Resection of the irradiated esophagus: the impact of lymph node yield on survival.

There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal (<9) or extensive (≥9) lymph node yield. Demographic, operative, and postoperative outcomes were compared between the groups. Kaplan-Meier analysis with the log rank test was used to compare survival between the yield groups. Cox proportional hazards model was used to determine the association between lymph node yield and survival. In total, 886 cases were included: 349 (39%) belonging to the minimal node group and 537 (61%) to the extensive group. Unadjusted 5-year survival was similar between the minimal and extensive groups, respectively (37.3% vs. 38.8%; P > 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66-0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

Fatal SV40-associated pneumonia and nephropathy following renal allotransplantation in rhesus macaque.

Recrudescence of latent and dormant viruses may lead to overwhelming viremia in immunosuppressed hosts. In immunocompromised hosts, Simian virus 40 (SV40) reactivation is known to cause nephritis and demyelinating central nervous system disease. Here, we report SV40 viremia leading to fatal interstitial pneumonia in an immunosuppressed host following renal allotransplantation.

Thrombalexin: Use of a Cytotopic Anticoagulant to Reduce Thrombotic Microangiopathy in a Highly Sensitized Model of Kidney Transplantation.

Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anticoagulation is difficult due to bleeding. A novel "cytotopic" agent, thrombalexin (TLN), combines a cell-membrane-bound (myristoyl tail) anti-thrombin (hirudin-like peptide [HLL]), which can be perfused directly to the donor organ or cells. Thromboelastography was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN versus HLL (without cytotopic tail) versus negative control. Both TLN- and HLL-treated rhesus or human whole blood result in significantly prolonged r-time compared to kaolin controls. Only TLN-treated human endothelial cells and neonatal porcine islets prolonged time to clot formation. Detection of membrane-bound TLN was confirmed by immunohistochemistry and fluorescence activated cell sorter. In vivo, perfusion of a nonhuman primate kidney TLN-supplemented preservation solution in a sensitized model of transplantation demonstrated no evidence of TLN systemically. Histologically, TLN was shown to be present up to 4 days after transplantation. There was no platelet deposition, and TMA severity, as well as microvascular injury scores (glomerulitis + peritubular capillaritis), were less in the TLN-treated animals. Despite promising evidence of localized efficacy, no survival benefit was demonstrated.

Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model.

Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity form and a transient, high-affinity form, expressed only during activation. We have shown that antibodies reactive with LFA-1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL-579, each of which targets the high-affinity form of LFA-1, to determine whether this more precise targeting prevents belatacept-resistant rejection. Despite evidence of ex vivo and in vivo ligand-specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL-579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA-1 blockade may not be a suitable adjuvant agent for CoB-resistant rejection.

Domestic abuse in the emergency department: can a risk profile be defined?

OBJECTIVES: The main purpose of this study was to determine whether any clinical or demographic characteristics could identify adult female patients presenting to the emergency department (ED) with a history of domestic abuse. A second objective was to describe the frequency, types, and severity of this abuse. METHODS: This study was a crosssectional survey of 611 women conducted in an academically-affiliated, urban ED. Domestic abuse was described as "recent" (within the preceding 12 months) or "lifetime" (recent or past). This included emotional, physical, and sexual abuse. RESULTS: Recent (7.9%, n = 48) and lifetime (38%, n = 232) domestic abuse was reported. For recently abused women, violence had been severe (87.5%, n = 42) and was associated with 1) trauma (OR 5.4, 95% CI = 2.6 to 11.6), 2) obstetrical and gynecological syndromes (OR 5.6, 95% CI = 2.4 to 13.2), and 3) psychiatric symptoms and substance use (OR 7.3, 95% CI = 2.4 to 22.0). The sensitivities and positive predictive values of these risk factors individually (<27.1% and <25.0%, respectively) and in aggregate (56.3% and 20.9%, respectively) were low. These indicators predicted only 27 (56.3%) of recently abused women. Lifetime domestic violence was more likely in homeless women (OR 5.8, 95% CI = 2.2 to 15.0), although less likely in immigrants (OR 0.4, 95% CI = 0.3 to 0.7). CONCLUSIONS: Clinical presentations and demographic characteristics of women presenting to the ED may not be sensitive or predictive indicators of domestic abuse. In the absence of typical clinical or demographic findings, asking all women in the ED about domestic abuse remains a necessary priority.

