In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

A method for sonographic counting of the lower vertebral bodies in newborns and infants.

PURPOSETo determine whether the lumbosacral junction of the vertebral column can be identified with sonography in newborns and infants and thus serve as a method for counting the lumbar and sacral vertebral bodies.METHODSIn 32 newborns and infants, the number of ossified vertebral bodies distal to the lumbosacral junction was counted with sonography and radiography.RESULTSSonographic and radiographic findings agreed in 29 of 32 examinations (91%).CONCLUSIONSThe lordotic transition at the lumbosacral junction can be identified with sonography in the majority of newborns and infants, allowing intraspinal structures to be related to a specific vertebral level.     

Second births among teenage mothers: program results and statistical methods

This paper uses survival analysis to examine three large-scale, multi-site, randomized, controlled programs that attempted to prevent or delay second births to teenagers. Statistically significant differences in the hypothesized direction were found between the intervention and the control groups in the Elmira and Memphis Home Visitation sites. No statistically significant differences in the hypothesized direction were found in the Teen Parent Welfare Demonstration overall or in any of its three sites or in all New Chance sites combined. Delaying second pregnancies among teenagers requires intensive efforts. Survival analysis is a more accurate and useful way of presenting program results than simple analysis of the proportion of women with a second birth.     

Neurokinin A with K channel blockade potentiates contraction to electrical stimulation in human bronchus

This study investigated the effects of neurokinin A (NKA) on cholinergic neural responses in human bronchus. NKA (0.1 nM) did not alter the contractile response to submaximal electrical field stimulation. However, K⁺ channel blockade with 4-aminopyridine (4-AP) (0.1 mM) potentiated the response to electrical field stimulation (to 182 ± 25% of control, n = 4, P < 0.05) and subsequent addition of NKA in the presence of 4-AP produced further potentiation (to 123 ± 6% of the response to 4-AP n = 4, P < 0.05). Neither 4-AP (0.01 or 0.1 mM) nor NKA in the presence of 4-AP potentiated the actions of exogenous acetylcholine but in these experiments 4-AP itself produced a marked direct contractile response. Thus NKA in the presence of K⁺ channel blockade potentiates cholinergic neural response in human bronchus and this occurs at a prejunctional site.     

Geriatric care on a ward without nurses

The Multiphasic Environmental Assessment Procedure (MEAP; Moos and Lemke, 1984) was used to assess three long-stay settings within a geriatric hospital, one of which is a non-nursing unit committed to the philosophy of residents viewing the setting as their own home. Findings suggest positive outcomes for residents on the nonnursing unit, and support the view that types of care fostering independence and personal responsibility of elderly residents in their setting may be associated with increased mental functioning and activity. The lack of trained nursing staff had no detrimental effect on any measure of resident life, and some specific caring practices on the unit may be interpreted as having a positive outcome for residents.     

Flexible Sigmoidoscopy Screening in an Industrial Setting

Little is known about the yield of colorectal cancer screening programs in an industrial setting. We therefore established a flexible sigmoidoscopy screening program at a chemical manufacturing plant and offered testing to all employees over the age of 40. After a Fleet enema preparation had been administered, a digital rectal examination and sigmoidoscopy were performed on each volunteer worker in the medical office of the plant. The plant had an average census of about 650 workers; 202 were screened during a 2-yr period. The mean (+/- SEM) age of participants was 52 +/- 0.4. Sixty-four employees had polyps (31.7%); data on follow-up colonoscopy were available in 69%. Colonoscopy revealed adenomatous polyps in 23 workers (53.5%), hyperplastic polyps in 10 (23%), and no evidence of neoplasia in 10 (23%). Seven workers did not arrange for follow-up colonoscopy and 12 individuals could not be contacted. No cancers were detected. In the 40- to 50-yr age group, polyps were detected in 19.5% of employees (25% adenomatous). Incidental findings were common, and included prostatic nodules, hemorrhoids, diverticulosis, and proctitis, among others. We conclude that screening sigmoidoscopy can be conveniently and economically performed at the workplace, with a high yield and good worker acceptance. The high yield suggests a possible association between polyp formation and work in a chemical plant. The finding of adenomatous polyps in the younger patients suggests that the threshold for flexible sigmoidoscopy at age 50 needs to be reassessed.     

Cytomegalovirus Disease in High-Risk Transplant Recipients Despite Ganciclovir or Valganciclovir Prophylaxis

The clinical patterns and predictors of cytomegalovirus (CMV) disease in kidney and/or pancreas transplant patients on ganciclovir (1.0 g po t.i.d.) or valganciclovir (450 mg po q.d.) prophylaxis were studied. This is a retrospective analysis of 129 transplant recipients. Median follow up was 12 months (range, 6-18 months). The overall incidence of CMV disease at 1-year post-transplant was 14% (4% tissue-invasive, 10% noninvasive). Seventeen of 18 patients were diagnosed with CMV after completion of 3 months' prophylaxis (median 8 weeks, range, 2-28 weeks). Induction treatment with thymoglobulin, and Donor +/Recipient - CMV status were the strongest predictors for the development of CMV disease. Cytomegalovirus incidence was not different between patients treated with ganciclovir or valganciclovir (15 vs. 17%, respectively). Valganciclovir (450 mg q.d.) is as effective as oral ganciclovir in CMV prophylaxis. High-risk individuals might require higher doses or longer duration of valganciclovir treatment.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.