Structural characteristics of the subscapularis muscle in children with medial rotation contracture of the shoulder after obstetric brachial plexus injury.

The aim of this study was to obtain a better understanding of the cause of the medial rotation contracture of the shoulder after obstetric brachial plexus lesions by studying the morphology of the shortened subscapularis muscle. Muscle biopsy specimens were harvested from 13 children with obstetric brachial plexus palsy who underwent corrective surgery for the rotation contracture. The majority of the subscapularis muscle biopsy samples had an essentially normal morphology and showed a predominance of type I myosin heavy chain isoform, while one biopsy showed signs of marked fibrosis and a predominance of type II myosin heavy chain isoform. The findings support the assumption that shortening of the subscapularis is caused primarily by the nerve injury, which weakens the antagonistic lateral rotators, but that direct injury to the muscle might be a contributory factor.

Immunohistochemical evidence of local production of catecholamines in cells of the muscle origins at the lateral and medial humeral epicondyles: of importance for the development of tennis and golfer's elbow?

BACKGROUND: Tennis elbow (TE) is a painful condition affecting the common extensor origin at the lateral humeral epicondyle. Colour Doppler examination has shown increased blood flow at this site and the sensory, and sympathetic innervation patterns have been delineated. However, it is not known whether there is local production of catecholamines and/or acetylcholine in this tissue, which is the case in patellar and Achilles tendinopathies. OBJECTIVE: To investigate the possible presence of local production of catecholamines and acetylcholine in non-neuronal cells (fibroblasts) in connective tissue at the muscle origin at the lateral humeral epicondyle in patients with TE. DESIGN: Immunohistochemical studies were performed on biopsies taken from the extensor origin in patients with TE and in pain-free controls. For reference purpose, biopsies from the flexor origin in patients with golfer's elbow (GE) were also studied. PATIENTS: Seven patients with TE and four patients with GE. Six healthy asymptomatic individuals served as controls. METHOD: Immunohistochemistry, using antibodies detecting synthesising enzymes for catecholamines (tyrosine hydroxylase; TH) and acetylcholine (choline acetyltransferase; ChAT). RESULTS: TH-like immunohistochemical reactions were seen in fibroblasts in four of the seven patients with TE and two of the four patients with GE. No such reactions were detected in controls (0/6). No ChAT reactions were seen in any of the investigated specimens. CONCLUSIONS: There is evidence of local, non-neuronal production of catecholamines, but not acetylcholine, in fibroblasts in the tissue at the muscle origin at the lateral and medial epicondyles in patients with TE and GE, respectively, which might have an influence on blood vessel regulation and pain mechanisms in these conditions.

Subscapularis muscle mechanics in children with obstetric brachial plexus palsy.

This study investigates the passive mechanical properties of the subscapularis muscle in children with a contracture as a result of obstetrical brachial plexus palsy. Muscle biopsies were harvested from nine children undergoing open surgery for shoulder contracture. Passive mechanical testing of single cells and muscle bundles was performed. Corresponding comparisons were made using muscle biopsies from seven healthy controls. Single muscle fibres from patients with obstetric brachial plexus palsy displayed a shorter slack sarcomere length, linear deformation of the fibre within a wider zone of sarcomere length and a greater relative increase in stiffness compared with muscle bundles. We conclude that secondary changes in muscle fibre properties will occur as a result of a longstanding lack of sufficient passive stretch, leading to compensatory changes in the extracellular matrix. These results suggest the presence of a dynamic feedback system constituting a muscle-to-extracellular matrix communication interface.

Ductal lavage for detection of cellular atypia in women at high risk for breast cancer.

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.

