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Carotid endarterectomy in nonagenarians.

HYPOTHESIS: The North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial demonstrated that a greater benefit from carotid endarterectomy (CEA) was seen in elderly compared with younger patients. However, no patients older than 89 years were included in either study. We hypothesized that CEA is safe and effective in patients 89 years and older. DESIGN AND SETTING: This is a retrospective review of 3 neurosurgeons' CEA experience with nonagenarian patients. PARTICIPANTS AND INTERVENTIONS: Of our 1800 patients who underwent CEA, 26 were 89 years or older. Twenty-three patients had had cerebral ischemic symptoms (unilateral hemispheric symptoms in 21 and 2 dizzy spells associated with bilateral high-grade stenosis). Cerebral angiography was performed in 3 patients. Twenty-three patients underwent noninvasive imaging. Four patients had bilateral high-grade stenosis and underwent staged bilateral CEA. All procedures were performed after the induction of general anesthesia with electroencephalographic (and, more recently, transcranial Doppler) monitoring and etomidate-induced burst suppression for cerebral protection during cross-clamping. RESULTS: Unusual technical difficulties were frequently noted, including high bifurcations, looping rotated internal carotid arteries, and marked adherence of surrounding soft tissues. In 3 of the 30 procedures, a shunt was used. There were no perioperative cerebral ischemic or cardiac events. The mean hospital stay was 2 days. One patient had a transient vocal cord paresis. Twenty-two patients were alive and well 24 months following the procedure. Four patients died of non-stroke-related causes. CONCLUSIONS: Carotid endarterectomy was successfully performed without perioperative cerebral or cardiac complications in our series of 26 patients 89 years and older undergoing 30 CEAs. Extrapolating from reported results from the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial, we believe CEA should be considered in nonagenarian patients with high-grade symptomatic carotid stenosis who are otherwise well medically. Our recommendations are less certain in the case of asymptomatic disease.

Age Factors↗

Third-color CD45 staining of paraformaldehyde-fixed peripheral blood lymphocytes.

Third-color CD45 gating is a useful procedure in various clinical applications (Borowitz et al.: Am J Clin Pathol 100:534-540, 1993; Steltzer et al.: Ann NY Acad Sci 677:267-280, 1993) allowing for the selective immunophenotyping of abnormal cell populations. In laboratories where dual-color protocols are in place, the need for CD45 gating may not become evident until after cells have been exposed to fixatives. This brief study demonstrates that third-color CD45 staining and gating is possible with paraformaldehyde fixed lymphocytes, eliminating the need to restain fresh cells with the entire antibody panel, and with a significant saving of time and money. Gates must be modified from those obtained by fresh cell staining in order to include both bright and dim CD45 populations. In a standard protocol, third-color CD45 staining intensity was decreased 10-fold post-fixation with paraformaldehyde except, unexpectedly, for CD8+ cells. The latter phenomenon could be explained if the spatial arrangement of CD45 and CD8 is such that the CD45 epitope is protected from cross-linking by paraformaldehyde fixation in CD8+ cells, but not others.

CD8 Antigens↗

Hepatitis B surface antigen (HBsAg) subtype-specific antibodies in persons vaccinated against hepatitis B.

One hundred sixty-three persons immunised against hepatitis B with a vaccine containing HBsAg either of adw or ayw subtype were examined for antibodies against the a, d, and y determinants of HBsAg. Sera were tested for antibodies against HBsAg adw and HBsAg ayw separately by a solid-phase radioimmunoassay using polystyrene beads coated with HBsAg of either adw or ayw subtype, and the relative amounts of antibodies against the single determinants were calculated. After the third immunisation, all vaccinees had antibodies against the common determinant a. A quantitative evaluation showed that on average about 50% of HBsAg-specific antibodies were directed against the a determinant, and about 50% against d or y, respectively. However, as only anti-a is protective against cross-infection with other HBsAg subtypes, the degree of immunity of a person vaccinated against hepatitis B should be evaluated by the determination of antibodies to a rather than antibodies against total HBsAg.

