Analysis of clonality by X chromosome inactivation in uterine cervix cancer.

The determination of a unicellular or a multicellular origin of a tumor is an important due for understanding its etiology. To investigate this issue, we performed clonality assay of cervix cancer using polymerase chain reaction based on highly polymorphic locus of the androgen receptor gene, in which methylation of DNA correlates with inactivation of X chromosome. DNA samples were obtained from formalin-fixed, paraffin-embedded tissue of 20 invasive epidermoid carcinomas and 10 carcinoma in situ. Seven of ten carcinoma in situ, heterozygous for the androgen receptor locus, were monoclonal pattern. Among twenty invasive epidermoid carcinomas, eighteen of which showed heterozygous, twelve were monoclonal pattern and six were polyclonal pattern. We conclude that carcinoma in situ arises from a single cell. In invasive epidermoid carcinoma, most cases were monoclonal, although some cases were polyclonal. These suggest that invasive carcinoma of the cervix does not always arise from a single cell, but may arise from several cells with different mechanisms.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K(alpha) and pandinustoxin-K(alpha)

The scorpion venom peptide toxins tityustoxin-K(alpha) (TsTx-K(alpha)) and pandinustoxin-K(alpha) (PiTx-K(alpha)) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K(alpha) preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K(alpha) is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists 4-aminopyridine (4-AP), an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca(2+)-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K(alpha) and PiTx-K(alpha) in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K(alpha) and PiTx-K(alpha) were 9 and 33 ng, respectively. 4-AP produced seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 microg. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and tonic seizures, whereas blockade of maxi K-type Ca(2+)-activated K+ channels does not. The convulsant effects may be related to enhanced glutamate release and, in the case of the limbic and clonic convulsions, activation of AMPA receptors.     

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.      

Bronchoscopic management of airway obstruction in pediatric endobronchial tuberculosis

The present report describes a case of severe airway obstruction caused by endobronchial tuberculosis in an 11-year-old girl who was successfully treated by bronchoscopic balloon dilation. This case illustrates the insidious presentation and the increasingly important role of bronchoscopic intervention in the management of endobronchial tuberculosis. In addition, a brief literature review of the condition in the pediatric age group is included.     

Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor

Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl- phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK- 74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.     

An integrative review exploring the physical and psychological harm inherent in using restraint in mental health inpatient settings

In Western society, policy and legislation seeks to minimize restrictive interventions, including physical restraint; yet research suggests the use of such practices continues to raise concerns. Whilst international agreement has sought to define physical restraint, diversity in the way in which countries use restraint remains disparate. Research to date has reported on statistics regarding restraint, how and why it is used, and staff and service user perspectives about its use. However, there is limited evidence directly exploring the physical and psychological harm restraint may cause to people being cared for within mental health inpatient settings. This study reports on an integrative review of the literature exploring available evidence regarding the physical and psychological impact of restraint. The review included both experimental and nonexperimental research papers, using Cooper's (1998) five‐stage approach to synthesize the findings. Eight themes emerged: Trauma/retraumatization; Distress; Fear; Feeling ignored; Control; Power; Calm; and Dehumanizing conditions. In conclusion, whilst further research is required regarding the physical and psychological implications of physical restraint in mental health settings, mental health nurses are in a prime position to use their skills and knowledge to address the issues identified to eradicate the use of restraint and better meet the needs of those experiencing mental illness.     

Renal cell carcinoma metastases to gallbladder

A 74-year old man underwent a radical cholecystectomy for presumed gallbladder cancer. The histology of the resected specimen in fact revealed the lesion to be metastatic renal cell carcinoma from his resected right nephrectomy performed 14 years previously.