THz-Spectroscopy of Biological Molecules.

The terahertz frequency absorption spectraof DNA molecules reflect low-frequencyinternal helical vibrations involvingrigidly bound subgroups that are connectedby the weakest bonds, including thehydrogen bonds of the DNA base pairs,and/or non-bonded interactions. Althoughnumerous difficulties make the directidentification of terahertz phonon modes inbiological materials very challenging, ourresearch has shown that such measurementsare both possible and fruitful. Spectra ofdifferent DNA samples reveal a large numberof modes and a reasonable level ofsequence-specific uniqueness. In an attemptto show that the long wavelength absorptionfeatures are intrinsic properties ofbiological materials determined by phononmodes, a normal mode analysis has been usedto predict the absorption spectra ofpolynucleotide RNA Poly[G]-Poly[C]. Directcomparison demonstrated a correlationbetween calculated and experimentallyobserved spectra of the RNA polymers, thusconfirming that the fundamental physicalnature of the observed resonance structureis caused by the internal vibration modesin the macromolecules.In this work we demonstrate results fromFourier-Transform Infrared (FTIR)spectroscopy of DNA macromolecules andrelated biological materials in theterahertz frequency range. Carefulattention was paid to the possibility ofinterference or etalon effects in thesamples, and phenomena were clearlydifferentiated from the actual phononmodes. In addition, we studied thedependence of transmission spectra ofaligned DNA and polynucleotide film sampleson molecule orientation relative to theelectromagnetic field, showing the expectedchange in mode strength as a function ofsample orientation. Further, the absorptioncharacteristics were extracted from thetransmission data using the interferencespectroscopy technique, and a stronganisotropy of terahertz characteristics wasdemonstrated.

Submillimeter-wave phonon modes in DNA macromolecules.

A detailed investigation of phonon modes in DNA macromolecules is presented. This work presents experimental evidence to confirm the presence of multiple dielectric resonances in the submillimeter-wave spectra (i.e., approximately 0.01-10 THz) obtained from DNA samples. These long-wave (i.e., approximately 1-30 cm(-1)) absorption features are shown to be intrinsic properties of the particular DNA sequence under study. Most importantly, a direct comparison of spectra between different DNA samples reveals a large number of modes and a reasonable level of sequence-specific uniqueness. This work establishes the initial foundation for the future use of submillimeter-wave spectroscopy in the identification and characterization of DNA macromolecules.

Outbreak of Legionnaires' disease associated with a display whirlpool spa.

BACKGROUND: Recognized outbreaks of Legionnaires' disease (LD) are rare; when they occur, they provide opportunities to understand the epidemiology of the illness and improve prevention strategies. We investigated a population-based outbreak. METHODS: After the confirmation of LD in October 1996 in five people in neighbouring towns in southwest Virginia, active surveillance for additional cases was undertaken. A case-control study was conducted to identify exposures associated with illness, followed by a cohort study among employees of the facility at which the source of the outbreak was located in order to assess unrecognized exposure and illness. Samples of likely sources of LD in the facility were cultured for LEGIONELLA: RESULTS: In all, 23 laboratory-confirmed cases of LD were eventually identified. Of the 15 cases in the case-control study, 14 (93%) reported visiting a home-improvement store, compared with 12 (27%) of 45 controls (matched odds ratio [MOR] = 23.3; 95% CI : 3-182). Among home-improvement centre patrons, 10 (77%) of 13 cases questioned recalled either visiting or walking by a display whirlpool spa, compared with 3 (25%) of 12 controls (MOR = 5.5; 95% CI : 0.7-256.0). Two cases' sputum isolates were an exact match, by monoclonal antibody subtyping and arbitrarily primed polymerase chain reaction, to a whirlpool spa filter isolate from the store. Employees reporting more exposure to the display spas were more likely to report symptoms of LD or to have an elevated titre. CONCLUSIONS: This investigation shows that LD can be transmitted from a whirlpool spa used for display only, and highlights the need for minimizing the risk of transmission of LD from all water-filled spas. Key messages This paper describes an investigation of a population-based outbreak of Legionnaires' disease (LD). A case-control study first identified a home-improvement store as the likely source of the outbreak. An environmental investigation later confirmed that finding, as two cases' sputum isolates were an exact match, by monoclonal antibody subtyping and arbitrarily primed polymerase chain reaction, to a whirlpool spa filter isolate from the store. The spa was intended and used for display only.

Succimer and the reduction of tissue lead in juvenile monkeys.

