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[Significance of the detection of staphylococcal enterotoxin A gene in low fat milk which caused a serious outbreak of food poisoning].

In June 2000, there was a large-scale outbreak of food poisoning after consumption of Snow Brand low fat milk. In the evening of a day the incident made public, some cartons of low fat milk were brought to our laboratory for examination. Next day, we detected only staphylococcal enterotoxin (SE) A gene among SE (A-E) genes by PCR in left-over milk samples or samples from the same lots that patients had consumed. We presumed that the outbreak was caused by the intake of SEA. We subsequently confirmed the presence of SEA in these samples. To investigate the existence of SE (A-E) genes in milk, we examined 100 samples of commercial low fat milk and milk by PCR, but none of the genes was detected. We estimated the detection limit of SEA gene in low fat milk by PCR. Four strains of SEA-producing Staphylococcus aureus cultures were serially diluted in low fat milk. The SEA gene was detected at levels of 5.5 x 10(2) to 1.6 x 10(4) cfu/mL of S. aureus. These amounts of S. aureus are higher than the values in raw milk reported previously. Therefore we consider that SE genes in low fat milk should usually be undetectable by our PCR. This study shows that quick detection of SE genes by PCR is very helpful to analyze outbreaks, especially if no significant bacterium can be cultured.

Animals↗

Pegasys: software for executing and integrating analyses of biological sequences.

BACKGROUND: We present Pegasys--a flexible, modular and customizable software system that facilitates the execution and data integration from heterogeneous biological sequence analysis tools. RESULTS: The Pegasys system includes numerous tools for pair-wise and multiple sequence alignment, ab initio gene prediction, RNA gene detection, masking repetitive sequences in genomic DNA as well as filters for database formatting and processing raw output from various analysis tools. We introduce a novel data structure for creating workflows of sequence analyses and a unified data model to store its results. The software allows users to dynamically create analysis workflows at run-time by manipulating a graphical user interface. All non-serial dependent analyses are executed in parallel on a compute cluster for efficiency of data generation. The uniform data model and backend relational database management system of Pegasys allow for results of heterogeneous programs included in the workflow to be integrated and exported into General Feature Format for further analyses in GFF-dependent tools, or GAME XML for import into the Apollo genome editor. The modularity of the design allows for new tools to be added to the system with little programmer overhead. The database application programming interface allows programmatic access to the data stored in the backend through SQL queries. CONCLUSIONS: The Pegasys system enables biologists and bioinformaticians to create and manage sequence analysis workflows. The software is released under the Open Source GNU General Public License. All source code and documentation is available for download at http://bioinformatics.ubc.ca/pegasys/.

Computational Biology↗

Coronary artery bypass surgery and minor aortic stenosis--to replace or not to replace?

Seven patients with a mean age of 65 years (range 50-76 years) who had minor aortic valve gradients (less than 25 mmHg) at preoperative cardiac catheterization underwent coronary artery bypass surgery without aortic valve surgery, but required a second operation for aortic valve replacement between five and nine years later because of symptomatic aortic valve stenosis with a valve gradient which had increased to between 60 and 100 mmHg. Serial hemodynamic observations in patients with aortic stenosis have demonstrated that the rate at which stenosis progresses is widely variable. However, replacement of aortic valves at the time of initial coronary artery surgery may subject the patients to an increased risk of operative mortality and prosthetic valve-related complications. On the other hand, the patient may miss the opportunity to obtain maximum benefit from valve replacement before deterioration of left ventricular function, particularly in the presence of coronary artery disease, and there are also the risks of resternotomy. We are currently inclined to replace the aortic valve in coronary patients with asymptomatic aortic stenosis, but our experience is not sufficient to draw final conclusions and the relevant literature does not provide a clear guidance. The aim of this publication is to expose this dilemma.

Aged↗

Longitudinal trends in antiretroviral use in a cohort of men and women in Ontario, Canada.

