Montgomery General Hospital

Medical pain management is in crisis; from the pervasiveness of pain to inadequate pain treatment, from the escalation of prescription opioids to an epidemic in addiction, diversion and overdose deaths. The rising costs of pain care and managing adverse effects of that care have prompted action from state and federal agencies including the DOD, VHA, NIH, FDA and CDC. There is pressure for pain medicine to shift away from reliance on opioids, ineffective procedures and surgeries toward comprehensive pain management that includes evidence-based nonpharmacologic options. This White Paper details the historical context and magnitude of the current pain problem including individual, social and economic impacts as well as the challenges of pain management for patients and a healthcare workforce engaging prevalent strategies not entirely based in current evidence. Detailed here is the evidence-base for nonpharmacologic therapies effective in postsurgical pain with opioid sparing, acute non-surgical pain, cancer pain and chronic pain. Therapies reviewed include acupuncture therapy, massage therapy, osteopathic and chiropractic manipulation, meditative movement therapies Tai chi and yoga, mind body behavioral interventions, dietary components and self-care/self-efficacy strategies. Transforming the system of pain care to a responsive comprehensive model necessitates that options for treatment and collaborative care must be evidence-based and include effective nonpharmacologic strategies that have the advantage of reduced risks of adverse events and addiction liability. The evidence demands a call to action to increase awareness of effective nonpharmacologic treatments for pain, to train healthcare practitioners and administrators in the evidence base of effective nonpharmacologic practice, to advocate for policy initiatives that remedy system and reimbursement barriers to evidence-informed comprehensive pain care, and to promote ongoing research and dissemination of the role of effective nonpharmacologic treatments in pain, focused on the short- and long-term therapeutic and economic impact of comprehensive care practices.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are two incretins that bind to their respective receptors and activate the downstream signaling in various tissues and organs. Both GIP and GLP-1 play roles in regulating food intake by stimulating neurons in the brain's satiety center. They also stimulate insulin secretion in pancreatic β-cells, but their effects on glucagon production in pancreatic α-cells differ, with GIP having a glucagonotropic effect during hypoglycemia and GLP-1 exhibiting glucagonostatic effect during hyperglycemia. Additionally, GIP directly stimulates lipogenesis, while GLP-1 indirectly promotes lipolysis, collectively maintaining healthy adipocytes, reducing ectopic fat distribution, and increasing the production and secretion of adiponectin from adipocytes. Together, these two incretins contribute to metabolic homeostasis, preventing both hyperglycemia and hypoglycemia, mitigating dyslipidemia, and reducing the risk of cardiovascular diseases in individuals with type 2 diabetes and obesity. Several GLP-1 and dual GIP/GLP-1 receptor agonists have been developed to harness these pharmacological effects in the treatment of type 2 diabetes, with some demonstrating robust effectiveness in weight management and prevention of cardiovascular diseases. Elucidating the underlying cellular and molecular mechanisms could potentially usher in the development of new generations of incretin mimetics with enhanced efficacy and fewer adverse effects. The treatment guidelines are evolving based on clinical trial outcomes, shaping the management of metabolic and cardiovascular diseases.

