)Li, (13)C, and (15)N NMR spectroscopies reveal that mixtures of lithium cyclopropylacetylide (RCCLi), a (+)-carene-derived amino alkoxide (ROLi), and lithium hexamethyldisilazide (LiHMDS) in THF/pentane afford a (RCCLi)(3)(ROLi) mixed tetramer, a C(2)-symmetric and asymmetric (RCCLi)(2)(ROLi)(2) mixed tetramer, and a C(3)-symmetric (RCCLi)(ROLi)(3) mixed tetramer. Analogous mixtures of RCCLi/ROLi in Et(2)O and Me(2)NEt also provide 3:1, 2:2, and 1:3 mixed tetramers. The stereochemistry of aggregation is highly sensitive to the medium. The C(2)-symmetric (RCCLi)(2)(ROLi)(2) mixed tetramer is formed in Et(2)O, whereas the asymmetric isomer is formed in Me(2)NEt. LiHMDS in THF is shown to be an efficient proton scavenger without forming LiHMDS-RCCLi or LiHMDS-ROLi mixed aggregates. LiHMDS-RCCLi mixtures form mixed aggregates in Me(2)NEt.

Predicting the risk of death from heart failure after coronary artery bypass graft surgery.

UNLABELLED: Heart failure is the most common cause of death among coronary artery bypass graft (CABG) patients. In addition, most variation in observed mortality rates for CABG surgery is explained by fatal heart failure. The purpose of this study was to develop a clinical risk assessment tool so that clinicians can rapidly and easily assess the risk of fatal heart failure while caring for individual patients. Using prospective data for 8,641 CABG patients, we used logistic regression analysis to predict the risk of fatal heart failure. In multivariate analysis, female sex, prior CABG surgery, ejection fraction <40%, urgent or emergency surgery, advanced age (70-79 yr and >80 yr), peripheral vascular disease, diabetes, dialysis-dependent renal failure and three-vessel coronary disease were significant predictors of fatal postoperative heart failure. A clinical risk assessment tool was developed from this logistic regression model, which had good discriminating characteristics (receiver operating characteristic clinical source = 0.75, 95% confidence interval: 0.71, 0.78). IMPLICATIONS: In contrast to previous cardiac surgical scoring systems that predicted total mortality, we developed a clinical risk assessment tool that evaluates risk of fatal heart failure. This distinction is relevant for quality improvement initiatives, because most of the variation in CABG mortality rates is explained by postoperative heart failure.

An efficient chiral moderator prepared from inexpensive (+)-3-carene: synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963.

The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.

Innovative uses of a cardiothoracic database.

This report describes the activities of the Northern New England Cardiovascular Disease Study Group. The group consists of representatives from six institutions: Eastern Maine Medical Center in Bangor, and Maine Medical Center in Portland, ME; Optima Health Care in Manchester and Dartmouth-Hitchcock Medical Center in Lebanon, NH; Fletcher Allen Health Care in Burlington, VT; and Beth Israel-Deaconess Medical Center in Boston, MA. The Northern New England Cardiovascular Disease Study Group maintains a voluntary primary cardiac surgical database that has risk-stratified information on more than 60,000 consecutive patients who have undergone open heart surgical procedures in northern New England since 1987. In 1991, the group reported that significant variation in mortality rate existed between centers, a difference not explained by case mix. The finding led to a regional retrospective review of deaths in an effort to identify "mode of death." Mode of death is defined as that event that started the chain of events ultimately leading to the death of the patient. The most common mode of death was found to be low cardiac output syndrome. This information has led to a regional effort toward prevention, early recognition, and successful treatment of low cardiac output syndrome in the perioperative period.

Lung cancer staging and treatment in multidisciplinary trials: Cancer and Leukemia Group B cooperative group approach. Thoracic Surgeons of CALGB.

BACKGROUND: Aggressive routine surgical staging is necessary to evaluate patients to be treated on cooperative oncology protocols. Less than 1% of lung cancer patients in the United States are currently being treated in a clinical trial. Only with results from large, prospective trials can the questions of neoadjuvant and adjuvant therapy be answered. METHODS: An outline describing the schema of preoperative patient evaluation, surgical staging, and the definition of surgical staging and resection procedures appropriate for patients considered for cooperative group protocol is presented. Current Cancer and Leukemia Group B (CALGB) protocols are used in the discussion as examples of this systematic approach. CONCLUSIONS: Over the next few years, it will be important to enter the maximum number of patients into combined modality studies to identify the role of neoadjuvant treatment in lung cancer. Entry of patients into protocols will also make their pathological specimens and clinical information available for basic science research related to treatment results. Adherence to a logical sequence of patient evaluation as outlined above will optimize patient care, as well as accrual to cooperative group studies.

Field triage of the pulseless trauma patient.