The extent to which succimer (2,3-dimercaptosuccinic acid, DMSA) chelation reduces target organ lead (Pb) levels, including the skeleton, relative to the cessation of Pb exposure is a primary consideration in evaluating its efficacy for reducing toxicity in children. Here, we utilized a rhesus monkey model of childhood Pb exposure and a sensitive stable (204)Pb isotope tracer methodology to determine the efficacy of succimer for reducing Pb in blood, liver, and skeletal tissues from chronic (>/=1 year) versus short-term (3-4 days) Pb exposures. Specific attention was paid to the efficacy of succimer treatment compared to the cessation of Pb exposure. Infant rhesus monkeys (n = 48) were exposed to Pb daily for 1 year or >1 year postpartum to reach and maintain a target blood Pb level of 35-40 microg/dL. Two successive 19-day succimer treatment regimens were administered at 53 and 65 weeks of age (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days). Blood was collected over the course of treatment, and liver and bone biopsy samples were collected on days 0, 5, and 20, relative to the start of treatment (day 0). Complete 24-h urine collections were conducted over the course of treatment. Results of the first chelation indicate that a single regimen of succimer treatment led to significant reductions in blood and liver Pb levels, relative to the placebo group. However, the cessation of Pb exposure alone (i.e., placebo) also led to significant reductions in blood and liver compared to pretreatment levels. Neither succimer nor the cessation of Pb exposure had a significant impact on bone lead levels. Blood Pb levels in the succimer-treated group rebounded within 5 days after treatment ended, becoming comparable with levels in the placebo group from that point on. Results from the second chelation indicate that succimer treatment is essentially equally efficacious in reducing blood Pb at moderate (20 microg/dL) levels where exposures ended >3 months previously and more elevated (40-50 microg/dL) levels where exposures ended just prior to treatment, relative to the placebo treatment. Finally, similar overall outcomes were observed for tissue Pb from recent exposures (i.e., (204)Pb tracer levels), indicating little or no apparent difference in the chelation of Pb from recent (3-4 days) versus long-term exposures. These data demonstrate that succimer does not reduce skeletal Pb levels, and they show that the efficacy of succimer for reducing blood Pb levels does not persist beyond the completion of treatment due to posttreatment rebounds in blood Pb from endogenous sources. They also demonstrate the relative benefit of eliminating Pb exposures, which serves to underscore the importance of primary prevention of Pb exposure. The extent to which these data reflect the efficacy of succimer for reducing neurocognitive impairment is not yet known, although those data are forthcoming.

Succimer and the urinary excretion of essential elements in a primate model of childhood lead exposure.

Succimer is considered to be a safe and effective treatment for lead (Pb) poisoning, since it reduces body Pb levels without an apparent diuresis of other essential elements. However, while existing clinical data indicate that succimer does not significantly increase the excretion of non-target elements, those studies have also reported a wide range of outcomes. Therefore, we investigated whether succimer treatment measurably increased the urinary excretion of essential elements in a primate model of childhood Pb exposure. Infant rhesus monkeys (Macaca mulatta) were exposed to Pb from birth through one year of age, and presented blood Pb levels of approximately 40-50 microg/dL at the start of treatment. Subsequently, they were treated with succimer (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days, n = 15) or vehicle (n = 14) for 19 days. Complete urine samples were collected over the first 5 days of treatment, and were analyzed for levels of calcium (Ca), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), magnesium (Mg), manganese (Mn), nickel (Ni), and zinc (Zn), using trace metal-clean techniques and magnetic sector-ICP-MS. Succimer treatment significantly (p < 0.05) reduced blood Pb levels when compared to the vehicle group over the treatment period, and concomitantly produced a significant >4-fold increase in urinary Pb excretion. Succimer treatment also significantly (p < 0.05, multivariate ANOVA) increased the urinary excretion of essential elements, but only when the cumulative total excretion over treatment days 1-5 for all elements were considered. None of these relative increases reached statistical significance for any particular element x day, although increases in Zn (day 3) excretion were only marginally non-significant (0.1 > p > 0.05). Multivariate analyses of a subset of elements (Cu, Fe, Mn, Zn) similarly indicated no significant effect of succimer treatment overall, although the urinary excretion of Mn was significantly increased on day 3 of treatment. Collectively, these data indicate that succimer does contribute to an increase in the urinary excretion of essential elements, although not significantly for any single element considered here. This may be important in Pb-exposed children, who can possess reduced trace element reserves due to nutritional deficiencies.

Model for quantifying photoelastic fringe degradation by imperfect retroreflective backings.

In any automated algorithm for interpreting photoelastic fringe patterns it is necessary to understand and quantify sources of error in the measurement system. We have been considering how the various components of the coating affect the photoelastic measurement, because this source of error has received fairly little attention in the literature. Because the reflective backing is not a perfect retroreflector, it does not preserve the polarization of light and thereby introduces noise into the measurement that depends on the angle of obliqueness and roughness of the reflective surface. This is of particular concern in resolving the stress tensor through the combination of thermoelasticity and photoelasticity where the components are sensitive to errors in the principal angle and difference of the principal stresses. We have developed a physical model that accounts for this and other sources of measurement error to be introduced in a systematic way so that the individual effects on the fringe patterns can be quantified. Simulations show altered photoelastic fringes when backing roughness and oblique incident angles are incorporated into the model.

