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Biomedical subjects

J E Zimmerman

Publications and source records attributed to J E Zimmerman.

At least 19 recordsLinked to original sources
PubMed2001

The importance of bacterial sepsis in intensive care unit patients with acquired immunodeficiency syndrome: implications for future care in the age of increasing antiretroviral resistance.

OBJECTIVE: To describe the clinical characteristics and outcomes of patients with acquired immunodeficiency syndrome (AIDS) admitted to the intensive care unit (ICU). DESIGN: An observational cohort study with retrospective chart review. SETTING: ICU of an urban university medical center. PATIENTS: Consecutive ICU admissions of patients with AIDS at an urban university medical center between December 1993 and June 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient, we recorded ICU admission diagnosis, clinical characteristics, and outcome. Among 129 ICU admissions of patients with AIDS, 102 (79%) were admitted for infections, of which (45%) had infections caused by bacteria. Pseudomonas aeruginosa, Staphylococcus aureus, and other enteric pathogens were the most frequent isolates. Pneumonia accounted for 65% of 102 admissions for infections. Overall hospital mortality was 54%, but mortality was higher (68%) for patients with bacterial sepsis. Neutropenia was associated with differences in unadjusted survival rates, whereas CD4 counts were not. Independent predictors of hospital mortality included increasing acute physiology scores and severity of sepsis. CONCLUSIONS: In our ICU, among patients with AIDS, sepsis resulting from bacterial infection is now a more frequent cause of admission than Pneumocystis carinii pneumonia. Severity of illness and the presence of severe sepsis were the clinical predictors most associated with increased mortality. Patients who are not receiving or responding to highly active antiretroviral therapy may become as likely to be admitted to an ICU with a treatable bacterial infection as with classic opportunistic infections. Therefore, broad-spectrum empirical antibacterial therapy is particularly important when the etiology of infection is uncertain.

AIDS-Related Opportunistic Infections↗
PubMed2000

Functional analysis of an eye enhancer of the Drosophila eyes absent gene: differential regulation by eye specification genes.

Genes involved in eye development are highly conserved between vertebrates and Drosophila. Given the complex genetic network controlling early eye development, identification of regulatory sequences controlling gene expression will provide valuable insights toward understanding central events of early eye specification. We have focused on defining regulatory elements critical for Drosophila eyes absent (eya) expression. Although eya has a complex expression pattern during development, analysis of eye-specific mutations in the gene revealed a region selectively deleted in the eye-specific alleles. Here we have performed detailed analysis of the region deleted in the eye-specific eya(2) allele. This analysis shows that this region can direct early eya gene expression in a pattern consistent with that of normal eya in eye progenitor cells. Functional studies indicate that this element will restore appropriate eya transcript expression to rescue the eye-specific allele. We have examined regulation of this element during eye specification, both in normal eye development and in ectopic eye formation. These studies demonstrate that the element was activated upon ectopic expression of the eye specification genes eyeless and dachshund, but does not respond to ectopic expression of eya or sine oculis. The differential regulation of this element by genes involved during early retinal formation reveals new aspects of the genetic hierarchy of eye development.

Animals↗
PubMed2000

Molecular genetic analysis of Drosophila eyes absent mutants reveals an eye enhancer element.

The eyes absent (eya) gene is critical for normal eye development in Drosophila and is highly conserved to vertebrates. To define regions of the gene critical for eye function, we have defined the mutations in the four viable eya alleles. Two of these mutations are eye specific and undergo transvection with other mutations in the gene. These were found to be deletion mutations that remove regulatory sequence critical for eye cell expression of the gene. Two other viable alleles cause a reduced eye phenotype and affect the function of the gene in additional tissues, such as the ocelli. These mutations were found to be insertion mutations of different transposable elements within the 5' UTR of the transcript. Detailed analysis of one of these revealed that the transposable element has become subject to regulation by eye enhancer sequences of the eya gene, disrupting normal expression of EYA in the eye. More extended analysis of the deletion region in the eye-specific alleles indicated that the deleted region defines an enhancer that activates gene expression in eye progenitor cells. This enhancer is responsive to ectopic expression of the eyeless gene. This analysis has defined a critical regulatory region required for proper eye expression of the eya gene.

