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Local inflammatory response around diffusion chambers containing xenografts. Nonspecific destruction of tissues and decreased local vascularization.

Immunoisolation of xenogeneic pancreatic islets within membrane-bound devices has been proposed as an approach to cure diabetes. We examined the local response to implanted xenografts and allografts in comparison with isografts in diffusion chambers with 0.4-microm pore membranes when implanted into epididymal fat pads of rats. These membranes prevented host cell entry into the device but did not prevent passage of large molecules such as IgG and IgM. Well-differentiated allogeneic tissues (Sprague-Dawley rat embryonic lung implanted into Lewis rats) survived for 1 year when implanted in intact devices, but similar tissues were destroyed within 3 weeks when implanted within devices with holes poked in the membrane to allow host cell contact. In contrast, xenografts (CF1 mouse embryonic lung implanted into Lewis rats) were destroyed within 3 weeks even when implanted in devices with intact membranes. The death of the xenogeneic tissues was accompanied by a severe local accumulation of inflammatory cells and a decrease in local vascularization. When isogeneic tissues (Lewis rat embryonic lung implanted in Lewis rats) were mixed with xenogeneic tissues, a local inflammatory response occurred and both iso- and xenogeneic tissues were destroyed within 5 weeks. These results suggest the possibility that xenografts are killed by local accumulation of inflammatory cells, perhaps mediated by the release of antigens from the tissues within the device and presentation by an indirect pathway. The observation that the local response to xenografts is sufficient to kill isografts complicates issues of immunoprotection, suggesting that successful immunoisolation will require membranes that not only provide protection of the encapsulated tissues from the host immune system but also have properties that diminish the release of xenogeneic antigens.

Animals↗

Efficacy of primary hormone therapy for localized or locally advanced prostate cancer: results of a 10-year follow-up.

OBJECTIVE: To evaluate the efficacy of primary hormone therapy for localized or locally advanced prostate cancer, by analysing the 10-year survival rates for men with localized or locally advanced prostate cancer treated with primary hormone therapy or prostatectomy. PATIENTS AND METHODS: Between February 1993 and March 1995, men with T1b, T1c or T2-3 N0M0 prostate cancer were enrolled. In all, 176 men who had a prostatectomy were assigned to Study 1 and were given adjuvant luteinizing hormone-releasing hormone (LHRH) agonist; 151 men who did not have a prostatectomy were assigned to Study 2 and had LHRH agonist monotherapy or combined androgen blockade. They were followed until death, loss to follow-up, or until the end of the observation period (31 March 2004). We analysed all cases in each study as a single population, and compared Study 1 with Study 2. RESULTS: The mean patient ages were 67.2 years in Study 1 and 75.7 years in Study 2. During a median of 10.4 years of follow-up, 20 men in Study 1 and 17 in Study 2 died from prostate cancer, and 21 men in Study 1 and 50 in Study 2 died from other causes. In Study 1, the 10-year overall survival rate was 73% and the 10-year cause-specific survival rate was 86%, vs 41% and 78% in Study 2. Overall survival curves were similar to expected survival curves in both studies. There was no significant difference between studies in cause-specific survival. CONCLUSIONS: The progression of prostate cancer was retarded by primary hormone therapy in men with localized or locally advanced prostate cancer. With primary hormone therapy or prostatectomy, the men had a life-expectancy similar to that of the normal population.

Aged↗

Subcellular localization of immunohistochemical signals: knowledge of the ultrastructural or biologic features of the antigens helps predict the signal localization and proper interpretation of immunostains.

