Organocatalytic enantioselective desymmetrisation.

Organocatalytic enantioselective desymmetrisation of achiral or meso compounds is a powerful strategy for the construction of enantiomerically enriched complex molecules, often with multiple stereocentres and in high selectivities. Recent years have seen increasing use of organocatalysts in desymmetrisation methodology, in contrast to traditional metal- or enzyme-catalysed reactions, with many impressive advances made in the current decade. This review will provide an overview of the field since 2010, with the aim of highlighting both the practical applications and elegance of enantioselective desymmetrisation to the wider synthetic community.

Predicting global atmospheric ice nuclei distributions and their impacts on climate.

Knowledge of cloud and precipitation formation processes remains incomplete, yet global precipitation is predominantly produced by clouds containing the ice phase. Ice first forms in clouds warmer than -36 degrees C on particles termed ice nuclei. We combine observations from field studies over a 14-year period, from a variety of locations around the globe, to show that the concentrations of ice nuclei active in mixed-phase cloud conditions can be related to temperature and the number concentrations of particles larger than 0.5 microm in diameter. This new relationship reduces unexplained variability in ice nuclei concentrations at a given temperature from approximately 10(3) to less than a factor of 10, with the remaining variability apparently due to variations in aerosol chemical composition or other factors. When implemented in a global climate model, the new parameterization strongly alters cloud liquid and ice water distributions compared to the simple, temperature-only parameterizations currently widely used. The revised treatment indicates a global net cloud radiative forcing increase of approximately 1 W m(-2) for each order of magnitude increase in ice nuclei concentrations, demonstrating the strong sensitivity of climate simulations to assumptions regarding the initiation of cloud glaciation.

Pathology of skull base tumors.

The multidisciplinary requirements of skull base surgery have evolved over the last 25 years. The heterogeneity of tissue types in the cranium base gives rise to a diverse group of benign and malignant neoplasms with vastly different prognoses. This article reviews the distinct clinicopathologic features of some of the unique and problematic neoplasms of this region.

Sarcoidosis severity and socioeconomic status.

Several chronic diseases are more severe in persons who are Black, of low socioeconomic status (SES), and underinsured. The authors ask if this is true for sarcoidosis. Associations among sarcoidosis disease severity, SES, insurance coverage, and functional limitations were analysed. Back and White sarcoidosis patients (n=110) of a municipal and university hospital sarcoidosis registry were interviewed by telephone. Data on disease severity were abstracted from patient charts. Most patients reported good or excellent health by demographic characteristics. Low SES and no or public insurance were associated with worse health status and more severe dyspnoea. More advanced radiographic stage was associated with lower income, and forced vital capacity impairment with less education. Physical and social activity limitations due to physical and emotional disability were related to no or public insurance and lower income, but not education. Sarcoidosis severity is associated with socioeconomic status and insurance indicators; no or public insurance and low income are associated with functional limitations. Sarcoidosis-associated limitations are substantial, emphasizing the social significance of sarcoidosis. Lack of private insurance may inhibit the use of medical care, contributing to disease severity and impairment.

Effects of temperature and intraspecific interaction on the development of Dermestes maculatus (Coleoptera: Dermestidae).

Studies were conducted to determine development rates of of Dermestes maculatus DeGeer at temperatures of 15, 20, 25, 30, and 35 degrees C. No individuals completed development to the adult stage at 15 degrees C. For the other temperatures, survivorship ranged from 9.3% at 20 degrees C to 36% at 35 degrees C. Time required for development varied inversely with temperature from a mean of 89.7 d at 20 degrees C to 36.4 d at 35 degrees C. For specimens held individually, survivorship was higher at 25 and 30 degrees C, i.e., 83.2 and 60.2%, respectively. No specimens held individually at 35 degrees C survived past the first larval instar. Mortality during the egg stage at 25 and 30 degrees C was 4.52-5.23%, whereas mortality during the first instar was significantly higher for the individuals held at 30 degrees C and 100% for those at 35 degrees C. There was an inverse relation observed between larval density and both survivorship and mean adult weights.

A tool to organize instructions at discharge after treatment of asthmatic children in an emergency department.