5' Untranslated Regions↗
PubMed2000

Molecular analysis of Drosophila eyes absent mutants reveals features of the conserved Eya domain.

The eyes absent (eya) gene is critical to eye formation in Drosophila; upon loss of eya function, eye progenitor cells die by programmed cell death. Moreover, ectopic eya expression directs eye formation, and eya functionally synergizes in vivo and physically interacts in vitro with two other genes of eye development, sine oculis and dachshund. The Eya protein sequence, while highly conserved to vertebrates, is novel. To define amino acids critical to the function of the Eya protein, we have sequenced eya alleles. These mutations have revealed that loss of the entire Eya Domain is null for eya activity, but that alleles with truncations within the Eya Domain display partial function. We then extended the molecular genetic analysis to interactions within the Eya Domain. This analysis has revealed regions of special importance to interaction with Sine Oculis or Dachshund. Select eya missense mutations within the Eya Domain diminished the interactions with Sine Oculis or Dachshund. Taken together, these data suggest that the conserved Eya Domain is critical for eya activity and may have functional subregions within it.

Alleles↗
PubMed2000

Intensive care unit length of stay: recent changes and future challenges.

OBJECTIVE: To compare case-mix adjusted intensive care unit (ICU) length of stay for critically ill patients with a variety of medical and surgical diagnoses during a 5-yr interval. DESIGN: Nonrandomized cohort study. SETTING: A total of 42 ICUs at 40 US hospitals during 1988-1990 and 285 ICUs at 161 US hospitals during 1993-1996. PATIENTS: A total of 17,105 consecutive ICU admissions during 1988-1990 and 38,888 consecutive ICU admissions during 1993-1996. MEASUREMENTS AND MAIN RESULTS: We used patient demographic and clinical characteristics to compare observed and predicted ICU length of stay and hospital mortality. Outcomes for patients studied during 1993-1996 were predicted using multivariable models that were developed and cross-validated using the 1988-1990 database. The mean observed hospital length of stay decreased by 3 days (from 14.8 days during 1988-1990 to 11.8 days during 1993-1996), but the mean observed ICU length of stay remained similar (4.70 vs. 4.53 days). After adjusting for patient and institutional differences, the mean predicted 1993-1996 ICU stay was 4.64 days. Thus, the mean-adjusted ICU stay decreased by 0.11 days during this 5-yr interval (T-statistic, 4.35; p < .001). The adjusted mean ICU length of stay was not changed for patients with 49 (75%) of the 65 ICU admission diagnoses. In contrast, the mean observed hospital length of stay was significantly shorter for 47 (72%) of the 65 admission diagnoses, and no ICU admission diagnosis was associated with a longer hospital stay. Aggregate risk-adjusted hospital mortality during 1993-1996 (12.35%) was not significantly different during 1988-1990 (12.27%, p = .54). CONCLUSIONS: For patients admitted to ICUs, the pressures associated with a decrease in hospital length of stay do not seem to have influenced the duration of ICU stay. Because of the high cost of intensive care, reduction in ICU stay may become a target for future cost-cutting efforts.

Adolescent↗
PubMed1998

Analysis of fluG mutations that affect light-dependent conidiation in Aspergillus nidulans.

Conidiation in Aspergillus nidulans is induced by exposure to red light but can also be induced by blue light in certain mutant strains. We have isolated a mutation in the fluG gene that abolishes responsiveness to red light but does not affect the response to blue light. It has been shown that the veA1 (velvet) mutation allows conidiation to occur in the absence of light. We have identified three other fluG mutations that suppress the veA1 phenotype; these double mutants do not conidiate in the dark. The mutations described here define two new phenotypic classes of fluG alleles that display abnormal responses to light. We have characterized these mutations with respect to their molecular identity and to their effect on fluG transcription. Although it has been shown that fluG is required for the synthesis of an extracellular factor that directs conidiation, we do not detect this factor under conditions that promote conidiation in the veA1 suppressors. Furthermore, extracellular rescue is not observed in fluG deletion strains containing the wild-type veA allele. We propose that a genetic interaction between fluG and veA influences the production of the extracellular signal and regulates the initiation of conidiation.

Alleles↗
PubMed1998

Evaluation of acute physiology and chronic health evaluation III predictions of hospital mortality in an independent database.