In the literature, sufficient attention has not been paid to the precise subcellular localization of immunohistochemical signals, the knowledge of which is essential for proper interpretation of immunostains and distinction of genuine staining from biotin-associated or other nonspecific stainings. The subcellular localization of the signals can in fact be easily deduced from the known biologic or ultrastructural characteristics of the antigens. Extracellular antigens obviously are located in the extracellular compartment. Cellular antigens fall into 3 major groups: membranous, nuclear, and cytoplasmic. Membranous antigens include cell adhesion molecules (such as E-cadherin, N-CAM), cell surface/transmembrane receptors and proteins (such as tyrosine kinase receptors, most leukocyte antigens, CD10, CEA), and molecules linking surface molecules to cytoskeleton (such as beta-catenin, dystrophin). Nuclear antigens include cell cycle-associated proteins (such as cyclins, p16, Ki-67), nuclear enzymes (such as TdT), transcription factors (such as TTF-1, CDX-2, myogenin, PAX-5), tumor suppressor gene products (such as p53, p63, WT1, Rb), steroid hormone receptors (such as ER, PR), calcium-binding proteins (such as S-100 protein, calretinin), and some viral proteins (such as CMV, herpes). Cytoplasmic antigens can take up a granular pattern due to localization in organelles, granules, or secretory vesicles (such as chromogranin, hormones, lysozyme, HMB-45), fibrillary pattern attributable to the filamentous nature of the molecules (intermediate filaments and microfilaments), or diffuse or patchy pattern due to localization in the cytosol or large vesicles (such as myoglobin, albumin, thyroglobulin). Aberrant localization of the molecules, when present, can provide important insight into disease processes and aid in their diagnosis, such as loss of membranous E-cadherin expression in lobular breast carcinoma, aberrant nuclear localization of beta-catenin in colorectal adenocarcinoma, pattern of ALK staining in anaplastic large cell lymphoma correlating with the different types of chromosomal translocations, presence of additional cytoplasmic CD10 staining in the enterocytes indicative of microvillous inclusion disease, and "reversed" staining for EMA in micropapillary mammary carcinoma.

Animals↗

Immunocytochemical localization of cathepsin B in rat anterior pituitary endocrine cells, with special reference to its co-localization with renin and prorenin in gonadotrophs.

We examined by immunocytochemistry the localization of cathepsin B in endocrine cells of rat anterior pituitary lobe, using a monospecific antibody to cathepsin B. By light microscopy, granular immunodeposits for cathepsin B were detected in most endocrine cells of anterior pituitary lobe. Cells immunoreactive for luteinizing hormone (LH) were diffusely immunostained by anti-cathepsin B. By electron microscopy, immunogold particles for cathepsin B were localized in lysosomes of thyrotrophs, somatotrophs, and mammotrophs. In mammotrophs, immunogold particles for cathepsin B were also detected in crinophagic bodies. Double immunostaining co-localized immunogold particles for LH and cathepsin B in secretory granules of gonadotrophs. Immunocytochemistry was also applied to demonstrate localization of renin and prorenin in LH-producing gonadotrophs; immunogold particles for renin were co-localized with those for LH, cathepsin B, or prorenin in their secretory granules. Immunogold particles for prorenin were also co-localized with those for LH or cathepsin B in secretory granules, but prorenin-positive granules appeared less frequently than renin-positive granules. These results suggest that cathepsin B not only plays a role in the protein degradation in lysosomes of anterior pituitary endocrine cells but also participates in the activation of renin in gonadotrophs, as has been demonstrated in secretory granules of juxtaglomerular cells.

Animals↗

Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology.

Ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia. Recent studies have shown that RPS19 expression decreases during terminal erythroid differentiation. Currently no information is available on the subcellular localization of normal RPS19 and the potential effects of various RPS19 mutations on cellular localization. In the present study, using wild-type and mutant RPS19 cDNA, we explored the subcellular distribution of normal and mutant proteins in a fibroblast cell line (Cos-7 cells). RPS19 was detected primarily in the nucleus, and more specifically in the nucleoli, where RPS19 colocalized with the nucleolar protein nucleolin. Using various N-terminal and C-terminal deletion constructs, we identified 2 nucleolar localization signals (NoSs) in RPS19: the first comprising amino acids Met1 to Arg16 in the NH2-terminus and the second comprising Gly120 to Asn142 in the COOH-terminus. Importantly, 2 mutations identified in DBA patients, Val15Phe and Gly127Gln, each of which localized to 1 of the 2 NoS, failed to localize RPS19 to the nucleolus. In addition to their mislocalization, there was a dramatic decrease in the expression of the 2 mutant proteins compared to the wild type. This decrease in protein expression was specific for the mutant RPS19, since expression of other proteins was normal. The present findings enable us to document the nucleolar localization signals in RPS19 and help define the phenotypic consequences of some mutations in RPS19 in DBA.

Anemia, Diamond-Blackfan↗

Binding of 14-3-3beta but not 14-3-3sigma controls the cytoplasmic localization of CDC25B: binding site preferences of 14-3-3 subtypes and the subcellular localization of CDC25B.

