Review of the prevalence, pathogenesis and management of OSA-COPD overlap.

PURPOSE: OSA-COPD overlap is an important and prevalent condition yet remains under-recognised among the vast majority of respiratory health professionals. Patients with OSA-COPD overlap experience more severe respiratory symptoms and worse quality of life, and the relative risk of exacerbations, hospitalisations, and mortality is higher than in either disease state alone. METHODS: Electronic databases PUBMED and Google Scholar were searched for studies and academic papers that discussed OSA-COPD overlap. Relevant papers that discussed prevalence, pathophysiology, microbiome studies, treatment regimens and outcomes were included in this paper. RESULTS: High-risk patients with either COPD or OSA should be screened for overlap syndrome as part of routine clinical practice. Screening questionnaires can identify high-risk patients with COPD who may benefit from formal polysomnography. Patients with OSA who are aged over 40 with a significant smoking history or environmental exposures have an increased pre-test probability of obstructive airway disease. The potential roles of gastro-oesophageal reflux disease and lung-gut microbiome are evolving and merit further investigation. A tailored approach to reach a timely diagnosis and thus optimisation of both conditions are key to management. CPAP is the primary therapy for OSA; however, patients with more advanced COPD, with daytime hypercapnia or severe nocturnal desaturations, may benefit from bilevel positive airway pressure. CONCLUSION: Increased awareness, access to timely investigations and initiation of therapy will improve overall outcomes in OSA-COPD overlap by reducing hospitalisations for exacerbations of COPD and improve mortality rates.

Radial scars and complex sclerosing lesions on core needle biopsy of the breast: upgrade rates and long-term outcomes.

PURPOSE: Radial scars and complex sclerosing lesions of the breast are part of a group of "indeterminate" breast lesions, which are excised due to risk of coexistent carcinoma. The aim of this study was to assess rate of upgrade of these lesions to invasive and in situ carcinoma and to quantify the risk of development of subsequent cancer in women diagnosed with these lesions. METHODS: A retrospective review of a prospectively maintained breast screening database was performed. All patients with radial scar identified at either core biopsy or final excision biopsy between January 2006 and July 2012 were identified. Full pathological reports for both core biopsy and final excision biopsy were reviewed. Patient outcomes were followed for a mean of 117.1 months. RESULTS: Of 451 B3 biopsies performed at our screening unit, 95 (22%) were found to have a radial scar or complex sclerosing lesion (CSL) on core needle biopsy. Within this group, 77 had no atypia on CNB, with 7 (9%) upgraded to invasive/in situ carcinoma on final excision. Of nine with definite atypia on CNB, 3 (33%) were upgraded. In those patients without atypia or malignancy on final excision, 7.5% developed cancer during 10-year follow-up. CONCLUSION: Patients with radial scar with atypia have a higher risk of upgrade to malignancy. Further research is needed to identify which patients may safely avoid excision of radial scar. Patients with a diagnosis of radial scar on CNB are at increased subsequent risk of breast cancer and may benefit from additional screening.

Breast cancer in young black women.

BACKGROUND: Young age at breast cancer diagnosis is associated with negative prognostic outcomes, and breast cancer in black women often manifests at a young age. This study evaluated the effect of age on breast cancer management and outcomes in black women. METHODS: This was a retrospective cohort study of all black women treated for invasive breast cancer between 2005 and 2010 at a specialized tertiary-care cancer centre. Clinical and treatment characteristics were compared by age. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 666 black women were identified. Median BMI was 30 (range 17-56) kg/m2 and median tumour size was 16 (1-155) mm. Most tumours were oestrogen receptor-positive (66·4 per cent). Women were stratified by age: less than 40 years (74, 11·1 per cent) versus 40 years or more (592, 88·9 per cent). Younger women were significantly more likely to have a mastectomy, axillary lymph node dissection and to receive chemotherapy, and were more likely to have lymphovascular invasion and positive lymph nodes, than older women. The 5-year OS rate was 88·0 (95 per cent c.i. 86·0 to 91·0) per cent and the 5-year DFS rate was 82·0 (79·0 to 85·0) per cent. There was no statistically significant difference in OS by age (P = 0·236). Although DFS was inferior in younger women on univariable analysis (71 versus 88 per cent; P < 0·001), no association was found with age on multivariable analysis. CONCLUSION: Young black women with breast cancer had more adverse pathological factors, received more aggressive treatment, and had worse DFS on univariable analysis. Young age at diagnosis was, however, not an independent predictor of outcome.