Diagnostic accuracy of fine-needle aspiration biopsy is determined by physician training in sampling technique.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been used with variable success as a diagnostic test for benign and malignant breast lesions. The goal of this study was to examine the effects of training physicians in the fine-needle aspiration sampling-technique on the diagnostic accuracy of FNAB of palpable breast masses. The settings for this study were private physicians' offices and university clinics of primary care physicians, surgeons, and cytopathologists. METHODS: We reviewed 1043 consecutive FNAB specimens of the breast obtained during 1 year (1992): 729 FNABs were performed by formally trained physicians (at least 150 FNABs performed previously under supervision during fellowship training or the equivalent) who had done at least 100 FNABs during the year; 314 FNABs were performed by physicians without formal training who had done a median of only 2 FNABs during the year (range, 1-43 FNABs). All FNAB specimens were reviewed microscopically and evaluated for cellularity and type of material present, for diagnostic accuracy, and for the rate of surgical intervention. A minimum of 2 years of follow-up was obtained by matching all cases to the population-based Northern California Cancer Registry. FNAB specimens were correlated with histologic specimens when they were available. RESULTS: Using FNAB, the formally trained physicians missed 2% of cancers, whereas the physicians without formal training missed 25%. Among the patients with benign lesions seen by the formally trained physicians, 8% went on to surgery, whereas 30% of those seen by physicians without formal training did so. Specimens obtained by the formally trained physicians were significantly more cellular and were significantly less likely to be nondiagnostic. CONCLUSIONS: FNAB, when performed by physicians who are well trained in the technique, is a highly accurate, cost-effective diagnostic method that carries minimal morbidity and could replace a large number of surgical biopsies. When performed by physicians without adequate training, FNAB is often misleading and potentially harmful.

Genetic changes in paired atypical and usual ductal hyperplasia of the breast by comparative genomic hybridization.

PURPOSE: Breast cancer is thought to develop from noninvasive precursor lesions, although the earliest steps of neoplastic transformation are still undefined. Usual ductal hyperplasia (UDH) is considered to represent a benign proliferation of ductal epithelial cells, whereas atypical ductal hyperplasia (ADH) may represent the first clonal neoplastic expansion of these cells. The aim of this study was to examine genetic alterations in UDH and ADH and to determine the relationship between these lesions in the same breast biopsy. EXPERIMENTAL DESIGN: Comparative genomic hybridization analysis was used to define copy number alterations in DNA extracted from archival sections of 18 patients. Nine patients showed ADH with adjacent UDH, and nine showed pure UDH. None showed evidence of invasive cancer or ductal carcinoma in situ. RESULTS: Five of the nine ADH lesions showed chromosome copy number alterations. 16q loss (five cases) and 17p loss (two cases) were the most frequent changes. The associated UDH lesions in these five patients also showed copy number alterations, always a subset of the changes present in the paired ADH. In one other patient, the UDH showed eight chromosomal alterations, whereas the paired ADH showed no changes. Only one of nine cases with pure UDH showed comparative genomic hybridization abnormalities. CONCLUSIONS: These data support the likelihood that UDH is a precursor of ADH, at least in some cases representing neoplastic growth. The frequencies of 16q and 17p losses suggest that alterations of candidate genes located in these chromosomal regions may play a role early in breast carcinogenesis.

Bone mass and breast cancer risk in older women: differences by stage at diagnosis.

BACKGROUND: Older women with low bone mineral density (BMD) have a decreased incidence of breast cancer. It is not known whether this association is confined to early-stage, slow-growing tumors. METHODS: We prospectively studied 8905 women who were 65 years of age or older during the period from 1986 through 1988 and had no history of breast cancer. At study entry, we used single-photon absorptiometry to measure each woman's BMD at three skeletal sites: the wrist, forearm, and heel. The women were followed for a mean of 6.5 years for the occurrence of breast cancer. All statistical tests were two-sided. RESULTS: During 57 516 person-years of follow-up, 315 women developed primary invasive or in situ breast cancer. Multivariate analyses that adjusted for age, obesity, and other covariates revealed that the risk of breast cancer for women in the highest quartile of BMD for all three skeletal sites was 2.7 (95% confidence interval [CI] = 1.4 to 5.3) times greater than that for women in the lowest quartile at all three skeletal sites. The magnitude of increased risk associated with high BMD differed by the stage of disease at diagnosis and was greater for more advanced tumors (relative risk [RR] for TNM [i.e., tumor-lymph node-metastasis] stage II or higher tumors = 5.6; 95% CI = 1.2 to 27.4) than for early-stage disease (RR for in situ/TNM stage I tumors = 2.2; 95% CI = 1.0 to 4.8). CONCLUSIONS: Elderly women with high BMD have an increased risk of breast cancer, especially advanced cancer, compared with women with low BMD. These findings suggest an association between osteoporosis and invasive breast cancer, two of the most prevalent conditions affecting an older woman's health.

Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability.

We studied the effects of thiazolidinedione treatment (rosiglitazone 1 or 10 micromol.kg(-1).day(-1) or darglitazone 1.3 micromol.kg(-1).day(-1) for 3 weeks) on lipid metabolism in obese Zucker rats. In the basal 7-h fasted state, rosiglitazone (10 micromol.kg(-1).day(-1)) and darglitazone corrected the hypertriglyceridemia by increasing plasma triglyceride (TG) clearance and decreasing hepatic TG production, as assessed using Triton WR 1339. Free fatty acid (FFA) metabolism was assessed using 3H-palmitate tracer by estimating rates of plasma FFA appearance (Ra), whole-body FFA oxidation (Rox), and tissue-specific nonoxidative FFA disposal (Rfs). Basal Ra, plasma FFA levels, and clearance were increased by both thiazolidinediones. Detailed studies were conducted with darglitazone, which under basal conditions increased Ra (+114%), Rox (+51%), and Rfs in adipose tissues. During euglycemic clamps performed at insulin levels corresponding to those observed postprandially, darglitazone increased the glucose infusion rate from 4.7 to 13.3 mg.min(-1) and, in contrast to the basal state, it decreased Ra (-67%), Rox (-84%), and Rfs in adipose tissue, muscle, and liver. We concluded that thiazolidinediones 1) ameliorate hypertriglyceridemia by lowered hepatic TG production and augmented TG clearance (two separate kinetic effects), 2) enhance insulin-mediated suppression of systemic FFA mobilization while increasing the capacity to mobilize FFA during fasting, 3) increase FFA trafficking into adipose tissue by increasing the ability of adipose tissue to take up and store FFA, and 4) enhance metabolic flexibility by improving glucoregulation under hyperinsulinemic conditions (possibly involving reduced skeletal muscle and liver exposure to fatty acids) and augmenting the capacity to utilize FFAs during fasting.

Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR.

If detected early, breast cancer is curable. We tested cells collected from the breast ducts by methylation-specific PCR (MSP). Methylated alleles of Cyclin D2, RAR-beta, and Twist genes were frequently detected in fluid from mammary ducts containing endoscopically visualised carcinomas (17 cases of 20), and ductal carcinoma in situ (two of seven), but rarely in ductal lavage fluid from healthy ducts (five of 45). Two of the women with healthy mammograms whose ductal lavage fluid contained methylated markers and cytologically abnormal cells were subsequently diagnosed with breast cancer. Carrying out MSP in these fluid samples may provide a sensitive and powerful addition to mammographic screening for early detection of breast cancer.

Impaired spermatogenesis in men with congenital absence of the vas deferens.

It is generally assumed that men with congenital bilateral absence of the vas deferens (CBAVD) have azoospermia because of obstruction and that sperm production is normal. This study examines spermatogenesis in men with CBAVD to assess the validity of this assumption. We identified all men with CBAVD who had undergone either a diagnostic or therapeutic fertility procedure. Procedures included diagnostic biopsy, testis fine needle aspiration (FNA) mapping, microscopic epididymal sperm aspiration (MESA), and testis sperm extraction (TESE). Among 33 CBAVD men, 18 underwent testis biopsy, 27 had MESA/TESE, and 10 had FNA mapping. On evaluation of these procedures, normal spermatogenesis was present in 29 men. Four men (12%) demonstrated impaired spermatogenesis. One patient had FNA testis cytology consistent with late maturation arrest, another demonstrated hypospermatogenesis on biopsy and low sperm yield by MESA, and two patients had pure Sertoli cell only histology on biopsy. Aetiologies for impaired spermatogenesis included varicocele and underlying genetic abnormalities. Although patients with CBAVD are assumed to have normal spermatogenesis and infertility due simply to obstruction, the potential for concomitant defects in sperm production exists. A clinical suspicion of testis failure should prompt further diagnostic evaluation of spermatogenesis prior to sperm retrieval. In addition, genetic counselling should be offered and testing for genetic lesions, including cystic fibrosis gene mutations and/or variants, Y chromosome microdeletions, and karyotype abnormalities, should be considered.

