Use of the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI) to assist with triage of patients with chest pain or other symptoms suggestive of acute cardiac ischemia. A multicenter, controlled clinical trial

BACKGROUND: Approximately 6 million U.S. patients present to emergency departments annually with symptoms suggesting acute cardiac ischemia. Triage decisions for these patients are important but remain difficult. OBJECTIVE: To test whether computerized prediction of the probability of acute ischemia, used with electrocardiography, improves the accuracy of triage decisions. DESIGN: Controlled clinical trial. SETTING: 10 hospital emergency departments in the midwestern, southeastern, and northeastern United States. PATIENTS: 10689 patients with chest pain or other symptoms suggestive of acute cardiac ischemia. INTERVENTION: The probability of acute ischemia predicted by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI), either automatically printed or not printed on patients' electrocardiograms. MEASUREMENTS: Emergency department triage to a coronary care unit (CCU), telemetry unit, ward, or home. Other measurements were the bed capacity of the CCU relative to that of the telemetry unit; training or supervision status of the triaging physician; and patient diagnoses and outcomes based on clinical, electrocardiographic, and creatine kinase data. RESULTS: For patients without cardiac ischemia, in hospitals with high-capacity CCUs and relatively low-capacity cardiac telemetry units, use of ACI-TIPI was associated with a reduction in CCU admissions from 15% to 12%, a change of -16% (95% CI, -30% to 0%), and an increase in emergency department discharges to home from 49% to 52%, a change of 6% (CI, 0% to 14%; overall P=0.09). Across all hospitals, for patients evaluated by unsupervised residents, use of ACI-TIPI was associated with a reduction in CCU admissions from 14% to 10%, a change of -32% (CI, -55% to 3%); a reduction in telemetry unit admissions from 39% to 31%, a change of -20% (CI, -34% to -2%); and an increase in discharges to home from 45% to 56%, a change of 25% (CI, 8% to 45%; overall P=0.008). Among patients with stable angina, in hospitals with high-capacity CCUs, use of ACI-TIPI was associated with a reduction in CCU admissions from 26% to 13%, a change of -50% (CI, -70% to -17%), and an increase in discharges to home from 20% to 22%, a change of 10% (CI, -29% to 71%; overall P=0.02). At hospitals with high-capacity telemetry units, use of ACI-TIPI was associated with a reduction in telemetry unit admissions from 68% to 59%, a change of -14% (CI, -27% to 1%), and an increase in emergency department discharges to home from 10% to 21%, a change of 100% (CI, 22% to 230%; overall P=0.02). Among patients with acute myocardial infarction or unstable angina, use of ACI-TIPI did not change appropriate admission (96%) to the CCU or telemetry unit at hospitals with high-capacity CCUs or telemetry units. CONCLUSIONS: Use of ACI-TIPI was associated with reduced hospitalization among emergency department patients without acute cardiac ischemia. This result varied as expected according to the CCU and cardiac telemetry unit capacities and physician supervision at individual hospitals. Appropriate admission for unstable angina or acute infarction was not affected. If ACI-TIPI is used widely in the United States, its potential incremental impact may be more than 200000 fewer unnecessary hospitalizations and more than 100000 fewer unnecessary CCU admissions.     

The use of high-density polyethylene implants in facial deformities

OBJECTIVE: To determine the usefulness of porous high-density polyethylene implants (Medpor) in a variety of facial skeletal deformities and subcutaneous defects, excluding those associated with acute maxillofacial trauma. DESIGN: Case series. SETTING: Academic tertiary care referral center in Baltimore, Md. PATIENTS: Thirty-four patients (age range, 20-74 years) with facial deformities requiring skeletal defect reconstruction or augmentation (38 cases), treated between January 1, 1992, and January 1, 1997. Follow-up ranged from 6 months to 40 months. MAIN OUTCOME MEASURES: Age, type and origin of the deformity treated, type of treatment, and complications. RESULTS: Types of deformities and defects treated include 7 patients with orbital defects (secondary traumatic or oncologic deformities), 8 with temporal fossa defects, 8 with frontocranial defects, 4 with maxillary or malar defects, 7 with calvarial bone graft donor site defects, 2 with microtia, and 2 with chin deficiency. Forty implants were placed. Complications included implant exposure in 4 patients and inappropriate augmentation in 1 patient (chin implantation). CONCLUSIONS: High-density polyethylene implants offer an excellent alternative to autogenous and other alloplastic materials in reconstruction of many facial defects and deformities. Advantages include its versatility and relatively ideal pore size that allows for excellent soft tissue ingrowth and coverage. Disadvantages include its rigid nature and difficulty in contouring to the surface of complex skeletal structures.     