Adolescent↗

Regions of 23 S ribosomal RNA proximal to transfer RNA bound at the P and E sites.

tRNAPhe transcribed in a T7 RNA polymerase system has been modified in such a way that 4-thiouridines have randomly replaced unmodified uridines. These 4-thiouridines serve as sites for conjugation of the cleavage reagent 5-iodoacetamido-1,10-phenanthroline (IOP). 1,10-Phenantholine, when complexed with Cu2+ in a reducing environment, causes hydrolysis of nearby nucleic acids. We show here that tRNA-phenanthroline (tRNA-OP) conjugates, when bound in situ to the P- and E-sites of 70 S ribosomes, cause cleavage, mainly in domains I, III and V of 23 S ribosomal RNA (rRNA). The cleavage sites in domain V predominantly occur very close to or in the peptidyl-transferase region. The regions of domain I and III that are cleaved are apparently folded in the 50 S ribosomal subunit so as to be proximal to the peptidyl-transferase center. Most of the cleavage events occur whether the tRNA-OP conjugate is bound to ribosomes alone, or yeast tRNA is also present in the P/P hybrid state. Cleavages that occur only in the absence of yeast tRNA are limited to the 1100 region of domain II, and the 2800 region of domain VI. Cleavages that occur only in the presence of yeast occur in the 2170 region of domain V. The regions of 23 S rRNA in which tRNA-OP induced cleavage occur complement those sites shown by chemical protection and cross-liking to be in a close proximity to the tRNA. However, the cleavage approach allows a more versatile and expanded view of the near neighborhood of rRNA surrounding the tRNA. These results provide considerable information which will allow a more detailed modeling of the tertiary structure of the 50 S ribosomal subunit.

Base Sequence↗

Descending thoracic aorta aneurysmectomy: left-left centrifugal pump versus simple clamping technique.

Forty-six patients who had had an elective repair of a descending thoracic aortic aneurysm were reviewed, in order to investigate the efficacy of support by a centrifugal pump on distal organ perfusion and spinal cord protection during cross-clamping of the thoracic aorta. Two concurrent groups were analysed: 36 patients (78%) were supported by left atriofemoral arterial bypass with a centrifugal pump and 10 (22%) had no distal circulatory support. No patient was fully heparinized. The demographic data and preoperative characteristics of the groups, including location and type of aneurysm, were similar. The mean(s.d.) duration of cross-clamping was 37.8 (16) min in the centrifugal pump group and 42.3(21) min in the simple clamping group. Preoperative haemodynamic and laboratory data were similar in both groups. During cross-clamping, parameters of pH and blood urea varied but were better in the centrifugal pump group; changes from pre-intervention to early aortic cross-clamping time were not significant (pH, P < 0.0006; bases, P < 0.0003). Differences in creatinine values were caused mainly by the change from pre-intervention to the first postoperative day (P < 0.03); this continued throughout the hospital stay. The cerebrospinal fluid pressure measurement indicated a significant difference in time change (P < 0.0001) and mean level over time (P < 0.0002): levels were significantly lower in the centrifugal pump group throughout aortic cross-clamping. Three patients in the simple clamping group and none in the centrifugal pump group (P < 0.02) required cerebrospinal fluid drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta, Thoracic↗

DNA microarray-based analysis of single nucleotide polymorphisms may be useful for assessing the risks and benefits of hormone therapy.

