Transposition of the malpositioned nipple-areola complex in breast reconstruction with implants.

BACKGROUND: The goal of breast reconstruction after breast cancer is to obtain symmetrical breasts, including the nipple-areola complex. However, in some cases the nipple-areola complex may not be symmetrical even though a symmetrical breast shape has been created. In such cases the nipple-areola complex has been transpositioned, leaving a scar to close the wound or skin graft in the original position. METHODS: To treat this problem, skin surrounding the areola is removed and two pedicles are created to bear the nipple-areola complex. The nipple-areola complex is then moved to the proposed position and the surrounding circular edge of the skin is closed using a purse-string suture. RESULTS: The author performed this technique in three nipple-areolae of two patients. All the nipple-areolae were transposed to the proposed position to create symmetrical breasts without any complications. CONCLUSION: This technique can be used when the malpositioned nipple-areola complex is not too far from the proposed position. The nipple-areola complex can be moved without leaving any scar at the original position of the complex.

Genetic and epigenetic alterations in the differential diagnosis of malignant melanoma and spitzoid lesion.

BACKGROUND: The histopathological differentiation of malignant melanoma and Spitz naevus often presents diagnostic problems. OBJECTIVES: We aimed to find out applicable diagnostic parameters other than routine pathology. METHODS: The cases included conventional melanomas and Spitz naevi as well as atypical spitzoid lesions that had posed diagnostic difficulties. We examined hotspots of mutation in the BRAF, NRAS and HRAS genes by polymerase chain reaction-based direct sequencing. We also analysed DNA copy number aberrations and the methylation of CpG sequences in several cancer-related genes by utilizing a novel methylation-specific multiplex ligation-dependent probe amplification method. RESULTS: Twenty three of 24 conventional melanomas showed at least one of the genetic and epigenetic alterations examined, although one acral melanoma did not show any alteration. By sharp contrast, 12 Spitz naevi with an unambiguous histopathology showed no or few chromosomal aberrations, no oncogene mutations and no methylation of CpG sequences. Of the 16 ambiguous spitzoid lesions, most of which were designated atypical Spitz tumour by one of the authors, all but one showed no mutations, no methylations and few copy number aberrations. However, three tumours showed copy number loss of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A), an alteration observed frequently in melanomas but not found in conventional Spitz naevi. These results show that, although most atypical Spitz tumours do not differ from conventional Spitz naevi showing virtually no genetic and epigenetic aberrations, some cases may have chromosomal aberrations that include copy number loss of the CDKN2A gene. CONCLUSIONS: Genetic and epigenetic analyses may be useful as an additional diagnostic tool to distinguish between melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz tumours.

Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12.

Two new human ABC transporters, ABCC11 and ABCC12, were cloned from a cDNA library of human adult liver. ABCC11 and ABCC12 genes consist of 30 and 29 exons, respectively, and they are tandemly located in a tail-to-head orientation on human chromosome 16q12.1. The predicted amino acid sequences of both gene products show a high similarity with ABCC5. The transcripts of ABCC11 and ABCC12 genes were detected by PCR in various adult human tissues, including liver, lung, and kidney, and also in several fetal tissues. By searching cDNA libraries from various human tissues, we have identified alternative splicing variants of ABCC11 and ABCC12 genes at significantly high frequencies. One splice variant lacking the exon 28 corresponded to about 25% of total ABCC11 gene transcripts. Furthermore, four splicing variants encoding putatively short peptides were predominant in ABCC12 gene transcripts. Those splicing variants may represent diverse biological functions of these ABC transporter genes.

Generalized Wegener's granulomatosis responding to sulfamethoxazole-trimethoprim monotherapy.

Wegener's granulomatosis (WG) has two different clinical phases: the initial phase and generalized phase. In patients with generalized WG, both steroids and cyclophosphamide have generally been used. We report a case of generalized WG that was temporarily, but successfully treated with sulfamethoxazole-trimethoprim (S/T) alone. S/T therapy reduced the elevated levels of soluble IL-2 receptor and IL-6 in parallel with improvement of the patient's symptoms and urinary protein excretion. In view of the high incidence of lethal adverse effects of cytotoxic drugs, S/T monotherapy may be worth trying not only for initial phase WG but also for generalized WG with careful follow-up when the patient is not acutely ill.