The dual specificity phosphatase CDC25B positively controls the G2-M transition by activating CDK1/cyclin B. The binding of 14-3-3 to CDC25B has been shown to regulate the subcellular redistribution of CDC25B from the nucleus to the cytoplasm and may be correlated with the G2 checkpoint. We used a FLAG-tagged version of CDC25B to study the differences among the binding sites for the 14-3-3 subtypes, 14-3-3beta, 14-3-3epsilon and 14-3-3sigma, and the relationship between subtype binding and the subcellular localization of CDC25B. All three subtypes were found to bind to CDC25B. Site-directed mutagenesis studies revealed that 14-3-3beta bound exclusively near serine-309 of CDC25B1, which is within a potential consensus motif for 14-3-3 binding. By contrast, 14-3-3sigma bound preferentially to a site around serine-216, and the presence of serine-137 and -309 enhanced the binding. In addition to these binding-site differences, we found that the binding of 14-3-3beta drove CDC25B to the cytoplasm and that mutation of serine-309 to alanine completely abolished the cytoplasmic localization of CDC25B. However, co-expression of 14-3-3sigma and CDC25B did not affect the subcellular localization of CDC25B. Furthermore, serine-309 of CDC25B was sufficient to produce its cytoplasmic distribution with co-expression of 14-3-3beta, even when other putative 14-3-3 binding sites were mutated. 14-3-3epsilon resembled 14-3-3beta with regard to its binding to CDC25B and the control of CDC25B subcellular localization. The results of the present study indicate that two 14-3-3 subtypes can control the subcellular localization of CDC25B by binding to a specific site and that 14-3-3sigma has effects on CDC25B other than the control of its subcellular localization.

14-3-3 Proteins↗

Virtual local target method for avoiding local minimum in potential field based robot navigation.

A novel robot navigation algorithm with global path generation capability is presented. Local minimum is a most intractable but is an encountered frequently problem in potential field based robot navigation. Through appointing appropriately some virtual local targets on the journey, it can be solved effectively. The key concept employed in this algorithm are the rules that govern when and how to appoint these virtual local targets. When the robot finds itself in danger of local minimum, a virtual local target is appointed to replace the global goal temporarily according to the rules. After the virtual target is reached, the robot continues on its journey by heading towards the global goal. The algorithm prevents the robot from running into local minima anymore. Simulation results showed that it is very effective in complex obstacle environments.

Algorithms↗

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program.

PURPOSE: We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. MATERIALS AND METHODS: This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. RESULTS: Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <<0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. CONCLUSIONS: Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.

Adult↗

Capacity-building activities for local leadership in Egypt from the local to the national and regional levels.

In order to make the Sustainable Ismailia Project institutionally sustainable, the National Project Manager identified the need to build the capacity of local leadership. The Training Section, in UNCHS, proposed a capacity-building program designed to respond to this demand focusing on the skill-training and attitude formation needed for effective local leadership. The proposed program is adapted from the "Training for Elected Leadership" series widely tested and used in many regions. It combines direct training for local officials from villages in Ismailia, and indirect training for trainers from the Ministry of Local Administration (MLA). After the course, the MLA trainers would design a training program which they will implement nationally. The Minister for Local Administration decided to finance the translation and production of the manuals, while the Governor of Ismailia offered to cover the trainees' expenses. The UNCHS Training and Capacity-Building Section would provide technical guidance and coordinate and implement the program. Once the Arabic version of the training materials would be available, UNCHS would use it regionally to reach out to other Arab States. This example illustrates how concerned stakeholders cooperate to address capacity-building needs. The UNCHS Training Section assumes the role of facilitator and acts as a catalyst for the formulation of such activities. The feeling of ownership of the locally produced/adapted training materials enhances the propensity of their effective and extensive use. This approach has succeeded across regions, cultures, and languages with out-reaching multiplier effects.

Africa↗

[Expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension].

OBJECTIVE: To investigate the expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension and to discuss their role in the pathogenesis of portal hypertensive vasculopathy. METHODS: RT-PCR was used to detect the expression of local angiotensinogen mRNA in 28 specimens of splenic artery and vein obtained during operation of elective separation and amputation on 28 portal hypertension (PH) patients, 20 males and 8 females, aged 51.7 +/- 10 (30 - 65), and in 12 specimens of normal vessel from 12 patients undergoing splenectomy due to traumatic rupture of spleen. Chemiluminescent electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-kappaB in splenic artery and vein. RESULTS: The levels of local angiotensinogen mRNA in the splenic artery and vein of PH group were 0.48 +/- 0.21 and 0.43 +/- 0.16 respectively, both significantly higher than those in the control group (0.23 +/- 0.12 and 0.18 +/- 0.10, both P < 0.05). There was no significant difference between the splenic artery and vein in the expression of local angiotensinogen mRNA in PH group. The activation levels of NF-kappaB in splenic artery and vein of the PH patients were 1.44 +/- 0.23 and 1.38 +/- 0.18 respectively, both significantly higher than those of the control group (0.19 +/- 0.20 and 0.25 +/- 0.16 respectively, both P < 0.05). However, there was no significant difference in the activation levels of NF-kappaB between the splenic artery and vein in the PH patients (P > 0.05). CONCLUSION: Local angiotensinogen and activation of NF-kappaB maybe one of the factors in the pathogenesis of portal hypertensive vasculopathy, which can cause and advance portal hypertensive vasculopathy.