Initial studies have shown impaired access to antiretrovirals and slower adoption of new therapies by women. It is unclear if similar treatment delays still occur, especially in those with a publicly funded health care system in Ontario, Canada. The objectives of this study were (1) to evaluate longitudinal patterns of antiretroviral use in patients with HIV in Ontario and (2) to determine if gender differences exist in access to and uptake of antiretroviral drugs over time. A retrospective medical chart review was undertaken. One hundred four HIV-positive patients were recruited from nine hospital-based HIV outpatient clinics throughout Ontario. From time of study enrollment in 1999-2001 to the first clinic visit (8.1 +/- 3.2 years; range, 2.3-16.8 years), CD4+ T-cell counts, date of and agents used in initial antiretroviral regimen, and first HAART regimen were evaluated by gender. Kaplan-Meier plots were used to evaluate time to drug initiation from known HIV diagnosis. Serial cross sections of numbers and types of antiretroviral drugs prescribed in March, June, September, and December 1988 to 2001 were also compared as was number of regimens used. There were few differences between men and women in antiretroviral use; both initiated therapy within 2.2 +/- 2.3 years of HIV diagnosis at an average CD4 counts of 300.3 +/- 150.1 cells per microliter. Antiretroviral treatment regimens changed over time, with limited variation by gender. In the period immediately surrounding the first highly active antiretroviral therapy (HAART) recommendations by the U.S. Department of Health and Human Services in July 1997, significantly more antiretroviral drugs were prescribed for men than women. Antiretroviral prescribing in patients attending hospital- based HIV outpatient programs in Ontario is consistent with antiretroviral treatment guidelines over time, without substantial differences in antiretroviral access and use by gender.

Adult↗

Surface plasmon resonance detection of interactions between peptide fragments of N-telopeptide and its monoclonal antibodies.

As populations age, osteoporosis is becoming an important public health care problem. Urinary level of the cross-linked N-telopeptide of type I collagen has been reported to be a sensitive marker of bone resorption. Recently, we synthesized and characterized 10 overlapping peptides covering the N-telopeptide of alpha-2 type I collagen and reported their relative binding response to anti-type I collagen cross-linked N-telopeptide (NTX) antibodies determined by a competitive-inhibition enzyme-linked immunosorbent assay (ELISA). In this study, we design an assay based on the surface plasmon resonance (SPR) technology to detect binding interaction of each peptide fragment of NTX with the anti-NTX monoclonal antibodies. Anti-NTX monoclonal antibodies were immobilized on the surface of sensor chip by amine-coupling procedure. Serial dilutions of each peptide were prepared and injected separately onto the antibodies-immobilized sensor chip. The real-time association and dissociation interactions of each peptide were detected and reported as sensorgrams. Binding response of each peptide to the monoclonal antibodies was determined, and the SPR results were compared with the ELISA results. We demonstrate that the trends of binding potency of peptide fragments detected by SPR are in good correlation to the results obtained by ELISA, indicating that our developed SPR-based method can be further applied to detect the NTX fragments in urine and to monitor the bone loss in humans. The potent peptide fragments identified by both assays are promising for further preparation of specific monoclonal antibodies in order to develop bioassays for bone loss in humans.

Antibodies, Monoclonal↗

Randomized, placebo-controlled trial of nonpegylated and pegylated forms of recombinant human alpha interferon 2a for suppression of dengue virus viremia in rhesus monkeys.

