Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory.

BACKGROUND: High functional antibody responses, establishment of immunologic memory, and unambiguous efficacy in infants suggest that an initial dose of conjugated pneumococcal polysaccharide (PnC) vaccine may be of value in a comprehensive adult immunization strategy. METHODS: We compared the immunogenicity and safety of 7-valent PnC vaccine (7vPnC) with that of 23-valent pneumococcal polysaccharide vaccine (PPV) in adults >/=70 years of age who had not been previously vaccinated with a pneumococcal vaccine. One year later, 7vPnC recipients received a booster dose of either 7vPnC (the 7vPnC/7vPnC group) or PPV (the 7vPnC/PPV group), and PPV recipients received a booster dose of 7vPnC (the PPV/7vPnC group). Immune responses were compared for each of the 7 serotypes common to both vaccines. RESULTS: Antipolysaccharide enzyme-linked immunosorbent assay antibody concentrations and opsonophagocytic assay titers to the initial dose of 7vPnC were significantly greater than those to the initial dose of PPV for 6 and 5 of 7 serotypes, respectively (P < .01 and P < .05, respectively). 7vPnC/7vPnC induced antibody responses that were similar to those after the first 7vPnC inoculation, and 7vPnC/PPV induced antibody responses that were similar to or greater than antibody responses after administration of PPV alone; PPV/7vPnC induced significantly lower antibacterial responses, compared with those induced by 7vPnC alone, for all serotypes (P < .05). CONCLUSION: In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels.

Methionine and its derivatives increase bladder excitability by inhibiting stretch-dependent K(+) channels.

BACKGROUND AND PURPOSE: During the bladder filling phase, the volume of the urinary bladder increases dramatically, with only minimal increases in intravesical pressure. To accomplish this, the smooth muscle of the bladder wall must remain relaxed during bladder filling. However, the mechanisms responsible for the stabilization of bladder excitability during stretch are unclear. We hypothesized that stretch-dependent K(+) (TREK) channels in bladder smooth muscle cells may inhibit contraction in response to stretch. EXPERIMENTAL APPROACHES: Bladder tissues from mouse, guinea pig and monkey were used for molecular, patch clamp, mechanical, electrical, Ca(2+) imaging and cystometric responses to methionine and its derivatives, which are putative blockers of stretch-dependent K(+) (SDK) channels. KEY RESULTS: SDK channels are functionally expressed in bladder myocytes. The single channel conductance of SDK channels is 89pS in symmetrical K(+) conditions and is blocked by L-methionine. Expressed TREK-1 currents are also inhibited by L-methioninol. All three types of bladder smooth muscle cells from mouse, guinea pig and monkey expressed TREK-1 genes. L-methionine, methioninol and methionine methyl ester but not D-methionine increased contractility in concentration-dependent manner. Methioninol further increased contractility and depolarized the membrane in the presence of blockers of Ca(2+)-activated K(+) conductance. L-methionine induced Ca(2+) waves that spread long distances through the tissue under stretched conditions and were associated with strong contractions. In cystometric assays, methioninol injection increased bladder excitability mimicking overactive bladder activity. CONCLUSIONS AND IMPLICATIONS: Methioninol-sensitive K(+) (SDK, TREK-1) channels appear to be important to prevent spread of excitation through the syncitium during bladder filling.

Characterization of the Mercury pulsed power x-ray source spectrum using multichannel density aerogel Cherenkov detectors.

The Aerogel Cherenkov Detector for Cygnus (ACD/C) is a time-dependent, x-ray spectral detector that uses SiO2 aerogels spanning an index of refraction (n = 1.02-1.07) corresponding to a 1.1-2.3 MeV x-ray energy threshold. The ACD/C was developed for pulsed power x-ray sources like Cygnus located at the Nevada National Site and Mercury located at the Naval Research Laboratory (NRL). Aerogels sit between the measurement capabilities of gas (>2 MeV) and solids such as fused silica (>0.3 MeV). The detector uses an aluminum converter to Compton scatter incoming x-rays and create relativistic electrons, which produce Cherenkov light in an aerogel or a fused silica medium. The ACD/C was fielded at the NRL when Mercury was tuned to produce up to 4.8 MeV endpoint bremsstrahlung. Despite a high radiation and electromagnetic interference background, the ACD/C was able to achieve high signal over noise across five aerogel densities and fused silica, including a signal to noise for a 1.1 MeV aerogel threshold. Previous experiments at Cygnus observed a signal that was comparable to the noise (1×) at the same threshold. The ACD/C observed time-resolved rise and fall times for different energy thresholds of the photon spectrum. Monte Carlo simulations of the ACD/C's aerogel response curves were folded with a simulation of Mercury's photon energy spectrum and agree within the error to the observed result.

