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Biomedical subjects

P S Dale

Publications and source records attributed to P S Dale.

At least 19 recordsLinked to original sources

Lexical and grammatical development: a behavioural genetic perspective.

The relation of lexical and grammatical knowledge is at the core of many controversies in linguistics and psycholinguistics. Recent empirical findings that the two are highly correlated in early language development have further energized the theoretical debate. Behavioural genetics provides an illuminating new tool to explore this question, by addressing the question of whether the empirical correlation simply reflects the fact that environments which facilitate one aspect of language growth also facilitate the other, or whether the same underlying acquisition mechanisms, influenced by the same genes, are responsible for the correlation. We explored this issue in a study of 2898 pairs of two-year-old twins born in England and Wales. Language development was assessed by their parents using an adapted version of the MacArthur Communicative Development Inventory which assesses vocabulary and grammar. Moderate heritabilities were found for both. As in previous studies, measures of vocabulary and sentence complexity were substantially correlated (r = 0.66). Behaviour-genetic modelling of the relation of vocabulary and grammar produced an estimated value of 0.61 for the genetic correlation, a measure of the overlap of the genetic effects that contribute to the two aspects of language development. In contrast, a measure of nonverbal cognitive development, the PARCA, was only weakly correlated at both the phenotypic level and at the level of genetic correlations with the language measures. Thus, although the distinction between verbal and nonverbal skills has a genetic basis underlying the phenotypic dissociation, there is little evidence either genetically or phenotypically for a dissociation between vocabulary and grammar within language.

Child Language↗

Sentinel lymphadenectomy for staging patients with intermediate-level melanoma.

Sentinel lymph node dissection (SLND) as originally described by D.L. Morton et al. (Surg Oncol Clin North Am 1992;1:247-59), is currently being used at most tertiary institutions for staging patients with intermediate-level melanomas. Identification and subsequent surgical resection of occult metastasis before the development of clinical disease may improve survival in these patients. This study is a retrospective review of patients with intermediate melanomas treated by the senior author (P.S.D.). Isosulfan blue dye and a radioactive technetium-labeled dye were used to identify the sentinel node. Sentinel nodes were evaluated by routine hematoxylin and eosin staining, immunohistochemical staining for S-100 and HMB-45, and later in the study with multipanel reverse transcriptase-polymerase chain reaction analysis. All patients were followed closely. Fifty-seven patients with primary melanoma were evaluated between December 1995 and June 1998. Thirty-two patients underwent SLND; two patients underwent SLND on two separate drainage basins, for a total of 34 procedures. The median age was 49 years (range, 19-77). There were 11 females and 21 males. The locations of the primary melanoma were: head and neck, seven; extremity, 8; and trunk, 18; 1 patient had a dual primary melanoma at presentation. Clark's levels of invasion among the patients were level III, 5; and level IV, 27; median Breslow thickness was 1.4 mm (range, 0.45-3.8 mm). A sentinel node was not identified in four procedures (11.1%). Twenty-two nodes (73%) were negative by all methods, and eight (27%) were positive by at least one method. All positive patients underwent complete lymphadenectomy, and routine hematoxylin and eosin stains identified no additional positive nodes. Median follow-up was 21 months (6-36 months). Two patients developed recurrent disease. The other 30 patients remain disease free at last follow-up. SLND is a low-morbidity technique that accurately stages patients with intermediate-level melanoma. Early intervention with complete therapeutic lymphadenectomy and possible interferon therapy may improve the survival of patients with stage III melanoma. A complete discussion of the technique for SLND and an update of this data is presented.

Adult↗

Genetic and environmental origins of verbal and performance components of cognitive delay in 2-year-olds.

The authors investigated the etiology of several measures of cognitive delay. Verbal (V) and performance (P) abilities were assessed in over 3,000 pairs of 2-year-old twins. Group-differences heritability for general delay (the lowest 5% of the V and P composite) was 35%. However, V and P delays considered independently showed large differences in group heritability (77% for V vs. 40% for P). Specific delays with comorbid cases eliminated showed an even greater difference in group heritability (78% vs. 22%, respectively). The small sample comorbid for both V and P delay also yielded high group heritability for both V (77%) and P (93%) scores. Shared environmental factors also differed in magnitude for V (20%) and P (41%) delays. Because the genetic and environmental origins of V and P delays in infancy differ, they are better considered separately rather than combined into a composite measure of general cognitive delay.