Dengue fever and dengue hemorrhagic fever are caused by infection with any one of the four dengue viruses (DVs) and are significant public health burdens throughout the tropics. Higher viremia levels are associated with greater dengue disease severity. A therapeutic intervention to suppress viremia early in DV infection could potentially ameliorate severe disease. Recombinant alpha interferon 2a (rIFN-alpha-2a, Roferon-A) suppressed DV replication in human peripheral blood mononuclear cells in vitro. We therefore examined the effects of rIFN-alpha-2a and pegylated recombinant IFN-alpha-2a (PEG-rIFN-alpha-2a, PEGASYS) on DV serotype 2 (DV-2) viremia in rhesus monkeys. Flavivirus-naïve monkeys were inoculated with DV-2 and randomized to receive a single dose of rIFN-alpha-2a (10 million international units/m2) versus placebo or PEG-rIFN-alpha-2a (6 microg/kg) versus placebo 1 day after the onset of viremia. Serial daily viremia levels were measured, and convalescent-phase DV-2 neutralizing antibody titers were determined. Compared to placebo, a single injection of rIFN-alpha-2a temporarily suppressed DV-2 replication and delayed the time to peak viremia by a median of 3 days. However, measures of total viral burden were not different between the two groups. A single injection of PEG-rIFN-alpha-2a significantly lowered daily viremia levels and improved virus clearance, starting 48 h after administration. There were no significant differences in DV-2 neutralizing antibody titers between the treatment and placebo groups at 30 and 90 days postinfection. Based on their individual effects, future studies should investigate a combination of rIFN-alpha-2a and PEG-rIFN-alpha-2a for suppression of dengue virus viremia and as a potential therapeutic intervention.

Animals↗

A Delphi approach to reach consensus on primary care guidelines regarding youth violence prevention.

OBJECTIVE: Anticipatory guidance is a cornerstone of modern pediatric practice. In recognition of its importance for child well being, injury prevention counseling is a standard element of that guidance. Over the last 20 years, there has been growing recognition that intentional injury or violence is one of the leading causes of morbidity and mortality among youth. The US Surgeon General identified youth violence as a major public health issue and a top priority. Yet, only recently has the scope of injury prevention counseling been expanded to include violence. Pediatric health care providers agree that youth violence-prevention counseling should be provided, yet the number of topics available, the already lengthy list of other anticipatory guidance topics to be covered, developmental considerations, and the evidence base make the selection of an agreed-on set a considerable challenge. The purpose of this study was to systematically identify and prioritize specific counseling topics in violence prevention that could be integrated into anticipatory guidance best practice. DESIGN: A modified electronic Delphi process was used to gain consensus among 50 national multidisciplinary violence-prevention experts. Participants were unaware of other participants' identities. METHODS: The process consisted of 4 serial rounds of inquiry beginning with a broad open-ended format for the generation of anticipatory guidance and screening topics across 5 age groups (infant, toddler, school age, adolescent, and all ages). Each subsequent round narrowed the list of topics toward the development of a manageable set of essential topics for screening and counseling about positive youth development and violence prevention. RESULTS: Forty-seven unique topics were identified, spanning birth to age 21 years. Topics cover 4 broad categories (building blocks): physical safety, parent centered, child centered, and community connection. Participants placed topics into their developmentally appropriate visit-based schedule and made suggestions for an appropriate topic reinforcement schedule. The resulting schedule provides topics for introduction and reinforcement at each visit. CONCLUSIONS: The Delphi technique proved a useful approach for accessing expert opinion, for analyzing and synthesizing results, for achieving consensus, and for setting priorities among the numerous anticipatory guidance and assessment topics relevant for raising resilient, violence-free youth.

Adolescent↗

Acute hepatitis E in Catania (eastern Sicily) 1980-1994. The role of hepatitis E virus.

Between 1980 and 1994, 540 patients with acute viral hepatitis were admitted to hospital at the Department of Infectious Diseases of Catania (eastern Sicily). Twenty-five patients out of 540 were assessed as having non-A, non-B, non-C hepatitis. These subjects were studied for anti-HEV IgM and IgG seroprevalence by testing serial serum samples collected 1, 4, 12 and 24 weeks after the onset of acute disease. Fourteen of 25 samples (56%) seroconverted to anti-HEV IgG antibodies. No sample was positive for anti-HEV IgG at week 1, ten samples were positive at week 4 and the remainder at week 12. Anti-HEV reactivity was maintained until week 24 in all cases. In 11 of the 14 patients seroconverting to anti-HEV, the presence of IgM anti-HEV was found, which appeared in the sample from week 1 and gradually disappeared thereafter. Identified risk factors for HEV transmission included travel in the tropics and shellfish ingestion (anti-HEV positive versus anti-HEV negative: p < 0.05). HEV-related hepatitis is not yet a major public health problem in Sicily but, from our data, the trend of its incidence is clearly upwards. The high incidence of faecally-orally transmitted diseases in Sicily, the crucial position of Sicily in the middle of the Mediterranean Sea (where HEV largely circulates) and the increase of migration from developing countries are all factors which should increase awareness for a more active surveillance of the spread of HEV in our area.