In isolated DNA, formamidopyrimidine-DNA glycosylase-sensitive sites determined by electrophoresis correspond to the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine by HPLC-ECD.

Several methods have been developed for determining the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in DNA. In the present study, we compared an electrophoretic method that uses formamidopyrimidine-DNA glycosylase (FPG protein) with a HPLC-ECD method. Firstly, we produced 8-oxodG in lambda DNA with methylene blue and visible light and cleaved it in one-half of the modified DNA enzymatically with FPG protein. Then, we determined the number of FPG protein-sensitive sites by electrophoresis (Y) and the number of 8-oxodGs by HPLC-ECD (X) per 10(5)dG of isolated DNA. Simple regression analysis of the data showed Y=1.07X+1.52 to be the most likely relationship. The correlation coefficient was 0.97. The values obtained by the two methods were very similar. This result is noteworthy because the number of FPG protein-sensitive sites determined by other methods have not yet come close to the number obtained by HPLC-ECD. Thus, this method might be more quantitative than other methods that measure FPG protein-sensitive sites. Another reason this electrophoresis method might be more useful than HPLC-ECD is that we can determine some other types of oxidative DNA damage well, by changing the DNA glycosylase.

Examination of the neighborhood activation theory in normal and hearing-impaired listeners.

OBJECTIVE: Experiments were conducted to examine the effects of lexical information on word recognition among normal hearing listeners and individuals with sensorineural hearing loss. The lexical factors of interest were incorporated in the Neighborhood Activation Model (NAM). Central to this model is the concept that words are recognized relationally in the context of other phonemically similar words. NAM suggests that words in the mental lexicon are organized into similarity neighborhoods and the listener is required to select the target word from competing lexical items. Two structural characteristics of similarity neighborhoods that influence word recognition have been identified; "neighborhood density" or the number of phonemically similar words (neighbors) for a particular target item and "neighborhood frequency" or the average frequency of occurrence of all the items within a neighborhood. A third lexical factor, "word frequency" or the frequency of occurrence of a target word in the language, is assumed to optimize the word recognition process by biasing the system toward choosing a high frequency over a low frequency word. DESIGN: Three experiments were performed. In the initial experiments, word recognition for consonant-vowel-consonant (CVC) monosyllables was assessed in young normal hearing listeners by systematically partitioning the items into the eight possible lexical conditions that could be created by two levels of the three lexical factors, word frequency (high and low), neighborhood density (high and low), and average neighborhood frequency (high and low). Neighborhood structure and word frequency were estimated computationally using a large, on-line lexicon-based Webster's Pocket Dictionary. From this program 400 highly familiar, monosyllables were selected and partitioned into eight orthogonal lexical groups (50 words/group). The 400 words were presented randomly to normal hearing listeners in speech-shaped noise (Experiment 1) and "in quiet" (Experiment 2) as well as to an elderly group of listeners with sensorineural hearing loss in the speech-shaped noise (Experiment 3). RESULTS: The results of three experiments verified predictions of NAM in both normal hearing and hearing-impaired listeners. In each experiment, words from low density neighborhoods were recognized more accurately than those from high density neighborhoods. The presence of high frequency neighbors (average neighborhood frequency) produced poorer recognition performance than comparable conditions with low frequency neighbors. Word frequency was found to have a highly significant effect on word recognition. Lexical conditions with high word frequencies produced higher performance scores than conditions with low frequency words. CONCLUSION: The results supported the basic tenets of NAM theory and identified both neighborhood structural properties and word frequency as significant lexical factors affecting word recognition when listening in noise and "in quiet." The results of the third experiment permit extension of NAM theory to individuals with sensorineural hearing loss. Future development of speech recognition tests should allow for the effects of higher level cognitive (lexical) factors on lower level phonemic processing.

Atypical Fabry's disease presenting with cholesterol crystal embolization.

We describe a 65-year-old man who presented with pulmonary hemorrhage and progressive renal insufficiency three months after resection surgery for an abdominal aortic aneurysm. Intensive treatment with corticosteroids and hemodialysis were not effective, and the patient died. Postmortem examination of the kidneys revealed widespread cholesterol clefts within the renal arterioles and a number of lamellar inclusion bodies were observed by electron microscopy. The diagnosis of Fabry's disease was made by the absence of plasma alpha-galactosidase A activity. This was a very rare case of subclinical Fabry's disease coexistent with cholesterol crystal embolization, mimicking pulmonary-renal syndrome.