Predictors of follow-up of atypical and ASCUS papanicolaou tests in a high-risk population.

OBJECTIVE: Our goals were to assess adherence to the National Cancer Institute clinical practice guideline for the management of atypical squamous cells of uncertain significance (ASCUS) Papanicolaou (Pap) test results in a community at high risk of cervical cancer. We also hoped to identify predictors of adherence to the guideline. STUDY DESIGN: We used an historical cohort and collected data by chart abstraction. POPULATION: Our study included women receiving care in 7 urban community health centers who had an initial ASCUS or atypical Pap test result in 1996. We excluded women with a history of cervical dysplasia or human immunodeficiency virus infection, yielding a final sample of 387 women. OUTCOMES: measured The outcome measured was the level of adherence to the guideline, defined as falling within 1 of 3 mutually exclusive categories (complete, moderate, or low). RESULTS: Care providers recommended colposcopy after an initial atypical Pap test result in 12% of cases and repeat cytology in 67%. Failure to document a plan for management was found in 19% of cases. Complete adherence was achieved for 27% of subjects, moderate adherence for 28%, and low adherence for 45%. The factors associated with complete versus moderate or low adherence included site of care, description of the abnormality (ASCUS vs atypia), availability of on-site colposcopy, and discussing the plan at a visit. CONCLUSIONS: Adherence with the National Cancer Institute clinical practice guideline in this setting was disappointing and varied substantially by site. Factors amenable to change that may improve follow-up include good communication of results with patients and providing colposcopy at the site of primary care.

Attitudes of New York City high school students regarding firearm violence.

OBJECTIVES: To assess prevalence of gun possession, attitudes regarding gun possession and gun violence, knowledge and influences of gun violence, and the potential role of physicians in gun violence prevention education among adolescents. METHODS: An anonymous questionnaire was distributed to 9th through 12th grade high school students at 3 public high schools in New York City. RESULTS: Three hundred forty-two surveys were distributed and returned. The prevalence of guns in the homes was 19.6%. Of respondents, 43.2% thought it was okay for anyone to have guns, and 57.3% had been injured or have had a relative injured by a gun. Although 11.6% of adolescents had felt the need to talk to an adult about guns, only 3.0% listed their physicians as one of these adults. However, if asked by their physician, 63.8% would discuss the issue with them. Only 5.7% of adolescents have had a physician speak to them about guns. CONCLUSIONS: The adolescent population surveyed is frequently exposed to gun violence. Although physicians rarely counsel adolescents regarding gun violence and firearm safety, many adolescents would be receptive to this mode of intervention.adolescence, attitude, firearm ownership, firearm violence, physician role.

Observational assessment of family functioning at mealtime in preschool children with cystic fibrosis.

OBJECTIVE: To examine functioning during a dinner meal in families of a child with a chronic illness that requires dietary treatment recommendations, as compared to families of a child without a chronic illness. METHODS: Ratings of seven dimensions of family functioning on the McMaster Mealtime Family Interaction Coding System (MICS) were obtained on 29 families of children with CF and 29 families of children with no chronic illness, ages 2 to 6 years, during a videotaped dinner meal at home. RESULTS: Ratings of families with a child with CF were significantly lower than those for families of children without a chronic illness on Overall Family Functioning and five of the six MICS dimensions: Communication, Interpersonal Involvement, Affect Management, Behavior Control, and Role Allocation and approached significance on the Task Accomplishment dimension. The ratings of families of a child with CF were in the "clinically significant" range on all subcales, including Task ACCOMPLISHMENT. CONCLUSIONS: This study suggests that family functioning at mealtimes may be different in families of children with CF in which explicit dietary guidelines exist than in families of children with no illness or dietary guidelines. These results are discussed in terms of global family functioning and treatment approaches to dietary treatment recommendations.

