Quantitative heel ultrasound in a population-based study in Italy and its relationship with fracture history: the ESOPO study.

We assessed the clinical usefulness of quantitative ultrasound (QUS) in defining the prevalence rates of osteoporosis and osteopenia and their association with fractures of the forearm, vertebrae, and hip. The ESOPO study was conducted in 2001 and assessed a random sample of 11,011 women and 4,981 men, in 83 centers spread all over Italy. A large array of risk factors was investigated, and self-reported history of fractures was collected in a questionnaire. After the patient had undergone interview and a brief physical examination, QUS of the heel was performed, using the Achilles apparatus (GE-Lunar, Madison, USA). The prevalence rate of osteoporosis in women 40-79 years old was approximately 18.5%, while the rate of osteopenia was about 44.7%; in men 60-79 years of age the rates were 10% and 36%, respectively. A strong association with fractures was found for osteoporosis and osteopenia in both men and women, independently of all traditional risk factors, including age. These results confirm the suitability of US measurements as a tool for detecting individuals at risk of fractures.

Change: a central concern of nursing.

The purpose of this paper is to explore the concept of change. More precisely, considering insights from Buddhism, existential philosophy, and modern developmental thought, this paper will discuss two aspects of change: (a) change as a fundamental, inevitable aspect of life, and (b) change as a process of risking to choose. The discussion includes an analysis of the correspondence of the concept with four nursing frameworks, and some implications for nursing theory, research, and practice.

Peroral extrusion of a ventriculoperitoneal shunt catheter.

A case of retrograde migration and peroral extrusion of a ventriculoperitoneal catheter is reported. A patient population at risk is defined, and preventive measures are discussed.

Mouse cells contain two distinct ras gene mRNA species that can be translated into a p21 onc protein.

The Kirsten (Ki) and Harvey (Ha) strains of murine sarcoma virus encode a 21,000-dalton protein (p21 ras) which is the product of the transforming gene of these viruses. Normal cells express low levels of p21 ras encoded by cellular genes (Ki-ras and Ha-ras) homologous to the Ki and Ha murine sarcoma virus transformation genes. A bone marrow-derived mouse cell line, 416B, has been shown to express unusually high levels of p21 ras. In this manuscript, we investigated the molecular biology of p21 ras gene expression in 416B and other normal mouse cells. We identified four distinct polyadenylated and polysome-associated RNAs, two related to Ki-ras and two to Ha-ras. The levels in 416B cells of the two Ki-ras RNAs, sized 5.2 and 2.0 kilobases, were both elevated approximately 25-fold over levels found in normal mouse cells; there was no corresponding change in 416B cells in the levels of the two Ha-ras RNAs. We partially purified the two Ki-ras mRNAs and separated them by velocity sedimentation in sucrose density gradients. Both the 5.2- and 2.0-kilobase mRNAs could be translated in vitro into p21 ras. These results show that a cellular onc protein can be translated from two distinct cellular mRNA species.

The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes.

The Harvey and Kirsten strains of murine sarcoma virus encode enzymatically and serologically related p21 src proteins which are required for virally mediated cellular transformation. The genes in each virus encoding p21 show such extensive divergence from each other that cloned probes from these genes detect distinct sets of cellular genes in the DNA from several vertebrate species. These data suggest that cellular p21 sarc genes constitute a divergent family of vertebrate genes that can regulate the growth of cells.

Transcription and site-specific hypomethylation of the delta-crystallin genes in the embryonic chicken lens.

Chicken delta-crystallin has at least two similar genes containing multiple intervening sequences. Hybridization experiments utilizing DNA probes derived from intervening sequences contained within cloned delta-crystallin gene fragments indicated that both of these two delta-crystallin genes are transcribed in the embryonic lens. No evidence for transcription of these genes was found in nuclei prepared from decapitated chicken embryos. Comparison of restriction enzyme digests of genomic DNA prepared from lens and non-lens tissues showed that the delta-crystallin gene sequences are not grossly rearranged in the lens during development. Msp I and Hpa II digests revealed that there are at lest three -CCGG- sites in the delta-crystallin genes that are hypomethylated in the embryonic lens DNA but are hypermethylated in sperm, red blood cell, or headless embryo DNAs. The delta-crystallin genes were not transcribed and these three sites were methylated in embryonic lens epithelial cells that were transformed with a temperature-sensitive Rous sarcoma virus. These results associate delta-crystallin gene transcription and site-specific hypomethylation of the delta-crystallin DNA.

Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus.

Harvey murine sarcoma virus (Ha-MuSV) is a mouse-rat recombinant retrovirus that encodes a protein designated p21, required for virally induced transformation. Using a radiolabeled DNA fragment from the p21 coding region, we have detected homologous DNA sequences in the normal DNA of rats and of several other vertebrate species. Moreover, many tested cells from these species contain low levels of a p21 protein that is highly related to viral 21. Now we report two independent fragments from normal rat DNA containing sequences (sarc) homologous to the Ha-MuSV transforming region that were cloned in the bacteriophage vector Charon 4A. Sarc sequences in the one fragment are completely colinear with the viral sequences and share apparently all restriction endonuclease sites. Sarc sequences in the second fragment have several sets of intervening sequences and lack some restriction endonuclease sites found in the viral transforming region. Despite the presence of these intervening sequences in the second sarc fragment, we have been able to ligate this sarc fragment to the long terminal repeat sequence of HaMuSV and to induce cellular transformation and high levels of p21 expression upon transfection of this DNA to NIH 3T3 mouse cells. These results suggest that elevated levels of p21, normally expressed at low levels in a variety of cells, can induce cellular transformation.

Double compartment hydrocephalus--a new clinical entity.

We are reporting eight patients who demonstrated double compartment hydrocephalus, i.e., supratentorial and infratentorial hydrocephalus in clinical sequence and separately. One infant with veil occlusion of the aqueduct was operated on to remove the veil and then later demonstrated panhydrocephalus. Six patients had been treated months to years earlier by the performance of a ventriculoperitoneal shunt for aqueductal hydrocephalus and then developed characteristic cerebellar-brain stem deficits from 4th ventricle enlargement. The work-up included computed tomographic scan, air study, isotope cerebrospinal fluid flow study, and direct 4th ventricle pressure studies. Operation with removal of a veil occlusion of the upper 4th ventricle aqueduct produced immediate recovery in five of six patients. The conversion of aqueductal stenosis to veil occlusion is postulated as the mechanism of "primary" veil obstruction found in infants. This new clinical entity is more common than realized. We report one patient with compartmental 4th ventricular hydrocephalus.

Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus.

Detailed restriction endonuclease maps were developed for Harvey murine sarcoma virus (Ha-MuSV) DNA (clone H-1), molecularly closed at its unique EcoRI site in pBR322, for three nonoverlapping subgenomic HindIII clones which together span the entire H-1 clone and for a molecularly cloned DNA copy of a portion of rat 30S RNA (which represents the majority of the rat genetic sequences in Ha-MuSV). Molecular hybridization of the 30S clone to small restriction fragments of clone H-1 revealed a 0.9-to-1.0-kilobase pair region in the 5' half of the Ha-MuSV genome not homologous to the 30S clone, although the 30S clone did contain related sequences in Ha-MuSV on both sides of this nonhomologous region. By using cloned sequences from a segment of the Ha-MuSV nonhomology region as a probe for hybridization to Southern blots of DNA from rat, mouse, bat, and chicken cells, one to three bands were detected in DNA of each species. By contrast, the 30S clone DNA was highly related to many sequences in rat DNA, partially related to fewer mouse DNA sequences, and homologous only to one to three bands in bat and chicken DNA. Earlier work had shown that the 5' half of the Ha-MuSV genome coded for transformation and for the viral p21 protein (Chang et al., J. Virol. 35: 76--92, 1980; Wei et al., Proc. Natl. Acad. Sci. U.S.A., in press). We used two subgenomic HindIII clones whose shared HindIII site mapped within the 5' region of clone H-1 nonhomologous to the 30S clone to test whether the nonhomologous segment might encode the transforming and p21 functions. Although neither of the subgenomic HindIII fragments by themselves induced transformation, ligation of these two nontransforming DNAs to each other did restore p21-mediated transformation. A conclusion consistent with these results is that a region in the 5' half of the Ha-MuSV genome evolutionarily distinct from and not present in rat 30S RNA is essential for transformation and for p21 encoding.

