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Specimen adequacy evaluation in gynecologic cytopathology: current laboratory practice in the College of American Pathologists Interlaboratory Comparison Program and tentative guidelines for future practice.

Routine specimen adequacy evaluation, as advocated by The Bethesda System (TBS), can play an important role in improving the sensitivity and accuracy of cervical cytopathology screening. The effectiveness of this measure, however, has been limited by the lack of uniform criteria for adequacy. Practice parameters are now emerging, through TBS development of tentative criteria and interlaboratory comparison of adequacy practices. This study reviews 1) nationwide responses to surveys of laboratory practices in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (CAP PAP); 2) the definitions of adequacy based on TBS; and 3) the results of implementation of these criteria in a private independent laboratory, university hospital laboratory, and private nonprofit hospital laboratory. In the initial CAP PAP survey in 1990, 35% of responding laboratories routinely reported specimen adequacy, increasing to 66% in 1991 and 85% in 1992. Interlaboratory variations in adequacy practices were observed, however, underscoring the need for consensus criteria. The experience in the authors' laboratories indicates that TBS criteria can serve as a sound guideline. Effective implementation of adequacy assessment in the individual laboratory requires careful attention to ensuring the quality of adequacy ratings, correlating clinical and prior laboratory information, issuing clear and concise reports, and giving recommendations judiciously. Through interlaboratory comparison and consistent intralaboratory emphasis on specimen adequacy, greater uniformity of adequacy assessment can be achieved, and adequacy evaluation can achieve its promise of improving the quality of cervical cytopathology.

Clinical Laboratory Techniques↗

Minimal alpha 1- and alpha 2-adrenoceptor-mediated coronary vasoconstriction in the anaesthetized swine.

alpha-Adrenoceptor-mediated coronary vasoconstriction contributes to the initiation and aggravation of experimental and clinical myocardial ischaemia. However, the extent of alpha 1- and alpha 2-adrenoceptor-mediated constriction has not been characterized in the porcine coronary circulation despite the frequent use of this experimental model. Fifteen swine were anaesthetized with either alpha-chloralose, enflurane or isoflurane to determine the amount of alpha-adrenoceptor-mediated coronary constriction elicited by either the selective alpha 1-adrenoceptor agonist methoxamine or the selective alpha 2-adrenoceptor agonist azepexole. The left anterior descending coronary artery was cannulated and perfused by an external pump delivering constant blood flow from the carotid artery. Following bilateral cervical vagotomy and beta-adrenoceptor blockade with propranolol (2 mg kg-1), graded dosages of either one of the alpha-adrenoceptor agonists (9-45 micrograms kg-1 min-1) were infused into the coronary perfusion line while coronary arterial pressure (CAP) was measured through a distal side arm of the cannula to detect changes in coronary vascular resistance. Infusion of the alpha-adrenoceptor agonists was terminated when systemic arterial pressure increased. Sonomicrometers were used to measure anterior left ventricular wall thickening for the assessment of regional contractile function. During methoxamine infusion, no increase in vascular resistance was observed during alpha-chloralose, enflurane or isoflurane anaesthesia, whereas the infusion of azepexole increased CAP from 103 +/- 31 mmHg to 120 +/- 35 mmHg (alpha-chloralose), from 101 +/- 16 mmHg to 122 +/- 11 mmHg (enflurane) and from 84 +/- 20 mmHg to 94 +/- 19 mmHg (isoflurane), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

The effects of vertical and horizontal vibrations on the human body.