Acute Disease↗

Bronchiolitis obliterans syndrome in popcorn production plant workers.

Following sentinel case recognition, an excess of fixed airways obstruction was found among current workers in a microwave popcorn plant associated with butter flavouring exposures. In order to characterise the clinical presentation of sentinel cases, the medical records of sentinel cases were reviewed, interviews conducted and serial spirometric testing performed. Cases worked in microwave popcorn production, and five of the nine cases had mixed flavourings. Most had never smoked or smoked minimally. Cases showed onset of cough, shortness of breath and wheezing 5 months to 9 yrs after starting work at the popcorn plant. Initial forced expiratory volume in one second ranged 14.0-66.8% of the predicted value. Eight high-resolution computed tomography scans showed marked bronchial wall thickening and mosaic attenuation with air trapping. Open lung biopsy results were consistent with, or diagnostic of, constrictive bronchiolitis in two of three cases. Five cases are on lung transplantation waiting lists. After leaving employment, nearly all cases experienced stabilisation of their lung function within 2 yrs. Astute clinicians can help identify new causes of airways obstruction by alerting public health authorities to unexplained disease cases occurring in groups of workers.

Adult↗

Advances in HIV treatment and treatment toxicities.

Among the different classes and complexities of antiretroviral regimens, maximal viral suppression, sustained durability, increased CD4 count, decreased evolving resistance, and fewer side effects combined with increased compliance resulting in decreased morbidity and mortality remain the goals of therapy. Serial viral load measurements help best guide the direction of therapy. According to the CDC 20% fewer people died of HIV in 1998 compared to 1997 in the United States. HAART, although expensive (sometimes exceeding $20,000 per year), is not readily available to 95% of the estimated 36 million HIV-infected people in the world. HAART therapy commonly consists of two NRTIs and a protease inhibitor, but other combination regimens exist. The disadvantage of HAART therapy is that antiretroviral agents are not virucidal, thus eradication with these drug cocktails cannot be achieved. When HAART therapy is stopped, viral loads return to pre-treatment levels. New drug classes under investigation may completely prevent fusion between the HIV virus and healthy cells. For now, the epidemic can only be controlled with good public awareness, such as education, condom use, or abstinence. Because a cure does not seem immediately foreseeable, an effective prophylactic vaccine may afford protection. Defined treatment regimens exist for occupational postexposure prophylaxis. Ultimately, an expert in the field should be involved in manipulating drug regimens; however, dermatologists remain an integral part of the health care team because most HIV patients experience cutaneous manifestations related either to their HIV or to their drug therapy.

Anti-HIV Agents↗

Safety of long-term treatment with HFA albuterol.