ANTECEDENTES: El diagnóstico de cáncer de mama a una edad joven se asocia con un pronóstico de resultados negativo, y en mujeres de raza negra, el cáncer de mama con frecuencia se manifiesta a edades tempranas. Este estudio analiza el efecto de la edad en el tratamiento y resultados del cáncer de mama en mujeres de raza negra. MÉTODOS: Estudio de cohortes retrospectivo de todas las mujeres de raza negra tratadas por cáncer de mama invasivo entre 2005-2010 en un centro oncológico terciario de alta especialización. Se compararon las características clínicas y del tratamiento en función de la edad. Se estimó la supervivencia global (overall survival, OS) y la supervivencia libre de enfermedad (disease-free survival, DFS) con el método de Kaplan-Meier y se utilizó la prueba de log-rank para las comparaciones entre grupos. RESULTADOS: Se identificaron un total de 666 mujeres de raza negra. La mediana del tamaño del tumor fue de 16 mm (rango 1-155 mm). La mayoría de los tumores fueron positivos para el receptor de estrógenos (66,4%); la mediana del índice de masa corporal (IMC) fue 30 kg/m2 (rango 17,2-56,5). Se estratificaron a las mujeres por su edad: < 40 años (n = 74; 11,1%) frente a ≥ 40 años (n = 592; 88,9%). La probabilidad de recibir una mastectomía, un vaciamiento ganglionar axilar y quimioterapia fue significativamente superior en las pacientes jóvenes y además fueron más propensas a presentar invasión linfovascular y ganglios linfáticos positivos en comparación con las mujeres mayores. Las OS y DFS a los 5 años fueron del 88,0% (i.c. del 95% 86-91%) y del 82% (i.c. del 95% 79-85%), respectivamente. No se observaron diferencias estadísticamente significativas en la OS (P = 0,236) en función de la edad. Aunque en el análisis univariado la DFS fue peor en las mujeres jóvenes (71% versus 88%, log-rank P < 0,001), en el análisis multivariable no se confirmó la asociación con la edad. CONCLUSIÓN: Las mujeres jóvenes de raza negra con cáncer de mama tuvieron más factores patológicos adversos, recibieron un tratamiento más agresivo y tuvieron una DFS peor en el análisis univariado. Sin embargo, la edad temprana en el momento del diagnóstico no fue un factor predictivo independiente del resultado.

The lady with the dragon tattoo.

BACKGROUND: Though the skin is affected in sarcoidosis in about one-third of cases, granulomatous tattoo reactions are an unusual manifestation of the disease. It is important phenomenon to recognize, as it frequently leads to the diagnosis of systemic sarcoidosis. CASE PRESENTATION: A 35-year-old Caucasian female with multiple tattoos presented with a 5-week history of tenderness of the black dye in a tattoo depicting a dragon. She also described a 15-month history of fatigue, polyarthralgia, and mild dyspnea. Skin biopsy demonstrated multiple dermal non-caseating granulomata with associated tattoo ink. Further investigation revealed the presence of systemic sarcoidosis. Her symptoms and skin changes improved with conservative management. CONCLUSION: Sarcoidal tattoo reactions in those without systemic sarcoidosis are a rare occurrence, and their presence should prompt a search for systemic involvement. The accurate identification of skin involvement in sarcoidosis is important, as it tends to occur early in the course of disease, and the skin is a readily accessible site for biopsy, allowing for prompt diagnosis.

A Positive Node on Ultrasound-Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma.

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.

Postmastectomy radiotherapy: indications and implications.