OBJECTIVES: To evaluate the literature on the effectiveness of bed and wheelchair positioning and repositioning in the prevention of pressure ulcers (PUs) in both the spinal cord injury (SCI) and non-SCI populations. DESIGN: Systematic review. METHODS: PubMed, CINAHL, PsycINFO, and EMBASE were queried with the subject heading terms "pressure sore," "pressure ulcer," "position or turn in bed, wheelchair," "pressure relief," and "pressure release." All study design types that assessed the effectiveness of bed and wheelchair positioning and pressure relief maneuvers in any patient group and in any setting were sought. Three independent reviewers extracted and summarized details of eligible trials using a standardized method. Two independent reviewers assessed the methodological quality of each trial using the American Academy of Neurology guidelines. When reviewers were not able to reach consensus, a third independent reviewer served as tiebreaker. RESULTS: We identified 2820 publications, of which 49 met inclusion criteria. Of these publications, the subject population was 2834 (923 persons with SCI, 717 persons without SCI, and 1194 healthy control subjects). Among studies examining pressure related to position or repositioning in bed or sitting, procedures for measuring skin pressure and metabolism were highly variable by anatomic location, measurement technique, outcome measure, study site, participant characteristics, and description of position/turning for bed and seated interventions. Numerous factors can influence tissue interface pressures, and no prospective studies had been performed to determine a causal relationship between interface pressure and skin breakdown. Several studies suggest that skin response to pressure differs between subjects with and without SCI. Conflicting results and insufficient evidence for optimal bed and seated positioning and turning and pressure relief maneuvers to prevent PUs in both SCI and non-SCI populations were limiting factors. CONCLUSIONS: Although there is no clear optimal positioning or turning frequency in bed, the evidence suggests avoiding the 90° lateral position because of high pressures and PU risk over the trochanters. During sitting, pressures are linearly redistributed from the sitting area during recline and tilt; however, reclining carries with it an increased risk of shear forces on this skin. The evidence does not support conclusive guidelines on positioning or repositioning techniques for PU prevention in bed or during sitting. We conclude that PU risk is highly individualized, with the SCI population at a higher risk, which demands flexible PU prevention strategies for bed/seated positioning and pressure relief maneuvers. Education has and will remain our most powerful ally to thwart this pervasive public health problem.

Angioedema and cough are known side effects of angiotensin-converting enzyme (ACE) inhibitors. Angiotensin-converting enzyme is a potent inhibitor of kinase II, which facilitates the breakdown of bradykinin. An increase in bradykinin levels results in continued prostaglandin E2 synthesis, vasodilation, increased vascular permeability, and increased interstitial fluid. In contrast, the angiotensin II receptor blockers (ARBs) do not increase bradykinin levels. Angioedema as a complication of ACE inhibitor therapy is not widely recognized; this complication is even less recognized with second-line ARBs. We report angioedema associated with losartan (an ARB) in a patient who had experienced angioedema secondary to enalapril (an ACE inhibitor). Almost half of patients with ARB-associated angioedema also had developed angioedema while receiving ACE inhibitor therapy. Clinicians should exercise caution when using ARBs in patients with a history of angioedema secondary to ACE inhibitors.

OBJECTIVE: As inspired oxygen availability falls with ascent to altitude, some individuals develop high-altitude headache (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies. METHODS: In high-altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea-level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores [0-4]≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea-level hypoxic study, 11 subjects underwent gadolinium-enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen=0.11, 1 hour). RESULTS: In the high-altitude studies, headache burden correlated with both RVD (Spearman rho=0.55, p=0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r=-0.56, p=0.03). It also related inversely to both the lateral+third ventricle summed volumes (Spearman rho=-0.5, p=0.05) and pericerebellar CSF volume (r=-0.56, p=0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r=-0.66, p<0.05 and r=-0.75, p<0.05, respectively). INTERPRETATION: Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur.

Pressures in the left ventricle and central aorta were recorded together with instantaneous aortic blood flow at the time of operation in 9 patients. Four patients had IHSS, 4 had valvular or discrete subvalvular aortic stenosis, and 1 was considered to have a normal aortic valve and left ventricular outflow tract. In each of the 4 patients with IHSS, the pattern of aortic blood flow was distinctly abnormal when significant obstruction was present and nearly 80% of total flow took place in the first half of systole. In contrast, [see figure in the PDF file] the distribution of flow was symmetrical in all patients with discrete aortic stenosis. When flow and the pressure gradient were related at brief intervals during systole, and the orifice size calculated, it was found that the orifice was always greatest at the onset of contraction, diminished rapidly in size, and often became totally obliterated toward the end of the ejection period in patients with IHSS. The size of the orifice remained constant during systole in the patients with discrete obstruction. The abnormalities of instantaneous aortic blood flow, and the rate of systolic narrowing of the subvalvular orifice were exaggerated following premature ventricular contractions, after the administration of pharmacologic agents with positive inotropic effects (isoproterenol and calcium chloride), and after reduction of the circulating blood volume. With valvular and discrete subaortic stenosis, however, these interventions did not change the symmetrical pattern of blood flow and the orifice area was constant. Augmentation of the circulating blood volume or partial occlusion of the ascending aorta decreased the severity of outflow obstruction in every patient with IHSS and converted the abnormal flow pattern to one characteristic of discrete stenosis. These studies provide the first evidence of the instantaneous changes which occur within the outflow tract of the left ventricle in patients with IHSS, and provide information concerning the various mechanisms by which the intensity of obstruction may be modified.