Child, Preschool↗

Cryosurgical ablation of unresectable hepatic metastases.

BACKGROUND AND OBJECTIVES: Recent advancements in the technology of cryosurgery along with the development and refinement of intraoperative ultrasound have led to a feasible alternative for some patients with unresectable hepatic malignancy. This paper reports our first year's experience with cryosurgical ablation of unresectable hepatic malignancies. METHODS: From May 1996 to July 1997, 12 patients with colorectal hepatic metastases underwent exploration for possible resection and/or cryosurgery. At surgery, three patients had extensive disease and were not candidates for any surgical treatment, three underwent formal right hepatic lobectomy, five underwent a combination of resection and cryoablation, while one underwent cryoablation alone. RESULTS: In the six patients who received cryosurgery, the mean number of metastatic lesions was four (range 1-6). The mean number of lesions frozen was two (range 1-4) with a mean size of 2.5 cm. (range 1-5 cm). There were no intraoperative deaths and no major postoperative complications. All patients were discharged home in stable condition with a mean hospital stay of eight days (range 5-14 days). At a mean follow-up of 17.3 months (range 10-22) three patients were alive with disease and three were disease free. CONCLUSIONS: Cryosurgical ablation is a safe method of treating unresectable hepatic malignancies and it may extend survival in carefully selected patients.

Adenocarcinoma↗

Genetic influence on language delay in two-year-old children.

Previous work suggests that most clinically significant language difficulties in children do not result from acquired brain lesions or adverse environmental experiences but from genetic factors that presumably influence early brain development. We conducted the first twin study of language delay to evaluate whether genetic and environmental factors at the lower extreme of delayed language are different from those operating in the normal range. Vocabulary at age two was assessed for more than 3000 pairs of twins. Group differences heritability for the lowest 5% of subjects was estimated as 73% in model-fitting analyses, significantly greater than the individual differences heritability for the entire sample (25%). This supports the view of early language delay as a distinct disorder. Shared environment was only a quarter as important for the language-delayed sample (18%) as for the entire sample (69%).

Child, Preschool↗

Axillary staging utilizing selective sentinel lymphadenectomy for patients with invasive breast carcinoma.

The clinical staging of the regional lymphatics in patients with breast carcinoma is currently receiving much attention in the medical literature. However, controversy still exists regarding surgical staging of the axilla. Most recently, the technique of selective sentinel lymphadenectomy has been applied to staging of breast carcinoma. Our experience with this technique is presented. From July 1, 1995 through December 31, 1996, 20 patients underwent 21 selective sentinel lymphadenectomies prior to level I, level II, and partial level III axillary dissections. There were 13 modified radical mastectomies and 8 segmental mastectomies. The median number of lymph nodes per specimen was 9 (range, 1-31). The sentinel node was identified in 14 patients (66%). Dual sentinel nodes were identified during 3 procedures. The sentinel nodes were negative in 9 procedures, of which all axillary nodes dissected were negative. The sentinel node was positive in 5 procedures for a 100 per cent predictive value. The sentinel node was the only positive node in 3 of the 5 patients, and 2 of these were microscopic (less than 2 mm). There were no associated complications due to the sentinel node biopsy. These results add to the growing literature supporting the feasibility of the sentinel node technique for accurately staging breast carcinoma. This technique is sensitive and specific and can be performed with minimal morbidity.

Adenocarcinoma↗

Metastasis of primary melanoma to two separate lymph node basins: prognostic significance.