Vertical and horizontal vibrations of a 100 kg human have been investigated. A new mechanical model has been developed, and an analogous electric simulation has been carried out, which in turn has been analysed by using computer software (MICRO-CAP II). The vibration force comes from (a) hand, (b) seat and (c) combination of the two. The theoretical results obtained have been tabulated and are presented in a graphical manner. It has been found that the body segments (lower arm, head, torso, cervical spine and lumbar spine) are affected by horizontal vibrations when the input force (F(i)) comes from both hand and seat more than when (F(i)) comes from the seat alone. Similar results have been found also for the case of the lower arms and torso when the body is subjected to vertical vibrations. The head is affected by vertical vibrations when (F(i)) comes from the seat more than when (F(i)) comes from both hand and seat. An experimental set-up has been designed and measurements of vibrational signals from the human lower arm, head and torso have been carried out. Similar trends are shown for both theoretical results and experimental findings.

Adult↗

Oral blast injury caused by an accident.

Blast trauma within the oropharyngeal cavity may be associated with superficial or deep injuries. Superficial injury generally needs only observation; deeper injury that violates the retropharyngeal space may produce dissecting emphysema into the neck and mediastinum followed by prevertebral soft tissue infections and mediastinitis. Injury involving the parapharyngeal space might damage vital cervical vessels. Life-threatening complications may result unless treatment is adequate. Three children who sustained oropharyngeal blast injury are presented. The direct cause was the blast effect of a new, spoiled, orange-flavor beverage just released on the market. The bottle cap of the soft drink and its effervescent liquid "exploded" into their mouths while they were trying to open the bottle with their teeth. Obviously, the failure to observe due precautions, as frequently happens among children, contributed to the occurrence of the accidents. This paper describes the diagnosis, management, and relevant educational and preventive measures of the problem.

Accidents↗

[A patient with recurrent uterine cervical cancer successfully treated by combined modality therapy including local injection of anticancer agents based on CDDP].

The patient was a 77-year-old woman who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy following the diagnosis of uterine cervical cancer at the age of 57. A recurrent tumor was detected on the anterior surface of the right iliopsoas muscle and fine needle aspiration of the tumor revealed squamous cell carcinoma. A needle was inserted into the tumor under transabdominal ultrasound guidance, and anticancer agents, chiefly cis-diamminedichloroplatinum [II] (CDDP), were injected. The patient also received systemic chemotherapy (CAP therapy) and radiotherapy. Subsequently, computed tomography showed a 73% reduction in the size of the tumor. A mass 7 cm in diameter was still present on the anterior surface of the iliopsoas after treatment, but tumor markers fell to normal levels. The patient is presently receiving UFT (600 mg/day) as maintenance therapy. At 48 months after recurrence, there has been no increase in the tumor size or tumor marker levels, and the performance status is grade 0. In conclusion, a good outcome was achieved by local injection of anticancer agents combined with systemic chemotherapy and radiotherapy, and there were few side effects.

Aged↗

A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent.

We synthesized a MCM-41-type mesoporous silica nanosphere (MSN)-based gene transfection system, where second generation (G2) polyamidoamines (PAMAMs) were covalently attached to the surface of MSN. The G2-PAMAM-capped MSN material (G2-MSN) was used to complex with a plasmid DNA (pEGFP-C1) that encodes for an enhanced green fluorescence protein. The gene transfection efficacy, uptake mechanism, and biocompatibility of the G2-MSN system with various cell types, such as neural glia (astrocytes), human cervical cancer (HeLa), and Chinese hamster ovarian (CHO) cells, were investigated. The mesoporous structure of the MSN material allows membrane-impermeable molecules, such as pharmaceutical drugs and fluorescent dyes, to be encapsulated inside the MSN channels. The system renders the possibility to serve as a universal transmembrane carrier for intracellular drug delivery and imaging applications.

Animals↗

Synaptic transmission in the decentralized middle cervical ganglion of the dog.