BACKGROUND: Insulin-like growth factor-I (IGF-I) peptide has beneficial effects on cardiomyocyte function and survival, many of which are mediated through the serine-threonine kinase, Akt. However, concerns about systemic effects of IGF-I peptide limit its clinical application. The present study tested whether local IGF-I expression could mediate cardioprotection without elevating serum [IGF-I]. METHODS: The ability of a recombinant adenovirus encoding IGF-IB (Ad.IGF-I) to activate Akt and protect cardiomyocytes from hypoxia-induced apoptosis in vitro was compared with the effects of IGF-I peptide or expression of constitutively active Akt (myr-Akt). In vivo, cardiac IGF-I gene transfer was performed prior to ischemia-reperfusion injury (IRI). Effects on the ischemic and infarcted areas were assessed while serum [IGF-I] was measured by radioimmunoassay. RESULTS: Compared with IGF-I peptide, Ad.IGF-I achieved more sustained activation of Akt and reduced hypoxia-induced apoptosis at lower media IGF-I concentrations. In a co-culture system, Ad.IGF-I protected both infected and uninfected cells from hypoxic injury, while myr-Akt protected only infected cells. In vivo cardiac injection of Ad.IGF-I mediated significant local IGF-I expression, without affecting serum [IGF-I] levels. After IRI, Ad.IGF-I did not affect the ischemic area but reduced infarct size approximately 50% (32 +/- 13 vs. 64 +/- 14% AAR in Ad.GFP rats, p < 0.003), although the transgene was expressed in only approximately 15% of the ischemic region, consistent with possible paracrine benefit. CONCLUSIONS: Somatic gene transfer of IGF-I may offer strategic advantages over both systemic delivery of IGF-I peptide and expression of cell autonomous cardioprotective transgenes such as Akt by mediating autocrine and paracrine cardiomyocyte protection without elevating serum [IGF-I] levels.

Summary— One hundred patients who have had nephrostomies performed for obstructive uropathy in the presence of extensive carcinoma have been retrospectively analysed. Patients with prostatic and cervical carcinoma had a moderately good long‐term survival and quality of life, but those with bladder carcinoma or other primary sites had poor results. Significant factors in the selection of patients for nephrostomy drainage in the presence of pelvic cancer are discussed.

PURPOSE: To understand the extent of off-label prescribing among pediatrics, the study assesses the prescribing patterns of antidepressants in ambulatory settings. METHODS: A cross-sectional analysis was conducted using the National Ambulatory Medical Care Survey from 2000 to 2006. The prevalence of off-label prescribing of antidepressants was estimated, and predictive factors were evaluated. PARTICIPANTS: Children and adolescents aged 6-18 years to private physicians' offices. MAIN OUTCOME MEASURES: Prevalence of antidepressant prescriptions including FDA and non-FDA-approved indications, types of antidepressants prescribed, and factors associated with off-label prescribing. RESULTS: Our study population made 18 646 visits to private physicians' offices, representing about 667 million weighted visits during the study period. The mean age of the patients was 12.2 years (SD = 3.7), and majority of the visits were made by White people (73.1%). Of all visits, 3.7% (95%CI: 3.2%-4.2%) were associated with antidepressants. The most prevalent form of antidepressants prescribed were selective serotonin reuptake inhibitors (63.7%). Only 9.2% of the visits were associated with FDA-approved indications. Visits made to pediatricians (adjusted OR = 2.4; 95%CI: 1.1-5.1), family physicians, and other offices (adjusted OR = 1.9; 95%CI: 1.2-3.1) were more likely to be associated with off-label prescribing as compared with visits to a psychiatrist's office. CONCLUSIONS: The study observed a very high prevalence of off-label antidepressant prescribing patterns among children and adolescents in US ambulatory care settings. Coordinated efforts should be placed to evaluate the potential reasons and ramifications of antidepressant off-label prescribing to guard patients' safety.