Loss of chromosome 16q in lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) and infiltrating lobular carcinoma may represent different forms of the same disease based on their frequent clinical association and similar histologic features. Patients with LCIS are at increased risk of multicentric and bilateral disease. Thus, LCIS may represent both a precursor to infiltrating lobular carcinoma and a marker of risk for breast cancer. To identify genomic alterations in LCIS, comparative genomic hybridization was performed on 17 cases without concurrent invasive carcinoma. Loss involving chromosome 16q was present in 88% of cases and was the sole detected alteration in 29%. Gain involving 1q was second in frequency, occurring in 41% of tumors, and in all cases was associated with loss of 16q. Other recurrent changes were loss involving 17p (18%), 8p (12%), and 12q24 (12%). E-cadherin immunohistochemistry was performed on all LCIS cases to evaluate the correlation of loss involving 16q22, the site of the E-cadherin gene, and altered protein expression. Most cases with 16q22 loss showed altered E-cadherin expression (12 of 13). These results in LCIS are similar to changes reported in infiltrating lobular cancer, confirming a genetic relationship between them. HUM PATHOL 32:292-296.

Testicular fine-needle aspiration in infertile men: correlation of cytologic pattern with biopsy histology.

Open testicular biopsy is the standard method for histopathologic assessment of spermatogenesis. The need for testis biopsy has been questioned with the increased success of minimally invasive techniques such as fine-needle aspiration (FNA) mapping. This study examines whether FNA can provide cytologic information equivalent to histologic patterns by correlating diagnoses from testis FNA cytology with biopsy histology. Men (n = 87) who had undergone both diagnostic FNA mapping and open testis biopsy in the evaluation of infertility were identified. Biopsies were assessed by recognized histologic patterns of normal, hypospermatogenesis, early and late maturation arrest, and Sertoli cell only. FNA cytologic specimens were examined for adequacy and were classified similarly. Mixed patterns were also identified. The correlation between the two methods was 94%, with no differences among the different histologies. Discrepancies between cytology and histology were primarily the result of inadequate sampling and evidence of mixed patterns on FNA mapping. FNA cytology is a minimally invasive method of obtaining testicular tissue for diagnostic purposes. These data demonstrate that FNA cytology can evaluate accurately all classically defined histologic types, and may have the potential to replace testis biopsy in the assessment of spermatogenesis.

Pharmacological treatment of insulin resistance in obesity.

AIM: To discuss new pharmacological possibilities for acting on the lipid metabolism abnormalities relating obesity, insulin resistance and arterial disease. DATA SYNTHESIS: Obesity is frequently associated with excess caloric fat dietary intake, especially in the form of fatty acids. An increased flux of fatty acids into muscle, liver and pancreas is probably a major cause of insulin resistance and possibly of pancreatic secretory disturbances. Liver exposure to fatty acid overload may also be the main reason for the atherogenic lipoprotein profile of insulin resistance and type 2 diabetes, which is characterised by prolonged post-prandial hypertriglyceridemia, high levels of large very low-density lipoproteins (VLDL) and small, dense low-density lipoproteins (LDL), and a reduced number of apoAl-containing high-density lipoproteins (HDL). This lipoprotein profile may be the main contributor to the high prevalence of arterial disease in patients with type 2 diabetes. The treatment of type 2 diabetes and insulin resistance in obese or non-obese subjects should therefore aim at normalising fatty acid fluxes because this can be expected to enhance insulin action and ameliorate the atherogenic lipoprotein abnormalities. The discovery of peroxisome proliferator-activated receptors (PPARs) and the elucidation of their function as master controllers of the genes involved in fatty acid metabolism have facilitated the development of potent modulating substances. Promising results have been obtained with the current generation of PPAR gamma ligands, but undesirable effects have also been reported. CONCLUSIONS: New knowledge concerning the structure and function of PPAR gamma and PPAR alpha is being used to develop non-TZD modulators with combined PPAR alpha and gamma actions in animal studies. This new generation of substances may offer a more balanced spectrum of activity that may be better suited for the treatment of the insulin resistance and type 2 diabetes frequently associated with obesity.