OBJECTIVE: To determine what percentage of women can be given individualized counseling based on genetic information, as single nucleotide polymorphisms (SNPs) are associated with risks and benefits of estrogen therapy and hormone therapy such as thrombosis, myocardial infarction, breast cancer, and bone protection. DESIGN: Cross-sectional study. SETTING: Academic research institution. PATIENT(S): A consecutive series of 2,507 perimenopausal and postmenopausal women. INTERVENTION(S): Peripheral venous puncture and multiplex polymerase chain reaction on a microarray system. MAIN OUTCOME MEASURE(S): Analysis of 22 SNPs of 17 genes: AGTMet235Thr, APOECys112Arg, APOEArg158Cys, COMTVal158Met, CYP17-34T>C, CYP191558C>T, CYP19Arg264Cys, CYP1A16235T>C, CYP1A1Ile462Val, CYP1B1Leu432Val, CYP1B1Asn453Ser, HSD17B1-27A>C, ER-alphaIVS-401T>C, prothrombin20210G>A, factor V Leiden, eNOS-786T>C, eNOSGlu298Asp, MRSer810Leu, MTHFR677C>T, PAI 15G>4G, SRD5A2Val89Leu, and VDRb>B. RESULT(S): Among the women in the study, 66% had at least two homozygous mutant SNPs of interest. A thrombophilic disposition was found in 9.9% of women, and 23% of women had at least two SNPs associated with an increased risk of breast cancer (COMT, CYP17, CYP19, CYP1A1, and CYP1B1). The SNPs predisposing women to cardiovascular pathologies (e.g., APOE, AGT, eNOS, and PAI 1) were found in 12.3% of women. Carriage of SNPs predisposing to early postmenopausal bone loss and osteoporosis (ER-alpha and VDR) were found in 26.7% of women. CONCLUSION(S): These data suggest that the assessment of SNPs associated with risks and benefits of estrogen/hormone therapy may be a new means to individualize counseling about and prescription of estrogen/hormone therapy in up to 66% of women.

Breast Neoplasms↗

Low doses of antigen coupled to anti-CR2 mAbs induce rapid and enduring IgG immune responses in mice and in cynomolgus monkeys.

The complement system and B cell complement receptor 2 (CR2), specific for C component C3dg, play important roles in both the innate and adaptive immune response. We used hapten and protein conjugates of anti-CR2 mAbs as models for C3dg-opsonized antigens and immune complexes to examine the handling of and immune response to these reagents in mice and in non-human primates (NHP). Mice immunized and boosted i.v. with only 100 ng of Alexa 488 rat anti-mouse CR1/2 mAb 7G6 had strong IgG immune responses to the Alexa 488 hapten and to rat IgG, compared to very weak immune responses in mice treated with a comparable isotype control; larger doses of Alexa 488 mAb 7G6 did not increase the immune response. A vaccine constructed by cross-linking anthrax protective antigen to mAb 7G6 proved to be effective at low doses in generating sufficiently high titer serum IgG antibodies to neutralize anthrax lethal toxin in vitro and to protect mice from i.v. challenge with anthrax lethal toxin. When biotinylated HB135, a mouse mAb specific for human CR2, was injected i.v. into NHP, the probe manifested the same initial marginal zone B cell binding and subsequent localization to follicular dendritic cells as we have previously reported for comparable experiments in mice. Moreover, i.v. immunization of NHP with 1 microg/kg of Alexa 488 mAb HB135 promoted an IgG immune response to the Alexa 488 hapten and to mouse IgG. Taken together, these results demonstrate the efficacy of using anti-CR2 mAbs as antigen carriers for i.v. immunization with small amounts of antigens without adjuvant.

Animals↗

Maternal immunization.

Maternal immunization embraces the concepts that vaccines given to pregnant women enhance their resistance to vaccine-preventable diseases and passive antibodies that cross the placenta protect the neonate for the first 3 to 6 months of life. It is a great public health move to get excellent protection at a small cost. Because all recommended vaccines for use in pregnancy are safe, it makes good sense to bring patients up to date on vaccines.

Chickenpox Vaccine↗

Mouth-to-mouth ventilation of cardiac arrested humans using a barrier mask.