OBJECTIVE: To assess the accuracy and validity of Acute Physiology and Chronic Health Evaluation (APACHE) III hospital mortality predictions in an independent sample of U.S. intensive care unit (ICU) admissions. DESIGN: Nonrandomized, observational, cohort study. SETTING: Two hundred eighty-five ICUs in 161 U.S. hospitals, including 65 members of the Council of Teaching Hospitals and 64 nonteaching hospitals. PATIENTS: A consecutive sample of 37,668 ICU admissions during 1993 to 1996; including 25,448 admissions at hospitals with >400 beds and 1,074 admissions at hospitals with <200 beds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used demographic, clinical, and physiologic information recorded during ICU day 1 and the APACHE III equation to predict the probability of hospital mortality for each patient. We compared observed and predicted mortality for all admissions and across patient subgroups and assessed predictive accuracy using tests of discrimination and calibration. Aggregate hospital death rate was 12.35% and predicted hospital death rate was 12.27% (p =.541). The model discriminated between survivors and nonsurvivors well (area under receiver operating curve = 0.89). A calibration curve showed that the observed number of hospital deaths was close to the number of deaths predicted by the model, but when tested across deciles of risk, goodness-of-fit (Hosmer-Lemeshow statistic, chi-square = 48.71, 8 degrees of freedom, p< .0001) was not perfect. Observed and predicted hospital mortality rates were not significantly (p < .01) different for 55 (84.6%) of APACHE III's 65 specific ICU admission diagnoses and for 11 (84.6%) of the 13 residual organ system-related categories. The most frequent diagnoses with significant (p < .01) differences between observed and predicted hospital mortality rates included acute myocardial infarction, drug overdose, nonoperative head trauma, and nonoperative multiple trauma. CONCLUSIONS: APACHE III accurately predicted aggregate hospital mortality in an independent sample of U.S. ICU admissions. Further improvements in calibration can be achieved by more precise disease labeling, improved acquisition and weighting of neurologic abnormalities, adjustments that reflect changes in treatment outcomes over time, and a larger national database.

APACHE↗
PubMed1998

Neurological intensive care admissions: identifying candidates for intermediate care and the services they receive.

OBJECTIVE: The high cost and scarcity of intensive care unit (ICU) beds has resulted in a need for improved utilization. This study describes the characteristics of patients who are admitted to the ICU for neurosurgical and neurological care, identifies patients who might receive all or most of their care in an intermediate care unit, and describes the services the patients would receive in an intermediate care unit. METHODS: We describe patients who received neurological care and who were part of a prospective study of 17,440 patients admitted to 42 ICUs at 40 United States hospitals. We identified patients who received only monitoring during ICU Day 1 and then used a previously validated equation to distinguish which patients were at low risk (< 10%) for subsequent active life-supporting therapy. We also describe the services these patients received during their ICU stay. RESULTS: Among 3000 patients admitted to the ICU for neurological care, 1350 received active therapy and 1650 (55%) underwent monitoring and received concentrated nursing care on ICU Day 1. After excluding those patients who received active therapy at admission, 1288 (78%) of the 1650 patients who underwent monitoring at admission were at low risk (< 10%) for subsequent active therapy; 95.8% received no active therapy. These patients who were at low risk for subsequent active therapy were significantly (P < 0.001) more often admitted postoperatively, were younger and less severely ill, and had lower ICU and hospital mortality rates (0.9 and 3.9%, respectively) than patients who received active treatment at admission. CONCLUSIONS: Patients receiving neurological care at an ICU who receive only monitoring during their 1st ICU day and have a less than 10% predicted risk of active treatment can be safely transferred to an intermediate care unit. Some of these patients may not require ICU admission. We suggest guidelines for equipping and staffing neurological intermediate care units based on the type and amount of therapy received by these patients.

Adult↗
PubMed1997

Inositol 1,4,5-trisphosphate receptor expression in odontoblast cells.