BACKGROUND AND METHODS: Depending on the location of the primary lesion, melanoma patients may develop metastases in more than one regional lymph node basin. To determine whether this is prognostically significant, we reviewed our experience with melanoma patients who had undergone regional lymphadenectomy (RLND) in two separate basins. RESULTS: Of 3,603 patients who underwent RLND between April 1971 and January 1993, 406 underwent procedures in two separate basins; of these, 120 (30%) had metastases in both basins and 124 (30%) had metastases in one basin. When calculated from the first positive RLND, 1-year, 3-year, and 5-year survival rates were 82%, 48%, and 33%, respectively, for patients with dual-basin involvement and 88%, 59%, and 48%, respectively, for patients with single-basin involvement (p = 0.0173). Median survival from the first positive RLND was 33.5 months for dual-basin involvement and 56.6 months for single-basin involvement. Univariate analysis demonstrated that Breslow thickness of the primary melanoma, clinical status of the regional lymph nodes, number of positive RLNDs, and tumor burden (total number of positive lymph nodes) were significant indicators of survival. The patient's age and gender, the anatomic location and Clark level of the primary melanoma, the disease-free interval before regional metastasis, and the site and timing of RLNDs were not significant by univariate analysis. Multivariate analysis demonstrated significance for Breslow thickness, number of positive RLNDs, and tumor burden. CONCLUSIONS: The survival rate of melanoma patients with regional metastases in two lymph node basins is lower than that of patients with an equal tumor burden confined to a single basin. This suggests that primary melanomas metastasizing to more than one lymph node basin may have a higher metastatic potential, or that dual-basin involvement may increase the risk of systemic spread. We advocate lymphatic mapping, sentinel node biopsy, and selective lymphadenectomy as a cost-effective technique with little morbidity to identify and manage occult metastases in patients who have two lymph basins at risk.

Adult↗

Early detection of cervical cancer by visual inspection: a population-based study in rural India.

A total of 3784 women aged 35 and above living in 26 villages in rural Maharashtra state, India, were invited to undergo a pelvic examination, to evaluate the performance of unaided visual inspection by trained paramedical workers in detecting cervical cancer. Of this number, 2135 (56.4%) women complied with the invitation. Paramedical workers scored 1120 (57.3%) and 118 (6%) women as having abnormal cervices using the low- and high-threshold criteria respectively. There was good agreement between the visual findings of the paramedical workers and those of a gynaecologist. All subjects had a cervical smear. A total of 10 cervical cancers were detected by cytology/histology. The sensitivity of visual inspection by paramedical workers to detect cervical cancer was 90.0% using the low threshold and 60.0% with the high threshold to define a positive test. The values for specificity were 42.8% and 94.5% respectively. The results obtained by the gynaecologist were very similar. Cost savings implied by limiting cytology/other investigations to approximately half of the population pre-selected on the basis of visual inspection are likely to be offset by the necessity to repeat the test at frequent intervals, repeated follow-up visits and other investigations.

Adult↗

Nipple-areolar preservation during breast-conserving therapy for subareolar breast carcinomas.

OBJECTIVE: To determine if women with subareolar breast carcinoma can be successfully treated by breast-conserving therapy consisting of segmental mastectomy that preserves the nipple-areolar complex, axillary lymph node dissection, and postoperative irradiation. DESIGN: Prospective study. SETTING: Tertiary care cancer center. PATIENTS: Twenty-five patients; median age, 56 years; median tumor diameter, 1.4 cm; and median follow-up, 48 months. INTERVENTION: Breast-conserving therapy for subareolar primary breast carcinoma. RESULTS: Two patients had positive surgical margins of resection, and another patient underwent simple mastectomy after developing a local recurrence. Nipple-areolar distortion was the most common cosmetic deformity after breast-conserving therapy, but overall cosmesis was good. At the most recent follow-up, all patients were free of disease. CONCLUSION: Patients who have small subareolar primary breast carcinomas without evidence of nipple involvement are candidates for breast-conserving therapy with nipple-areolar preservation.

Adult↗

Improved survival in cervical cancer cases in a rural Indian population.

In the first Rural Cancer Registry in India, 194 cervical cancer cases were registered during 1988-91. The 3 year survival was significantly higher in cases registered in 1990-91 (40.0%), than in those registered in the earlier years (26.6%). This improvement was due to the cancer education activities undertaken by the Registry.

Female↗

Improved stage at diagnosis of cervical cancer with increased cancer awareness in a rural Indian population.

As part of its strategy to identify cancer cases in a rural population, the cancer registry of Barshi, India, has developed a methodology which includes education of the population about likely symptoms of cancer, and motivation of symptomatic individuals to undergo medical investigation. Patients with cervical cancer from the registry area who attended Barshi Cancer Hospital (84% of the total) showed a significant improvement in stage at diagnosis between 1988-1989 (38% in stages I and II) and 1990-1992 (51% in stages I and II). No change was observed in those attending the same hospital from a control area (38% vs. 34%). Among a random sample of the population of the registry area, 76% of women were aware of the symptoms of cervical cancer, compared with 25% of the population of control areas. It is suggested that action to raise awareness of symptoms of cancer, and to encourage medical consultation, should form an important initial component of cervical-cancer control programmes.