The middle cervical ganglion (MCG) was decentralized in 30 dogs by cutting the thoracic vagus and rami on one side. Two or more cardiopulmonary nerves were then dissected free and placed on bipolar stimulating and recording electrodes in mineral-oil baths. Stimulation of one cardiopulmonary nerve generated a compound action potential (CAP) in one or two others. The CAP was altered by changing the frequency of stimulation and by stimulating preganglionic fibers in the rami. These alterations displayed latency changes and temporal summation or inhibition. The ansae were sectioned to neurally isolate the MCG from the stellate ganglion. A CAP generated after blockade by hexamethonium, atropine, propranolol and phentolamine was abolished transiently by chymotrypsin, and for longer periods by manganese, injected locally into the MCG. These results suggest that a CAP that is generated by stimulating one cardiopulmonary nerve in a decentralized MCG and recorded from another may result from synaptic activity in the MCG and that complex neuronal interactions occur within the MCG.

Animals↗

Feline endodontics.

One misconception in veterinary medicine is that fractured teeth do not need to be treated, or treatment should consist of extraction only. Two common causes of endodontic disease in the cat are fractures and secondary to cervical line lesions. Endodontic technique can be useful in returning a diseased tooth to normal, pain-free function. Conventional endodontics can be used to treat fractured canine teeth or partially destroyed molars. Surgical endodontics is useful in cases in which an apical seal cannot be established by conventional methods. Pulp capping can preserve a vital tooth as an alternative to extraction.

Animals↗

Amalgam repair: evaluation of bond strength and microleakage.

This study evaluated the tensile bond strength of "repaired" amalgams and compared the degree of microleakage. Amalgam (Cavex avalloy) was condensed into plastic tubes (3 mm in diameter, 10 mm in height) to the half-length. After storage in water at 37 degrees C for two days, the remaining parts of tubes were filled with amalgam (A), cavity varnish (CV)+A, Liner Bond 2V (LB2V)+A, 3M Opal Luting Cement (3MOLC)+A, Panavia F(PF)+A, Metabond(MB)+A, Fuji BondLC(FB)+A, HytacOSB(HOSB)+Hytac Aplitip (H), Liner Bond2V+Clearfil AP-X(CAP). The bond strengths for 15 samples of each restoration group were determined. For the microleakage study, MOD cavities of 90 extracted human premolars were used. The distal half of cavities were filled with amalgam. After storage in water at 37 degrees C for two days, the mesial half of the cavities were filled to simulate a clinical repair. The "repair" was placed using the procedures applied in the bond strength study. The teeth were stained with basic fuchsine (0.5%), sectioned and evaluated for dye penetration. In both parts of study, the data were analyzed by ANOVA and Duncan's multiple range tests. Bond strength values (MPa) were: A+PF+A 3.84+/-1.08, A+LB2V+A 3.15+/-0.97, A+LB2V+CAP 3.05+/-0.53, A+MB+A 2.86+/-0.88, A+HOSB+H 2.58+/-0.51, A+3MOLC+A 2.11+/-0.75, A+FB+A 0.68+/-0.59. The repaired A+A and A+CV+A groups were separated before testing. The A+PF+A group showed the highest bond strength (p<0.05). Microleakage in the cervical margins of repaired restorations was lower in the amalgam groups than microleakage in the resin composite and compomer groups. PF, MB, 3MOLC and FB performed better at the amalgam "repair" interface. The A+LB2V+A group showed no microleakage at both the occlusal and gingival test regions.

Analysis of Variance↗

The early distribution and possible role of nerves during odontogenesis.

Neural crest cells migrate along specific pathways to reach the mandibular and maxillary arches where they condense under specific areas of the ectoderm which will give rise to the primary and permanent dentition. In the mouse, the trigeminal ganglion becomes evident on E9 and the superior cervical sympathetic ganglion E13. Several studies have suggested that nerves in the vicinity of the developing teeth could influence the surrounding tissues and initiate tooth development, whereas other investigators have suggested that tooth development will proceed without an intact innervation. Innervation of the dental papilla has been reported as early as the cap stage in human teeth using an antibody to PGP 9.5. A large variety of putative neurotransmitters have been localized in the nerves of the dental pulp. Many of the putative neurotransmitters function in vasoregulation while others have unknown functions. A hypothesis is presented describing a possible signal transduction pathway between odontoblasts and nerve terminals.