More than 10 years of unrecognized nosocomial transmission of legionnaires' disease among transplant patients

OBJECTIVE: To investigate a cluster of cases of legionnaires' disease among patients at a hospital. SETTING: A university hospital that is a regional transplant center. DESIGN: Retrospective review of microbiology and serology data from the hospital laboratories and prospective surveillance via the radiology department; a case-control study and environmental sampling within the hospital and from nearby cooling towers. RESULTS: Diagnosis of seven cases of legionnaires' disease in the first 9 months of 1996 led to recognition of a nosocomial outbreak that may have begun as early as 1979. Review of charts from 1987 through September 1996 identified 25 culture-confirmed cases of nosocomial or possibly nosocomial legionnaires' disease, including 18 in bone marrow and heart transplant patients. Twelve patients (48%) died. During the first 9 months of 1996, the attack rate was 6% among cardiac and bone marrow transplant patients. For cases that occurred before 1996, intubation was associated with increased risk for disease. High-dose corticosteroid medication was strongly associated with the risk for disease, but other immunosuppressive therapy or cancer chemotherapy was not. Several species and serogroups of Legionella were isolated from numerous sites in the hospital's potable water system. Six of seven available clinical isolates were identical and were indistinguishable from environmental isolates by pulsed-field gel electrophoresis. Initial infection control measures failed to interrupt nosocomial acquisition of infection. After extensive modifications to the water system, closely monitored repeated hyperchlorinations, and reduction of patient exposures to aerosols, transmission was interrupted. No cases have been identified since September 1996. CONCLUSIONS: Legionella can colonize hospital potable water systems for long periods of time, resulting in an ongoing risk for patients, especially those who are immunocompromised. In this hospital, nosocomial transmission possibly occurred for more than 17 years and was interrupted in 1996, after a sudden increase in incidence led to its recognition. Hospitals specializing in the care of immunocompromised patients (eg, transplant centers) should prioritize surveillance for cases of legionnaires' disease. Aggressive control measures can interrupt transmission of this disease successfully.     

Prognostic significance of allelic losses in primary melanoma

Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each significantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also significantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained significant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 over-expression was significantly associated with improved survival (P=0.041).     

Von Willebrand disease: characteristics and response to desmopressin. Study of 103 cases

BACKGROUND: To describe the main characteristics and response to desmopressin infusion in 103 patients suffering from von Willebrand disease (vWD). PATIENTS AND METHODS: The criteria for diagnosis were (except for type 2N) the coexistence of von Willebrand factor ristocetin cofactor (vWF:RCo) activity < 50 U/dl with bleeding disease or one of the following data: von Willebrand factor antigen (vWF:Ag) activity < 50 U/dl, factor VIII (FVIII) activity < 50 U/dl or the existence of a increased bleeding time (BT). Multimeric studies of vWF were performed in 51 cases and ristocetin induced platelet aggregation (RIPA) was also performed. RESULTS: Spontaneous bleeding was found in 36 patients, while in 18 cases the diagnosis was done after surgical bleeding. Thirteen patients (6 presenting with mild bleeding) were studied for abnormalities in the routine preanestesic tests. Other 22 patients were diagnosed with vWD by familial studies. There were 3 patients with type 2B, 1 case with type 2N and other patient with type 3. BT was found increased in 26 out of 58 patients. The activities of vWF:CoR and vWF:Ag were 38.4 (9.4) U/dl and 45.8 (23.2) U/dl, respectively, while the activity of FVIII was 49.9 (20.8) U/dl. Prophylactic DDAVP (desmopressin) was infused in 32 patients. After 1 h, basal activities of vWF:CoR and vWF:Ag were increased by 3.1 (3.2) and 3.4 (3.1) times, respectively, and maintained for 3 h. FVIII activity increased 3.6 (2.3) times the basal levels decreasing after 3 h (2.9 [2.1]; p < 0.01). The BT was corrected in 8 out of ten patients. CONCLUSIONS: vWD is a major cause of surgical bleeding. Preanestesic anamnesis and coagulation tests can be useful to identify vWD. Many patients with vWD have normal BT. A failure in the response to desmopressin infusion is unusual.     

Stability of orthopedic and surgically assisted rapid palatal expansion over time

At the present time no reports are available on the stability between orthopedic and surgically assisted rapid palatal expansion. This study was designed to examine and compare the dental and skeletal changes over time for both orthopedic maxillary expansion and surgically assisted palatal expansion. The study was divided into two groups. Group one was orthopedically expanded and consisted of 14 males and 10 females. The ages ranged from 6 years to 12 years with a mean of 8.5 years. Group two received surgically assisted rapid palatal expansion and consisted of 12 males and 16 females with ages ranging from 13 years to 35 years and a mean age of 19.25 years. All 52 subjects were white, from the same geographic area, and were treated by the same two operators. Dental models and posterior anterior cephalograms were obtained immediately before and after expansion, at removal of the expansion device, and 1 year after removal of the appliance. A repeated measures analysis of variance test was applied to assess changes over time between groups. The surgical and nonsurgical techniques displayed similar trends over time although the surgical group contained a greater quantity of expansion. Both the orthopedic and the surgical groups showed stable results.     