Asthma exacerbations continue to be a major cause of visits to emergency departments (ED). Comprehensive care in the outpatient setting, with planning for early intervention for exacerbations, can reduce emergency visits. Thus, a major goal of ED intervention is to establish a link between the patient and the provider of ongoing asthma care, where complete education can be achieved and reinforced over time. When designing the Asthma 1-2-3 Plan discharge teaching tool for the ED, consideration was given to educational format, readability, patient population, and setting in which education was to be delivered. To evaluate use of the plan, ED records of patients enrolled in a separate asthma study, the Neighborhood Asthma Coalition (NAC), were audited for two 8-month intervals, May-December 1993 (before initiation of the plan) and May December 1994 (starting 1 month after completion of pilot testing on the plan in the ED). To evaluate effectiveness of the plan, records of physicians who cared for children in the NAC were evaluated. The database was reviewed for the date of the first visit for planned review of asthma that occurred after the acute asthma ED visit. After introduction of the plan, the proportion of children told to return to the physician for follow-up increased from 54% to 81%. The proportion of children given advice to return to their physician within the recommended 3 days or less increased from 11% to 54%. Chi2 Analyses showed that these changes were both statistically significant (p<0.0001). The plan was not effective in achieving increased follow-up visits for regular asthma care, in that 7% returned for follow-up within 7 days after an ED visit before the plan and only 6% returned for such a visit after the Plan. Successful initiation of a focused discharge teaching tool into the routine of the ED increased appropriate advice given at time of discharge from the ED. Although unsuccessful in increasing appropriate follow-up, the present intervention uses the ED not as a base for asthma education, but as a point for contacting patients in need of regular care and education, and for promoting access to that regular care.

Pulmonary sarcoidosis: comparison of patients at a university and a municipal hospital.

Charts and radiographs of sarcoidosis patients seen at a private university hospital and at a municipal hospital were reviewed to determine whether there was a difference in the severity of disease retrospectively. A standardized abstract form was used to identify and abstract information on new and continuing sarcoidosis patients seen at either Georgetown University Medical Center (GUMC) or District of Columbia General Hospital (DCGH) during a 2-year period. Because there were too few white sarcoidosis patients for comparison, analysis was done for African-American patients only. African-American patients at GUMC were slightly older, with a higher percentage of women. For GUMC patients, 76% had private insurance and 21% had public insurance, and for DCGH patients, one-half had public insurance and 29% had no insurance. Significantly fewer GUMC patients (7% versus 36%) reported moderate to severe dyspnea. Chest radiographs showed a larger percentage of patients with stage 1 disease at GUMC and more patients with stage 4 disease at DCGH. Spirometry showed more impairment of forced expired volume in one second (FEV1) in GUMC patients, but diffusing capacity of the lung for carbon monoxide (DLCO) values were significantly lower among DCGH patients. Less than 8% of GUMC patients showed disease progression compared with almost one-third of DCGH patients. These results demonstrate that substantially less severe pulmonary sarcoidosis was seen in African-American patients treated at a private, nonprofit university hospital compared with a municipal hospital. Factors that determine the use of municipal hospitals, such as limited financial access to care and sources of patients, may have played a major role in the differences seen.

Cyclosporine-induced hemolytic uremic syndrome and hemorrhagic colitis following renal transplantation.

Nephrotoxicity remains one of the most common side-effects of cyclosporine in the setting of transplantation. Acute reversible decreases in glomerular filtration rate and chronic irreversible renal damage are the most common manifestations, but hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have been reported. Prognosis of cyclosporine-associated de novo hemolytic uremic syndrome (CyA-HUS) is poor, with nearly half of affected patients losing function in the transplanted kidney. Therapeutic options are limited, but good outcomes have been reported by switching patients from cyclosporine to tacrolimus. We report an unusual presentation of CyA-HUS associated with hemorrhagic colitis following renal transplantation. The patient was successfully managed by switching from cyclosporine to tacrolimus.

Immunohistochemical staining for Ki-67 antigen, carcinoembryonic antigen, and p53 in the differential diagnosis of glandular lesions of the cervix.