Animals↗

A POU protein regulates mesodermal competence to FGF in Xenopus.

XLPOU91, a POU-homeobox gene is expressed in a narrow window during early Xenopus development. We show that ectopic expression of XLPOU91 RNA causes severe posterior truncations in embryos without inhibiting the formation of Spemann's organizer. Ectopic XLPOU91 expression also inhibits mesoderm induction by fibroblast growth factor (FGF) and activin in animal cap explants. Using antisense RNA, we depleted endogenous XLPOU91 protein in animal caps. Gastrula-stage animal caps expressing XLPOU91 antisense RNA do not lose competence to FGF, unlike controls, these animal caps express XBra after FGF treatment. Endogenous XLPOU91 levels are peaking when FGF mesoderm-inducing competence is lost in animal caps. Thus XLPOU91 protein may act as a competence switch during early development, as XLPOU91 levels increase in the embryo, the mesoderm response to FGF is lost.

Animals↗

Gynecologic malignancies.

Several general conclusions are beginning to emerge from the series of prospective trials in the treatment of ovarian cancer. Combination chemotherapy continues to demonstrate higher overall response rates and higher complete remission rates than single alkylating agents, although in some studies survival is not significantly different. Nevertheless, long-term disease-free survivals, although uncommon, are more frequent with combinations, particularly when the dose intensity of the combination is adequate. Although CAP is the most commonly used combination, evidence continues to suggest that cyclophosphamide/cisplatin alone may be equivalent. Several studies have incorporated alkylating agent maintenance into their clinical trials and each reports acute leukemic complications. In light of the absence of a major contribution for this approach, alkylating agent maintenance in ovarian cancer should not be encouraged. Several studies this year emphasize the discouraging results associated with the use of total abdominal radiation therapy post-induction chemotherapy even with patients with minimal or no residual disease. In light of the publications this year and of previously published studies, this approach, although based on sound rationale, appears to be of limited benefit. Salvage chemotherapy, in general, has been unsatisfactory. The 2 interesting reports this year were the activity of low-dose mitomycin C and the potential utility of VP-16/cisplatin combinations in a salvage setting. In cervix carcinoma, trials have documented significant activity for the new drugs, carboplatin (28% response) and ifosfamide (30%), but each has significant side effects. Whether these will prove more active than cisplatin or whether they may be used in combination is unresolved. The continued investigation into the use of radiation sensitizers in cervical carcinoma is of interest and several studies using weekly low-dose cisplatin have established the feasibility of this approach, although long-term survival benefits have not yet been documented. In endometrial carcinoma, epidemiologic studies continue to define the role of postmenopausal estrogens in endometrial carcinoma risk. This year a Swedish study documents a smaller overall risk from estrogen treatment, perhaps related to a substantially lower use of conjugated estrogens in that country. Combination chemotherapy continues to show some activity, although the contribution of combinations in excess of the single agent activity of doxorubicin is still poorly documented. One study does demonstrate significant activity for the commonly used CAP regimen with an overall response rate of 56% and 28% complete remissions.(ABSTRACT TRUNCATED AT 400 WORDS)

Combined Modality Therapy↗

Compliance with doxycycline therapy in sexually transmitted diseases clinics.