Abstract Aside from the language-selective left-lateralized fronto-temporal network, language comprehension sometimes additionally recruits a domain-general bilateral fronto-parietal network implicated in executive functions: the multiple demand (MD) network. However, the nature of the MD network’s contributions to language comprehension remains debated. To illuminate the role of this network in language processing, we conducted a large-scale fMRI investigation using data from 30 diverse word and sentence comprehension experiments (481 unique participants, 678 scanning sessions). In line with prior findings, the MD network was active during many language tasks. Moreover, similar to the language-selective network, which is robustly lateralized to the left hemisphere, these responses were stronger in the left-hemisphere MD regions. However, in stark contrast with the language-selective network, the MD network responded more strongly (i) to lists of unconnected words than to sentences, and critically, (ii) in paradigms with an explicit task compared to passive comprehension paradigms. In fact, many passive comprehension tasks failed to elicit a response above the fixation baseline in the MD network, in contrast to strong responses in the language-selective network. In tandem, these results argue against a role for the MD network in core aspects of sentence comprehension like inhibiting irrelevant meanings or parses, keeping intermediate representations active in working memory, or predicting upcoming words or structures. These results align with recent evidence of relatively poor tracking of the linguistic signal by the MD regions during naturalistic comprehension, and instead suggest that the MD network’s engagement during language processing likely reflects effort associated with extraneous task demands. Significance Statement Domain-general executive processes, like working memory and cognitive control, have long been implicated in language comprehension, including in neuroimaging studies that have reported activation in domain-general multiple demand (MD) regions for linguistic manipulations. However, much prior evidence has come from paradigms where language interpretation is accompanied by extraneous tasks. Using a large fMRI dataset (30 experiments/481 participants/678 sessions), we demonstrate that MD regions are engaged during language comprehension in the presence of task demands, but not during passive reading/listening—conditions that strongly activate the fronto-temporal language network. These results present a fundamental challenge to proposals whereby linguistic computations, like inhibiting irrelevant meanings, keeping representations active in working memory, or predicting upcoming elements, draw on domain-general executive resources.

The use of ultrasound in the diagnostic and therapeutic management of 5 patients with renal abscesses is described. A spectrum of ultrasonic findings was noted, with the majority of the lesions being anechoic (3 cases). However, a few lesions showed a mixed pattern (2 cases). Ultrasonic aspiration of abscess fluid for culture and sensitivity obviated an operation in 1 case. For the first time, ultrasonically guided, percutaneous, indwelling catheter drainage of a renal carbuncle is reported. Since the patient had failed to respond to systemic antibiotic therapy this technique saved the patient from undergoing an operation. The clinical and ultrasonic findings in the 6 previous case reports of abscesses are reviewed.

Human kallikreins (hK) 2, 3, 6 and 10 are expressed in breast and prostate tissue. hK2 and hK3 (prostate-specific antigen, PSA) are used to screen for prostate cancer. hK6 and hK10 are downregulated in breast cancer compared to normal breast tissue. We demonstrated that levels of PSA in nipple aspirate fluid (NAF) are lower in women with breast cancer than in normal women. We hypothesize that the expression of hK2, 3, 6 and 10 are related and important in detecting breast cancer. The goals of this study are to determine the level of expression of kallikreins in NAF and serum, the association of hK2, 3, 6 and 10 in NAF, and the association of each of the kallikreins with breast cancer. In NAF from 275 women, hK3, 6 and 10 were detectable in >/= 90% and hK2 in 74% of samples analyzed. NAF levels were highest for hK6 and lowest for hK2, regardless of cancer and menopausal status. hK3 was detectable in 15/29 (52%) and hK2 in 0/29 serum samples collected from 6 women. hK2 and hK3 were concentrated in NAF vs. matched serum. The 4 kallikreins were associated with the exception of hK2 with hK6 or hK10. PSA levels were higher in normal pre- than postmenopausal subjects (but not women with breast cancer), whereas levels of hK2, 6 and 10 did not differ by menopausal status. hK2 and PSA were associated with both pre- and postmenopausal breast cancer; hK6 and 10 were not. hK2 and PSA were more associated with pre- than postmenopausal breast cancer. Using logistic regression, PSA and menopausal status provided the best model of breast cancer prediction, with a sensitivity of 91% and specificity of 39%. In conclusion, 4 kallikreins are expressed in NAF. hK2 and PSA, and hK6 and hK10 are highly associated. Higher premenopausal PSA levels suggest the influence of ovarian steroids. PSA shows the most promise in aiding in the early detection of breast cancer.