Adult↗

Comparative estimation of general and local humoral immunity indicators in connection with local immunotherapeutic treatment.

All classes of immunoglobulins in blood and in the nasal secretions of 75 patients were studied in different phases of disease. There were 20 healthy persons in the control group. Forty patients were treated by preseasonal local immunotherapy through the application of water-salt extracts of pollen allergens intranasally, with the help of drops and aerosol during 2 years. It was found that the patients had a high level of total IgE in the nasal secretion, both in the phase of remission and especially in the phase of exacerbation, though the concentration of IgE in the nasal secretion, on the whole, was several times lower than in serum. Quantification of the level of IgE in the nasal secretion can be recommended to diagnosis allergy, "in vitro". The level of sIgA in the nasal secretion of the patients with pollen allergy was lower in comparison with the test group of healthy persons, being most remarkable in the phase of exacerbation. Patients with pollen allergy had a heightened level of IgD in blood with a marked reliability in the exacerbation phase. IgD was not detected in the nasal secretion. Local immunotherapy was found to have a high effectiveness of 80% after one course of treatment, and nearly 95% success with two courses. Therefore, we consider that local immunotherapy should be widely used. With the background of the local immunotherapy there were changes in the concentration of immunoglobulins, mainly in the nasal secretion of the immunoglobulins. IgE in the nasal secretion was lowered to a great extent after two courses of treatment. sIgA after local immunotherapy had a tendency to increase considerably after two courses of treatment. The increase of sIgA level and the lowering of IgE in the nasal secretion can be considered as immunologic criteria of local immunotherapy effectiveness.

Administration, Intranasal↗

Proprioceptive inputs to nonspiking local interneurons contribute to local reflexes of a locust hindleg.

Local reflexes of a leg of the locust Schistocerca gregaria (Forskal) can be elicited by selective stimulation of a proprioceptor (the femoral chordotonal organ) at the femorotibial joint. Motor neurons are either excited or inhibited, so that a coordinated reflex response of a leg results. At the same time, some nonspiking local interneurons are either excited or inhibited by the inputs from these proprioceptive afferents. Altering the membrane potential of an individual, nonspiking interneuron can either increase or decrease the response of the participating motor neurons to the proprioceptive stimulus and thereby alter the gain of the reflex. To determine the pathways, and to understand the role of the nonspiking interneurons in mediating these reflex effects, recordings were made simultaneously from these interneurons and afferent neurons. The excitation of a particular nonspiking local interneuron is produced monosynaptically by the afferent neurons. Chemically mediated EPSPs consistently follow sensory spikes with a latency that is the same as that for the known parallel, direct connections made by these sensory neurons with motor neurons (Burrows, 1987a). The chordotonal afferents and the branches of the local interneurons project to the same regions of neuropil. In contrast, the simplest inhibitory pathway is disynaptic, involving spiking local interneurons. The afferents make direct excitatory connections with some of these spiking interneurons, which then make direct inhibitory connections with a nonspiking interneuron. Interactions between the local interneurons add to the complexity of the pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sestamibi parathyroid scanning and preoperative localization studies for patients with recurrent/persistent hyperparathyroidism or significant comorbid conditions: development of an optimal localization strategy.