The cellular distribution of inositol 1,4,5-trisphosphate receptors was examined in rodent maxillary incisor teeth. In situ hybridization studies with a transmembrane probe of type I inositol 1,4,5-trisphosphate receptor indicated that this receptor/channel was highly expressed in odontoblast cells of incisor teeth. In contrast, very low labeling was observed in dental pulp. Northern analysis showed a message size of approximately 9.5 kilobases for this receptor, and demonstrated that type III inositol 1,4,5-trisphosphate receptor was expressed in incisor teeth. Immunocytochemical studies confirmed that types I and III inositol 1,4,5-trisphosphate receptors were both highly expressed in odontoblasts while very low expression was detected in dental pulp. Finally, antibodies that recognized alpha subunits of the Gq class of GTP binding proteins also stained odontoblasts. These results indicate that receptor-mediated regulation of calcium release through inositol 1,4,5-trisphosphate receptors may occur in odontoblasts of rat incisor teeth. These findings also suggest that inositol 1,4,5-trisphosphate receptor/channels regulate calcium flux in odontoblasts during mineralization of dentin, or in growth and differentiation of incisor tissue.

Animals↗
PubMed1997

Inositol 1,4,5-trisphosphate receptor expression in mammalian olfactory tissue.

Two cDNAs encoding inositol 1,4,5-trisphosphate (IP3) receptors were amplified from rat olfactory tissue, and both exhibited 100% sequence identity to the short (Segment II - ) variant of type I IP3 receptor. Type III IP3 receptor was also expressed in olfactory tissue. The distribution of IP3 receptors included the olfactory epithelium, lamina propria, and glandular tissue. These results demonstrate the co-expression of multiple IP3 receptor subtypes in olfactory cells, and suggest multiple functions for IP3 receptors in this tissue.

Animals↗
PubMed1997

Evaluating laboratory usage in the intensive care unit: patient and institutional characteristics that influence frequency of blood sampling.

OBJECTIVES: To develop a predictive equation to estimate the frequency of blood drawing for intensive care unit (ICU) laboratory tests and to evaluate variations in ICU blood sampling practices after adjusting for patient and institutional factors. DESIGN: Prospective, inception, cohort study. SETTING: Forty-two ICUs in 40 hospitals, including 20 teaching and 17 nonteaching ICUs. PATIENTS: A consecutive sample of 17,440 ICU admissions, in which 14,043 blood samples were drawn for laboratory testing on ICU days 2 to 7. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographic, physiologic, and treatment data were obtained on ICU day 1; the type and number of blood samples for laboratory testing were recorded on ICU days 1 to 7. In the 42 ICUs, a mean of 16.2 blood samples were drawn for tests on ICU days 2 to 7, but varied between 23 samples in the teaching ICUs and 9.9 samples in nonteaching ICUs. Using only ICU day 1 patient data, we predicted the subsequent number of samples drawn on ICU day 2 (R2 = .26 across individual patients) and on ICU days 2 to 7 (R2 = .26 across individual patients). The most important determinants of the number of blood samples drawn on ICU days 2 to 7 were the ICU day 1 Acute Physiology Score and admission diagnosis. After controlling for patient variables, hospital teaching status, number of beds, and location in the East and South were significantly (p < .05) associated with increased blood sampling on ICU day 2 and on ICU days 2 to 7. More frequent use of an arterial cannula and mechanical ventilation were also associated with increased blood sampling on subsequent days. CONCLUSIONS: The ability to adjust for patient and institutional variables and to predict the number of blood samples drawn for laboratory tests can allow ICUs to compare their practices with those of other units. When integrated into a continuous quality improvement process, this information can be used to identify and focus on opportunities for improving blood conservation and reducing excessive diagnostic testing.

APACHE↗
PubMed1997

Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene.

The Drosophila eyes absent (eya) gene plays an essential role in the events that lead to proper development of the fly eye and embryo. Here we report the analysis of two human and two mouse homologs of the fly eya gene. Sequence comparison reveals a large domain of approximately 270 amino acids in the carboxyl terminus of the predicted mammalian proteins that shows 53% identity between the fly sequence and all of the vertebrate homologs. This Eya-homology domain is of novel sequence, with no previously identified motifs. RNA hybridization studies indicate that the mouse genes are expressed during embryogenesis and in select tissues of the adult. Both mouse Eya genes are expressed in the eye, suggesting that these genes may function in eye development in vertebrates as eya does in the fly. The mouse Eya2 gene maps to chromosome 2 in the region syntenic with human chromosome 20q13, and the mouse Eya2 gene maps to chromosome 4 in the region syntenic with human chromosome 1p36. Our findings support the notion that several families of genes (Pax-6/eyeless, Six-3/sine oculis, and Eya) play related and critical roles in the eye for both files and vertebrates.