Relationship between classic histological pattern and sperm findings on fine needle aspiration map in infertile men.

Systematic testis fine needle aspiration (FNA) mapping has been proposed as an adjunctive or alternative diagnostic procedure to biopsy to determine the presence of spermatozoa within infertile testes. This study related testis histology to the global presence or absence of spermatozoa in the same testes determined by FNA cytology. Testis biopsies and FNA mapping were performed in 87 infertile, azoospermic men. A mean of 1.3 biopsies and 14 FNA sites were taken per patient. Biopsies were assessed by recognized histological patterns of normal, Sertoli cell-only, hypospermatogenesis, early and late maturation arrest, sclerosis as well as mixed patterns that included at least two of these histologies. FNA cytological specimens were assessed for sperm presence by an experienced cytologist. Overall, spermatozoa were found by FNA mapping in 52% of patients. A comparison of histology and FNA findings revealed that pure patterns of Sertoli cell-only and early maturation were associated with a very poor likelihood of sperm detection (4-8%). In contrast, patients with other pure pattern histologies or mixed patterns had high rates of FNA sperm detection (77-100%). Similar to reported testicular sperm extraction (TESE) findings, sperm detection with FNA shows wide variation depending on testis histology. Unlike most TESE reports, however, some histological patterns generally reflect a more global testicular dysfunction and poorer likelihood of sperm identification, suggesting the possibility that these phenotypes have a genetic origin. Systematic testis sampling with FNA offers additional geographical information about spermatogenesis that routine biopsies lack and can further guide couple decision-making in severe male factor infertility.

The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67.

Proliferation indices are intended to help patients and clinicians make treatment decisions. We have previously demonstrated that a proliferation index based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices. With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M2 BrdUrd during 30 min immediately preceding surgery. We used IU-4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 cases). Patients received standard surgical and adjuvant treatment. No patients were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had better disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall survival (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison, a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiority of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multivariate survival analyses we found that BrdUrd LI proliferative index significantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.

Diagnostic findings from testis fine needle aspiration mapping in obstructed and nonobstructed azoospermic men.

PURPOSE: Although helpful for defining extratesticular obstruction, the testis biopsy offers limited information on nonobstructive azoospermic testes. Guided by diagnostic biopsies, testis sperm extraction procedures fail in 25% to 50% of patients with nonobstructive azoospermia, largely because it is clinically difficult to know where sperm are located. To provide a more complete assessment of spermatogenesis in nonobstructive azoospermic patients and to simplify the confirmation of sperm production in men with obstruction, we use a systematic, fine needle aspiration "mapping" procedure. We summarize the diagnostic findings in a series of azoospermic men. MATERIALS AND METHODS: From 118 azoospermic infertile men (22 with obstructed and 96 with nonobstructed azoospermia) fine needle aspiration data were used to generate location specific, sperm frequency maps for obstructed and nonobstructive azoospermic testes to determine if "sperm rich" locations existed. RESULTS: Fine needle aspiration map analysis revealed that all aspiration locations from obstructed cases showed sperm. In men with nonobstructive azoospermia, sperm was identified in the right testis in 134 of 652 (20.5%) and in the left testis in 151 of 716 (21.1%) separate aspirations. Rates of sperm detection among various intratesticular sites were not statistically different. In 27.1% of cases the fine needle aspiration map found sperm in men with sperm negative biopsies. The likelihood of heterogeneity in fine needle aspiration sperm findings was 25% within individual nonobstructive azoospermic testes and 19.2% between testis sides. At post-procedure followup of 88 patients (74%), no clinical or surgical complications were observed. CONCLUSIONS: Testis fine needle aspiration mapping is a simple, reliable and informative diagnostic tool in the evaluation of azoospermic infertile men.

Fine needle aspiration in the diagnosis of metastatic melanoma.