Millimeter wave-induced vibrational modes in DNA as a possible alternative to animal tests to probe for carcinogenic mutations.

Developing methods for alternative testing is increasingly important due to dwindling funding resources and increasing costs associated with animal testing and legislation. We propose to test the feasibility of a new and novel method for detecting DNA mutagenesis using millimeter wave spectroscopy. Although millimeter wave spectroscopy has been known since the 1950s, the cost was prohibitive and studies did not extend to large biological proteins such as DNA. Recent advances have made this technology feasible for developing laboratory and field equipment. We present preliminary findings for lesion-induced vibrational modes in DNA observed from 80 to 1000 gigahertz (GHz). These findings suggest that there are vibrational modes that can be used as identification resonances. These modes are associated with localized defects of the DNA polymers. They are unique for each defect/lesion, and should be easy to detect. We described a field-detecting detector based on the local modes.

Female circumcision: an emerging concern in college healthcare.

Female circumcision (clitoridectomy), a traditional practice in some Third World societies, is discussed, and related medical procedures are described. Medical and psychosexual implications for the patient are considered, and college health clinicians are encouraged to be prepared to see patients who have been subjected to the procedure and help these young women deal with attendant medical, emotional, and cultural issues. One female student's experience at her college health service is described.

Ability of Medicare claims data and cancer registries to identify cancer cases and treatment.

The objective of this study is to compare the ability of Medicare and cancer registry data to identify incident cancer cases and initial surgical therapy both singly and in combination. Data from the Virginia Cancer Registry (VCR) were linked to Medicare claims files (Medical Provider Analysis and Review File (MEDPAR)) for Virginia residents aged 65 years and over with breast, colorectal, lung, or prostate cancer diagnosed between 1986 and 1989. MEDPAR found 73-83% of cancer cases identified by VCR. Factors significantly associated with MEDPAR missing a case that was reported to VCR included younger age, male gender, living in an urban area, higher social class, in situ disease, and lack of cancer treatment. A total of 70-82% of cancer cases identified through Medicare claims were reported to the VCR. Older age, female gender, nonwhite race, comorbid conditions, no surgical procedures, multiple cancer admissions, and the position of the cancer diagnostic code on the MEDPAR record were factors significantly related to being missed by the VCR. The rate of capturing initial surgical therapies was similar to that of identifying cases. Combining information from VCR and MEDPAR resulted in increasing sensitivity for identifying incident cases to 92-97%. Using combined data from independent sources may improve reporting, increase the accuracy of cancer incidence estimates, and provide an opportunity to identify reasons for missing data.

Student health services at four rural colleges: implications for healthcare reform.

This study investigated services available at health centers at four rural colleges. It also investigated the healthcare accessible to students at those institutions if college health services were unavailable. The authors used a survey and interview procedure to establish the existence of healthcare resources in two adjacent communities and to identify barriers to student use. Findings from the study indicate that, for many students attending rural colleges, the student health center may be the only source of primary healthcare available. The data support the need to include student health centers at rural colleges in the national healthcare reform agenda because closing any one of these schools' health centers could result in a healthcare disaster for some students.

Sedative-analgesic agent administration in children: analysis of use and complications in the emergency department.

The frequency of, indications for, and complications from non-acetaminophen sedative-analgesic agents (SAAs) administered to children less than 16 years of age in the emergency department (ED) were determined by a retrospective review. All 21,353 charts from a single university hospital ED over a 16-month period were included. Few children (N = 759; 3.5%) received SAAs. Of 919 total doses, 13% of children received a second and 4.5% received a third SAA. The group was 59% male. Most children were < or = 10 years of age. Sixty-two percent of SAAs were either sedatives or opioids. Sedatives given included chloral hydrate, diazepam, lorazepam, midazolam, and phenobarbital. Opioids given included morphine, codeine, and meperidine. Indications for SAAs included painful procedures, analgesia, radiographic imaging, and seizure activity. Complications (N = 51; 6.7%) included inadequate sedation, vomiting, and respiratory depression or oxygen desaturation. Respiratory depression or oxygen desaturation occurred only after intravenous administration of SAAs for seizures. In children, non-acetaminophen SAAs are used most commonly in younger patients requiring sedation for painful procedures or for radiologic imaging. Respiratory depression was observed only after intravenous administration of anticonvulsants.

Evaluation of a method for detecting outbreaks of diseases in six states.

