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Biomedical subjects

J Bennett

Publications and source records attributed to J Bennett.

At least 91 records · Page 5Linked to original sources
PubMed1999

bcl-2 gene therapy exacerbates excitotoxicity.

The protooncogene bcl-2 can block neuronal death from both naturally occurring apoptosis and exogenous insults. bcl-2 is therefore a promising candidate for the prevention of excitotoxic neuronal death. Using an adeno-associated viral vector, we delivered the bcl-2 gene to the ganglion cell layer of the rat eye. We hypothesized that infection with bcl-2 would protect ganglion cells against excitotoxic cell death. However, retinal infection with bcl-2 increased ganglion cell susceptibility to both axonal injury and intravitreal NMDA. Our study--intended to explore the possibility of bcl-2 transduction as an in vivo therapeutic approach--revealed a deleterious effect of bcl-2 transduction.

Animals↗
PubMed1999

Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa.

BACKGROUND: Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children. METHODS: Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound. FINDINGS: Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months. INTERPRETATION: Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

Adolescent↗
PubMed1999

Results of a randomized double-blind placebo-controlled trial evaluating sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy with or without granulocyte/macrophage-colony-stimulating factor in high-risk myelodysplastic syndromes.

A prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the impact of granulocyte/macrophage-colony-stimulating factor (GM-CSF) on the efficacy of sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy (S-HAM) in adult patients with high-risk myelodysplastic syndromes (MDS). GM-CSF or placebo was given subcutaneously once daily at a dose of 250 microg/m2, starting 48 h prior to chemotherapy, and continued until neutrophil recovery. Owing to high toxicity and slow patient recruitement the study was closed and unblinded after 31 patients had been enrolled; 15 were randomized to receive placebo and 16 to receive GM-CSF. A total of 29 patients were evaluable for response; their median age was 57 years. Ten patients achieved a complete remission (34.5%), 9 patients had persistent MDS (31%), 10 patients died within 6 weeks after the onset of treatment (early death) (34.5%). The median remission duration was 190 days (range: 2.5-45 months). Among the 29 evaluable patients no significant differences could be found between the two study arms regarding complete remission rate [GM-CSF: 31% (5/16) versus placebo: 38% (5/13) P = 0.45], rate of persistent MDS [GM-CSF: 25% (4/16) versus 38% (5/13) P = 0.35), early death rate [44% (7/16) versus 23% (3/13) P = 0.22] and remission duration (GM-CSF: 87 days versus placebo 221 days). Duration of granulocytopenia (median: 33 days with GM-CSF) versus 35 days with placebo) and frequency of infectious episodes were not significantly influenced by GM-CSF. The small number of patients finally analyzed means that no definite conclusions about the effect of GM-CSF can be reached.

Adult↗
PubMed1999

Bacterial resistance and antibiotic use in the emergency department.

Antibiotic resistance among bacteria that are commonly encountered in the pediatric emergency department is a fact of nature. New antibiotics will provide some help, but probably only temporarily. Vaccine strategies seem to provide the best answer to resistance, and many physicians eagerly await the conjugated pneumococcal vaccines, which we can only hope to be as successful as the H. influenzae type b vaccines. Vaccines against other resistant organisms are likely further off. At this point, a major goal must be to limit the prevalence of antibiotic resistance. In considering this goal, two complementary strategies are key. The first is to avoid antibiotics in situations in which they are unlikely to provide benefit, such as for colds, URIs, and bronchitis. The second is to use narrow-spectrum antibiotics as much as possible to minimize selective pressure. Emerging evidence shows that these strategies can be effective. In a day-care center in Omaha, Nebraska, Boken et al showed that nasopharyngeal carriage of highly resistant S. pneumoniae decreased dramatically among attendees when antibiotic use decreased. In Iceland, a nationwide campaign that resulted in decreased antibiotic use was followed by a decrease in the incidence of penicillin-resistant pneumococcal infections from 20.0% to 16.9% and a decrease in the rate of carriage of resistant pneumococci among day-care-center attendees from 49% to 15%. In Finland, erythromycin resistance in Group A streptococci recovered from pharyngeal and pus samples had reached 13% in 1990. National guidelines that recommended a reduction in the use of erythromycin and other macrolide antibiotics in the treatment of outpatients with respiratory and skin infections were instituted, and by 1996, macrolide antibiotic consumption had decreased by 50%, with a similar 50% decrease in frequency of erythromycin-resistant isolates. In the absence of such national strategies, it is incumbent on physicians treating infections on a daily basis in the emergency department to consider carefully the judicious use of antibiotics.