BACKGROUND: Although breast conservation surgery, when combined with radiotherapy, has been shown to provide excellent locoregional control for breast cancer, approximately one third of women with breast cancer require mastectomy. Many of these women are offered immediate reconstruction. Postmastectomy radiotherapy (PMRT) is indicated in some cases, but is associated with side-effects, including its impact on the reconstructed breast. OBJECTIVE: To review the pertinent issues surrounding PMRT, including patient selection for radiotherapy and the effect of radiotherapy on reconstructive decisions. METHODS: A literature review was performed using the Medline database. CONCLUSIONS: PMRT is indicated in patients who are deemed to have a high risk of loco-regional recurrence. Although PMRT is strongly recommended for patients with four or more positive lymphnodes, other indications for PMRT remain controversial. Immediate reconstruction post mastectomy has been shown to have favorable outcomes. However, PMRT may increase the need for revision surgery post immediate reconstruction. There are few randomized trials looking at these key issues, and the evidence is largely derived from observational retrospective studies. Patients should be carefully counseled before a decision is made to proceed with immediate reconstruction, where there is a high chance that PMRT may be indicated.

Ultrasound predictors of malignancy in indeterminate thyroid nodules.

BACKGROUND: Asymptomatic thyroid nodules are an increasingly common clinical problem. Lesions greater than a centimetre require cytological assessment. Indeterminate lesions often need surgical excision to establish a definitive diagnosis and plan further management. If a definitive diagnosis could be accurately predicted pre-operatively, the most appropriate surgical procedure could be performed at the initial operation. AIM: The aim of this study was to identify whether specific thyroid ultrasound features could predict malignancy in indeterminate thyroid nodules. METHODS: A retrospective review of all patients undergoing surgery for an indeterminate thyroid lesion between 2006 and 2012 was performed. Demographic features, surgical intervention and final histological findings were determined. Pre-operative ultrasound findings and final histology were correlated and the ultrasonic markers predictive of malignancy were determined. RESULTS: A total of 40 patients were identified as having undergone surgical intervention for indeterminate thyroid nodules. The majority of patients were diagnosed with a follicular adenoma (n = 22; 55 %). Papillary thyroid carcinoma was identified in three patients (7.5 %) and follicular carcinoma in a further 3 (7.5 %). Ultrasound features associated with malignancy included poorly defined nodule borders and increased vascularity. The presence of malignancy was not related to nodule size, echogenicity or the presence of calcifications. CONCLUSIONS: The majority of indeterminate thyroid lesions are benign on final histological assessment. High nodule vascularity associated with ill-defined borders is associated with malignancy. Further research is warranted to identify predictors of malignancy in indeterminate nodules in order to avoid unnecessary or repeated procedures.

Fishing top predators indirectly affects condition and reproduction in a reef-fish community.

To examine the indirect effects of fishing on energy allocation in non-target prey species, condition and reproductive potential were measured for five representative species (two-spot red snapper Lutjanus bohar, arc-eye hawkfish Paracirrhites arcatus, blackbar devil Plectroglyphidodon dickii, bicolour chromis Chromis margaritifer and whitecheek surgeonfish Acanthurus nigricans) from three reef-fish communities with different levels of fishing and predator abundance in the northern Line Islands, central Pacific Ocean. Predator abundance differed by five to seven-fold among islands, and despite no clear differences in prey abundance, differences in prey condition and reproductive potential among islands were found. Body condition (mean body mass adjusted for length) was consistently lower at sites with higher predator abundance for three of the four prey species. Mean liver mass (adjusted for total body mass), an indicator of energy reserves, was also lower at sites with higher predator abundance for three of the prey species and the predator. Trends in reproductive potential were less clear. Mean gonad mass (adjusted for total body mass) was high where predator abundance was high for only one of the three species in which it was measured. Evidence of consistently low prey body condition and energy reserves in a diverse suite of species at reefs with high predator abundance suggests that fishing may indirectly affect non-target prey-fish populations through changes in predation and predation risk.

The ALSSQOL: balancing physical and nonphysical factors in assessing quality of life in ALS.