Human thyroperoxidase is largely retained and rapidly degraded in the endoplasmic reticulum. Its N-glycans are required for folding and intracellular trafficking

Human thyroperoxidase (hTPO), a type I transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis and plays a major role in thyroid autoimmunity. Whereas hormonosynthesis occurs at the apical membrane of thyroid cells, TPO localizes mainly in the perinuclear membrane and the endoplasmic reticulum. To establish the intracellular trafficking and the structural characteristics of hTPO in the various cell compartments, hTPO was stably expressed in the Chinese hamster ovary cell line, and its folding was studied with two monoclonal antibodies (mAbs): mAb 47, recognizing a linear epitope; and mAb 15, recognizing a conformational epitope present in the mature protein. The results show that only 15-20% of hTPO molecules were able to acquire a conformation suitable for the recognition by mAb 15. On the other hand, only a part (approximately 15%) of the latter were able to reach the plasma membrane. The hTPO, unable to fold correctly, was more rapidly degraded than that recognized by mAb 15 (half-time, 2 h vs. 7 h). Study of the carbohydrate content of hTPO showed that N-glycans with complex-type structure were found only on hTPO at the cell surface, whereas intracellular hTPO bore high-mannose-type structures. Taken together, these data demonstrate that the intracellular pool of enzyme is formed of newly synthesized molecules and is not caused by recycling of mature hTPO from the cell surface. Complete inhibition of hTPO N-glycosylation with tunicamycin led to a 95% decrease in hTPO at the plasma membrane and, thus, to a decrease in enzymatic activity at the cell surface, emphasizing the role of N-glycans in the intracellular trafficking of hTPO. However, inhibition of formation of complex-type structures with deoxymannojirimycin and of O-glycans with phenyl-alpha-GalNAc did not influence the intracellular trafficking and enzymatic activity of hTPO.     

Residual and recurrent shunts after implantation of Cook detachable duct occlusion coils

Cough and chest wall pain at high altitude have only received passing mention in the medical literature. Increased minute ventilation of cold dry air at very high altitude is likely to cause airway irritation. This in turn may result in airway drying, mucus production, postnasal drip from vasomotor rhinitis, and bronchospasm acting individually or in combination to stimulate the vagal cough reflex. The cough is exacerbated further at extreme altitudes above 5500 m, and may result in intercostal muscle strain and single or multiple rib fractures. We present a case of multiple cough induced stress fractures and arthropathy documented by technetium-99 bone scan in a high altitude climber and suggest the addition of the term High Altitude Cough Syndrome (HACS) to the medical syntax to identify this discrete medical problem of exposure to very high altitude.     

Stroke in pregnancy and the puerperium

Recent studies suggest that the risk of cerebral infarction is increased during the puerperium but not during pregnancy itself. Most of the known causes of ischaemic stroke in the young have been reported during pregnancy. In most of these conditions, it is uncertain whether pregnancy is coincidental or plays a role in the occurrence of stroke. Eclampsia is the main pregnancy-specific cause, which may be associated with focal neurological deficits of sudden onset, consistent with a clinical diagnosis of stroke. However, the precise pathogenesis of these stroke-like focal deficits remains poorly understood. The two other pregnancy-specific conditions (choriocarcinoma and amniotic fluid embolism) are rarely responsible for focal cerebral ischaemia. In a significant number of patients, the cause of the stroke remains undetermined, despite an extensive aetiological investigation. Whether a hypercoagulable state and vessel wall changes associated with pregnancy may play a role in the occurrence of these otherwise unexplained ischaemic strokes remains unknown. The occurrence of cerebral venous thrombosis is clearly linked to the puerperal state, suggesting a direct role of the latter. However, cerebral venous thrombosis during pregnancy or the puerperium has been related to various aetiologies, stressing the need for an aetiological study, particularly when the thrombosis occurs during pregnancy. Pregnancy may increase the risk of subarachnoid haemorrhage, The most common cause is rupture of an arterial aneurysm. Although this is a controversial issue, the increased tendency of an aneurysm to bleed with advancing gestational age suggests that haemodynamic, hormonal or other physiological changes of pregnancy may play a role in aneurysmal rupture. The classic notion that rupture of an arterial aneurysm occurs more frequently during labour has not been confirmed. Most authors agree that surgical management after subarachnoid haemorrhage in pregnancy should be the same as that in the non-pregnant state. Data specifically devoted to intraparenchymal haemorrhage in pregnancy are scarce. Pregnancy and in particular the puerperium seem to be associated with an increased risk of intracerebral haemorrhage. The most common causes are eclampsia and ruptured vascular malformations. Whether pregnancy increases the risk of rupture of an arteriovenous malformation is controversial.     

9th International Congress on Isozymes, Genes, and Gene Families: an overview

The 9th International Congress on Genes, Gene Families, and Isozymes marked a historic transition in the series formerly known as the International Congress on Isozymes. The name of the congress was changed to reflect the broadened scope of this field and the new directions in which it is moving. To recognize and promote this transition, a number of new features were incorporated into this congress. Accordingly, the broad-based program featured preeminent biologists from 29 different countries. A total of 350 people attended the congress. A special new feature of this congress was the Student/Fellow Program, which was designed to enhance participation by advanced undergraduate and graduate students and postdoctoral fellows. This congress celebrated the progress that has occurred during the past 40 years beginning with studies of isozymes and leading into studies of specific genes and gene families. As we move into the next millennium, it is clear that our field is strongly positioned and will continue to be the focus of exciting and important new research.