Anti-Bacterial Agents↗
PubMed1999

Persistent transgene product in retina, optic nerve and brain after intraocular injection of rAAV.

Recombinant adeno-associated virus (rAAV) is a promising vector for retinal application as it transduces photoreceptors and retinal pigment epithelium cells efficiently and in a stable fashion. Because rAAV also transduces retinal ganglion cells, we reasoned that ocular application of rAAV might result in delivery of transgenic protein to the CNS. Here we describe high levels of green fluorescent protein (GFP) persisting at least 6 months in optic nerves and brains of mice and dogs after intravitreal delivery of rAAV-GFP. There was no clinical or histological evidence of inflammatory response although a mild humoral Th-2 response to viral capsid proteins was detected. These findings have important implications with respect to therapeutic applications of rAAV.

Animals↗
PubMed1999

Perioperative rehydration in ambulatory anesthesia for dentoalveolar surgery.

OBJECTIVE: Patient recovery after anesthesia is dependent not only on the lingering pharmacologic effects of sedatives but also on the physiologic effects that patients experience after surgery. Preoperative fasting results in a perioperative dehydration that may contribute to these physiologic effects, resulting in complaints of headache, nausea, vomiting, fatigue, lightheadedness, dizziness, and thirst. The purpose of this study was to investigate the effects of perioperative hydration in the ambulatory oral and maxillofacial surgery patient who receives deep sedation or general anesthesia (nonintubated). STUDY DESIGN: This was a prospective, randomized, blinded study that administered either a high volume (16-17 mL/kg) or a low volume (1-2 mL/kg) of an isotonic solution to each of 77 patients who were scheduled to have their third molars extracted with deep sedation or general anesthesia. Each patient completed 3 postoperative questionnaires designed to evaluate potential adverse outcomes. RESULTS: Nonparametric analysis of the data demonstrated a more favorable outcome with respect to subjective feelings for the high volume hydration group; this was evident both during the immediate postoperative period and in the evening of the day of surgery, and it persisted into the first postoperative day. CONCLUSIONS: This study demonstrated that appropriate perioperative rehydration decreases postoperative adverse outcomes and improves the patient's perception of the postoperative period.

Ambulatory Surgical Procedures↗
PubMed1999

A nasopalatine cyst in an 8-year-old child.

The nasopalatine cyst (NPC) was first described in 1914 and it is considered the most common non-odontogenic cyst. Most studies show a higher incidence of NPC among males than females, with a male/female ratio of 1.7:1. The majority of the cases described in people in their fifth decade involve Afro-Caribbeans, while those in their sixth decade are mainly caucasians. These cysts are normally asymptomatic, unless they are infected. The most commonly reported clinical symptom is swelling in the anterior part of the palate. The treatment of choice is enucleation. Even though it has been stated that NPCs may occur at any age no reports have been made on children less than 9 years old. Some reports support a predisposition in young Afro-Caribbeans, where NPCs appear to be more aggressive, larger and symptomatic. We present a case of a NPC in an 8-year-old caucasian female.

Child↗
PubMed1999

Position of the internal jugular vein in children. A study of the anatomy using ultrasonography.

The relative anatomy of the internal jugular vein (IJV) was studied in 25 patients undergoing cardiac catheterization under general anaesthesia, with the use of a portable ultrasound probe. In 14 of cases the IJV was anterior, 1 anterolateral and in 10 lateral to the carotid artery between the two heads of the sternocleidomastoid muscle. At the level of the cricoid cartilage, in six cases the IJV was anterior, three anterolateral and in 16 of children the IJV was lateral to the carotid artery. When attempting to cannulate the IJV, because of the variability in relationship of the IJV to CA the technique used should be modified depending upon the level at which cannulation is attempted. The position of the IJV in the child appears to be so variable extra care should be taken when cannulating the IJV and it should not be assumed that the techniques used in adults are directly transferable.