An examination of graduate students' statistical judgments: statistical and fuzzy set approaches.

The present study examined how statistical significance levels are treated and interpreted by graduate students who use hypothesis-testing in their scientific investigation. To test underlying psychological aspects of hypothesis-testing, the idea of fuzzy set theory was employed to identify the uncertain points in judgments. 34 graduate students in a psychology department made judgments about hypothetical statistical decisions. The results indicated that (1) the majority of these students treated significance levels on a continuum and rated them according to the magnitude of statistical significance; (2) the subjects shifted their decisions based on the types of hypothetical scenarios but not by the sample sizes; instead, they interpreted a smaller sample size as being less reliable. (3) The subjects frequently chose formally used statistical terms, e.g., Significant and Not Significant, more than graduated verbal expressions, e.g., Marginally Significant and Borderline Significant; and (4) the Fuzziness (degree of confidence in decision-making) was dependent on individuals and existed more in the critical points of transition where judgments are most difficult. The Fuzziness Index illustrated the subtle shifts of human decision-making patterns in statistical judgments. Underlying decision uncertainties and difficulties can be illustrated by functions generated from fuzzy set theory, which may more closely resemble human psychological mechanism. This integrative study of fuzzy set theory and behavioral measurements appears to provide a technique that is more natural for examining and understanding imprecise boundaries of human decisions.

Relation between coronary thrombus and angiographic no-flow during primary angioplasty in patients with acute myocardial infarction.

No flow is an unsolved issue in primary percutaneous transluminal coronary angioplasty (PTCA) for patients with acute myocardial infarction (AMI), and the pathophysiology of no-flow is undetermined. To evaluate the potential participation of coronary thromboembolism in no-flow during primary PTCA, the present study reviewed cinefilms of 256 consecutive patients who underwent primary PTCA for AMI within 24h after the onset of chest pain between January 1992 and June 1998, focusing on the thrombus size. Angiographic no-flow was defined as the cessation of flow into the distal coronary circulation of the treated vessel with a to-and-fro contrast movement, not attributable to high-grade stenosis or spasm of the original target lesion. The coronary thrombus size was determined by using the 2-cm balloon catheter as a reference after crossing the infarct-related occluded artery with a guide wire. Angiographic no-flow was observed in 37 patients (37/256, 14%): 14 of 29 cases (48%) with a large thrombus (> or =2cm) versus 23 of 227 cases (9%) with a small thrombus (<2cm, 14/29 vs 23/227, p<0.01). Among 37 patients who experienced angiographic no-flow, overt distal emboli were observed in 14 patients. A thrombolytic agent was used through a guiding catheter in 102 cases prior to or after balloon dilatation to prevent or attenuate distal embolism, particularly in all those cases with a large thrombus (29/29 100%), and angiographic no-flow was seen in 27 cases of this subgroup (27/102, 26%). It is suggested that distal thromboembolism plays an important role in the mechanism of angiographic no-flow during primary PTCA performed for AMI.

Primary small cell carcinoma of the esophagus with achalasia in a patient in whom pro-gastrin-releasing peptide and neuron-specific enolase levels reflected the clinical course during chemotherapy.

We report a case of primary small cell carcinoma of the esophagus in a patient with achalasia in whom pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) levels were measured. Although chemotherapy markedly reduced the size of the primary tumor and lymph node metastases, it had no effect on liver metastases. The tumor marker levels decreased after chemotherapy as the primary tumor and lymph node metastases decreased in size, and they increased as the liver metastases enlarged. However, there was a discrepancy between the levels of ProGRP and NSE during the patient's clinical course. We demonstrate the usefulness of measuring ProGRP and NSE levels to assess the effect of chemotherapy in patients with esophageal small cell carcinoma.

Subjective judgements of clarity and intelligibility for filtered stimuli with equivalent speech intelligibility index predictions.