OBJECTIVE: To determine rates of compliance with doxycycline therapy for patients attending two inner city sexually transmitted diseases (STD) clinics using the MEMS (Medication Event Monitoring System) technology (Aprex Corporation, Fremont, CA). DESIGN: An observational study. SETTING: Two STD clinics in Brooklyn, New York and Birmingham, Alabama. PATIENTS: Patients warranting doxycycline as antichlamydial therapy by usual clinical criteria (e.g., documented chlamydial infections, gonococcal urethritis, mucopurulent cervicitis) were enrolled consecutively from both clinics into four separate categories according to gender and the presence or absence of symptoms: symptomatic men (77), asymptomatic men (30), symptomatic women (83), asymptomatic women (33). INTERVENTION: In the clinic area, patients were given their doxycycline in standard 30-dram medication bottles fitted with the MEMS cap, which is capable of recording the date and time of each bottle opening and closing. This information was then retrieved using a software program developed by the manufacturer. Patients were instructed to return the bottle and cap at the completion of therapy. Efforts were made to contact those who did not return their bottles by both telephone and mail. OUTCOME MEASURES: Bottle openings as recorded by the MEMS were considered to represent use of medication. Patients were considered strictly compliant with prescription instructions if bottle openings and closings occurred at least twice daily for 6 consecutive days. Noncompliance was defined as initially opening the medication more than 48 hours after leaving the clinic or opening the bottle less than once daily for 5 consecutive days. Usage between these extremes was classified as intermediate. RESULTS: Eighty percent of 223 patients enrolled completed the study by returning their bottles. The rate of strict compliance with prescription instruction was 25%. The rate of noncompliance was 24%. Fifty-one percent used some intermediate amount of medication. There was no statistical difference in compliance by gender, presence or absence of symptoms, or site of enrollment. CONCLUSIONS: Few patients administered doxycycline in an STD clinic can be expected to take medication precisely as prescribed. Although most probably take enough to eradicate uncomplicated chlamydial infections, a sizable portion can be expected to use an inadequate amount of medication. This may contribute to persistence of genital chlamydia infections in the community.

Adult↗

Cervical neural foraminal canal stenosis: computerized tomographic myelography diagnosis.

The surgical and computerized tomographic myelography (CTM) features of 134 stenotic foraminal canals were correlated retrospectively in 95 patients. The myelographic site of stenosis was the entrance to the foraminal canal in 70 cases (52%) and the canal itself in 37 (28%); the site was not identified definitively in 27 (20%). At the entrance to the foraminal canal, encroachment on the adjacent nerve root was by a cartilaginous cap in 10 cases (8%), a bony osteophyte in 17 (13%), a synovial cyst in one (1%), and a combination of a bony and cartilaginous osteophyte in 42 (31%). The diagnostic features of stenosis within the foraminal canal were more variable. Small bone spurs arising from the uncovertebral process encroached on the anterior aspect of the foramen in 29 instances (22%), accompanied in all cases by either a congenitally narrow canal (in 16) or a diffuse osteophytically narrowed canal (in 13); osteophytes arising from the superior facet in eight instances (6%) were larger and encroached on the posterior aspect of the foramen. Diagnosis on the basis of CTM is difficult because stenosis was readily evident as a bone spur in only 13% of cases, could not be distinguished from prolapsed disc in 39%, had to be differentiated from a congenitally narrow foraminal canal in 27%, and was frankly missed in 20% of the instances of stenosis.

Adult↗

Superior mediastinal widening from spine fractures mimicking aortic rupture on chest radiographs.

Mediastinal widening on chest radiographs associated with lower cervical and upper thoracic spine fractures can mimic the radiographic findings of aortic rupture. Frontal chest radiographs from 54 patients with traumatic fractures of at least one vertebral body from C6 to T8 were examined for signs suggestive of aortic rupture. These signs included (1) mediastinal width equal to or greater than 8 cm; (2) presence of a left apical cap; (3) a right paratracheal stripe of 5 mm or more; and (4) deviation of the nasogastric tube, when present, to the right of the T4 spinous process. Thirty-seven patients (69%) had radiographic signs suggestive of aortic rupture on the initial anteroposterior chest film. The single patient in this group who actually had an aortic rupture died in the emergency department shortly after admission. The spine fracture could be identified on the initial chest radiograph in 19 (51%) of the 37 patients. These results show that a widened mediastinum on chest radiographs after trauma is not a specific finding of aortic rupture. In these cases, the upper thoracic spine should be examined closely on the initial frontal chest radiograph for evidence of fracture. If a fracture of the upper thoracic spine is identified, an aortic rupture is unlikely in the absence of clinical signs and symptoms supporting this diagnosis.