Adolescent↗
PubMed1999

Caring for people with HIV in Zambia: are traditional healers and formal health workers willing to work together?

This study of traditional healers and formal health workers determined their knowledge and practices in the field of HIV/AIDS and examined their training needs and attitudes to collaboration, in preparation for planning joint training workshops. Several misconceptions concerning symptoms and transmission of HIV disease were found in both groups, particularly among traditional healers. Twenty healers (51%) and four formal health workers (15%) claimed a cure existed for AIDS. The majority of traditional healers interviewed expressed difficulties discussing a diagnosis of HIV directly with patients, mainly due to fear of the patient becoming depressed and suicidal. Most interviewees wanted more training--the majority of traditional healers in recognizing symptoms of HIV/AIDS and their treatment, and the majority of formal health workers in HIV counselling. Most were interested in supplying condoms. Almost all healers and half of the formal health workers were keen to collaborate in training and patient care. The study indicates that there is willingness amongst Zambian traditional healers and formal health workers to collaborate in training and patient care in the field of HIV/AIDS. As well as covering symptoms, transmission and prevention of HIV/AIDS, training should aim to increase ability to openly discuss HIV with patients, which many traditional healers and some formal health workers find difficult. Involving traditional healers in supplying condoms may improve acceptability and availability, particularly in rural areas.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Seroconversions in unvaccinated infants: further evidence for subclinical measles from vaccine trials in Niakhar, Senegal.

BACKGROUND: Increases in measles antibodies without rash-illnesses have been documented in previously vaccinated children exposed to measles cases. The phenomenon has been incompletely evaluated in young unvaccinated infants with immunity of maternal origin. METHODS: Monthly cohorts of newborns were prospectively randomized to vaccine and placebo control groups during a trial of high-titre vaccines in Niakhar, Senegal. Measles antibodies were assayed in blood samples of enrolled children collected at 5 months old, when controls received a placebo injection, and at 10 months, when the placebo group was given measles vaccine. Intensive prospective surveillance for measles was conducted throughout the trial. RESULTS: One-fifth (n = 53) of the placebo controls seroconverted, with known exposure to a measles case in only three of them. None of the seroconverters developed a measles-like rash. Sixteen-fold or greater increases in titres were noted in about one-quarter of them. Compared with placebo controls who did not seroconvert, seroconverters were more likely to have had exposure to a measles case and to travel, more likely to be boys than girls, and had significantly lower baseline antibody titres. Measles was endemic in the study area throughout the trial. Seroconversions did not adversely effect subsequent nutritional indices or mortality. CONCLUSIONS: Although laboratory errors and inadvertent injection of vaccine rather than placebo may have played some role, they do not fully explain the above observations, which are consistent with subclinical measles in the seroconverters. The possible role of subclinical measles in occult transmission, its potential effect on the type and duration of subsequent immunity, and its impact on response to primary vaccination need to be determined.

Analysis of Variance↗
PubMed1999

Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics.

BACKGROUND: Previous case-control studies have paradoxically suggested that circumcisions protect against neonatal tetanus (NNT), but these observations have not been adjusted for differences in the length of survival of cases and controls. METHODS: Boy cases (n = 133) and their sex-matched controls (n = 399) were extracted from a population-based study of NNT undertaken in Punjab Province, Pakistan. In the resulting file, circumcisions were censored such that analysis was restricted to only those that occurred before onset in cases or before age of onset in the matched case for controls. The effect of topical antibiotics in circumcision wounds was then evaluated. RESULTS: After adjusting for confounders, circumcision before onset posed a significant risk for NNT (matched odds ratio [OR] = 3.1, 95% CI: 1.2-8.0). The risk of NNT in those circumcised before onset and treated with topical antibiotics did not differ significantly from the referent group who had not been circumcised before onset (matched OR = 1.1, 95% CI: 0.2-6.8), whereas the lack of topical use was associated with significant risk (matched OR = 4.2, 95% CI: 1.4-12.6). This suggests that topical antibiotics are likely to be highly effective in preventing NNT from circumcision wounds. We estimated an overall risk of about 16 fatal NNT cases per 1000 live boy births with circumcision wounds that were not protected by topical antibiotics, and that circumcision and umbilical wounds each accounted for about half of this overall risk in these boys. CONCLUSIONS: Topical antibiotics should be routinely applied to all wounds created by traditional circumcisions, to prevent NNT and sepsis from these frequently unsterile procedures.