A new statistical method, developed for detection of changes in reporting, has proved useful in analysis of provisional data reported by state health departments to the National Notifiable Diseases Surveillance System (NNDSS). In this system, data from the current four-week period can be compared with data from the previous, same, and subsequent four-week periods from each of the preceding five years, and reports exceeding historical limits are highlighted in a horizontal bar graph. To evaluate the usefulness of this method at the state level, we applied it to weekly reports of seven notifiable diseases in six states over a four-month period. Participating state health departments investigated all events exceeding historical limits and reported known outbreaks that were not identified by the method. During the four-month period, the method identified 27 episodes of disease reports exceeding historical limits. Of these, 14 (52%) represented outbreaks. None was detectable by analysis of aggregate national surveillance data. Five outbreaks known to state health department officials were not identified by the method, because of increased disease activity during the baseline period or lack of timely provisional reporting of outbreak-related cases. Methods for detection of increases in reporting at the state level may identify events of public health importance that are obscured in aggregate national data and may supplement other local sources of information available to state health departments in the recognition of significant public health events.

ViraPap: can it help to reduce the need for colposcopy?

Two new tests recently became available for identifying cervical human papillomavirus (HPV). This study investigated the usefulness of the ViraPap and ViraType in the clinical setting. Thirty-six subjects considered to be at risk for HPV infection were examined; had specimens obtained for Papanicolaou smear (Pap smear), ViraPap, and ViraType; and were then referred for colposcopy. Results of these examinations were then compared to the findings of colposcopy and/or colposcopic biopsy. The sensitivity and specificity of the ViraPap in predicting an abnormality being found on colposcopic examination were 61.5% and 70%, respectively. Identifying the specific viral type by use of the ViraType did not prove to be clinically helpful in this population.

Screening for Chlamydia trachomatis at a university health service.

Chlamydia trachomatis is the most common sexually transmitted infection in the United States. The aim of this study was to determine the prevalence of Chlamydia in college family planning patients and to identify diagnostic indicators associated with Chlamydia. A thorough history and physical examination was performed, including culture for gonorrhea, cancer (papanicolaou test), and Chlamydia trachomatis. Chlamydia occurred in 12.6% of 419 subjects. The lack of signs and symptoms and the possibility of inaccurate historical data limit the clinical predictability of chlamydial infections. Routine screening of college women is recommended.

An economic comparison of Tubex injection systems with traditional ampuls and vials.

A time and motion study was performed at the Hospital of the University of Pennsylvania to measure and compare the direct and indirect costs of the original Tubex and Tubex Fast-Trak injection systems with comparable costs associated with single dose ampuls, vials, and multi-dose vials. Data collection involved observation of 170 injections prepared by 29 nurses on two oncology units over a 7-week period. The time and nondrug supply costs of the Tubex Fast-Trak were lower than those of all other injection systems observed, including the original Tubex. Although the drug acquisition component was higher for the Tubex systems than for conventional injection methods, an analysis of the total cost of the use of Tubex Fast-Trak demonstrated that on an annual basis, the system is nearly equal in cost to the use of single ampuls and vials. Important advantages of the prefilled cartridge system should be considered in addition to labor, supply, and drug costs when selecting cost-effective injection systems. Systems like Tubex offer advantages that may lower total cost of care, such as reduction in wastage, pilferage, contamination, dosage error, and improved cost allocation accuracy. When polled about their opinion, the majority of nurses who participated in the study indicated that Tubex Fast-Trek was their first choice over other injection methods observed.

Outpatient use of ceftriaxone: a cost-benefit analysis.

Patients who participated in an outpatient intravenous therapy program designed to limit hospitalization for those who could be maintained on ceftriaxone at home were interviewed regarding costs and benefits. Of the 79 patients interviewed concerning 83 therapeutic episodes, 43.4 percent were able to perform their usual activities as soon as they began the program, 28.9 percent were restricted for part of the time, and 27.7 percent never resumed their usual activities. The 83 therapeutic episodes represent a total of 2,409 outpatient days (mean 29.7; standard deviation [SD] 17.7), 1,406 of which represent unrestricted activities. Costs and benefits of the program were calculated separately for four employment groups: not employed; usually employed, but not while on intravenous therapy; employed while on intravenous therapy, with time off for follow-up visits; and employed while on intravenous therapy, no time off for follow-up required. The mean total benefit, weighted across all four groups, was $6,588.14 (SD = $3,802.90) per patient. Mean weighted costs totalled $1,768.02 (SD = $1,129.36). The overall weighted benefit/cost ratio was approximately 5:1. Although private insurers reimbursed 63 percent of the patients for all hospitalization costs, only 39 percent were fully covered for the follow-up physician visits required during outpatient therapy.