INTRODUCTION: Concern for possible disease transmission during mouth-to-mouth resuscitation has decreased the incidence of bystander cardiopulmonary resuscitation (CPR). Barrier masks have become available that may be effective in CPR as well as protective against cross-contamination. HYPOTHESIS: A silicone rubber barrier mask incorporating a one-way-valved airway (Kiss of Life [KOL]) designed to prevent contamination of the rescuer, permits satisfactory mouth-to-mouth ventilation of victims of cardiopulmonary arrest. METHODS: Ten adult patients who did not survive non-traumatic cardiac arrest were ventilated with exhaled room air using a KOL barrier mask while external cardiac massage continued. Arterial blood gases were obtained every two minutes for a maximum of 10 minutes. The operator was blinded to the results of these blood tests. RESULTS: Eight men and two women with ages from 55 to 99 years were studied. Four patients were edentulous and two of these had marked mandibular atrophy. The two patients with mandibular atrophy were poorly ventilated with the barrier mask. One other patient was not ventilated successfully. This patient had undergone multiple attempts at endotracheal intubation and had transtracheal needle ventilation performed prior to use of the barrier mask. One patient had elevated PaCO2 despite being well-ventilated clinically. Six patients were ventilated well clinically and had satisfactory PaCO2 and PaO2 values. CONCLUSION: The barrier mask studied appears to be an effective aid to ventilation in CPR. Patients without facial support, as in edentulous patients with mandibular atrophy, are not ventilated well with this device.

Aged↗

Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration.

Alzheimer's disease and primary tauopathies are marked by changes in adaptive immunity, with increased brain CD8+ T cells correlating with tau pathology severity. However, how peripheral T cells get primed to enter the brain and contribute to tau-mediated neurodegeneration remains unclear. In different disease conditions, conventional type 1 dendritic cells (cDC1s) cross-present antigens to prime CD8+ T cells into effector cells. We show that tauopathy mice lacking cDC1s or antigen cross-presentation are protected from neurodegeneration, with reduced brain CD8+ T cell infiltration and glial activation. The remaining CD8+ T cells exhibit limited clonal expansion, consistent with impaired priming. We further demonstrate that brain-derived antigens are presented in secondary lymphoid tissues, suggesting a site of T cell activation. Together, these findings establish cDC1-dependent peripheral priming as a key driver of CD8+ T cell accumulation in the brain and tau-mediated neurodegeneration.

Journal Article↗

The elimination of cross-infection in dental practice--a 5-year follow-up.

A survey in 1983 showed that 16% of general dental practitioners in the Lothian Region wore operating gloves when treating patients; 9% wore them continually and 7% only when performing dento-alveolar surgery. Twelve per cent replied that they would not consider wearing operating gloves and 72% stated that they might consider their use. A similar survey has now been completed 5 years later, involving practitioners in the Lothian and Borders regions. This shows that 163 (97%) of the 168 practitioners who replied now wear operating gloves; 51% restrict their use to the treatment of 'potentially infectious patients' and dento-alveolar surgery; 46% wear them continually. The main objections given to wearing gloves continually were loss of tactile sensation (67%) and cost (13%). The most difficult task to perform wearing gloves was root canal therapy (56%). The majority of practitioners (84%) believed that gloves reduced the dangers of cross-infection. The methods stated to be available for instrument sterilisation in 99.5% of practices were acceptable. This paper proposes that to eliminate cross-infection and protect the dental practitioner, operating gloves should be worn when treating all patients.

Attitude to Health↗

Flexible nasendoscope with a disposable-sheath system versus standard nasendoscopy: a prospective, randomized trial.

There are no published guidelines for the sterilization of the flexible nasendoscope and various techniques exist. We have conducted a randomized, prospective, blinded trial of the barrier Endosheath system versus immersion in Cidex disinfectant. Using a visual analogue assessment, there were no differences at a 99% confidence interval (CI) between the two techniques from the nursing assistant and patient perspectives. Image quality was assessed blinded and no difference could be detected at a 99% CI. The Endosheath offers the advantage of increasing the productivity of each nasendoscope as the sterilization time is reduced. It also provides barrier protection against cross-contamination, including prion diseases.