BACKGROUND: Chlorofluorocarbons (CFCs) used as propellants in metered-dose inhalers deplete stratospheric ozone, which results in serious public health concerns. Albuterol has been reformulated in the non-ozone-depleting propellant, hydrofluoroalkane-134a (HFA albuterol). OBJECTIVES: The primary objective was to compare the safety of HFA albuterol to an albuterol product formulated in chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in asthmatics. Bronchodilator efficacy of the two products was assessed as a secondary objective. METHODS: The results from two open-label, parallel-group trials of similar design in asthmatics requiring short-acting beta-agonists for symptom control were combined. Patients took two puffs bid of either HFA albuterol or CFC albuterol for 1 year. Additional puffs of study drug were allowed as needed to control asthma symptoms. Adverse events were recorded at clinic visits. Patients self-administered study drug at quarterly visits and underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve. Differences between products and changes over time in efficacy variables were assessed using an analysis of variance model. Regression analyses with FEV1 as a covariate were performed post-hoc to analyze changes in bronchodilator efficacy over time. RESULTS: Demographic and baseline characteristics were similar for patients receiving HFA albuterol (n = 337) and CFC albuterol (n = 132). Total reported adverse events were similar for the two treatments. Differences in only four individual adverse events were noted: the HFA albuterol group reported more gastroenteritis and dizziness; the CFC albuterol group reported more epistaxis and expectoration. Adverse events attributed to study drug use were infrequent. No serious adverse events were related to study drug use. Predose FEV1 at quarterly visits increased to a small extent in both groups from month 0 to month 12. The bronchodilator efficacy of HFA albuterol was comparable to that of CFC albuterol at the quarterly visits, but decreased from baseline for both products over the 12 months of treatment. Use of inhaled corticosteroids, nasal corticosteroids, or theophylline did not explain the increase in predose FEV1 over time and did not protect patients from developing reduced bronchodilator efficacy by month 12. The change in predose FEV1 did not entirely account for the reduced bronchodilator efficacy over time. CONCLUSIONS: HFA albuterol has a safety profile similar to that of CFC albuterol during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol and CFC albuterol provided comparable bronchodilator efficacy, but bronchodilator efficacy decreased for both products with 1 year of use.

Administration, Inhalation↗

Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1.

In situ hybridization (ISH) of human glioblastoma tissue sections revealed expression of interleukin-1 (IL-1)alpha and/or beta and IL-1 receptor types I and II (IL-1R I and II) in the majority of cases evaluable. To understand the function of IL-1-family members in human glioblastomas, we have studied 6 glioblastoma cell lines. RT-PCR, ISH, ELISA and 125I-IL-1-binding assays revealed expression of IL-1 and high-affinity receptors for human (h)IL-1 in all but 1 cell line. Using a colony growth assay in semi-solid media for testing serial plating efficacy (PE, number of colonies per number of cells seeded in %), only the IL-1R-negative cell line was not influenced by recombinant human (rh)IL-1alpha or -beta, whereas IL-1 down-regulated the self-renewal of clonogenic cells of the other glioblastomas. Tritiated thymidine uptake was down-regulated by rhIL-1 in all cell lines studied. Cell viability remained unchanged by rhIL-1. Wherever growth modulation by rhIL-1 was detected, it could be reversed by either soluble IL-1R I or II or by rhIL-1 receptor antagonist (ra). IL-1ra not only was able to reverse rhIL-1-induced growth modulation but alone could modulate glioblastoma growth in comparison with control in cell lines producing IL-1. Our results show the presence of public autocrine loops for IL-1 leading to growth inhibition in some glioblastomas. To understand these loops, we have studied expression and function of IL-1ra in glioblastomas. ISH of human glioblastoma tissue sections revealed expression of hIL-1ra in all 8 cases evaluable. In 4 of 6 cell lines, IL-1ra was found in the supernatant under constitutive conditions, the IL-1R-negative line being among the 2 non-producers. The other non-producing cell line, HTB 17, showed expression of hIL-1R II. Most interestingly, a neutralizing antibody against IL-1ra down-regulated growth of IL-1- and IL-1ra-producing glioblastoma cells to approx. 30% of the controls. Thus, public autocrine loops for IL-1 in human glioblastomas exist and result in growth inhibition. An autocrine production of IL-1-antagonizing molecules such as IL-1ra by these tumors can counteract this IL-1 function and represent a basic escape mechanism supporting malignant growth in some glioblastomas.

Binding Sites↗

Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle.