Cytoplasmic carcinoembryonic antigen (CEA) positivity assists in the distinction of benign and malignant glandular lesions of the cervix, but some cases remain problematic. The accumulation of p53 protein and an increased proliferative index, as measured by the expression of Ki-67 antigen, have not been used as adjuncts to the diagnosis of these lesions. Immunohistochemical stains for CEA, p53 protein, and Ki-67 antigen were performed on 31 formalin-fixed, paraffin-embedded endocervical lesions including invasive adenocarcinoma, adenocarcinoma in situ, adenoma malignum, tunnel clusters, florid microglandular hyperplasia, mesonephric remnants, florid glandular hyperplasia, atypical glandular hyperplasia, and normal controls. Ki-67 antigen expression was quantitated as negligible, low, moderate, or high on the basis of the percentage (< 5%, 5-10%, 11-40%, > 40%, respectively) of glandular nuclei that were positive with MIB-1 antibody. Strong staining of more than 10% of the glandular epithelial nuclei was interpreted as positive for p53 protein overexpression. CEA positivity was determined by either diffuse or focal cytoplasmic staining of columnar epithelial cells equalling glycocalyceal staining in intensity. The combination of CEA positivity and a moderate-to-high proliferative index was limited to cases of invasive adenocarcinoma, adenoma malignum, and adenocarcinoma in situ, as compared with benign glandular lesions (P = 0.005). A high Ki-67 proliferative index and/or CEA positivity were features of malignant lesions rather than benign mimickers; there were no false positives or false negatives. Similarly, only malignant neoplasms shared a combination of p53 overexpression and CEA positivity (P = 0.043). The combination of cytoplasmic CEA positivity in glandular cells and a moderate-to-high Ki-67 proliferative index is diagnostic of malignancy in endocervical lesions. With the exception of florid microglandular hyperplasia, p53 expression is only seen in neoplastic lesions of the endocervix. An immunohistochemical battery consisting of MIB-1 (Ki-67), p53 protein, and CEA is useful in discriminating between benign and malignant endocervical lesions.

New air-fluid levels in bullous lung disease: a reevaluation.

Air-fluid levels appearing in lung bullae are always considered to indicate infection and therefore conservative management with prolonged antibiotics and observation to resolution is the recommended approach. This article presents a case of bullous lung disease with new air-fluid levels, in which a diagnosis of malignancy was made by aspiration of the fluid. This association is discussed and a more aggressive evaluation of such patients to include computed tomography of the chest and fluid sampling is recommended before a presumption of benignity is made.

Pleuropulmonary blastoma: a marker for familial disease.

OBJECTIVE: To catalog and evaluate patterns of disease in families of children with pleuropulmonary blastoma (PPB). METHODS: Data have been collected since 1988 on 45 children with PPB and their families. All pathologic materials were centrally reviewed. Preliminary molecular genetic analyses were performed when possible. RESULTS: In 12 of 45 patients, an association was found between PPB and other dysplasias, neoplasias, or malignancies in the patients with or in their young relatives. The diseases found to be associated with PPB include other cases of PPB, pulmonary cysts, cystic nephromas, sarcomas, medulloblastomas, thyroid dysplasias and neoplasias, malignant germ cell tumors, Hodgkin disease, leukemia, and Langerhans cell histiocytosis. Abnormalities of the p53 tumor suppressor gene, Wilms tumor suppressor gene (WT1), and the putative second genetic locus for Wilms tumor (WT2) were not found in preliminary investigations. CONCLUSIONS: The occurrence of PPB appears to herald a constitutional and heritable predisposition to dysplastic or neoplastic disease in approximately 25% of cases. All patients with PPB and their families should be investigated carefully. Further research of this new family cancer syndrome may provide insight into the genetic basis of these diseases.

A new system to record reliable pulse oximetry data from the Nellcor N-200 and its applications in studies of variability in infant oxygenation.