Female↗

Resection of the inferior vena cava for recurrent Wilms' tumor.

Wilms' tumor is one of the most common solid tumors of childhood. Approximately 500 cases occur annually in the United States, and the overall incidence is 0.8 per 100,000 children per year. Direct involvement of the inferior vena cava occurs in 5% to 10% of cases. The National Wilms' Tumor Study (NWTS), an intergroup cooperative clinical trial, indicates that aggressive primary surgical management combined with chemo-radiation therapy improves (with respect to both survival and recurrence) the long-term prognosis for children who have extrarenal involvement. In addition, aggressive surgical resection may further improve the survival rate for patients with recurrent Wilms' tumor after initial multimodal therapy.

Child↗

Resection and adjuvant immunotherapy for melanoma metastatic to the lung and thorax.

Although melanoma that metastasizes to distant sites is generally associated with a median survival of only 6 to 8 months, certain metastatic sites including the lung may carry a better prognosis than others. Surgical therapy for pulmonary metastases remains controversial because of the variable survival rates reported for previous small series. To determine the prognosis and optimal management of patients with melanoma with pulmonary metastases, we reviewed our 22-year melanoma database of over 6100 patients. Of 984 patients with metastatic melanoma involving the lung or thorax, 106 underwent resection by posterior lateral thoracotomy or median sternotomy. There were no operative deaths, and the median follow-up period for surgical patients was 55 months. The remaining 878 patients were treated without operation with immunotherapy, chemotherapy, radiation therapy, or a combination. In both treatment groups the male/female ratio was approximately 2:1. The primary lesion's Clark level of invasion and Breslow thickness and the patient's age at diagnosis of metastatic disease were not significantly different between the two groups. The 1-year, 3-year, and 5-year survival rates for surgical patients were 77%, 37%, and 27%, respectively, compared with 32%, 7%, and 3% for nonsurgical patients; these differences were highly significant (p = 0.0001). The highest 5-year survival rate (39%) occurred in those patients with a single metastatic lesion. Sixty-three percent of the surgical patients received some form of immunotherapy, compared with 34% of the nonsurgical patients. Multivariate analysis showed that resection and immunotherapy with a melanoma cell vaccine were both independent predictors of survival (p < 0.0001). These results indicate that the prognosis associated with metastatic melanoma may be less dismal than previously thought when distant metastases involve thoracic sites. We believe that surgical resection is the treatment of choice for patients with melanoma with pulmonary metastases; when combined with immunotherapy, this regimen offers the best chance for long-term survival.

Cancer Vaccines↗

Desmoid tumor occurring after reconstruction mammaplasty for breast carcinoma.

We present a case of desmoid tumor associated with prior alloplastic breast reconstruction. Wide local excision that includes chest wall resection, if necessary, is the primary treatment of choice. Patients with extensive nonresectable or recurrent disease may benefit from radiation therapy. Systemic therapy is a possibility in certain cases, but its toxicity generally precludes its use with this nonmetastatic tumor. Although this is the fourth reported case of desmoid tumor arising after implantation of a silicone prosthesis, we cannot claim a causal relationship. Careful follow-up consisting of yearly physical and mammagraphic examinations may facilitate early diagnosis and treatment of locally aggressive desmoid tumors but is not warranted, except in the context of routine screening for breast carcinoma.

Aged↗

Improved axillary staging of breast cancer with sentinel lymphadenectomy.