BACKGROUND: There is no generally accepted instrument for measuring quality of life (QOL) in patients with ALS. Current instruments are either too heavily weighted toward strength and physical function or useful for the evaluation of individuals but of less utility in assessing large samples. OBJECTIVE: To develop and evaluate the psychometric properties of an ALS-specific QOL instrument (the ALSSQOL) that would reflect overall QOL as assessed by the patient and would be valid and reliable across large samples. METHODS: The ALSSQOL is based on the McGill Quality of Life Questionnaire (MQOL), modified by changes in format and by adding questions on religiousness and spirituality, items derived from interviews with ALS patients, and items identified from open-ended questions administered during the MQOL. The psychometric properties of the ALSSQOL were assessed by a prospective multicenter study in which participants completed the ALSSQOL, other instruments measuring overall QOL, and instruments assessing religiousness, spirituality, and psychological distress. RESULTS: A 59-item ALSSQOL was developed; 342 patients evaluated its psychometric properties. Completion time averaged 15 minutes. Forty-six items loaded on six factors. The ALSSQOL demonstrated concurrent, convergent, and discriminant validity for the overall instrument and convergent validity for its subscales. Analysis of individual items permitted insight into variables of clinical importance. CONCLUSIONS: This new ALS-specific quality of life instrument is a practical tool for the assessment of overall quality of life in individuals with ALS and appears to be valid and useful across large samples. Validation studies of a shortened version are now under way.

Uterine artery embolization: reduced radiation with refined technique.

PURPOSE: To determine the estimated absorbed ovarian dose (EAOD) and absorbed skin dose (ASD) that occurs during uterine artery embolization (UAE) using pulsed fluoroscopy and a refined procedure protocol. MATERIALS AND METHODS: The absorbed dose was measured in 20 patients who underwent UAE procedures. Radiation was limited by using low frequency pulsed fluoroscopy, bilateral catheter technique with simultaneous injections for embolization as well as pre-and postembolization exposures and focus on limitation of magnified and oblique fluoroscopy. Lithium fluoride dosimeters were placed both in the posterior vaginal fornix and on the skin at the beam entrance site. The vaginal dose was used to approximate the EAOD. Fluoroscopy time and exposures were recorded. The mean values for all patients were calculated and compared to our previous results obtained with conventional fluoroscopy and to threshold doses for the induction of deterministic skin injury. RESULTS: Mean fluoroscopy time was 10.95 min. (range 6-21.3 min.) and the mean number of angiographic exposures was 20.9 (range 14-53). The mean EAOD was 9.5 cGy (range 2.21-23.21 cGy) and the mean ASD was 47.69 cGy (range 10.83-110.14 cGy). This compares to previous results with non-pulsed fluoroscopy of an EAOD of 22.34 cGy (range 4.25-65.08 cGy) and an ASD of 162.32 cGy (range 66.01-303.89 cGy) as well as threshold doses for induction of deterministic radiation injury to the skin (400-500 cGy). CONCLUSION: When pulsed fluoroscopy is used with emphasis on dose reduction techniques, the EAOD and ASD can be substantially reduced to less than 1/2 (P = .017) and 1/3 (P < .0001) when compared to UAE performed with nonpulsed fluoroscopy. These radiation reduction tools should therefore be applied whenever possible.

Quality of life in ALS is maintained as physical function declines.

OBJECTIVES: To study patients with ALS to determine how physical function, quality of life (QOL), and spirituality or religiousness change over time, and what relationship these changes have to one another. METHODS: Sixty patients with ALS were studied prospectively. They were assessed at baseline, 3 months, and 6 months, using questionnaires designed to measure general quality of life (McGill Quality of Life questionnaire), religiosity (Idler Index of Religiosity), ALS-specific health-related quality of life (SIP/ALS-19), and ALS-specific function (ALS functional rating scale). RESULTS: A two-way repeated measures multivariate analysis of variance revealed that both the passage of time and the specific QOL scales used were factors in predicting patient quality of life (F[1, 59]= 9.87, p < 0.003 and F[3, 177]= 16.90, p < 0.001) Despite a progressive decline in physical function as measured by the ALS-specific function score, the general QOL and religiosity scores changed little. In contrast, the ALS-specific health-related QOL score declined in parallel with the ALS-specific function score. CONCLUSIONS: QOL in patients with ALS appears to be independent of physical function, which agrees with a previous cross-sectional study. The ALS-specific health-related QOL score is primarily a measure of physical function. QOL instruments that assess spiritual, religious, and psychological factors produce different results than those obtained using measures of physical function alone.