We have developed a simple system for internal validation of oximetry data collected over many hours from the Nellcor N-200 pulse oximeter (Nellcor, Inc., Hayward, CA). This system uses signals from the oximeter alone and a validation algorithm that is based in a computer connected to the oximeter. Unlike other validation systems, this system does not require connections to other monitors. The system was tested on 10 acutely ill newborns in an intensive care nursery over 16 hr of continuous recording for each infant (birthweight, 2.50 +/- 0.73 kg; age, 3.4 +/- 3.2 days). Oximetry data were accepted as valid using the new system if they surpassed a minimum level of quality (empirically derived, and equal to a 60% fractional success in pulse detection). The validated oximetry data were compared to data obtained using a conventional "compared to the electrocardiogram (ECG)" algorithm. For the new and the conventional algorithms, the distributions of validated SpO2 percents were nearly identical, with data rejection rates of 28.9% for the new system and 37.3% for the conventional system. In the newborns, the new system was used to demonstrate that as the mean saturations decreased, there were striking increases in variability about the reported mean saturation (p < 0.001). While variability in infant SpO2 is a well-known phenomenon, the amount seen here was unexpected. For example, the range of true saturations frequently recorded was quite wide at a reported mean SpO2 of 90% (from 81 to 94%; but, the range was only from 92 to 98% at a mean SpO2 of 96%). These findings demonstrate the usefulness of the new system and, if substantiated in more detailed studies, have important implications for the use of pulse oximeters to assess oxygenation in newborns.

Pulmonary complications associated with illicit drug use. An update.

STUDY OBJECTIVE: In earlier years, nonopportunistic infectious pulmonary complications of illicit drug use were most common. We designed this study to update the pulmonary complications associated with illicit drug use in the 1990s. DESIGN: Concurrent and retrospective chart review. SETTING: Inner-city municipal hospital. PATIENTS: All illicit drug users with pulmonary complications seen by the pulmonary consult service were enrolled in the study. There were 105 hospital admissions of 97 patients in a 14-month study period. RESULTS: Sixty percent of the patients had HIV infection. The most common pulmonary complications were Pneumocystis carinii pneumonia (30%) followed by community-acquired pneumonia (12%) and tuberculosis (9%). CONCLUSIONS: The spectrum of pulmonary disease in illicit drug users has changed since 1988. Opportunistic HIV-related disease is much more common. Community-acquired pneumonia and tuberculosis remain relatively frequent complications. Septic pulmonary embolism is now rare.

MR of cystic aberrant cervical thymus.

The clinical, MR imaging, surgical, and histologic findings in two cases of cystic aberrant cervical thymus were reviewed. Aberrant cervical thymic tissue was sharply circumscribed and extended deep to the posterior pharyngeal wall at the level of the piriform sinus in both cases. Both lesions had cyst contents that were of increased signal intensity on T1-weighted images. Solid components displayed MR signal characteristics identical to normal thymus.

Doxycycline pleurodesis for pneumothorax in patients with AIDS.

Since first described in 1984, nontraumatic pneumothoraces in patients with AIDS has become more common. When compared with spontaneous pneumothorax in the general population, pneumothoraces in patients with AIDS are often complicated by prolonged air leaks as well as higher recurrence rates. Chemical pleurodesis has an important role in the management of these complications. The most experience with chemical pleurodesis uses tetracycline hydrochloride as the sclerosing agent; however, this agent is no longer available. Doxycycline has been used in pleurodesis of malignant effusions, but its use in managing pneumothoraces is limited. We present five patients who have AIDS with a total of seven pneumothoraces. Each patient experienced a persistent air leak. Six of the pneumothoraces were managed successfully with doxycycline. Although the follow-up period was limited, there were no recurrences noted and the only side effect seen was chest pain in four which was easily controlled with narcotics. Doxycycline sclerotherapy can be used effectively for pleurodesis in the management of nontraumatic pneumothorax in the patient with AIDS.

Metastatic clear-cell hidradenocarcinoma of the vulva.

Clear-cell hidradenocarcinoma is a malignant tumor of sweat gland origin. It is most often found on the trunk, head, and extremities. This case report describes a rare occurrence of this tumor on the vulva of a young woman. The discovery of metastatic disease reflects the potentially aggressive nature of this tumor.