OBJECTIVE: The authors evaluated the effect of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) on the axillary staging of patients with carcinoma of the breast. SUMMARY BACKGROUND DATA: The accurate staging of patients with breast cancer is essential to guide management and determine prognosis. The authors previously reported the feasibility and accuracy of SLND in breast carcinoma. Sentinel lymphadenectomy identifies the first ("sentinel") axillary lymph node draining the site of a primary tumor; because this node is the most likely site of axillary metastasis, histopathologic examination of the sentinel node correlates well with examination of the entire axillary contents. The current study compares SLND with standard axillary lymphadenectomy (ALND) for the staging of breast carcinoma. METHODS: The incidence of axillary node metastasis and micrometastasis in SLND and ALND specimens from patients undergoing operative treatment of a primary breast carcinoma was compared prospectively. Multiple sections of each sentinel lymph node in SLND specimens were examined by hematoxylin and eosin (H&E) staining and by immunohistochemical techniques using antibodies to cytokeratin. One or two sections of each nonsentinel lymph node in ALND specimens were examined by routine H&E staining. RESULTS: One hundred thirty-four patients underwent ALND (ALND group), and 162 underwent successful SLND followed by completion ALND (SLND group). Both groups were similar with respect to age (median, 55 and 54 years, respectively), palpable primary tumors (54.5% and 59.3%, respectively), palpable axillary nodes (5.2% and 7.4%, respectively), size of primary tumor (median, 1.5 cm in each group), and total number of axillary lymph nodes examined (median, 19 and 21, respectively). The number of patients with axillary metastasis was 39 (29.1%) in the ALND group and 68 (42.0%) in the SLND group (p < 0.03). Of these, 4 of 39 (10.3%) ALND patients (3.0% of all ALND patients) and 26 of 68 (38.2%) SLND patients (16.0% of all SLND patients) had micrometastasis (< or = 2 mm), a highly significant difference (p < 0.0005) CONCLUSIONS: Sentinel lymphadenectomy with multiple sectioning and immunohistochemical staining of sentinel nodes increases the accuracy of axillary staging in breast cancer and can identify significantly more patients with lymph nodes metastases, especially micrometastases, than can ALND with routine histopathologic processing of lymph nodes.

Adult↗

Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay.

PURPOSE: The objective of the study was to develop a sensitive multimarker polymerase chain reaction (PCR) assay to detect circulating melanoma cells in patient blood. The rationale was that malignant melanoma is heterogeneous in regards to antigen expression. PATIENTS AND METHODS: A PCR assay that uses four melanoma-associated gene markers (tyrosinase, p97, MUC18, and MAGE-3) was developed. Sensitivity and specificity of the PCR assay for individual markers were assessed using 10 melanoma cell lines and peripheral-blood lymphocytes (PBL) from 39 normal volunteers as controls. The assay's sensitivity and specificity were improved using nested primers and Southern blot analysis. Patients (N = 119) with American Joint Committee on Cancer (AJCC) stages I to IV disease were evaluated for circulating melanoma cells using the four gene markers under optimal conditions. RESULTS: All melanoma-associated gene markers were expressed in at least 80% of the melanoma lines, whereas 37 of 39 normal PBL tested negative for all markers; the remaining two PBL were positive for MUC18. Using four markers in the PCR assay was significantly better than using tyrosinase alone. There was a significant correlation between the number of positive PCR markers, AJCC stage of disease, and progression of disease. In all AJCC stages, there were more PCR-positive patients with disease than without disease. CONCLUSION: A multimarker PCR assay is more reliable and sensitive than a single-marker assay for detection of melanoma cells in blood of patients. This assay can provide important insight into tumor progression kinetics without major surgical or conventional radiologic diagnostic procedures.

Antigens, Neoplasm↗

Variability in early communicative development.

Data from parent reports on 1,803 children--derived from a normative study of the MacArthur Communicative Development Inventories (CDIs)--are used to describe the typical course and the extent of variability in major features of communicative development between 8 and 30 months of age. The two instruments, one designed for 8-16-month-old infants, the other for 16-30-month-old toddlers, are both reliable and valid, confirming the value of parent reports that are based on contemporary behavior and a recognition format. Growth trends are described for children scoring at the 10th-, 25th-, 50th-, 75th-, and 90th-percentile levels on receptive and expressive vocabulary, actions and gestures, and a number of aspects of morphology and syntax. Extensive variability exists in the rate of lexical, gestural, and grammatical development. The wide variability across children in the time of onset and course of acquisition of these skills challenges the meaningfulness of the concept of the modal child. At the same time, moderate to high intercorrelations are found among the different skills both concurrently and predictively (across a 6-month period). Sex differences consistently favor females; however, these are very small, typically accounting for 1%-2% of the variance. The effects of SES and birth order are even smaller within this age range. The inventories offer objective criteria for defining typicality and exceptionality, and their cost effectiveness facilitates the aggregation of large data sets needed to address many issues of contemporary theoretical interest. The present data also offer unusually detailed information on the course of development of individual lexical, gestural, and grammatical items and features. Adaptations of the CDIs to other languages have opened new possibilities for cross-linguistic explorations of sequence, rate, and variability of communicative development.

Birth Order↗