The purpose of this investigation was to determine whether subjective judgments of clarity or intelligibility would be rated equally among conditions in which speech was equated for predicted intelligibility (using the Speech Intelligibility Index, SII) but varied in bandwidth. Twenty listeners with normal hearing rated clarity and intelligibility for sentence material (Hearing In Noise Test) in speech-shaped noise at six paired low- and high-pass filtered conditions in which SII was equated for each pair. For three paired conditions, predicted intelligibility increased as SII increased monotonically (0.3, 0.4, 0.5). In the remaining paired conditions, SII continued to increase monotonically (0.6, 0.7, 0.8) but predicted intelligibility was held at a maximal level (> or = 95%). Predicted intelligibility was estimated from the transfer function relating SII to speech recognition scores determined in preliminary experiments. Differences in ratings between paired low- and high-pass filtered sentences did not reach statistical significance for either clarity or intelligibility, indicating that the spectral differences at equivalent SIIs did not influence the judgments for either of the two dimensions. For conditions in which predicted intelligibility increased, both clarity and intelligibility ratings increased in a similar manner. For conditions in which predicted intelligibility was maximized, intelligibility ratings remained the same statistically across conditions while clarity ratings changed modestly. Although high correlations were observed between clarity and intelligibility ratings, intelligibility ratings were consistently higher than clarity ratings for comparable conditions. The results indicated that listeners with normal hearing produced clarity and intelligibility ratings for the same speech material and experimental conditions that were highly related but differed in magnitude. Caution is required when substituting clarity for intelligibility.

Sulfolobus hakonensis sp. nov., a novel species of acidothermophilic archaeon.

We characterized a microbial strain that was isolated from a hot spring at a geothermal area in Hakone, Japan. This isolate, whose lobed-shaped cells were about 1.0 micron in diameter, was a facultative chemolitho-autotroph that required aerobic conditions for growth. The optimum pH was 3.0 (pH range, 1.0 to 4.0), and the optimum temperature was 70 degrees C (temperature range, 50 to 80 degrees C). Lithotrophically, this strain grew on elemental sulfur and reduced sulfur compounds. The G+C content of the genomic DNA was 38.4 mol%. This organism contained calditoglycerocaldarchaeol, which is characteristic of members of the Sulfolobaceae. The levels of 16S rRNA sequence similarity between the new isolate and Sulfolobus acidocaldarius, Sulfolobus solfataricus, and Sulfolobus shibatae were less than 89.8%. Unlike S. acidocaldarius, S. solfataricus, and S. shibatae, the new isolate utilized sugars and amino acids poorly as sole carbon sources, and the levels of DNA-DNA hybridization between the new isolate and these Sulfolobus species were very low. Phenotypically, the new isolate was also distinct from the obligately lithotrophic organism Sulfolobus metallicus. We concluded that the new organism belongs to a new Sulfolobus species, for which we propose the name Sulfolobus hakonensis.

Varicella pneumonia in a healthy adult presenting with severe respiratory failure.

We describe a case of varicella pneumonia in a 24-year-old healthy man presenting with severe respiratory failure. A chest radiograph showed diffuse, bilateral airspace consolidation; additional complications included liver dysfunction and thrombocytopenia. However, treatment with intravenous acyclovir and gamma-globulin improved his clinical symptoms and signs. A greater than four-fold change in paired titers of the varicella-zoster virus antibody was observed. Bronchoalveolar lavage performed during the recovery phase revealed increased total cell and lymphocyte counts and a decreased CD4:CD8 ratio of T lymphocytes. Transbronchial lung biopsy findings were compatible with a diagnosis of interstitial pneumonia.

Redundant leading and following zeros in comparative numerical judgment.

The objective was to provide a more comprehensive understanding of how people make numerical comparative judgments when digits are contained in numbers with redundant leading or following zeros, e.g., 00080 and 800.000. These sequences of numbers often appear on computer display terminals (VDT) as line numbers, but surprisingly little research has been done on this. The experiment manipulated three aspects of numerical stimuli: (1) redundant leading zeros, (2) redundant following zeros, and (3) length of string of digits. The subjects were to push one of the two button-switches to respond whether two stimulus numbers shown on the computer screen were equal or unequal. The target stimuli contained several forms of redundant zeros, and each performance was assessed by response RT of the subjects. Analysis indicated five significant findings: (1) Redundant leading zeros hindered performance, (2) The effect of redundant following zeros depended on the stimulus type, (3) Over-all, longer digits took more processing time, (4) The RTs for the second-block trials were significantly faster than the first, and (5) Task performance was facilitated when the redundant zero representations were identical in both stimuli of a pair. Nonlexicographic processing seems to occur when feature identification can be used for numerical identification, that is, when the format is consistent. The research has implications for those in computer science to provide numerical formats which make comparative judgments as easy as possible.