HYPOTHESIS: Trauma patients who are pulseless at the scene of injury and whose electrical cardiac activity is less than 40 beats/min cannot be revived. DESIGN: Retrospective review. SETTING: University hospital, level I trauma center. PATIENTS: Pulseless trauma patients who had cardiopulmonary resuscitation at the scene, en route, or in the emergency department and presented between January 1, 1991, and July 1, 1996. MAIN OUTCOME MEASURE: Survival after traumatic cardiopulmonary arrest. RESULTS: Sixteen thousand seven hundred twenty-four trauma patients were admitted. The study cohort comprised 604 victims of traumatic cardiopulmonary arrest, 304 as a result of blunt injury and 300 as a result of penetrating injury. Transport time for the study patients was 11+/-6.1 minutes (mean +/- SD). Cardiopulmonary resuscitation was performed on them for 22+/-11 minutes. Three hundred four patients (50%) had resuscitative thoracotomy in the emergency department; 160 patients were taken to the operating room for further resuscitation and treatment of their injuries. Sixteen patients (2.6%) survived to discharge from the hospital; 7 had severe neurologic disabilities. No patient (0/212) with electrical asystole survived. Five of 134 patients with an initial electrical heart rate between 1 and 39 beats/min survived long enough to reach the intensive care unit but died within 48 hours (4 died within 24 hours). No patient survived to leave the hospital if the initial electrical heart rate was less than 40 beats/min. All 16 survivors had an initial heart rate of 40 beats/min or greater. CONCLUSION: Trauma victims who are pulseless and have asystole or agonal electrical cardiac activity (heart rate <40 beats/min) should be pronounced dead at the scene of injury.

Results of a regional study of modes of death associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: It is well known that surgeon-specific in-hospital mortality rates for coronary artery bypass grafting vary, but this aggregate measure does not suggest specific opportunities for improvement. METHODS: We performed a regional prospective study of 8,641 consecutive patients undergoing isolated coronary artery bypass grafting by all of the 23 cardiothoracic surgeons practicing in northern New England during the study period. Mode of death was assigned by an end points committee using predetermined definitions. Surgeons were ranked according to risk-adjusted mortality rates and grouped in terciles, and cause-specific mortality rates were determined. RESULTS: The mortality rate was 3.3% in the lowest surgeon mortality tercile and 5.8% in the highest tercile. Fatal heart failure accounted for 80.0% of the difference in aggregate mortality rates, ranging from 1.9% in lowest surgeon mortality tercile to 4.0% in the highest tercile (p < 0.001). Rates of other causes did not differ significantly across surgeon mortality terciles. Differences in rates of fatal heart failure could not be explained by differences in preoperative left ventricular dysfunction or other patient characteristics. CONCLUSIONS: Most of the difference in observed mortality rates across surgeons is attributable to differences in rates of heart failure.

Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group.

OBJECTIVE: To assess mortality and risk factors associated with reexploration for hemorrhage in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Regional cohort study. Patient characteristics, treatment variables, and outcome measures were collected prospectively. SETTING: All 5 centers performing cardiac surgery in Maine, New Hampshire, and Vermont. PATIENTS: A consecutive cohort of 8586 patients undergoing isolated CABG between 1992 and 1995. MAIN OUTCOME MEASURES: Postoperative hemorrhage leading to reexploration, in-hospital mortality, and length of stay. RESULTS: A total of 305 patients (3.6%) underwent reexploration for bleeding. In these patients, in-hospital mortality was nearly 3 times higher (9.5% vs 3.3% for patients not requiring reoperation, P<.001) and average length of stay from surgery to discharge was significantly longer (14.5 days vs 8.6 days, P<.001). High rates of reexploration for hemorrhage were observed in patients with prolonged (> 150 minutes) cardiopulmonary bypass (39 [11.1%] of 351) and in those requiring an intra-aortic balloon pump intraoperatively (12 [8%] of 139). In multivariate analysis, older age, smaller body surface area, prolonged cardiopulmonary bypass, and number of distal anastomoses were associated with increased bleeding risks. The use of thrombolytic therapy within 48 hours of surgery was weakly but not significantly associated with the need for reexploration. Factors not significantly associated with reexploration included patient sex, preoperative ejection fraction, surgical priority, history of liver disease, myocardial infarction, prior CABG, renal failure, and diabetes mellitus. CONCLUSIONS: Hemorrhage requiring reexploration after CABG is associated with markedly increased mortality and length of stay. Patients predicted to have increased risks of bleeding may benefit from prophylactic use of aprotinin, aminocaproic acid, or other agents shown to reduce hemorrhage.

Non-small cell lung cancer at the extremes of age: impact on diagnosis and treatment.

BACKGROUND: Early detection and surgical resection offers the highest likelihood of cure for patients with lung cancer. Patients presenting at the extremes of age may fail to benefit maximally from these interventions. To study the impact of age on stage, histology, symptom, and treatment of patients with non-small cell lung cancer, we undertook a retrospective review. METHODS: One thousand eight hundred two patients with non-small cell lung cancer were identified between 1983 and 1993. Patients were selected by age as less than 45 years (55 patients) and 80 years or more (108 patients), and their medical records were reviewed. RESULTS: Three younger patients (6%) presented with stage I or II disease, yet 15 (32%) underwent thoracic operation. Twenty-seven elderly patients (33%) presented with early stage disease and only 6% underwent operation. The median survival was significantly longer for the younger population with surgically resectable stages of disease (stage I to IIIA) (p < 0.05), whereas no significant difference in survival was seen for the two groups with advanced disease (stage IIIB and IV). CONCLUSIONS: Age significantly affects the presentation and treatment of non-small cell lung cancer patients. Although thoracic operation imparts the greatest survival advantage, this benefit is diminished due to advanced disease in the younger patients and lack of surgical intervention in the elderly.