Immunogenicity of malondialdehyde-modified low density lipoproteins. Studies with monoclonal antibodies.

Malondialdehyde (MDA)-modified low density lipoprotein (LDL) can stimulate the accumulation of cholesteryl esters in cultured macrophages through its interaction with specific scavenger receptors. It has been speculated that such interaction occurs in vivo thus contributing to the formation of foam cells within atherosclerotic lesions. This report describes the development of new tools in the form of a specific assay for MDA-LDL to investigate this hypothesis. We have immunized BALB/c mice with malondialdehyde mouse low density lipoproteins and antibodies against malondialdehyde human low density lipoproteins were generated. Monoclonal antibodies were produced using hybridoma techniques and one particular clone (EB 7-3) was expanded for further studies. The immunoreactivity of several antigens was tested using antibody EB 7-3 in an enzyme-linked immunosorbent assay (ELISA). In a typical assay malondialdehyde human LDL (with at least 40% of lysines modified) was coated (2 micrograms/ml, 100 microliter) in 96-well microtiter plates. Antibody plus one of several antigens were then added and the interaction between the antibody and coated antigen was measured using alkaline phosphatase-conjugated affinity purified goat anti-mouse immunoglobulin. The binding of antibody EB 7-3 to wells coated with malondialdehyde-LDL was competitively inhibited by malondialdehyde-LDL added in solution, with half maximal inhibition occurring at 150 +/- 80 ng/ml. In addition, the ability of malondialdehyde-LDL to inhibit this interaction was proportional to the degree of modification: the more lysines were modified the more did malondialdehyde-LDL inhibit the binding of antibody EB 7-3 to coated malondialdehyde-LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychosocial, behavioral, and medical outcomes in children with epilepsy: a developmental risk factor model using longitudinal data.

OBJECTIVE: We studied factors predicting the risk of adverse long-term psychosocial, behavioral, and medical outcomes in children with epilepsy. METHODS: Children (N = 157, 4.5 to 13 years) were enrolled in a prospective longitudinal study when first seen. Potential subjects were excluded if they were moderately or severely mentally retarded, had motor or sensory handicaps interfering with testing, or did not speak either English or Spanish. MEASURES: To develop risk predictors, we collected information regarding the child's medical and seizure history, cognitive functioning, and behavior problems, and family functioning. Children and their families were followed for a minimum of 18 months, then underwent reassessment of medical status, parent's attitudes toward epilepsy, and the child's behavioral and cognitive functioning. Data were analyzed by confirmatory factor analysis to develop baseline factors (Sociocultural Risk, Seizure Risk, and Behavior Problems) and outcome factors (Medical/Seizure Problems, Parent's Negative Attitudes Toward Epilepsy, and Behavior Problems), followed by structural equation modeling to determine across-time causal effects. Eighty-eight subjects completed all baseline and outcome measures. RESULTS: Among significant across-time effects, Medical Outcome was predicted by Seizure Risk. An increased number of stressful life events predicted better Medical Outcome. Low acculturation increased Parent's Negative Attitudes and was associated with increased Behavior Problems at baseline. Behavior Problems were stable across time. It is interesting that IQ did not affect any of the outcomes, although its effect may have been mediated through other baseline measures. CONCLUSIONS: Seizure history was the best predictor of ongoing medical difficulties, whereas the most important causes of ongoing parental anxiety and negative attitudes toward epilepsy were sociocultural. Variation in medical or attitudinal outcomes was not influenced by either the child's IQ or reported behavioral problems. These findings suggest that to alter attitudes toward epilepsy, programs should be tailored to the sociocultural background of the family. Studies of quality of life of children with epilepsy should include appropriate sociocultural measures.

Self-inflicted and unintentional firearm injuries among children and adolescents: the source of the firearm.