Administration, Topical↗
PubMed1999

Neonatal tetanus associated with topical umbilical ghee: covert role of cow dung.

BACKGROUND: Previous studies in Pakistan have shown that ghee (clarified butter) is commonly applied to umbilical wounds of neonates, and have documented that such applications are a risk factor for neonatal tetanus (NNT). In-use contamination of ghee with Clostridium tetani has been demonstrated, but mechanisms underlying the risk of ghee have been incompletely evaluated epidemiologically. METHODS: Detailed information on ghee usage, including fuels used to heat it, was obtained from cases of NNT (n = 229) and their matched controls (n = 687) from a population-based study of NNT in Punjab Province, Pakistan. Design variables were created to evaluate the impact of different fuel sources on risk of ghee applications. RESULTS: Nearly one-third of all infants had ghee applied, and it was nearly always heated before application to umbilical wounds of newborns. After controlling for all factors found to be significantly associated with NNT in conditional logistic regression, only ghee that had always been heated with dried cow dung fuel was significantly associated with NNT. Topical antimicrobials and ghee were never applied together. CONCLUSIONS: Ghee applications to umbilical wounds, when heated with 'clean' fuels, appear to pose no increased risk of NNT, although handling practices undoubtedly result in hazardous microbial contamination. In contrast, ghee heated with dung fuel was significantly associated with NNT. The effective promotion of topical antimicrobials might help reduce ghee use, since the intended purpose of each is to enhance healing.

Administration, Topical↗
PubMed1999

Ulnar nerve pressure: influence of arm position and relationship to somatosensory evoked potentials.

BACKGROUND: Although the ulnar nerve is the most frequent site of perioperative neuropathy, the mechanism remains undefined. The ulnar nerve appears particularly susceptible to external pressure as it courses through the superficial condylar groove at the elbow, rendering it vulnerable to direct compression and ischemia However, there is disagreement among major anesthesia textbooks regarding optimal positioning of the arm during anesthesia. METHODS: To determine which arm position (supination, neutral orientation, or pronation) minimizes external pressure applied to the ulnar nerve, we studied 50 awake, normal volunteers using a computerized pressure sensing mat. An additional group of 15 subjects was tested on an operating table with their arm in 30 degrees, 60 degrees, and 90 degrees of abduction, as well as in supination, neutral orientation, and pronation. To determine the onset of clinical paresthesia compared to the onset and severity of somatosensory evoked potential (SSEP) electrophysiologic changes, we studied a separate group of 16 male volunteers while applying intentional pressure directly to the ulnar nerve. Data are presented as mean (median; range). RESULTS: Supination minimizes direct pressure over the ulnar nerve at the elbow (2 mmHg [0; 0-23]; n = 50), compared with both neutral forearm orientation (69 mmHg [22; 0-220]; P < 0.0001), as well as pronation (95 mmHg [61; 0-220]; P < 0.0001). Neutral forearm orientation also results in significantly less pressure over the ulnar nerve compared to pronation (P < or = 0.04). The estimated contact area of the ulnar nerve with the weight-bearing surface was significantly (P < 0.0001) smaller in the supine position (2.2 cm2 [0.5; 0-9]; n = 50) compared with both neutral orientation (5.5 cm2 [5.0; 0-13]) and pronation (5.8 cm2 [6; 0-12]). With the forearm in neutral orientation, ulnar nerve pressure decreased significantly (P < or = 0.01; n = 15) as the arm was abducted at the shoulder from 0 degrees to 90 degrees. In the 16 male subjects tested, notable alterations in ulnar nerve SSEP signals (decrease > or = 20% in N9-N9' amplitude) were detected in 15 of 16 awake males during application of intentional pressure to the ulnar nerve. However, eight of these subjects did not perceive a paresthesia, even as SSEP waveform amplitudes were decreasing 23-72%. Two of these eight subjects manifested severe decreases in SSEP amplitude (> or = 60%). CONCLUSIONS: Extrapolating these results to the clinical setting, the supinated arm position is likely to minimize pressure over the ulnar nerve. With the forearm in neutral orientation, pressure over the ulnar nerve decreases as the arm is abducted between 30 degrees and 90 degrees. In addition, up to one half of male patients may fail to perceive or experience clinical symptoms of ulnar nerve compression sufficient to elicit SSEP changes.