Adolescent↗

Liver-specific expression of human insulin-like growth factor binding protein 1: functional role of transcription factor HNF1 in vivo.

Tissue-specific expression of insulin-like growth factor binding protein 1 (IGFBP-1) in the liver has been studied using differentiated (H4II and C2Rev7) and dedifferentiated (H5 and C2) rat hepatoma cell lines. Northern blot analysis showed that endogenous IGFBP-1 mRNA was expressed only in the differentiated cell lines. The first 341 base pairs 5' to the transcription initiation site of the human IGFBP-1 gene were inserted upstream of the chloramphenicol acetyltransferase reporter gene (pBP-1(341)). Expression of this gene from the human IGFBP-1 promoter was 10-16 times more efficient in the H4II line than in the other hepatoma cell lines and 40 and approximately 12 times more so than in rat fibroblasts (FR3T3) and a human cervical carcinoma cell line (C33), respectively. Cotransfection of pBP-1(341) and pRSV-HNF1 and/or pRSV-v-HNF1 (eukaryotic expression vectors that drive the synthesis of the liver-enriched trans-acting factor HNF1 or of v-HNF1, a related form) in C33 recipient cells yielded a 6-fold increase in IGFBP-1 promoter activity by HNF1 and a 2-fold increase by v-HNF1. These increases were dependent on the integrity of an HNF1 binding site located 58-74 nucleotides upstream of the cap site. Stimulation of promoter activity by cotransfection of both HNF1 and v-HNF1 fell between these values. Our results indicate that HNF1 is instrumental in human IGFBP-1 promoter activity in vivo and that v-HNF1 modulates this functional role.

Animals↗

The distribution of substance P-containing neurons in the cat Edinger-Westphal nucleus: relationship to efferent projection systems.

The light microscopic localization of substance P-like immunoreactivity (SPLI) was examined in the cat Edinger--Westphal complex using the peroxidase--antiperoxidase method. A high density of cell bodies and processes staining for SPLI were found in the caudal part of the Edinger--Westphal complex (EWc) capping the somatic divisions of the oculomotor nucleus. This distribution continued rostrally into the anteromedian nucleus (AM). Cells labeled with SPLI were also found arranged in a thin layer dorsally capping the oculomotor nucleus, and scattered cells were found in the periaqueductal gray region at the same level. This distribution of SPLI-positive cells was then compared with the distribution of cells in EWc and AM that are retrogradely labeled by horseradish peroxidase or Nuclear Yellow injections into spinal cord, cerebellum, or ciliary ganglion. Injections of horseradish peroxidase into both cervical and lumbar cord labeled a large number of cells throughout the length of EWc and the more rostral AM. A similar pattern of labeling was seen following injections of Nuclear Yellow into the deep cerebellar nuclei. In contrast, cells innervating the ciliary ganglion were found predominantly outside of the Edinger--Westphal complex in AM, the rostral periaqueductal region, and the tegmentum ventral to the oculomotor complex. The distribution of cells projecting to spinal cord or cerebellum and the pattern of SPLI staining was found to closely overlap, evidence that substance P may be contained in cells that give rise to the central projections of the Edinger--Westphal complex.

Animals↗

Vibration effects on setting pregnant women--subjects of various masses.

An electrical simulation of a mechanical model of a 60 kg pregnant woman subjected to horizontal and vertical vibrations has been investigated by using a computer software package (MICRO-CAP II). The results have shown that mechanical vibrations affect the body segments differently based on their location, the kind of vibration and pregnancy development. The vibrations' effect on the body varies from segment to segment and a lady driver is affected by vibrations more than a lady passenger. Horizontal vibrations affect body segments (lower arm, upper arm, head, thorax, torso, cervical spine, and lumbar spine) more than vertical vibrations, while the thorax is affected by vertical vibrations, more than horizontal vibrations.

Female↗