BACKGROUND: Fine needle aspiration is an accurate technique to diagnose metastatic melanoma. Few reports exist in the literature describing its usefulness in many patients with melanoma confirmed by open biopsy. OBJECTIVE: The purpose of this study was to determine the utility and predictive value of fine needle aspiration in patients with malignant melanoma who presented with lesions suspected to be metastatic. METHODS: We retrospectively reviewed 99 cases of fine needle aspiration and the corresponding histologic findings obtained by open biopsy in 82 patients. RESULTS: Of the 99 cases, 86 were positive for melanoma, 12 were negative, and one was indeterminate. The positive predictive value of fine needle aspiration was 99%. One patient had a false-positive diagnosis. CONCLUSION: Fine needle aspiration is a rapid, accurate, and minimally invasive procedure that is useful in the diagnosis of metastatic melanoma. Patients with a positive aspirate of palpable regional nodes can proceed directly to surgery, bypassing the need for an open biopsy.

Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences.

BACKGROUND: Ductal carcinoma in situ (DCIS) recurs in the same breast following breast-conserving surgery in 5%-25% of patients, with the rate influenced by the presence or absence of involved surgical margins, tumor size and nuclear grade, and whether or not radiation therapy was performed. A recurrent lesion arising soon after excision of an initial DCIS may reflect residual disease, whereas in situ tumors arising after longer periods are sometimes considered to be second independent events. The purpose of this study was to determine the clonal relationship between initial DCIS lesions and their recurrences. METHODS: Comparative genomic hybridization (CGH) was used to compare chromosomal alterations in 18 initial DCIS lesions (presenting in the absence of invasive disease) and in their subsequent ipsilateral DCIS recurrences (detected from 16 months to 9.3 years later). RESULTS: Of the 18 tumor pairs, 17 showed a high concordance in their chromosomal alterations (median = 81%; range = 65%-100%), while one case showed no agreement between the paired samples (having two and 20 alterations, respectively). Morphologic characterization of the DCIS pairs showed clear similarities. The mean number of CGH changes was greater in the recurrent tumors than in the initial lesions (10.7 versus 8.8; P =.019). The most common changes in both the initial and the recurrent in situ lesions were gains involving chromosome 17q and losses involving chromosomes 8p and 17p. The degree of concordance was independent of the time interval before recurrence and of the presence of positive surgical margins. CONCLUSIONS: In this study, DCIS recurrences were clonally related to their primary lesions in most cases. This finding is consistent with treatment paradigms requiring wide surgical margins and/or postoperative radiation therapy.

In vivo investigation of ECRB tendons with microdialysis technique--no signs of inflammation but high amounts of glutamate in tennis elbow.

We used the microdialysis technique to study concentrations of substances in the extensor carpi radialis brevis (ECRB) tendon in patients with tennis elbow. In 4 patients (mean age 41 years, 3 men) with a long duration of localized pain at the ECRB muscle origin, and in 4 controls (mean age 36 years, 2 men) with no history of elbow pain, a standard microdialysis catheter was inserted into the ECRB tendon under local anesthesia. The local concentrations of the neurotransmitter glutamate and prostaglandin E2 (PGE2) were recorded under resting conditions. Samplings were done every 15 minutes during a 2-hour period. We found higher mean concentrations of glutamate in ECRB tendons from patients with tennis elbow than in tendons from controls (215 vs. 69 micromoL/L, p < 0.001). There were no significant differences in the mean concentrations of PGE2 (74 vs. 86 pg/mL). In conclusion, in situ microdialysis can be used to study certain metabolic events in the ECRB tendon of the elbow. Our findings indicate involvement of the excitatory neurotransmitter glutamate, but no biochemical signs of inflammation (normal PGE2 levels) in ECRB tendons from patients with tennis elbow.

Menstrual and reproductive factors for salivary gland cancer risk in women.

Several observations suggest that salivary gland cancer may be, in part, a hormonally dependent disease. We examined associations between hormonally mediated life events and salivary gland cancer risk in a population-based case-control study. Of 76 women diagnosed between 1989 and 1993, 63 (83%) were interviewed. Of 111 population controls, 83 (75%) were interviewed. Early menarche (OR = 4.1, 95% CI = 1.4-12.1) and nulliparity (OR = 2.6, 95% CI = 1.0-6.7) were associated with increased risk whereas late age at first full-term pregnancy (OR = 0.19, 95% CI = 0.3-1.2) and longer duration of oral contraceptive use (OR = 0.31, 95% CI = 0.10-1.0) were associated with diminished risk. These findings are consistent with a hormonal component in salivary gland cancer risk.