The potential role of the heparin-binding growth factor pleiotrophin in breast cancer

Summary We propose that the secreted protein pleiotrophin (PTN) is a major factor in the malignant progression of breast cancer. This hypothesis is based on the growth-stimulatory effects of PTN on cellsin vitro andin vivo and on its high levels of expression in 60% of tumor samples from breast cancer patients. The stimulation of proliferation and tube formation of endothelial cells by PTN suggests that it can serve as an angiogenesis factor during tumor growth. We hypothesize that PTN has the potential to support growth of breast cancer at its primary site and to enhance the ability of tumor cells to metastasize. Furthermore, we suggest that specific endocrine signals interact to regulate the expression of PTNin vitro andin vivo. Finally, we propose that understanding the functions of PTN and its hormonal regulation can lead to the development of novel therapeutic strategies for breast cancer.     

The incidence of error in young children's Wh-questions.

Many current generativist theorists suggest that young children possess the grammatical principles of inversion required for question formation but make errors because they find it difficult to learn language-specific rules about how inversion applies. The present study analyzed longitudinal spontaneous sampled data from twelve 2-3-year-old English speaking children and the intensive diary data of 1 child (age 2;7 [years;months] to 2;11) in order to test some of these theories. The results indicated significantly different rates of error use across different auxiliaries. In particular, error rates differed across 2 forms of the same auxiliary subtype (e.g., auxiliary is vs. are), and auxiliary DO and modal auxiliaries attracted significantly higher rates of errors of inversion than other auxiliaries. The authors concluded that current generativist theories might have problems explaining the patterning of errors seen in children's questions, which might be more consistent with a constructivist account of development. However, constructivists need to devise more precise predictions in order to fully explain the acquisition of questions.     

EPUAP pressure ulcer prevalence survey in Sweden: a two-year follow-up of quality indicators.

OBJECTIVE: The aim of this study was to determine the effects of quality improvement programs for pressure ulcer prevention by conducting a follow-up survey in a hospital in Sweden. DESIGN: A cross-sectional survey design with comparison between data collected in 2002 and 2004. SETTING AND SUBJECTS: All inpatient areas were surveyed in the surgical, medical, and geriatric departments in a university hospital. A total of 369 patients were included. INSTRUMENTS: The European Pressure Ulcer Advisory Panel data collection form including some additional questions. METHODS: The 1-day survey was conducted on March 23, 2004. Each patient was visited by 2 registered nurses, who inspected the patient's skin for any pressure ulcer classified according to the EPUAP grading system. RESULTS: There were no significant differences in gender, age, or Braden score between the patients in surgical, medical, or geriatric care in 2002 and 2004. The overall prevalence of pressure ulcers was 33.3% (grade 1 excluded: 10.9%) in 2002 and 28.2% (grade 1 excluded: 14.1%) in 2004. In surgical care, the prevalence was reduced from 26.8% to 17.3% (P = .051). In medical care, the prevalence was 23.6% in 2002 and 26.7% in 2004. Corresponding prevalence figures for geriatric care were 59.3% and 50.0%. A quarter of the patients in surgical care, a third in medical care, and more than half in geriatric care had a pressure ulcer upon arrival at the ward. The use of pressure-reducing mattresses had increased significantly from 16.0% to 42.7% in medical care (P = .000). CONCLUSIONS: The EPUAP methodology has facilitated the introduction of pressure ulcer as a quality indicator at hospital level. Pressure ulcer prevalence surveys with a standardized methodology should be repeated on a regular basis in order to stimulate quality improvement.     

Congenital absence of the inferior rectus muscle--diagnosis and management.

BACKGROUND: Congenital absence of the inferior rectus muscle is a rare cause of apparent inferior rectus palsy especially in the absence of associated cranial facial anomalies. METHODS: We report three cases of isolated congenital absence of the inferior rectus muscle and its successful surgical management. RESULTS: Failure of the normal embryologic development of the mesodermal complex around the eye can lead to agenesis of the extraocular muscles. In apparent palsies of the inferior rectus muscle and no definite cause, a high index of suspicion and orbital imaging can confirm the diagnosis of congenitally absent inferior rectus preoperatively. Surgical correction may involve inferior transposition of the horizontal rectus muscles. CONCLUSIONS: Although rare, congenital absence of the inferior rectus muscle is a possible cause of apparent inferior rectus muscle palsy particularly in the absence of another identifiable cause. Strabismus surgery in conjunction with intramuscular botulinum toxin injection can offer significant improvement in function and cosmesis of these patients.     

CADASIL or CADVaSIL?