CONTEXT: The source and ownership of guns used by children to shoot themselves or others is largely unknown. OBJECTIVE: To determine the ownership and usual storage location of firearms used in unintentional and self-inflicted intentional firearm deaths and injuries. DESIGN: Retrospective case series. SETTING: King County, Washington. PATIENTS: Youths aged from birth to 19 years who sought medical treatment at a level I trauma center for a self-inflicted or unintentional firearm injury between 1990 and 1995 or who presented to the county medical examiner with a fatal self-inflicted or unintentional firearm injury between 1990 and 1995. DATA SOURCES: County medical examiner records, regional police investigative reports, medical records from a level I trauma center, and surveys of victims' families. MAIN OUTCOME MEASURES: Source and ownership of the associated firearm. RESULTS: Fifty-six fatal injuries and 68 nonfatal firearm injuries that met the criteria were identified. Of these, 59 were intentionally self-inflicted deaths and injuries and 65 were unintentional deaths and injuries. A firearm owned by a household member living with the victim was used in 33 (65%) of 51 suicides and suicide attempts and 11 (23%) of 47 unintentional injuries and deaths. Additionally, a firearm owned by another relative, friend, or parent of a friend of the victim was used in 4 (8%) of the 51 suicides and suicide attempts and 23 (49%) of the 47 unintentional injuries and deaths. Parental ownership accounted for 29 (57%) of the 51 suicides and suicide attempts and 9 (19%) of the 47 unintentional injuries and deaths. More than 75% of the guns used in suicide attempts and unintentional injuries were stored in the residence of the victim, a relative, or a friend. CONCLUSION: Most guns involved in self-inflicted and unintentional firearm injuries originate either from the victim's home or the home of a friend or relative.

Reaction time, impulsivity, and attention in hyperactive children and controls: a video game technique.

Maturation of sustained attention was studied in a group of 52 hyperactive elementary school children and 152 controls using a microcomputer-based test formatted to resemble a video game. In nonhyperactive children, both simple and complex reaction time decreased with age, as did variability of response time. Omission errors were extremely infrequent on simple reaction time and decreased with age on the more complex tasks. Commission errors had an inconsistent relationship with age. Hyperactive children were slower, more variable, and made more errors on all segments of the game than did controls. Both motor speed and calculated mental speed were slower in hyperactive children, with greater discrepancy for responses directed to the nondominant hand, suggesting that a selective right hemisphere deficit may be present in hyperactives. A summary score (number of individual game scores above the 95th percentile) of 4 or more detected 60% of hyperactive subjects with a false positive rate of 5%. Agreement with the Matching Familiar Figures Test was 75% in the hyperactive group.

Beliefs about condoms and their association with intentions to use condoms among youths in detention.

PURPOSE: Youths in detention have been identified as a high-risk group for AIDS. To help inform AIDS-prevention efforts targeted for these youths, we surveyed youths in detention regarding their sexual behaviors, beliefs about condoms, intentions to use condoms, and actual condom use. We examined race and gender differences in these beliefs and behaviors, and we studied the relationship of these beliefs to condom-use intentions. METHODS: Questionnaires were administered to a sample of 201 youths in detention who were, on average, 16 years old. The sample was stratified on gender and race (African-American and white), with approximately equal numbers in each group. RESULTS: The results indicate that these youths had engaged in behaviors that put them at high risk of acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases. Although they used condoms somewhat more consistently with casual partners than with their steady partners, the majority did not use condoms consistently with either partner type. Very few race or gender differences were found with regard to condom use, intentions to use condoms, or beliefs about the consequences of using condoms. Beliefs associated with intentions to use condoms with steady partners included protection against sexually transmitted diseases (STDs), and the beliefs that condoms reduce pleasure, are artificial, unromantic, and interrupt sex. In contrast, only the belief that condoms prevent pregnancy was related to intentions to use condoms with casual partners. CONCLUSION: The results suggest that interventions targeted at African-American and white males and females in detention need not differ greatly in content as long as they include the most salient concerns of each group; that interventions include content on the two protective benefits of condom use (pregnancy and STD prevention), as well as on how to minimize the perceived negative aspects of condom use; that they stress the need for condom use with steady as well as casual partners; and that they stress that anal intercourse is especially risky with regard to AIDS transmission.