For patients with previous thyroid or parathyroid surgery and for those with significant comorbid conditions, noninvasive and invasive modalities exist for the preoperative localization of pathologic parathyroid tissue. Formal localization at our institution involves obtaining two studies that are independently positive for the same location. The studies utilized have included ultrasound, CT scans, MRI, technetium-99m/thallium-201 (Tc-Tl) imaging, and more recently, (99m)Tc-sestamibi (20-25 mCi) (MIBI) scans. These were followed by arteriography and/or venous sampling if necessary. From January 1992 through October 1995, 25 patients underwent preoperative parathyroid localization (10 reoperation, 3 grave hypercalcemia, 2 concurrent goiter, 2 cerebral vascular accident, 1 bleeding disorder, and 1 malignant ventricular arrhythmia) and were evaluated prospectively during the changeover from Tc-Tl to MIBI scanning at our institution. A total of 92 studies were obtained. All 25 patients were operated on by a single surgeon, and in each case the parathyroid adenoma was successfully resected with minimal morbidity (1 permanent hypoparathyroid and 1 temporary recurrent laryngeal nerve injury). True positives interpreted preoperatively: MIBI, 14 of 19 (74%); CT scan, 13 of 19 (68%); Tc-Tl, 4 of 8 (50%), ultrasound, 9 of 20 (45%); MRI, 8 of 14 (57%); arteriography, 3 of 7 (43%); venous sampling, 3 of 4 (75%); and positron emission tomography, 0 of 1. There were no false-positive MIBI scans. These results suggest that when formal parathyroid localization is needed in reoperative/complicated patients, 1) MIBI appears to be the most sensitive and specific study, and 2) the MIBI scan should be the initial study in any situation in which preoperative localization is needed. Ultrasound can be useful for patients with significant comorbidities who have not been previously explored. CT or MRI should then be used if further evaluation is needed. If the use of these noninvasive modalities does not produce positive gland localization, selective venous sampling should be utilized as the definitive procedure.

Adenoma↗

Visual object localization through vestibular and neck inputs. 1: Localization with respect to space and relative to the head and trunk mid-sagittal planes.

Object localization in space signals in the absence of an external reference (visual, auditory, haptic) involves a signal of the head in space (vestibular). The present study asks whether signals of body position relative to the support surface (proprioceptive) are involved as well, by investigating the role of vestibular-neck interaction (dissociating head and trunk position). Normal human subjects saw a light spot (object) and continuously nulled displacement steps of the spot. They did so before and after vestibular and/or neck rotational stimulation in the horizontal plane, reproducing a predesignated object localization in space (i), relative to the head mid-sagittal (ii), and relative to the trunk mid-sagittal (iii). The predominant frequency contained in the stimuli was varied (0.05, 0.1, and 0.4 Hz). (I) Object localization in space upon whole-body rotation (vestibular stimulus) at high frequency was veridical, whereas that at low frequency fell short. Almost identical results were obtained for trunk rotation about the stationary head (neck stimulus). In contrast, when combining the stimuli in the form of head rotation on the stationary trunk, the results were veridical, independent of stimulus frequency. Additional findings obtained with a large variety of vestibular-neck stimulus combinations suggest a linear summation of vestibular and neck signals. (II) Object localization with respect to the head was approximately veridical, being independent of vestibular and neck stimulation. However, this only applied if subjects were not biased by a head-in-space motion illusion of neck origin. (III) Object localization with respect to the trunk was veridical in all conditions tested. The findings support a recently developed concept, according to which humans evaluate the kinematic state of a visual object in space by (a) relating it to that of the body support by means of an essentially ideal proprioceptive coordinate transformation, and (b) relating, in turn, the kinematic state of the support to a vestibularly derived notion of space, using a proprioceptive coordinate transformation that "knows" the vestibular transfer characteristics. One important aspect is that object localization in space always is veridical during head and trunk rotation relative to a stationary support (for example, the ground) despite non-ideal vestibular transfer characteristics. Additional findings in patients with chronic loss of vestibular function confirm this concept.

Adult↗

The use of local anesthesia in second generation extracorporeal shock wave lithotripsy: eutectic mixture of local anesthetics.

Extracorporeal shock wave lithotripsy (ESWL&) can be painful. Of our population of patients treated with a Siemens Lithostar device 51.4% needed intravenous analgesia. A eutectic mixture of local anesthetics, a hydrophylic cream containing 25 mg. lidocaine and 25 mg. prilocaine per gm., proved to be effective for local analgesia. Therefore, we investigated its effectiveness during ESWL. With randomized, double-blind application the eutectic mixture of local anesthetics and placebo were evaluated in 83 patients according to the percentage of patients who required intravenous analgesia during ESWL. Of 40 patients treated with the eutectic mixture of local anesthetics 12 (30%) needed supplementary fentanyl citrate, compared to 23 of 43 (53%) placebo treated patients. Although there is no statistical significance (p = 0.32), the eutectic mixture of local anesthetics does decrease pain during ESWL and it should be particularly useful for patients in whom intravenous analgesia is contraindicated.

Adult↗

The assessment of pain sensation during local anesthesia using a computerized local anesthesia (Wand) and a conventional syringe.