Evaluation of a risk assessment questionnaire used to target tuberculin skin testing in children.

CONTEXT: Universal tuberculin skin testing of children has been shown to be costly and inefficient. In response, several authorities have recommended targeted screening based on epidemiological risk. In 1996, the New York City Department of Health (NYCDOH) developed questions to identify children who require a tuberculin skin test. OBJECTIVE: To determine the sensitivity, specificity, and predictive validity of the NYCDOH tuberculosis risk assessment questionnaire. DESIGN: Prospective criterion standard study in which tuberculin skin tests and the NYCDOH questionnaire were administered simultaneously between August 1996 and January 1998. Specific questions asked about contact with a tuberculosis case, birth in or travel to endemic areas, regular contact with high-risk adults, and human immunodeficiency virus infection in the child. SETTING: Ambulatory clinic in South Bronx, New York, NY. PARTICIPANTS: Consecutive sample of 2920 children aged 1 to 18 years. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values of the questionnaire, and odds ratio (OR) of reactive skin test results. RESULTS: The NYCDOH questionnaire identified 413 children (14%) as having at least 1 risk factor. Of these, 23 (5.6%) had a positive skin test result; 4 (0.16%) of the 2507 without risk factors had a positive result. Results for the full NYCDOH questionnaire were sensitivity, 85.2%; specificity, 86.0%; negative predictive value, 99.8%; positive predictive value, 5.4%; and OR, 35.2 (95% confidence interval, 12.1-102.4). CONCLUSION: The NYCDOH questionnaire is a valid instrument for identifying children for tuberculin skin testing.

State practice variations in the use of tube feeding for nursing home residents with severe cognitive impairment.

OBJECTIVE: To describe the differences in prevalence of tube feeding among states and to examine possible factors that could explain practice patterns. DESIGN: Analysis of random samples from an interstate data bank comprised of the Minimum Data Set (MDS), a standardized, federally mandated assessment instrument for nursing home residents. SETTING: Nursing homes in four states participating in a federal demonstration project of case mix payment plus five others with existing MDS data systems. PARTICIPANTS: Individuals 65 years of age and older (N = 57,029), who had very severe cognitive impairment, including total dependence in eating, and who resided in nursing homes during 1994, the most recent year for which uniform data were available. MEASUREMENTS: State-by-state differences in prevalence of tube feeding, controlling for demographic and clinical variables. RESULTS: The prevalence of tube feeding ranged from 7.5% in Maine to 40.1% in Mississippi. Each state had a significantly elevated prevalence of tube feeding compared with Maine, with odds ratios (ORs) ranging from 1.50 to 5.83, P < .001. Specific directives not to provide tube feeding (OR 0.41, P < .001), and white race (OR 0.45, P < .001) were strongly and negatively associated with tube feeding. CONCLUSIONS: Wide regional variations exist in the use of tube feeding of nursing home residents with equivalent impairments. Sociodemographic factors could be important, but more study is needed to determine whether physician characteristics, such as race, attitudes, or knowledge, have an impact and to clarify medical standards for the use of tube feeding in this population.

Parent and child mealtime behavior in families of children with cystic fibrosis.