PIP: The authors surveyed 201 teenagers of mean age 15.9 years in a large urban juvenile detention center in the Northwest US on their sex behaviors, beliefs about condoms, intentions to use condoms, and actual condom use. The group was comprised of 51 African American males, 50 African American females, 50 white males, and 50 white females. Aged 14-19, all had engaged in heterosexual intercourse during the previous three months. 66% had not finished high school and 78% were unemployed prior to incarceration. The average age of first intercourse was 13 years. 77% reported having had sex with five or more partners, 15% reported having had paid sex, at least 10% had sex with a needle user, and less than 4% reported having sex with a same-sex partner. 85% had a steady partner with whom they had had sex during the past three months. 16% used condoms every time with the partner, while more than 33% reported never using a condom with the partner. 18% reported having anal sex with a steady partner in the past three months, 10% of whom reported using a condom for each such act. 52% reported having had sex with a casual partner in the past three months, not including paid or paying partners. 55% of these youths reported using a condom during the most recent act of sexual intercourse with a casual partner. 13% of the 23% reporting having anal sex in the previous three months with a casual partner used a condom. Very little difference was seen according to race or gender with regard to condom use, intentions to use condoms, or belief about the consequences of using condoms. Beliefs associated with intentions to use condoms with steady partners included protection against sexually transmitted diseases (STD) and beliefs that condoms reduce pleasure, are artificial, unromantic, and interrupt sex. Only the belief that condoms prevent pregnancy was related to intentions to use condoms with casual partners. Pregnancy and STD prevention programs targeted to this population should take these findings into consideration.

Transcutaneous electrical nerve stimulation for postlaparotomy pain.

This study was designed to evaluate the transcutaneous electrical nerve stimulation (TENS) postoperative program administered by a physical therapy department. A surgeon, a physical therapist, a recovery room nurse, and unit nurses participated in the program which included preoperative evaluation and patient education, application of sterile electrodes parallel to the incision in the operating room, TENS activation in the recovery room, follow-up visits, and data collection. Seventy-five patients who underwent laparotomy and received TENS at the most comfortable machine settings were compared by chart review to 75 patients who had undergone similar surgical procedures performed by the same surgeon before TENS postoperative pain management had been instituted. The TENS was applied for an average of five days; machine settings of intensity, frequency, and pulse width tended to be midrange. The TENS group took significantly less pain medication, but the length of hospital stay was not significantly different. Patients with TENS rated their pain on 10-point scales as more intense than uncomfortable. This study demonstrated that a well-structured interdisciplinary program of postoperative TENS management can reduce the amount of pain medication taken by patients after laparotomy.

Methemoglobinemia: the hidden diagnosis.

Although methemoglobinemia is not commonly seen in the ER or the critical care setting, it can be life threatening if unrecognized and left untreated. A detailed case history illustrates the symptoms and some of the possible precipitating factors, and outlines treatment for a successful patient outcome.

Parents' behavioral norms as predictors of adolescent sexual activity and contraceptive use.

The influence of parental factors on adolescent sexual behavior and contraceptive use has been examined previously, and findings have been contradictory. Previous studies, which found little relationship between parental norms and adolescent sexual activity, have been limited by their failure to recognize developmental differences in the relative weight of parent and peer influences between younger and older teens and by use of selected samples, resulting in a restriction of range. The current study differs in that it utilizes a clustered sample household survey of 329 males and females, aged 14 to 17, and 470 of their parents. Using multiple regression analysis, it was found that parents' reported behavioral norms account for 5% of the variance in whether adolescents have had intercourse, and for 33% of the variance in use of contraception at last intercourse. The study suggests that while parents' normative beliefs have limited effect in the decision to become sexually active, they have considerable impact on later contraceptive use.

PIP: The influence of parental factors on adolescent sexual behavior and contraceptive use has been examined previously, and findings have been contradictory. Previous US studies, which found little relationship between parental norms and adolescent sexual activity, have been limited by their failure to recognize developmental differences in the relative weight of parent and peer influences between younger and older teens and by use of selected samples, resulting in a restriction of range. The current study differs in that it utilizes a clustered sample household survey of 329 males and females, aged 14 to 17, and 470 of their parents. Using multiple regression analysis, it was found that parents' reported behavioral norms account for 5% of the variance in whether adolescents have had intercourse, and for 33% of the variance in use of contraception at last intercourse. The study suggests that while parents' normative beliefs have limited effect in the decision to become sexually active, they have considerable impact on later contraceptive use.

An investigation of the effect of 2 sedation regimens on patient mood state following upper extremity surgery using local anesthesia.

Sedation techniques for patients undergoing minor outpatient surgery frequently include a variety of intravenous agents. The present study was designed to look for differential effects of 2 different sedation regimens on perioperative mood states. Twenty-two patients undergoing upper extremity surgery using local anesthesia were randomized to receive either propofol or midazolam intravenously for intraoperative sedation. Subjects were asked to complete a Profile of Mood States survey before and after surgery. The results of this survey were examined for differences in mood between the 2 groups that may be attributable to differences in drug effect. No significant differences were identified between propofol or midazolam regarding their effect on patient mood. Patients in both groups experienced a reduction in perioperative anxiety.