Although heredity has been previously suggested as a cause of congenital trigger thumb (stenosing tenovaginitis), no cases in succeeding generations have been reported. The occurrence of 2 cases in a father and son adds credence to a hereditary etiology.

Journal Article From Ideological to Competency-Based: The Rebranding and Maintaining of Medical Social Work's Identity Get access Ed Silverman, PhD, MBA Ed Silverman, PhD, MBA director and associate faculty member Resource Management, Montgomery General Hospital, 18101 Prince Philips Drive, Olney, MD 20832; e-mail: esilverm@montgomerygeneral.com, Johns Hopkins School of Education, Baltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar Social Work, Volume 53, Issue 1, January 2008, Pages 89–91, https://doi.org/10.1093/sw/53.1.89 Published: 01 January 2008 Article history Received: 11 June 2007 Accepted: 11 July 2007 Published: 01 January 2008

A nuchal cord (or Cord-Around-the Neck (CAN)) occurs when the umbilical cord becomes wrapped around the fetal neck 360 degrees. Nuchal cords are very common, the incidence of nuchal cord increases with advancing gestation from 12% at 24 to 26 weeks to 37% at term [1]. Most are not associated with perinatal morbidity and mortality. In some fetuses and newborns CAN may cause problems, especially when the cord is tightly wrapped around the neck. The cluster of cardiorespiratory and neurological signs and symptoms associated with unique physical features that occur secondary to tight cord-round-the-neck has been referred to as 'tCAN syndrome' (tight Cord Around the Neck Syndrome) [2]. A small number of studies have shown that nuchal cord and or tCAN can affect the outcome of delivery and may have long-term effects on the infant [3] and but as a causative factor for stillbirth it is debatable [4,5]. However, some case reports of postmortem findings on stillbirths show negative pathology reports and tight cord around the neck being the only cause of death [6]. It is the unique physical features of tCAN syndrome that distinguishes it from birth asphyxia even though there are many similarities between these two conditions. Umbilical cord abnormalities are considered as one of the causative factor for birth asphyxia. The manifestation of tCAN symptomatology seems to happen both in the presence of normal and depressed AGPAR scores [7]. Umbilical cord compression due to tCAN may cause obstruction of blood flow first in thin walled umbilical vein, while infant’s blood continues to be pumped out of baby through the thicker walled umbilical arteries thus causing hypovolemia and hypotension resulting in acidosis [8]. Anemia [9] and mild respiratory distress may occur. Some of these infants may also have facial and conjuctival petechiae [10] and rarely petechiae of the neck and upper part of the chest and skin abrasion of neck [11] where the cord was tightly wrapped and facial suffusion [12], all of which can also be seen in some postmortem findings of stillbirth infants who had tCAN [Archana Bargaje, personal communication]. If born alive, some of these infants may also be somewhat obtunded with a low tone and have transient feeding difficulties. These findings raise the possibility of transient encephalopathy, which may lead to long-term complications. A stillbirth attributed to a cord problem should have evidence of cord obstruction or circulatory compromise. Other potential causes of stillbirth need to be excluded prior to labelling cord abnormalities as the causative factor, since cord abnormalities seen in more than a third of all normal live births. The tCAN Syndrome may conceptually be similar to strangulation which may result in non lethal problems or death. The pathophysiological mechanisms of strangulation injuries (lethal and non lethal) involves venous, arterial obstruction (arterial spasm due to carotid pressure) in the neck and vagal collapse (increased parasympathetic tone) [13]. This can lead to cerebral stagnation, hypoxia, and unconsciousness, which, in turn, produces loss of muscle tone. The same pathophysiology of strangulation may possibly be applicable to tCAN syndrome in neonates. A study on potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight showed evidence of association of tCAN in children with quadriplegia [14]. Intermittent umbilical cord occlusion in preterm and near term sheep caused a decline in pO2 and pH, and higher PCO2 and altered brain protein synthesis/degradation [6]. Whether human fetal intermittent strangulation by tCAN have similar brain protein alterations and thus long-term effects remains to be seen. Using specific placental histologic criteria for umbilical blood flow restriction in unexplained stillbirth Parast et al [4] showed significant correlation of placental changes of “minimal histologic criteria” with cord accidents (as tCAN is part of cord accidents). Nuchal cords showed highest rates of thrombosis-related placental histopathology and fetal thrombotic vasculopathy and thrombosis seems to be highly specific for cord related stillbirths [4,5].