Pain after uterine artery embolization for leiomyomata: can its severity be predicted and does severity predict outcome?

PURPOSE: To determine whether the severity of postprocedure pain associated with uterine artery embolization (UAE) for leiomyomata can be predicted and if its severity can predict outcome. MATERIALS AND METHODS: Eighty-one patients underwent UAE and had postprocedure pain managed with use of patient-controlled analgesia (PCA) in the form of an intravenous morphine pump. Baseline uterine and dominant fibroid volumes were calculated for each patient. Attempted doses, doses given, total morphine dose, and maximum numerical rating scale (NRS) score during postprocedure hospitalization were recorded. At 3 months postprocedure, repeat imaging was used to determine uterine and dominant fibroid volume reduction. Each patient also completed a questionnaire assessing change in menstrual bleeding, pelvic pain and pressure symptoms, and satisfaction with symptomatic outcome. Simple regression analysis was used to determine if baseline volumes predicted postprocedure pain and if the pain-related variables could be used to predict outcome. RESULTS: Neither baseline uterine volume nor dominant fibroid volume predicted the severity of postprocedure pain. Similarly, none of the pain-related variables predicted uterine or fibroid volume reduction, symptomatic improvement, or satisfaction with outcome. CONCLUSIONS: Postprocedural pain cannot be predicted based on baseline uterine or fibroid volume and the severity of pain experienced cannot be used to predict outcome.

Quality of life in ALS depends on factors other than strength and physical function.

OBJECTIVES: To study patients with ALS to determine the following: 1) the relationship between physical function and quality of life (QOL); 2) the instruments that best reflect patients' own ratings of QOL; and 3) whether spiritual/religious factors play a role in determining QOL. METHODS: The authors prospectively studied 96 patients with ALS using several instruments, including the McGill Quality of Life (MQOL) instrument, the Idler Index of Religiosity, the Sickness Impact Profile (SIP)/ALS-19, and several measures of strength and physical function. RESULTS: QOL as assessed by patients (MQOL single item score) did not correlate with measures of physical function and strength, but correlated with the total MQOL score (p < 0.0005), the psychological and existential subscores of MQOL (p < 0. 0005), the support subscore of MQOL (p = 0.001), and the total Idler score (p = 0.001). In contrast, correlations between SIP/ALS-19 and these measures were not significant, although SIP/ALS-19 correlated with measures of physical function and strength. CONCLUSIONS: QOL, as assessed by the patient with ALS, does not correlate with measures of strength and physical function, but appears to depend on psychological and existential factors, and thus may be measured well by the MQOL scale. Spiritual factors and support systems appear to play roles as well. SIP/ALS-19 is a good measure of physical function, but not of overall QOL.

Uterine fibroid embolization: measurement of health-related quality of life before and after therapy.

OBJECTIVE: To determine the change in health-related quality of life associated with uterine fibroid embolization (UFE). MATERIALS AND METHODS: A health-related quality-of-life questionnaire was administered before and after therapy. The questionnaire contained validated scales from the Medical Outcomes Study, with additional domains and symptom items specific to fibroids. Patients treated with UFE for symptomatic uterine leiomyomata completed a health-related quality of life questionnaire before therapy. A follow-up quality of life questionnaire and an additional brief questionnaire to assess symptom improvement were completed 3 and 6 months postprocedure. Confirmatory reliability and validity testing was also conducted. Mean scores for each scale on the quality of life questionnaire were calculated and change scores were computed. RESULTS: Fifty women were enrolled in the study and completed the baseline assessment. Health-related quality of life scores improved in all instances at follow-up. Mean change scores were statistically significant for all domains between baseline and month 3 (P < .01) and between baseline and month 6 (P < .05) except backache (P = .12). CONCLUSION: Patients undergoing UFE report significant improvements in health-related quality of life and fibroid-specific symptoms. These findings suggest that the measurement of health-related quality of life may be an effective means of comparing the outcome of UFE with other fibroid therapies.