A human-derived strain of the agent of human granulocytic ehrlichiosis, a recently described emerging rickettsial disease, has been established by serial blood passage in mouse hosts. Larval deer ticks acquired infection by feeding upon such mice and efficiently transmitted the ehrlichiae after molting to nymphs, thereby demonstrating vector competence. The agent was detected by demonstrating Feulgen-positive inclusions in the salivary glands of the experimentally infected ticks and from field-derived adult deer ticks. White-footed mice from a field site infected laboratory-reared ticks with the agent of human granulocytic ehrlichiosis, suggesting that these rodents serve as reservoirs for ehrlichiae as well as for Lyme disease spirochetes and the piroplasm that causes human babesiosis. About 10% of host-seeking deer ticks were infected with ehrlichiae, and of these, 20% also contained spirochetes. Cotransmission of diverse pathogens by the aggressively human-biting deer tick may have a unique impact on public health in certain endemic sites.

Animals↗

Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection.

Malignant mesothelioma (MM) is associated with asbestos exposure and the presence of SV40 viral sequences. Recently, we reported that SV40 infection of human mesothelial cells (HM) causes aberrant methylation of the tumor suppressor gene (TSG) RASSF1A. We investigated methylation of 12 genes by methylation-specific PCR in 63 MMs, six MM cell lines, and two foci of SV40-infected HM. Methylation percentages of the tested genes ranged from 3 to 65%. The frequencies of HPP1, RASSF1A, Cyclin D2, and RRAD methylation, and the value of the methylation index, were significantly higher in SV40 sequence-positive MMs than in SV40-negative MMs. Methylation of TMS1 and HIC-1 was associated with shortened survival. SV40-infected HM showed progressive aberrant methylation of seven genes (RASSF1A, HPP1, DcR1, TMS1, CRBP1, HIC-1, and RRAD) during serial passage. Our results demonstrate a relationship between SV40 and methylation of multiple genes in MM, indicating that the virus plays a role in the pathogenesis of MM.

Cell Line, Tumor↗

Levels of prothrombin activation peptide F1+2 in patients with a bleeding tendency.

Numerous recent publications point to significant improvements in haemostasis in the bleeding patient suffering from haemophilia with inhibitors when a recombinant activated factor VII (rFVIIa) molecule is administered in high doses. In theory, activated factor VII (FVIIa) is believed to initiate haemostasis through its physiological interaction with tissue factor at sites of cellular injury, whereby factor X (FX) activation and, in consequence, thrombin formation is amplified. There has been speculation, however, whether high circulating FVII procoagulant (FVII:C) levels may induce systemic coagulation activation. The present retrospective investigation was undertaken to study, ex vivo, the influence of treatment with rFVIIa as assessed by the sensitive marker of prothrombin conversion, prothrombin fragment F1+2, in plasma samples. Study subjects consisted of: seven people suffering from thrombocytopenia participating in a study of the influence of rFVIIa on the bleeding time, in whom serial plasma samples had been collected before and subsequently at 10, 60 and 180 min after infusion of rFVIIa; four haemophilia A patients with inhibitors to FVIII undergoing surgery; two haemophilia A patients with inhibitors treated with rFVIIa for minor bleedings on 16 occasions in whom plasma samples had been collected before and 10-15 min after rFVIIa infusion; and two FVII-deficient patients undergoing treatment with rFVIIa. A group of seven haemophilia A patients with no signs of inhibitors subjected to a pharmacokinetic study of a plasma-derived FVIII concentrate served as controls. In the group of thrombocytopenic patients our results showed a mean increase in F1+2 following doses of 50 microg/kg body weight and 100 microg/kg body weight of rFVIIa of 1.1 and 1.4 nmol/l, respectively, with a gradual increase over time, but there was no significant correlation between FVII:C and the corresponding values of F1+2. During and after haemophilic inhibitor surgery, a mean increase in F1+2 of 1.44 nmol/l (range 0.6-3.2 nmol/l) was found, whereas 16 matched samples collected during treatment for minor bleedings showed a mean increase in F1+2 of 0.10 nmol/l (range -0.12 to 0.20 nmol/l). In FVII-deficient individuals, the mean rise in F1+2 was <0.10 nmol/l. In the control group, the mean elevation of F1+2 was 0.13 nmol/l (range -0.5 to 0.7 nmol/l). Hence, our results show that only discrete changes in F1+2 follow administration of rFVIIa.