Adult↗

Successful post-bypass ventricular assist with a centrifugal pump.

A 56 year old male with massive anterior wall infarction and development of a large aneurysm underwent aneurysmectomy and aorto-coronary bypass grafting to the RCA. Preoperative ejection fraction was 20%, LVedP was 30 mm Hg. During induction of anesthesia the patient sustained ventricular fibrillation and was successfully resuscitated. With the patient in progressive cardiogenic shock the operation was performed under emergency conditions. Despite adequate myocardial protection and cross-clamp time as well as prolonged reperfusion and balloon counterpulsation the patient could not be weaned off cardiopulmonary bypass. In this situation a centrifugal pump system was connected between the left atrium and the ascending aorta. With a pump flow of 5 l/min the patient was taken off cardiopulmonary bypass. After 20 hours of extracorporeal support without anticoagulation the device could be removed: explantation of the IABP followed 48 hours later. The patient gradually recovered and finally was discharged home in fair condition.

Assisted Circulation↗

Relationship between serum antibodies and subclinical infections with poliomyelitis virus.

Three families in which cases of poliomyelitis had recently occurred were studied for the extent of subclinical infection and the presence of serum antibodies to both the mouse-adapted Lansing strain and the specific strain of poliomyelitis isolated from members of the family. Virus was recovered from the stools of all 5 cases and from 8 of 17 familial associates at the time of the first collection of specimens. Only two of the associates were still carrying virus 3 weeks later. The individuals from whom virus was recovered were younger than 11 years of age with two exceptions, one of them a frank case. Antibodies to the mouse-adapted Lansing strain of poliomyelitis virus were demonstrated in the sera of every person 11 years of age or older but in none from individuals under this age with the possible exception of one whose second specimen was weakly positive. Antibodies for the specific agent isolated from each family were likewise found at the beginning of the study in every person over 11 years of age but also in 4 of 9 under that age. The neutralization indices of sera of the second collection were generally higher than those of the sera collected soon after the disease occurred in the family, reflecting the antigenic stimulus of the "family" viruses. The inverse relationship of demonstrable antibodies to virus isolations strongly suggests that the presence of serum antibodies is effective in limiting subclinical infection with poliomyelitis virus. The question of cross-immunity in protection against infection with poliomyelitis virus is discussed.

Animals↗

Minimally invasive cardiac surgery: a new frontier.

Modern cardiac surgery has been based on cardiopulmonary bypass, myocardial protection, aortic cross-clamping, and median sternotomy. Coronary artery bypass graft (CABG) has proven to be an effective treatment for patients who require surgical revascularization of the myocardium. Reports regarding the systemic effects of cardiopulmonary bypass abound in the literature. Such effects include hematologic, metabolic, pulmonary, cardiac, and cognitive dysfunction. Less invasive procedures have initiated a dramatic shift in treatment paradigms as well as reducing the cost of treatment. This article will discuss the MIDCAB--its history, a description of the surgical procedure, indications for use and patient selection, advantages and a perioperative plan including patient education and physical assessment.

Coronary Artery Bypass↗

A cost-analysis of two approaches to infection control in a lung function laboratory.