OBJECTIVES: We investigated the hypothesis that children with cystic fibrosis (CF) and their parents would show more maladaptive behaviors during dinner than children without CF and their parents. STUDY DESIGN: Children with CF (n = 32) and their parents were compared with 29 children without CF and their parents on the rate and frequency of parent-child behaviors during a typical dinner in the families' homes by using multivariate analyses of variance. RESULTS: When the rate of behavior, controlling for meal length, was examined, no differences were found between groups. However, parents of children with CF were found to differ from parents of control subjects in the frequency of direct and indirect commands (P <.05), coaxes (P <.01), physical prompts (P <.01), and feeding their child (P <.05). Children with CF were found to engage in more talk, spend more time away from the table, refuse food, and exhibit more noncompliance toward commands to eat than control children (P <.05 for all child variables). When behaviors were examined as a function of meal phase, parents of children with and without CF both showed an increase in commands (P <.01), coaxes (P <.05), feeds (P <.01), and physical prompts (P <.01) in the second half of the meal as compared with the first. Children with CF and the control children showed an increase in behaviors incompatible with eating during the second half of the meal compared with the first (P <.01). When faster eaters were compared with slower eaters, faster eaters consumed a higher percentage of the recommended daily allowance of energy (P <.01) than slower eaters and showed a trend to be at higher weight percentiles for age and sex (P =.08) regardless of group (CF or control). CONCLUSIONS: Children with CF and their parents do not differ from children without CF and their parents in the rate of behaviors exhibited or types of strategies used to encourage eating. However, children with CF and their parents engage in these behaviors more frequently. Our data do not support typical parenting behaviors as effective in meeting the CF dietary requirements. Additional support in the form of child behavior management training may be needed to assist parents in meeting their child's caloric requirements.

Assessing the validity of tuberculin skin test readings by trained professionals and patients.

STUDY OBJECTIVES: To assess the validity of purified protein derivative (PPD) readings by patients and trained health-care professionals as compared with a calibrated model. DESIGN AND PARTICIPANTS: Survey of a group of patients, nurses, medical assistants, and physicians at five neighborhood health centers in the Bronx, NY. INTERVENTIONS: Participants were asked to read a calibrated model with four PPD indurations measuring 0 mm, 3 mm, 7 mm, and 13 mm. Indurations > or = 5 mm were to be considered "positive" reactions. MEASUREMENTS AND RESULTS: Data were obtained from 233 patients and 80 trained professionals. All patients correctly measured the 0-mm induration site and were able to detect the presence of an induration in 99.3% of possible observations. Compared with professionals, patients had more variability in measurements and interpretations of the 3-, 7-, and 13-mm sites. Professionals detected 100% of all indurations. Patients' specificity for the 0- and 3-mm sites was 97.4% and 62.7%, respectively; whereas sensitivity for the 7- and 13-mm sites was 68.2% and 89.3%, respectively. Professionals' specificity for the 0- and 3-mm sites was 98.7% and 65.3%, respectively; their sensitivity for the 7- and 13-mm sites was 86.7% and 97.3%, respectively. Seventy percent of professionals agreed that the model was a realistic representation of PPD indurations. CONCLUSIONS: Patients can reliably distinguish between the presence and absence of an induration at a PPD injection site. They are not as reliable in the measurement and interpretation of test reactions. Professionals had considerable variability in their assessments of PPDs but were more precise overall in their assessments than patients.

Barriers to follow-up of abnormal Papanicolaou smears in an urban community health center.

OBJECTIVE: To determine factors predictive of failure to return for colposcopy among women with significant abnormalities on Papanicolaou smears in a high-risk clinical population. DESIGN: Telephone survey. SETTING: An urban community health center. PARTICIPANTS: Two hundred seventy-nine women randomly selected from all women seen at the health center with abnormal Papanicolaou smears requiring colposcopy during 1993 to 1994. Six (2%) refused participation, and 19% could not be reached for inclusion. Subjects were mostly minority women receiving Medicaid. MAIN OUTCOME MEASURE: Completion of colposcopy. RESULTS: Of the 279 selected women, 79% were interviewed. The rate of adherence with colposcopy was 75% for the respondents. Women who did not know the results of their smear or who incorrectly understood their results were significantly less likely to return for colposcopy (P = .001). Younger women, especially teenagers, were less likely to return (P = .02). Socioeconomic status, education, primary language, health beliefs, fear of cancer, and clinician's gender or discipline were not associated with rate of follow-up. Barriers involving transportation, child care, and insurance also did not predict follow-up. CONCLUSIONS: Effective communication of results is the most important factor related to follow-up after abnormal Papanicolaou smear in this setting. In other settings, other factors may be of greater importance.

The prevalence of eye disease in nursing home and non-nursing home geriatric populations.