Quantitative Gait Analysis Detects Significant Differences in Movement between Osteoarthritic and Nonosteoarthritic Guinea Pig Strains before and after Treatment with Flunixin Meglumine.

A computer-aided gait analysis system was used to contrast two guinea pig strains with differing propensity for osteoarthritis (OA), with/without administration of a nonsteroidal anti-inflammatory drug. Walking speed and static/dynamic gait parameters were determined at baseline. Flunixin meglumine was given and animals were evaluated 4, 24, and 72 hours after treatment. Body weight was compared using unpaired t-tests. Knee joints were histologically evaluated using species-specific criteria; indices were analyzed using one-way ANOVA, Kruskal-Wallis test, followed by Dunn's multiple comparisons. A generalized linear model followed by Tukey's posttests juxtaposed gait parameters; walking speed was a covariate for other outcome measures. Body weight was not different between strains; OA-prone animals demonstrated more progressive chondropathy. At baseline, OA-prone animals had slower walking speeds, narrower hind limb bases of support, shorter stride lengths, and slower limb swing speeds relative to OA-resistant animals. These differences were not detected 4 or 24 hours after treatment. By 72 hours, OA-prone animals had returned to baseline values. These findings indicate a distinct voluntary gait pattern in a rodent model of bilateral primary OA, modification of which may allow rapid screening of novel therapies. Flunixin meglumine temporarily permitted OA-prone animals to move in a manner that was analogous to OA-resistant animals.

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) when given as a toddler dose to children immunized with PCV7 as infants.

13-Valent pneumococcal conjugate vaccine (PCV13) administered as a 4-dose series in infants, and as a toddler dose in infants previously vaccinated with PCV7 elicited comparable vaccine serotypes IgG responses to the seven common serotypes. PCV13 elicited functional responses to the six additional serotypes in both schedules after the toddler dose. The toddler dose boosted immune responses. The two regimens had comparable safety profiles. A toddler dose of PCV13 given in children previously vaccinated with PCV7 should be effective in preventing pneumococcal disease caused by common serotypes, providing protection against the additional serotypes, and supporting the transition from PCV7 to PCV13.

Occupational biohazards affecting clinical engineers & BMETs. Part V: Skin and urogenital diseases.

BMETs and clinical engineers must be aware of the biological hazards they face in the hospital so they can take precautions to avoid work-related illnesses. A need for educational material on the subject prompted this series of papers examining various biohazards. This paper, the last in the series, reviews a variety of common diseases of the skin and urogenital systems. Common pathogens, their routes of transmission, isolation precautions, and infection control techniques are discussed. The precautions cited are not intended to constitute a full infection control program. Persons interested in further information are advised to contact the infection control officer at their facility, or the Centers for Disease Control.

Occupational biohazards affecting clinical engineers & BMETs. Part IV: Respiratory and gastrointestinal systems.

A previously published survey indicated that clinical engineers and BMETs may not be aware of the scope of biological hazards they may encounter in their work (Baker, 1989). In this third article of a four-part series, various pathogens affecting the respiratory and gastrointestinal systems are discussed. Infection hazards and methods of transmission are examined, and recommendations are provided to help ensure the safety of CEs, BMETs, and patients. The recommendations presented include suggested disinfection procedures for contaminated equipment. Persons interested in further information are advised to contact the infection control officer at their facility, or the Centers for Disease Control.

Airborne transmission of respiratory diseases.

In surveys during the past decade, CEs and BMETs have reported an increasing frequency of respiratory illnesses they believed to be acquired as a result of their occupation. These illnesses varied from mild to severe in terms of long-term prognosis. With the increasing numbers of cases of drug-resistant organisms, respiratory infections are a growing concern for healthcare workers, employers, and government officials. Armed with a better knowledge base about symptoms, transmission and prevention, CEs and BMETs will be more aware of potential biohazardous situations and the necessary personal protective measures to be employed. Both the Occupational Safety and Health Administration (OSHA) and the Centers for Disease Control and Prevention (CDCP) have issued guidelines for preventing airborne transmission of infectious diseases. This paper addresses the respiratory illnesses reported by CEs and BMETs as occupational concerns, as well as briefly discussing potential epidemic pulmonary conditions.