BACKGROUND: The Thoracic Society of Australia and New Zealand (TSANZ) guidelines for infection control in respiratory laboratories are based on a 'Universal Precautions' approach to patient care. This requires that one-way breathing valves, flow sensors, and other items, be cleaned and disinfected between patient use. However, this is impractical in a busy laboratory. The recent introduction of disposable barrier filters may provide a practical solution to this problem, although most consider this approach to be an expensive option. AIM: To compare the cost of implementing the TSANZ infection control guidelines with the cost of using disposable barrier filters. METHODS: Costs were based on the standard tests and equipment currently used in the lung function laboratory at The Alfred Hospital. We have assumed that a barrier filter offers the same degree of protection against cross-infection between patients as the TSANZ infection control guidelines. Time and motion studies were performed on the dismantling, cleaning, disinfecting, reassembling and re-calibrating of equipment. Conservative estimates were made as to the frequency of replacing pneumotachographs and rubber mouthpieces based on previous equipment turnover. Labour costs for a scientist to reprocess the equipment was based on $20.86/hour. The cost of employing a casual cleaner at an hourly rate of $14.07 to assist in reprocessing equipment was also investigated. The new high efficiency HyperFilter disposable barrier filter, costing $2.95 was used in this cost-analysis. RESULTS: The cost of reprocessing equipment required for spirometry alone was $17.58 per test if a scientist reprocesses the equipment, and $15.56 per test if a casual cleaner is employed to assist the scientist in performing these duties. In contrast, using a disposable filter would cost only $2.95 per test. Using a filter was considerably less expensive than following the TSANZ guidelines for all tests and equipment used in this cost-analysis. CONCLUSIONS: The TSANZ infection control guidelines are expensive and impractical to implement. However, disposable barrier filters provide a practical and inexpensive method of infection control.

Australia↗

Occupational allergic contact dermatitis and contact urticaria caused by polyfunctional aziridine hardener.

Polyfunctional aziridine (PFA) is increasingly used as a water-based cross-linker in 2-component paints, paint primers, lacquers, topcoats and other protective coatings. The cross-linker (PFA hardener) is made by reacting multifunctional acrylic monomer with a highly reactive aziridine compound. During 1992-1993, we came across 2 patients with allergic patch test reactions provoked by PFA hardener. One of the patients was a parquet layer, and the other a printer. Allergic contact dermatitis (ACD) was diagnosed by positive allergic patch test reactions to PFA hardener in a dilution series in pet.:0.3%-1% gave ++ to allergic reactions in both patients, whereas 0.1% gave a weak (+) or questionable reaction (?+), respectively. The methacrylate patch test series was negative in both patients, although gas chromatography/mass spectrometry analysis showed that PFA hardener contained 0.3% of trimethylolpropane triacrylate (TMPTA), a multifunctional acrylic monomer. One of the patients also had symptoms of contact urticaria, and a prick test with PFA hardener (1% aq.) induced a histamine-sized prick test reaction. The positive reactions with the PFA hardener and the negative reactions with the starting chemicals and additives in PFA, namely acrylates, propyleneimine and dimethylethanolamine, indicate that PFA caused ACD. This is in accordance with our previous observations, but differs from the reports of others, whose patients had been sensitized to acrylates present as remnants in the PFA hardener. As test substance, 0.5% PFA hardener in pet. is recommended for patch testing. Testing should be performed in patients with contact dermatitis if exposure to PFA has occurred. Skin prick tests may be of help to detect contact urticaria.

Acrylates↗

Characterization of a mitomycin-binding drug resistance mechanism from the producing organism, Streptomyces lavendulae.

In an effort to characterize the diversity of mechanisms involved in cellular self-protection against the antitumor antibiotic mitomycin C (MC), DNA fragments from the producing organism (Streptomyces lavendulae) were introduced into Streptomyces lividans and transformants were selected for resistance to the drug. Subcloning of a 4.0-kb BclI fragment revealed the presence of an MC resistance determinant, mrd. Nucleotide sequence analysis identified an open reading frame consisting of 130 amino acids with a predicted molecular weight of 14,364. Transcriptional analysis revealed that mrd is expressed constitutively, with increased transcription in the presence of MC. Expression of mrd in Escherichia coli resulted in the synthesis of a soluble protein with an Mr of 14,400 that conferred high-level cellular resistance to MC and a series of structurally related natural products. Purified MRD was shown to function as a drug-binding protein that provides protection against cross-linking of DNA by preventing reductive activation of MC.

Amino Acid Sequence↗