Amino Acid Sequence↗
PubMed1996

Intensive care unit admissions with cirrhosis: risk-stratifying patient groups and predicting individual survival.

Prognosis for acutely ill patients with cirrhosis is influenced by the severity of hepatic abnormalities and by dysfunction of other organ systems. The purpose of this study was to examine the usefulness of the Acute Physiology, Age, and Chronic Health Evaluation (APACHE III) prognostic system for risk-stratifying groups of intensive care unit (ICU) patients with cirrhosis and in predicting individual survival. We used data for 17,440 ICU admissions at 40 American hospitals to select 117 of the 537 patients with a history of cirrhosis who were ventilated on ICU day 1, a group known to have a high mortality rate. We then calculated each patient's probability of hospital death on ICU days 1 through 7, using seven previously validated multivariate equations. Hospital mortality was 63% for the 117 study patients. The most important determinants of risk for hospital death on ICU day 1 were the acute physiology score of APACHE III, ICU admission diagnosis, and operative status. Daily changes in the acute physiology score caused a rise or fall in the probability of hospital mortality and was useful in assessing individual response to therapy. APACHE III accurately risk stratifies critically ill patients with cirrhosis because it accounts for many of the factors known to influence prognosis. This capability can be used to assess severity of illness and risk-stratify patients with cirrhosis during clinical trials. Daily prognostic estimates based on physiological changes over time reflect patient response and can help physicians to assess the incremental benefit of therapy.

Adult↗
PubMed1996

Application of the APACHE III prognostic system in Brazilian intensive care units: a prospective multicenter study.

OBJECTIVE: To compare patients and their outcomes at ten Brazilian intensive care units (ICUs) with those reported from the United States. DESIGN: Prospective multicenter inception cohort study. SETTING: Ten Brazilian adult medical-surgical ICUs. PATIENTS: 1734 consecutive adult ICU admissions. MEASUREMENTS AND RESULTS: We used demographic, clinical and physiologic information and the APACHE III prognostic system to predict risk of hospital death for 1734 ICU admissions. We then divided the observed by the predicted hospital death rate to calculate standardized mortality ratios (SMRs) for patient groups and each ICU. Hospital mortality for Brazilian patients (34%) was double that found in the United States (17%, p < 0.01). Discrimination of survivors from non-survivors using APACHE III was good (area under a receiver operating characteristic curve = 0.82), but the predicted risk of death was significantly (p < 0.0001) lower than observed outcome (SMR = 1.67). Three of the ten Brazilian ICUs, however, had SMRs of 1.01 to 1.1 and no significant difference between observed and predicted outcomes; the remaining seven ICUs had significantly higher SMRs, ranging from 1.50 to 2.30. CONCLUSION: The APACHE III prognostic system was a good discriminator of hospital mortality for ICU admissions at 10 Brazilian ICUs. There was substantial and significant variation, however, in SMRs among the Brazilian ICUs, which suggests that further evaluations of international differences in intensive care using a common risk assessment system should be performed and factors associated with variations in risk-adjusted mortality scrutinized.

APACHE↗
PubMed1996

The importance of technology for achieving superior outcomes from intensive care. Brazil APACHE III Study Group.

OBJECTIVE: To test the hypothesis that technology availability, staffing, and diagnostic diversity in an intensive care unit (ICU) are associated with the ability to decrease hospital mortality. DESIGN: Prospective multicenter descriptive cohort study. SETTING: Ten Brazilian medical-surgical ICUs. PATIENTS: 1734 consecutive adult ICU admissions. MEASUREMENTS AND RESULTS: We recorded the amount of technology, number of diagnoses, and availability of nurses at each ICU. We also used demographic, clinical and physiologic information for an average of 173 admissions to each ICU to calculate standardized mortality ratios (SMRs) for each ICU. The mean SMR for the ten ICUs was 1.67 (range 1.01-2.30). A greater availability of ICU equipment and services was significantly (p < 0.001) associated with a lower SMR. CONCLUSION: The ability of Brazilian ICUs to reduce hospital mortality is associated with the amount of technology available in these units.

Adult↗