Age-dependent variation of T1 and T2 relaxation times of adenocarcinoma in mice

The T1 and T2 values of adenocarcinoma EO 771 inoculated into the hind leg of mice are characterized and correlated with the histopathologic state of the tumor. Growth-dependent changes (indicated by a T1 of 630-910 msec and a T2 of 68-185 msec) can be separated into four characteristic phases. The increase in relaxation times in the early phases (A and B) is due to an increasing amount of viable tumor tissue relative to normal muscle tissue. In the later phases (C and D), a decline of the relaxation parameters is observed that is parallel to an increase in the fraction of necrotic tissue. By multiexponential analysis, two relaxation components (indicated by and, respectively) for T1 and T2 and the corresponding fractions alpha 1 and alpha 2 can be observed for both tumor and surrounding muscle tissue. A tissue criterion ("magnetic resonance fingerprint") is defined by a combination of these multiple parameters. This criterion allows separation of not only muscle and tumor tissue but also viable (early state) and necrotic (late state) tumor tissue.     

Giving a voice to patient experiences through the insights of pragmatism

As a philosophical position, pragmatism can be critiqued to distinguish truth only with methods that bring about desired results, predominantly with scientific enquiry. The article hopes to dismiss this oversimplification and propose that within mental health nursing, enquiry enlightened by pragmatism can be anchored to methods helping to tackle genuine human problems. Whilst pragmatists suggest one reality exists, fluctuating experiences and shifting beliefs about the world can inhabit within; hence, pragmatists propose reality has the potential to change. Moreover, pragmatism includes being cognisant of what works to whom reality concerns, making reality context-driven, with a view to understand how actions shape experiences so what is generated has usefulness. Hence, it somewhat follows pragmatism can inform mental health nursing, after all, nursing is a discipline of action, and awareness is needed in how actions produce experiences that patients find helpful. Given the principles of recovery are preferably adopted in mental health care, the paper will explore how pragmatism can help nurses move towards that goal; specifically, with patients voicing their experiences. This is because like pragmatism, recovery subscribes to hope that reality can progress, and through meaningful experiences and beliefs, patients have expertise about personal difficulties alongside how life may flourish, despite mental illness.     

Neuroendocrine mechanisms that delay and initiate puberty in higher primates

This paper highlights a series of studies using the male rhesus monkey that has led to a model for the control of the onset of puberty in higher primates. The model proposes that the timing of puberty in these species is governed by the duration of a central brake that, during juvenile development, holds in check the hypothalamic network of gonadotropin-releasing hormone (GnRH) neurons, which, in the adult, drive the pituitary-gonadal axis. The neurobiology of this hypothalamic brake, and the physiological mechanisms that time its application and removal, are incompletely understood. Nevertheless, the pubertal resurgence of pulsatile GnRH release, which terminates the juvenile phase of primate development and triggers the initiation of puberty in man and monkeys, is associated with structural and molecular remodeling of the hypothalamus. A major component of this developmental plasticity appears to involve neuropeptide Y (NPY). NPY inhibits GnRH release, and NPY gene expression in the hypothalamus is elevated during juvenile development when GnRH release is restrained. Since the changes in hypothalamic function and morphology that trigger primate puberty unfold in the absence of gonadal steroid feedback, the possibility is raised that, in addition to activating the pituitary-gonadal axis at this stage of development, they may also contribute directly to the causation of behaviors and affective states that emerge at adolescence.     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

Viatical settlements: what case managers should know

Culturally we are taught not to discuss money and other people's financial circumstances, particularly if financial hardship exists. The reluctance is even greater if that hardship involves dire circumstances like a serious illness. Added to this reticence is anecdotal evidence that case managers (and other professionals who may be called to interact with clients regarding a broad range of stressful issues during ill health) are hesitant to discuss financial matters other than those directly pertaining to payment for specific, predetermined medical treatment.     