Repeated delivery of adeno-associated virus vectors to the rabbit airway.

Efficient local expression from recombinant adeno-associated virus (rAAV)-cystic fibrosis (CF) transmembrane conductance regulator (CFTR) vectors has been observed in the airways of rabbits and monkeys for up to 6 months following a single bronchoscopic delivery. However, it is likely that repeated administrations of rAAV vectors will be necessary for sustained correction of the CF defect in the airways. The current study was designed to test the feasibility of repeated airway delivery of rAAV vectors in the rabbit lung. After two doses of rAAV-CFTR to the airways, rabbits generated high titers of serum anti-AAV neutralizing antibodies. Rabbits then received a third dose of a rAAV vector containing the green fluorescent protein (GFP) reporter gene packaged in either AAV serotype 2 (AAV2) or serotype 3 (AAV3) capsids. Each dose consisted of 1 ml containing 5 x 10(9) DNase-resistant particles of rAAV vector, having no detectable replication-competent AAV or adenovirus. Three weeks later, GFP expression was observed in airway epithelial cells despite high anti-AAV neutralizing titers at the time of delivery. There was no significant difference in the efficiency of DNA transfer or expression between the rAAV3 and rAAV2 groups. No significant inflammatory responses to either repeated airway exposure to rAAV2-CFTR vectors or to GFP expression were observed. These experiments demonstrate that serum anti-AAV neutralizing antibody titers do not predict airway neutralization in vivo and that repeated airway delivery rAAV allows for safe and effective gene transfer.

Gene transfer by DNA-gelatin nanospheres.

A DNA and gelatin nanoparticle coacervate containing chloroquine and calcium, and with the cell ligand transferrin covalently bound to the gelatin, has been developed as a gene delivery vehicle. In this study, the coacervation conditions which resulted in the formation of distinct nanoparticles are defined. Nanospheres formed within a narrow range of DNA concentrations and achieved incorporation of more than 98% of the DNA in the reaction. Crosslinking of gelatin to stabilize the particles does not effect the electrophoretic mobility of the DNA. DNA in the nanosphere is partially resistant to digestion with concentrations of DNase I that result in extensive degradation of free DNA but is completely degraded by high concentrations of DNase. Optimum cell transfection by nanosphere DNA required the presence of calcium and nanospheres containing transferrin. The biological integrity of the nanosphere DNA was demonstrated with a model system utilizing DNA encoding the cystic fibrosis transport regulator (CFTR). Transfection of cultured human tracheal epithelial cells (9HTEo) with nanospheres containing this plasmid resulted in CFTR expression in over 50% of the cells. Moreover, human bronchial epithelial cells (IB-3-1) defective in CFTR-mediated chloride transport were complemented with effective transport activity when transfected with nanospheres containing the CFTR transgene.

DNA-polycation nanospheres as non-viral gene delivery vehicles.

Nanospheres synthesized by salt-induced complex coacervation of cDNA and polycations such as gelatin and chitosan were evaluated as gene delivery vehicles. DNA-nanospheres in the size range of 200-750 nm could transfect a variety of cell lines. Although the transfection efficiency of the nanospheres was typically lower than that of lipofectamine and calcium phosphate controls in cell culture, the beta-gal expression in muscle of BALB/c mice was higher and more sustained than that achieved by naked DNA and lipofectamine complexes. This gene delivery system has several attractive features: (1) ligands can be conjugated to the nanosphere for targeting or stimulating receptor-mediated endocytosis; (2) lysosomolytic agents can be incorporated to reduce degradation of the DNA in the endosomal and lysosomal compartments; (3) other bioactive agents or multiple plasmids can be co-encapsulated; (4) bioavailability of the DNA can be improved because of protection from serum nuclease degradation by the polymeric matrix; (5) the nanosphere can be lyophilized for storage without loss of bioactivity.