Adult↗

Effect of Herbst treatment on temporomandibular joint morphology: a systematic literature review.

The purpose of this systematic review was to evaluate the effect of Herbst appliance therapy on temporomandibular joint (TMJ) morphology, with special reference to glenoid fossa remodeling, condylar remodeling, condylar position, and articular disc position. Publications of controlled trials of Herbst treatment of Class II patients using magnetic resonance imaging (MRI), computerized tomography scans, or tomography to assess TMJ morphology were identified with Medline (1966-2001), Best Evidence (1991-2001), Cochrane Database of Systematic Reviews (second quarter, 2001), and Embase (1998-2001). Case reports were excluded. Based on our search, only 5 studies met the selection criteria. All studies used internal controls with pretreatment and posttreatment imaging. Four studies used MRI, and 1 used tomograms. The 4 MRI studies used overlapping patient samples and were not considered as independent evidence. The MRI studies did not provide conclusive evidence of osseous remodeling or condyle position change. The tomography study demonstrated minor condyle position change. Methodological deficiencies prevented major conclusions regarding disc position. The reviewed studies highlight the importance of further research. Prospective controlled studies using serial MRI and tomography are required to establish the effect of Herbst treatment on TMJ morphology.

Bone Remodeling↗

Failure of prophylactically administered phenytoin to prevent late posttraumatic seizures.

This randomized double-blind placebo-controlled study was undertaken in a series of 179 patients to determine whether phenytoin administered soon after head injury lessens the incidence of late posttraumatic epilepsy. When delayed hypersensitivity to phenytoin developed, the patient was switched to phenobarbital. The patients were followed for 18 months to detect the occurrence of seizures and to serially measure plasma phenytoin concentrations. There was no significant difference in the percentage of patients having late seizures in the treated and placebo groups (p = 0.75). The time between injury and seizures did not significantly differ between the two groups. The results provide no support for the continued use of phenytoin in the low therapeutic range for prophylaxis against late posttraumatic seizures. It cannot be concluded that higher phenytoin plasma concentrations and higher compliance rates than obtained in this study would not have significantly decreased the occurrence of late posttraumatic epilepsy. The finding that no patient with a phenytoin plasma concentration of 12 microgram/ml or higher had a seizure raises the question of whether phenytoin in blood concentrations in higher therapeutic ranges might lessen the occurrence of posttraumatic epilepsy, and should be studied further. Posttraumatic epilepsy is a major public health problem deserving a large cooperative trial to determine if phenytoin at higher blood levels than obtained in this study, or other currently available or newly developed drugs, can prevent the occurrence of posttraumatic epilepsy.

Adolescent↗

Seasonal variation in mortality in Scotland.

BACKGROUND: Seasonal patterns in mortality have been recognized for many years. This study assesses seasonal variation in mortality in Scotland between 1981 and 1993 and considers its association with socioeconomic status and outdoor temperature. METHODS: Lagged Poisson regression analysis of numbers of deaths and average weekly temperature with adjustment for serial autocorrelation and influenza epidemics. RESULTS: There was significant seasonal variation in weekly death rates with a difference of about 30% between a summer trough and a winter peak. This variation was principally attributable to respiratory disease, cerebrovascular disease and coronary artery disease. Seasonal variation in mortality fell from around 38% in 1981-1983 to around 26% in 1991-1993. There was no clear evidence of a relationship between socioeconomic status and seasonal mortality, however the extent of the fall in seasonal variation was greater in deprived areas than in affluent areas. Overall, a 1 degree C decrease in mean temperature was associated with a 1% increase in deaths one week later. The lag in this relationship varied by cause of death and underlying temperature. CONCLUSIONS: Seasonal variations in mortality and the relationship between temperature and mortality are a significant public health problem in Scotland. It is likely that the strength of this relationship is a result of the population being unable to protect themselves adequately from the effects of temperature rather than the effects of temperature itself.

Adolescent↗