The objective of this study was to determine whether rates of eye disease among the elderly are higher for residents of nursing homes than for persons who reside elsewhere. Articles reporting the prevalence of eye disease in geriatric populations (classified as nursing home or non-nursing home) were identified through a Medline search and a search of articles' bibliographies. Identified articles were reviewed, and the relevant data compared with prevalence rates obtained from 738 residents of two nursing homes in New York City. Each of the nursing home residents received an ocular examination upon admission that determined the presence or absence of four varieties of eye disease-i.e. cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. Demographic data were obtained through chart review. Results indicate that prevalence rates of eye disease found in geriatric nursing home populations are generally higher than those found in other geriatric populations. With the exception of the rates for diabetic retinopathy, the rates found in the combined nursing home population sampled in this study were much higher than those reported in any previous study. It is concluded that eye disease is a more serious problem for elderly residents of nursing homes than for the elderly who reside in the community. Possible reasons for this are discussed.

Barriers to completion of health care proxies: an examination of ethnic differences.

BACKGROUND: Advance directives have not been uniformly used by different segments of the US population and studies have consistently shown a lower prevalence of advance directives among African Americans and Hispanics compared with non-Hispanic whites. OBJECTIVE: To examine barriers to completion of health care proxies for different ethnic groups. METHODS: One hundred ninety-seven subjects aged 65 years or older self-identified as African American (n = 65), Hispanic (n = 65), or non-Hispanic white (n = 67) attending a geriatrics and internal medicine outpatient clinic of a large New York City teaching hospital were administered a questionnaire. Questionnaires were developed to examine potential barriers to completion of health care proxies. Barriers were drawn from the literature and from focus groups. RESULTS: Significant predictors of proxy completion using logistic regression analysis included knowledge of health care proxies, availability of a health care agent, exposure to mechanical ventilation, age, and self-reported health status as fair to poor. Subjects who believed that a health care agent was irrelevant in the setting of involved family were significantly less likely to have completed a health care proxy. Although there were significant differences in the baseline completion rates of health care proxies for the 3 ethnic groups, ethnicity did not predict prior appointment of a health care agent in multivariate analysis. CONCLUSIONS: Differences in health care proxy completion rates across white, African American, and Hispanic elderly individuals in this New York City population seem to be related to potentially reversible barriers such as lack of knowledge and the perceived irrelevance of advance directives in the setting of involved family. Enhanced educational efforts of both health care personnel and patients could increase the rate of formal health care proxy appointment.

Quality of student learning and preceptor productivity in urban community health centers.

BACKGROUND AND OBJECTIVES: Clinicians in community health centers find it difficult to balance the demands of increased productivity and effective teaching. We hypothesized that precepting third-year students would decrease clinical productivity and that many elements related to the quality of the learning experience (e.g., amount of patient contact, student autonomy) would be adversely affected by pressure to see increasing numbers of patients. METHODS: Students and preceptors in a 6-week family medicine clerkship completed daily surveys that measured the presence of quantifiable elements of the ambulatory teaching experience. They also rated the overall quality of learning during each session. RESULTS: For 62 sessions for which both students and preceptors completed evaluations, students rated the overall quality of learning more highly than preceptors. For students, the elements most positively associated with quality of learning were total teaching time and the frequency with which family issues were raised. For preceptors, the elements that predicted quality of learning were the number of patients that students saw independently and total teaching time. The clinical productivity of preceptors did not differ for sessions with and without a student. CONCLUSIONS: Preceptors can be effective teachers who encourage student autonomy and who model behaviors central to family practice, without decreasing productivity.

Attitudes and beliefs about organ donation among different racial groups.