PURPOSE: The purpose of this study was to compare the behavior reaction of children who received local anesthesia with a conventional syringe injection and a computerized device (Wand). METHODS: One hundred and two children ages 3 to 10 years were selected for this study. In 1 group there were 55 children between the ages of 3 to 5 years old, and in the other group there were 47 children ages 6 to 10 years old. They all needed at least 2 clinical sessions of operative procedures, preceded by a local anesthetic injection, 1 on either side of the same jaw. The local anesthesia was delivered using either the Wand or the traditional syringe. A random crossover design was used so that each child served as his/her own control. RESULTS: There were 25 girls and 30 boys in group A (mean 4.1 +/- 0.6 years), and 26 boys and 21 girls in group B (mean 7.2 +/- 1.3 years). Most of the children had a good reaction to both techniques of local anesthesia. No significant difference in either group was found between boys and girls. The children's reactions to injection in the mandible or the maxilla with the Wand or the conventional technique, regarding crying, facial expression, hands, legs and torso movements were similar with no statistically significant difference. There was no statistical difference when the maxillary infiltration was delivered to 1 or multiple teeth. No significant difference was found when the Wand was delivered during the first or second visit. CONCLUSIONS: The results suggested there was no difference in the pain behavior of children during the administration of local anesthesia with a conventional injection or a computerized device when the operator was an experienced pediatric dentist. This was true for maxillary infiltration and mandibular block. For other techniques, such as palatal injection and periodontal ligament injection, more studies should be conducted.

Anesthesia, Dental↗

Mammographically detected duct carcinoma in situ. Frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence.

Seventy-nine patients with mammographically detected foci of duct carcinoma in situ (DCIS) of histologically confirmed extents of 25 mm or less, were treated by tylectomy without irradiation or axillary dissection. Adequacy of excision was confirmed histologically, by radiographic-pathologic correlation and by postoperative mammographic examination. Eight patients (10.1%) have recurred locally in the immediate vicinity of the biopsy site. Four patients developed recurrent in situ disease identified mammographically, and all were initially treated by reexcision. One of these patients subsequently elected to undergo mastectomy; no residual in situ or invasive disease was detected in the breast or in axillary lymph nodes. Four patients developed recurrent invasive disease; 50% of these recurrences were detected mammographically. All patients were treated by mastectomy with node dissection. Three had confirmed minimal invasive carcinomas and were N0, one patient had a 13-mm invasive lobular carcinoma with a single Group I micrometastasis. All patients, including those treated for a recurrence, are presently free of disease but three patients died of heart disease. Nuclear grade would appear to identify subsets of DCIS more likely to produce local failure after tylectomy alone. Duct carcinoma in situ with high-grade nuclear morphology and comedo-type necrosis was associated with a 19% local recurrence rate after an average interval of 26 months; only one of ten patients with intermediate-grade DCIS developed a local recurrence at 87 months; and none of 33 patients with DCIS of micropapillary/nonnecrotic cribriform type and low-grade nuclear morphology developed local recurrence in the follow-up period.

Breast Neoplasms↗

Prediction of local recurrence and survival of carcinoma of the rectum by surgical and histopathological assessment of local clearance.

The surgeon and histopathologist were asked to assess whether clearance of the resected primary rectal tumour was complete or not. The results of each assessment were related to survival and recurrence rates. Of 478 patients entered, full information was available for 396 who were followed to death or for at least 5 years. The surgeon and pathologist agreed on the clearance in 341 of the 396 patients. The 5-year local recurrence rate was 15 per cent in the 331 patients with complete local clearance and 62 per cent in those with incomplete clearance. There was disagreement regarding 55 patients (14 per cent) (39 pathologist 'incomplete'/surgeon 'complete'; 16 surgeon 'incomplete'/pathologist 'complete'). Local recurrence occurred later where the pathologist assessed resection to be incomplete (log rank chi 2 = 11.0, 1 d.f., P = 0.001). Of 321 patients without metastatic disease, the surgeon and pathologist agreed in 290 that 284 had complete and six incomplete clearance. The 5-year survival rates were 53 and 0 per cent respectively. There was disagreement regarding 31 patients (10 per cent) (11 surgeon 'incomplete'/pathologist 'complete'; 20 pathologist 'incomplete'/surgeon 'complete'). The 5-year survival rates were 18 and 10 per cent respectively (log rank chi 2 = 1.5, 1 d.f., P = 0.2). Surgical and histopathological assessments of local clearance are important in determining local recurrence and survival.

Adenocarcinoma↗