Adult↗
PubMed1999

Increased long term mortality associated with rash after early measles vaccination in rural Senegal.

OBJECTIVES: To examine whether clinical symptoms, including rash, were more common after measles immunization compared with placebo and to study the association between postvaccination symptoms and later mortality. DESIGN: Examination of side effects in the 3 weeks after immunization in a trial of high titer and standard titer measles vaccines. PATIENTS: Two hundred twenty-four children randomly selected to be included in the surveillance for diarrhea, fever and rash. RESULTS: There was no difference in fever and diarrhea between recipients of high titer vaccines and recipients of placebo. However, high titer recipients tended to have more measles-like rashes than placebo recipients [relative risk, 2.12 (range, 0.90 to 5.03)]. Among recipients of high titer vaccines, children who presented a rash had higher mortality in the following 5 to 7 years than those who did not develop rash [mortality rate ratio, 3.85 (range, 1.52 to 9.79)]. High titer recipients without a rash had the same mortality as children in the placebo group who were given standard doses of measles vaccine at 10 months of age [mortality rate, 0.76 (range, 0.35 to 1.62)]. CONCLUSIONS: These observations suggest that in this particular study, rash after high titer measles vaccine may identify children who received a particularly high dose of vaccine or children with more severe and persistent postvaccination immunosuppression. Whether high titer vaccine is more likely than standard titer measles vaccine to provoke such reaction is not known, given that we did not compare side effects after different titers of measles vaccine. Future trials of live measles vaccine should monitor the development of rash.

Cause of Death↗
PubMed1999

Poor serologic responses five to seven years after immunization with high and standard titer measles vaccines.

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.

Antibodies, Viral↗
PubMed1999

Medication adherence in rheumatoid arthritis patients: older is wiser.

OBJECTIVES: To create a profile of individuals nonadherent to their medications in an age-stratified sample (ages 34-84) of community-dwelling rheumatoid arthritis patients. The relative contributions of age, cognitive function, disability, emotional state, lifestyle, and beliefs about illness to nonadherence were assessed. DESIGN: A direct observation approach was used in conjunction with structural equation modeling. All participants were administered a preliminary assessment battery. Medications were then transferred to vials with microelectronic caps that recorded medication events for all medications for the next 4 weeks. PARTICIPANTS AND SETTING: A volunteer sample of 121 community-dwelling rheumatoid arthritis (RA) patients were recruited from newspaper ads, posters, and via informal physician contact from private rheumatology practices in Atlanta and Athens, Georgia. Written verification of the RA diagnosis and a disease severity rating were obtained from personal physicians before patients were enrolled in the study. Patients were tested in a private physician's office, and their medication adherence was monitored electronically for a month in their every-day work and home settings. MEASUREMENTS AND RESULTS: Structural equation modeling techniques were used to develop a model of adherence behavior. Cognitive and psychosocial measures were used to construct latent variables to predict adherence errors. The model of medication adherence explained 39% of the variance in adherence errors. The model demonstrated that older adults made the fewest adherence errors, and middle-aged adults made the most. A busy lifestyle, age, and cognitive deficits predicted nonadherence, whereas coping with arthritis-related moods predicted adherence. Illness severity, medication load, and physical function did not predict adherence errors. Omission of medication accounted for nearly all errors. CONCLUSION: Despite strong evidence for normal, age-related cognitive decline in this sample, older adults had sufficient cognitive function to manage medications. A busy lifestyle and middle age were more determinant of who was at risk of nonadherence than beliefs about medication or illness. Thus, practicing physicians should not assume that older adults have insufficient cognitive resources to manage medications and that they will be the most likely to make adherence errors. Very busy middle-aged adults seem to be at the greatest risk of managing medications improperly.

Adaptation, Psychological↗