Serotonin uptake and its modulation in rat jejunal enterocyte preparation.

In order to determine the properties of the intestinal serotonin (5-HT) transport system, we studied 5-HT uptake by villous cell preparations isolated from the rat jejunum. These enterocytes, probably heterogenous in cell population, accumulated 5-HT against concentration gradient up to a concentration 28 times that in the medium; this accumulation occurred in a temperature-dependent fashion. Most of the uptake was the result of a saturable process at low substrate concentrations. The saturable uptake was inhibited by 1 mM potassium cyanide or 1 mM ouabain or by substitution of other cations and sugars for Na+ in the medium. On the other hand, neither several amino acids nor putrescine had any effect on 5-HT uptake. Kinetic analysis yielded a Km value of 3.63 x 10(-7) M and a Vmax value of 5.76 pmol.10(6) cells-1.min-1 for this uptake process. Imipramine inhibited 5-HT uptake in a concentration-dependent fashion, with a Ki value of 3.66 x 10(-7) M. 5-HT uptake was also inhibited by ethyleneglycol-0,0'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid, by verapamil, by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide and by phorbol 12-myristate 13-acetate. These findings suggest that the present enterocyte preparation had a relatively specific secondary active transport system for 5-HT.

DNA Damage Levels Determine Cyclobutyl Pyrimidine Dimer Repair Mechanisms in Alfalfa Seedlings.

Ultraviolet radiation in sunlight damages DNA in plants, but little is understood about the types, lesion capacity, and coordination of repair pathways. We challenged intact alfalfa seedlings with UV doses that induced different initial levels of cyclobutyl pyrimidine dimers and measured repair by excision and photoreactivation. By using alkaline gel electrophoresis of nonradioactive DNAs treated with a cyclobutyl pyrimidine dimer-specific UV endonuclease, we quantitated ethidium-stained DNA by electronic imaging and calculated lesion frequencies from the number average molecular lengths. At low initial dimer frequencies (less than ~30 dimers per million bases), the seedlings used only photoreactivation to repair dimers; excision repair was not significant. At higher damage levels, both excision and photorepair contributed significantly. This strategy would allow plants with low damage levels to use error-free repair requiring only an external light energy source, whereas seedlings subjected to higher damage frequencies could call on additional repair processes requiring cellular energy. Characterization of repair in plants thus requires an investigation of a range of conditions, including the level of initial damage.

Influence of mood and adjustment to cancer on compliance with chemotherapy among breast cancer patients.

Approximately 75% of the 181,000 breast cancer patients newly diagnosed in 1992 will survive for at least 5 yr, but survival often depends on receiving adjuvant chemotherapy. We determined that mood variables and attitude toward cancer could predict compliance with IV-administered chemotherapy. The participants were seventy-four women diagnosed with primary breast cancer receiving treatment at a state-supported medical center in one of three southeastern metropolitan areas in the U.S. Most patients were members of minority and lower socioeconomic groups. The design was prospective in the sense that mood and attitude variables were assessed before determination of compliance. Two psychological instruments were used in this study, the Mental Adjustment to Cancer (MAC) Scale and the Affects Balance Scale (ABS). Patients who kept fewer than 85% of their appointments were classified as noncompliant; those keeping 85% or more were classified as compliant. Sixty-three percent of the patients for whom the compliance information was complete were classified as compliant; 37% were noncompliant; and four patients were not included in the analysis because their records were incomplete. The discriminant function was able to correctly classify 86% of the patients according to chemotherapy compliance, a 36% improvement over the chance level. High scores on MAC Fighting Spirit and ABS Anxiety, Depression, and Vigor scales were associated with greater adherence to a chemotherapy regimen. High scores on ABS Guilt and Hostility scales predicted lower levels of compliance.