Many people on the waiting list for organ donation die each year without receiving organs. The shortage of organs is even more pronounced in minority communities. Despite the fact that minorities are at higher risk, they may be less likely to support or consent to organ donation. This investigation was undertaken to study racial factors in organ donation, by focusing on differences in awareness, attitudes, and behavior. Three family practice centers in the Bronx with racially diverse but socioeconomically homogenous communities were studied. The study population consisted of a convenience sample of 163 patients who were approached for participation while they waited to see a doctor. Respondents filled out a 25-item survey that measured demographic information; their exposure to, awareness of, and attitudes toward organ donation; and whether they had signed an organ donor card. The results demonstrated overwhelming support for organ donation across all racial groups. Racial differences were found on awareness of and attitudes toward organ donation, and in the signing of organ donation cards. In contrast to other studies, racial minorities were not less likely than whites to support organ donation. These results suggest that making it easier for racial minorities to obtain organ donor cards could increase their rates of consenting to donate organs.

Descriptive analysis of eating behavior in school-age children with cystic fibrosis and healthy control children.

STUDY OBJECTIVE: To investigate calorie intake, behavioral eating styles, and parent perception of eating behavior of school-age children with cystic fibrosis (CF) compared with healthy peers. DESIGN: A two-group comparison study. SETTING: A clinical sample of 28 school-age children with CF and a community sample of 28 healthy peers matched for age (6 to 12 years) and socioeconomic status. MEASUREMENTS AND MAIN RESULTS: The children with CF consumed more calories per day (2175 cal/d) than the control children (1875 cal/d) and achieved a significantly higher recommended daily allowance (RDA) of energy (128% of the RDA) than the control children (91.61% of the RDA). Fifty-four percent of the CF sample were achieving the CF dietary recommendations of 120% of the RDA. Despite this energy intake, the CF sample was significantly below the control sample on weight (24.56 vs 31.23 kg), height (125.48 vs 133.06 cm), and z score for weight (-0.811 vs 0.528) and height (-0.797 vs 0.371). On measures of behavioral eating style, the CF sample had significantly longer meals (23.90 min) than the control sample (17.34 min) and had a significantly slower pace of eating (43.27% 10-second intervals with bites) than the control sample (51.29% 10-second intervals with bites) but did not differ significantly on the number of calories consumed during dinner. On a measure of parent report of mealtime behaviors, parents of the children with CF rated mealtime behavior problems of "dawdles" and "refuses food" as more intense (mean, 3. 46) than did the parents of control children (mean, 2.67). For the CF sample, a significant correlation was found between the parent intensity ratings of problem behavior in general and meal duration (r = .48), and a significant negative correlation was found between the parent intensity ratings of problem mealtime behaviors and the percentage of intervals with bites (pace of meal) (r = -.533). CONCLUSIONS: Although the school-age children with CF were consuming more calories per day than their healthy peers, and more than 50% of the children in the CF sample were at or above the CF dietary recommendations, the children in the CF sample were significantly below the control children on measures of weight and height. The behavioral data suggest that increased caloric intake is not without cost, because the CF sample spent an additional 7 minutes per day at dinner and ate their meals at a slower pace than their healthy peers. These data were associated with higher intensity ratings of mealtime behaviors by parents of children with CF. These findings point to the need for individualized assessment of energy needs for school-age children with CF and comprehensive programs that teach parents behavioral strategies to motivate their children to meet these higher energy requirements in an adaptive manner.

The synthesis of enantiomerically pure, highly functionalized heterocycles: the products of amino acid based acylnitroso hetero Diels-Alder reactions.

The diastereoselectivities of several chiral acylnitroso dienophiles (9a-h, 12 and 15) derived from optically pure, N-protected alpha-amino hydroxamic acids (2a-h, 4 and 7) were determined in an intermolecular hetero Diels-Alder reaction with cyclopentadiene. The diastereomeric excesses ranged from 0 to 72%. Hydroxamic acids with polar functionality were examined extensively to determine the effect of hydrogen bonding on the cycloaddition. The largest increase in diastereoselectivity was observed with increasing the steric bulk at the alpha-position of the hydroxamic acids and not with potential hydrogen bonding interactions. The cycloadditions afforded synthetically useful quantities of functionally rich, enantiomerically pure heterocycles (10a-h, 11a-h, 13, 14, 16 and 17), which have been elaborated into a variety of biologically interesting products.