A 34-year-old white man is described with multifocal invasive squamous cell carcinoma of the penis. Adequate circumcision had been performed at birth.

DESCRIPTION: The American Society of Addiction Medicine (ASAM) has partnered with nine other medical societies and professional associations representing a wide range of clinical settings and patient populations to provide guidance on evidence-based strategies for tapering benzodiazepine (BZD) medication across a variety of settings. METHODS: The guideline was developed following modified GRADE methodology and clinical consensus process. The process included a systematic literature review as well as several targeted supplemental searches. The clinical practice guideline was revised based on external stakeholder review. RECOMMENDATIONS: Key takeaways included the following: Clinicians should engage in ongoing risk-benefit assessment of BZD use/tapering, clinicians should utilize shared decision-making strategies in collaboration with patients, clinicians should not discontinue BZDs abruptly in patients who are likely to be physically dependent and at risk of withdrawal, clinicians should tailor tapering strategies to each patient and adjust tapering based on patient response, and clinicians should offer patients adjunctive psychosocial interventions to support successful tapering.

The authors were both privileged and challenged to provide art therapy groups for children and their families in the aftermath of the Pentagon attack on 9/11/01. As part of a comprehensive family support program provided by the Pentagon Family Assistance Center, the therapists provided interventions for many children whose lives were directly affected by the loss of a close family member. They endeavored to provide a holding environment and opportunities for these children to creatively experience what had occurred. This paper chronicles their participation with these children, describes their methods of working, and includes some information on the theoretical basis for the use of art in the treatment of trauma.

To date, a standard for pin site care has yet to be identified. Pin site care recommendations are more often based upon clinician preference rather than research findings. Further, there are great variations in recommendations for pin care treatments from clinician to clinician. The nursing and medical literature were reviewed in an attempt to identify a pin site care standard based upon scientific findings. Unfortunately, the research on prophylactic treatment of pin sites is limited. The pin site care protocol recommended by this author is based on pathophysiologic processes involved in the development of pin site infections, as well as information found in the research literature. The recommended protocol includes the following: (a) using normal saline as the cleansing agent; (b) avoiding ointments for postcleansing care; (c) removing crusts; (d) using sterile technique for the hospitalized patient while clean technique is used once the patient is discharged from the hospital; (e) applying dressings to pin sites; and (f) providing pin care three times a day if drainage is present or once daily in the absence of drainage.

PURPOSE: Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been identified in a variety of human cancers. The purpose of this prospective study was to determine whether (a) DNA can be isolated from nipple aspirate fluid (NAF) and PCR amplified to large fragments, (b) LOH and MSI are detectable in NAF, and (c) LOH and MSI in tissue and NAF increase with disease progression from precursor lesions to cancer. EXPERIMENTAL DESIGN: Forty-six matched samples from breast lesions, normal breast, and NAF were microdissected, and DNA was extracted. Eleven microsatellite markers from seven chromosomes that have a high frequency of LOH/MSI in breast cancer were designed and respectively amplified. RESULTS: LOH and/or MSI were identified in 22 of 46 (48%) breast lesions, including LOH in 8 of 36 (22%) proliferative/papilloma (P/Pap) and 7 of 10 (70%) cancer specimens, whereas MSI was found in 14 of 36 (39%) P/Pap and 6 of 10 (60%) cancer specimens. LOH/MSI loci in which alterations were detected in the 22 tissue specimens were PCR amplified using matched NAF DNA. LOH/MSI was detected in NAF from both P/Pap (5 of 15; 33%) and breast cancer (3 of 7; 43%) samples. CONCLUSIONS: Our findings suggest that (a) DNA from NAF, a physiological fluid collected noninvasively, can be PCR amplified and used to screen for LOH and MSI alterations that are known to be linked to breast cancer, suggesting that this methodology might prove useful for breast cancer screening, and (b) similar to findings in breast tissue, LOH and MSI alterations increase in frequency with disease progression in NAF, which suggests that NAF is a surrogate for breast tissue which has important prognostic implications.