Cerebrospinal fluid rhinorrhea as a presentation of pituitary adenoma.

We report a patient with a pituitary adenoma who presented with only cerebrospinal fluid rhinorrhea. A radiologically unrecognized defect in the floor of the sella was observed at operation.

Experimental brain stem displacement. Its implications in the upward and downward herniation syndromes.

6 dogs were anesthetized and a silver clip attached to a cotton plug as surgically placed in the aqueduct of Sylvius. An immediate postoperative lateral skull film was obtained to demonstrate the position of the clip. The animals developed signs of hydrocephalus within hours after the procedure. 2 weeks after placement of the aqueduct plug, the animals recieved a permanent ventriculostomy. Immediate pre- and postoperative ventriculostomy lateral skull films were taken again to indicate position of the silver clip. Finally, a lateral skull film was taken 2 weeks after ventriculostomy and just prior to sacrifice. Radiological techniques were standardized. In this experimental setting downward brain stem herniation predominated and upward herniation of the brain stem was an infrequent occurrence.

Cerebrospinal fluid bulk flow study: radioiodinated serum albumin (R131ISA) and technetium-99m-labeled diethylenetriaminepentaacetic acid (DTPA) retention in the ventricles of normal and hydrocephalic dogs.

Eight normal dogs were studied and then made hydrocephalic (kaolin induced) to demonstrate and compare the use of R131ISA and 99mTcDTPA in cerebrospinal fluid (CSF) bulk flow studies. The radioisotopes were simultaneously injected into the CSF space in the cisterna magna of normal dogs and into the lateral ventricles of hydrocephalic dogs after an equal volume of CSF had been removed. The average dose of RISA was 100 muCi, and for TcDTPA it was 7 mCi. A bag of lactated Ringer's solution (500 ml) was used as a control phantom after being injected with the same dose of isotope as used in the animals. Brain scans were obtained with the gamma ray camera at 4 and 24 hours after injection. We used four criteria to evaluate results: clinical state of the animal, CSF ventricular pressures with challenges, percentage of retained isotope in counts per minute, and ventricular size at postmortem examination. The results demonstrate that the amount of isotope retention over 20 hours and the clinical state of the dog are better correlated when RISA is used than when TcDTPA is used. The study indicates that RISA is more reliable than TcDTPA as an indicator of CSF bulk flow in both normal and hydrocephalic dogs.

Complete obliteration of a carotid cavernous fistula with sparing of the carotid blood flow using a detachable balloon catheter.

A detachable balloon catheter system is described which has several distinct advantages over pre-existing methods of "intervention radiology". It is anticipated that further refinements in this technique will continue to expand the uses for this procedure.

Induction of plasminogen activator in cultured cells by macrocyclic plant diterpene esters and other agents related to tumor promotion.

In vitro systems that are responsive to tumor-promoting agents may facilitate the identification of such agents and the analysis of their mode of action. We have previously reported that the potent tumor promoter phorbol-12-myristate-13-acetate induces the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts. We have, therefore, tested various compounds for their ability to induce plasminogen activator in chicken embryo fibroblasts. Among these, phorbol esters and other macrocyclic diterpene esters isolated from species of the families Euphorbiaceae and Thymelaeaceae were potent inducers of plasminogen activator. These compounds maximally induced enzyme to the same levels, although they differed in their relative molar potencies. Structural requirements for in vitro activity paralleled the requirements for activity in vivo. These results indicate that induction of plasminogen activator is a useful marker for the biologically active macrocyclic diterpene esters. On the other hand, tumor-promoting agents such as anthralin, cantharidin, Tween 60, and tobacco leaf extract failed to induce plasminogen activator.