足反射疗法对前列腺增生效果分析

目的　前列腺增生是男性中老年的常见病、多发病。单纯药物治疗效果不明显 ,手术治疗会给患者造成痛苦和不便。了解足反射疗法对此病的疗效。方法　对 90例前列腺增生患者进行了分组对比 ,A组 3 0例 ,采用足反射疗法。B组 3 0例 ,采用药物疗法。C组 3 0例 ,采用足反射疗法与口服药物双重治疗。三组均以B超声诊断仪测定。结果　治疗前与第一疗程后 ,前列腺三径之差进行比较。显效 :两次差≥ 1 5cm。有效二两次差≥ 1 0cm。结果 :A组显效率 3 6 60 % ,有效率 5 3 3 3 % ,总有效率 89 99%。B组 :显效率 3 3 3 %。有效率 10 % ,总有效率 13 3 3 %。C组 :显效率 5 6 66%、有效率 3 6 66% ,总有效率 93 3 2 %。结论　证实了足反射疗法可作为治疗前列腺增生及前列腺炎的首选方法。如与药物疗法配合使用 ,效果更好 ,并可解除有手术禁忌患者的痛苦。     

The effect of temporal frequency variation on threshold contrast sensitivity deficits in optic neuritis.

The effect of increasing temporal frequency on contrast sensitivity anomalies in unilateral optic neuritis has been investigated. For 4 c/deg gratings no change in the deficit was observed at any temporal frequency whereas there was a tendency for the deficit to decrease with increase in temporal frequency for 0-5 c/deg gratings. The latter effect was not observed in a case of optic neuritis with severe deficit and not in two cases of other optic nerve pathology. An explanation based on the assumption that "threshold scotomata" might be present in cases of demyelinating optic nerve disease is proposed.     

Communicating oesophageal duplication

Oesophageal duplications are rare congenital abnormalities. Most of them do not communicate with the oesophageal lumen. We present a very uncommon finding of communicating oesophageal duplication in which the connection between the oesophagus and its duplicate portion was demonstrated by CT.     

Regulation of the epithelial Na+ channel by Nedd4 and ubiquitination

The epithelial Na+ channel (ENaC) is comprised of three subunits, alpha, beta and gamma, and plays an essential role in Na+ and fluid absorption in the kidney, colon and lung. We had identified proline-rich sequences at the C termini of alpha beta gamma ENaC, which include the sequence PPxY, the PY motif. This sequence in beta or gamma ENaC is deleted or mutated in Liddle's syndrome, a hereditary form of arterial hypertension. Our previous work demonstrated that these PY motifs bind to the WW domains of Nedd4, a ubiquitin protein ligase containing a C2 domain, three or four WW domains and a ubiquitin protein ligase Hect domain. Accordingly, we have recently demonstrated that Nedd4 regulates ENaC function by controlling the number of channels at the cell surface, that this regulation is impaired in ENaC bearing Liddle's syndrome mutations, and that ENaC stability and function are regulated by ubiquitination. The C2 domain is responsible for localizing Nedd4 to the plasma membrane in a Ca(2+)-dependent manner, and in polarized epithelial MDCK cells this localization is primarily apical. In accordance, electrophysiological characterization of ENaC expressed in MDCK cells revealed inhibition of channel activity by elevated intracellular Ca2+ levels. Thus, in response to Ca2+, Nedd4 may be mobilized to the apical membrane via its C2 domain, where it binds ENaC via Nedd4-WW:ENaC-PY motifs' interactions, leading to ubiquitination of the channel by the Nedd4-Hect domain and subsequent channel endocytosis and lysosomal degradation. This process may be at least partially impaired in Liddle's syndrome due to reduced Nedd4 binding, leading to increased retention of ENaC at the cell surface.     

Analysis of Voice Changes After Thyroplasty Using Linear Predictive Coding

Objective measurement of vocal quality is difficult in patients with severe voice disorders. Improved success has been reported using a modeling technique known as linear predictive coding. This technique uses an inverse filter to estimate a glottic excitation signal. The pitch amplitude is defined as the height of the first peak of the autocorrelation of the glottic excitation signal. In this study linear predictive coding was used to analyze voice disorders in patients with vocal fold immobility. Voice recordings were made in 16 patients undergoing vocal fold medialization and 10 patients who had no surgical procedure between measurements. The voice quality was rated by three speech pathologists. Five acoustic parameters were calculated from the samples. The best agreement with the listeners' perceptual analysis was achieved using the pitch amplitude. Both pitch amplitude and the perceptual ratings of voice quality improved in patients undergoing vocal fold medialization. Therefore the linear model of speech production and inverse filtering are useful in measuring vocal quality in patients with vocal fold immobility.