In the present study, morphological examination of patients from two unrelated Polish families with CADASIL was performed. Using light microscopy, there were evident changes characteristic to the disease. On electron microscopy, deposits of granular osmiophillic material (GOM) were found not only in cerebral arteries and veins but also in cerebral capillaries and vessels of the internal organs. These findings indicate that pathological process in CADASIL is generalized and involves also small vessels devoid of smooth muscle cells. Therefore, we propose to consider a replacement for the name CADASIL that better reflects the morphological picture of the disease like, for example, cerebral autosomal dominant vasculopathy with subcortical infarcts and leukoencephalopathy (CADVaSIL) or, to preserve the commonly known acronym, cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy.     

Progressive increase in the angle of deviation in acquired nonaccommodative esotropia of childhood.

PURPOSE: Although the angle of deviation in patients with congenital esotropia has been shown to increase during the early preoperative period, few data exist regarding this change in other forms of childhood esotropia. The primary objective of this study was to investigate whether the angle of deviation increases with time in patients with acquired nonaccommodative esotropia (ANAET). METHODS: The medical records of all children whose ANAET was diagnosed at East Tennessee State University College of Medicine from August 1, 1995, through October 1, 2001, were retrospectively reviewed. All patients were assessed for any change in the amount of their strabismic angle and associated risk factors. RESULTS: Eighty-two patients with ANAET were identified, and all except 3 underwent more than one examination. Of the 79 children who underwent more than one examination, 26 (32.9%) displayed an angle increase of > or =10 prism diopters (PD) during a median follow-up period of 2.9 months. The ANAET of those patients whose angle increased by > or =10 PD was diagnosed (28.4 months of age vs 45.5 months of age, P =.003), and they underwent surgery (35.9 months of age vs 53.3 months of age, P =.003) at a significantly younger median age than those whose angle increased <10 PD. CONCLUSIONS: The angle of deviation of approximately one third of patients with ANAET in this study increased at least 10 PD in the early preoperative period. This increase occurs more often in younger patients and underscores the importance of performing serial measurements of the deviating angle before surgical intervention is undertaken.     

Congenital disseminated malignant rhabdoid tumor and cerebellar tumor mimicking medulloblastoma in monozygotic twins: pathologic and molecular diagnosis.

Malignant rhabdoid tumors are highly aggressive childhood tumors. Recently, all of the malignant rhabdoid tumors, whatever their location, have been related to the inactivation of the hSNF5/INI1 gene. A subset of cerebral tumors, associated with malignant rhabdoid tumors or isolated ones arising in siblings, showed similar molecular alterations. We report for the first time in monozygotic twins a congenital disseminated malignant rhabdoid tumor in one twin and a cerebellar tumor mimicking a medulloblastoma in the other. Molecular analysis revealed similar alterations for both tumors: a deletion of exon 7 of the hSNF5/INI1 gene in one allele, and a point mutation in the same exon in the other, suggesting a common genetic pathway. Analysis of constitutional DNA revealed a germline mutation. These findings are in favor of a common etiology for rhabdoid tumor and a subset of brain tumors developing in infancy.     

Iron-mobilizing properties of the gadolinium-DTPA complex: clinical and experimental observations.

BACKGROUND: Gadolinium (Gd) magnetic resonance imaging (MRI) contrast agents are considered to be safe in patients with impaired renal function. Our study investigates a mechanism of severe iron intoxication with life-threatening serum iron levels in a haemodialysis patient following MRI with Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) administration. His previous history was remarkable for multiple blood transfusions and biochemical evidence of iron overload. We hypothesized that Gd-DTPA may have an iron-mobilizing effect in specific conditions of iron overload combined with prolonged exposure to the agent. METHODS: For the in vitro study, Gd-DTPA was added to mice liver homogenate and iron metabolism parameters were measured after incubation in comparison with the same samples incubated with saline only. For the in vivo study, an experimental model of acute renal failure in iron-overloaded rats was designed. Previously iron-overloaded and normally fed rats underwent bilateral nephrectomy by renal pedicle ligation, followed by Gd-DTPA or saline injection. Iron and iron saturation levels were checked before and 24 h after Gd-DTPA or vehicle administration. RESULTS: Significant mobilization of iron from mice liver tissue homogenate in mixtures with Gd in vitro was seen in the control (saline) and in the experimental (Gd) groups (513+/-99.1 vs 1117.8+/-360.8 microg/dl, respectively; P<0.05). Administration of Gd-DTPA to iron-overloaded rats after renal pedicle ligation caused marked elevation of serum iron from baseline 143+/-3.4 to 570+/-8 microg/dl (P<0.0001). There were no changes of the named parameter, either in iron-overloaded anuric rats after saline injection or in normal diet uraemic animals, following Gd-DTPA administration. CONCLUSIONS: The combination of iron overload and lack of adequate clearance of Gd chelates may cause massive liberation of iron with dangerous elevation of free serum iron. It is highly recommended that after Gd contrast study, end-stage renal disease patients with probable iron overload should undergo prompt and intensive haemodialysis for prevention of this serious complication.