Telepsychiatry for stable Chinese psychiatric out-patients in custody in Hong Kong: a case-control pilot study.

INTRODUCTION: In Hong Kong, persons in custody receive primary medical care within the institutions of the Correctional Services Department (CSD). However, for psychiatric care, persons in custody must attend specialist out-patient clinics (SOPCs), which may cause embarrassment and stigmatisation. The aim of this interventional pilot study was to compare teleconsultations with face-to-face consultations for a group of stable Chinese psychiatric out-patients in custody. METHODS: A total of 86 stable Chinese male out-patients in custody were recruited for psychiatric teleconsultations. They were compared with 249 age-matched Chinese male out-patients in custody attending standard face-to-face psychiatric consultations at other SOPCs. The two groups had comparable baseline characteristics including age, education level, and 12-item Chinese General Health Questionnaire (C-GHQ-12) score. A satisfaction survey of patients towards the teleconsultation was also carried out. RESULTS: Compared with the face-to-face consultation group, the teleconsultation group showed a significantly better result in the difference in C-GHQ-12 scores before and after consultations (P=0.023). The correlation between the first and second teleconsultations also showed a moderate positive relationship (r=0.309). The satisfaction survey showed a favourable response to teleconsultations. No significant adverse events were identified for the teleconsultation group. CONCLUSIONS: The results suggest that teleconsultations are a sustainable and safe alternative to face-to-face consultations for stable Chinese psychiatric out-patients in custody.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

Oesophageal gastro-intestinal stromal tumour presenting with rupture into pleural cavity.

Gastro-intestinal stromal tumours are rarely found in the oesophagus and it is uncommon for these tumours to present with rupture. In this paper, we report a case where the tumour ruptured through the distal oesophagus. As a result, the patient underwent surgical tumour dissection. A histopathological examination of the tumour mass confirmed that it was a gastro-intestinal stromal tumour. In this report, we review the diagnosis, pathology, and treatment of a patient presenting with a ruptured oesophageal gastro-intestinal stromal tumour.

Acute adverse reactions to magnetic resonance contrast media--gadolinium chelates.

The objective of this study was to evaluate the clinical safety of intravenous gadolinium-based contrast media used in patients who underwent MRI at a single institution. Acute adverse reactions to intravenous gadolinium-based contrast media used for MRI at the Princess Margaret Hospital, Hong Kong, SAR, from January 1999 to November 2004 were recorded in an incidence log book. The medical records of patients' demographics were retrospectively reviewed and the nature, frequency and severity of the adverse reactions were investigated and documented. The incidence of acute adverse reactions to intravenous gadolinium-based contrast media was 0.48% (45 patients with 46 adverse reactions). The severity of these adverse reactions were 96% mild, 2% moderate (one patient developed shortness of breath that required oxygen supplementation and intravenous steroidal management) and 2% severe (one patient developed an anaphylactoid reaction, but successfully recovered through timely resuscitation). No patients were recorded as having contrast extravasation and none died as a result of any adverse reaction. Among the 45 patients who developed adverse reactions, three patients (6.7%) had prior adverse reactions to iodinated contrast media, three (6.7%) had prior reactions to a different gadolinium-based contrast agent, one (2%) had asthma and nine (20%) had a history of drug/food allergy. Overall, 41% of the adverse reactions were not documented in the final MRI report or the clinical medical records. Gadolinium-based contrast media are safe and well tolerated by the vast majority of patients. In our study, the adverse reaction rate (0.48%) and the incidence of severe anaphylactoid reaction (0.01%) concur with those reported in the literature. Although most of the symptoms are mild and transient, these adverse reactions must be accurately documented and managed.

Paediatric Tolosa-Hunt syndrome.

Tolosa-Hunt syndrome is characterized by a dull, persistent pain around the affected eye, ophthalmoplegia and, sometimes, involvement of other cranial nerves passing through the cavernous sinus. Corticosteroid administration is valuable in the treatment and frequently has a dramatic effect. We report a boy with Tolosa-Hunt syndrome who fails to respond to the initial steroid treatment. The role of the MRI in the management of this condition is discussed.

Inhibitory role of the host apoptogenic gene PKR in the establishment of persistent infection by encephalomyocarditis virus in U937 cells.

Persistent infections by viruses such as HIV-1 and hepatitis B virus can pose long-term health hazards. Because establishment of persistent infections involves close interactions and adjustments in both host and virus, it would be informative to establish a paradigm with which a normally cytolytic viral infection can be easily converted to persistent infection, so that the different stages in developing persistent infection can be examined. Such a model system is described in this paper. Highly cytolytic encephalomyocarditis virus (EMCV) infection was shifted to persistent infection as a result of repressed expression of the double-stranded RNA-dependent protein kinase (PKR) in the promonocytic U937 cells. Because of the apoptogenic potential of PKR, a deficiency of PKR resulted in a delay in virus-induced apoptosis in EMCV-infected U937 cells, allowing the eventual establishment of persistent EMCV infection in these cells (U9K-AV2). That this was a bona fide persistent infection was demonstrated by the ability of infected cells to propagate as long-term virus-shedding cultures; electron microscopy studies showing presence of intracellular EMCV virions and chromatin condensation; detection of virus-induced chromosomal DNA fragmentation and sustained expression of apoptogenic p53 and IL-1beta converting enzyme; and demonstration of active EMCV transcription by reverse transcription-PCR. In addition, a host-virus coevolution was observed in U9K-AV2 cultures over time: U9K-AV2 cells exhibited slower growth rates, resistance to viral super-infection, and cessation of IFN-alpha synthesis, whereas the infectivity of EMCV was drastically attenuated. Finally, data are presented on the suitability of this model to study establishment of persistent infection by other viruses such as Sendai virus and reovirus.

Large needle core biopsy--avoidance of biopsy table bombardment by the biopsy needle in stereotactic guided breast biopsy.

Table bombardment by automated biopsy needle is an occasional technical problem during stereotactic core biopsy of the breast. It is most commonly encountered in small breasts and when lesions are close to the biopsy table. A reference chart is devised for stereotactic core biopsy using an add-on erect stereotactic biopsy table and automated spring-loaded biopsy gun. The chart serves as a reference for pre-biopsy assessment of the feasibility of core biopsy in the vertical approach due to the constraints of lesion depth and breast thickness. It allows easy and quick reference for the required needle length input for the stereotactic system to prevent table bombardment.

Tumor suppressor p53 as a component of the tumor necrosis factor-induced, protein kinase PKR-mediated apoptotic pathway in human promonocytic U937 cells.

Despite what is known about the early signaling events in tumor necrosis factor (TNF) alpha-induced apoptosis, characterization of the downstream events remains largely undefined. It is now known that a cross-talk exists between the interferon and TNF-alpha pathways. This linkage allows recruitment of the cell proliferation suppressor PKR (dsRNA-dependent protein kinase) from the interferon pathway to play a pivotal role in TNF-alpha-induced apoptosis. In this study, we took advantage of the differential TNF-alpha susceptibilities of human promonocytic U937 subclones, deficient in or overexpressing PKR, to further characterize the role of PKR in apoptosis. By reverse transcription-polymerase chain reaction, we demonstrated that TNF-alpha transiently induces the tumor suppressor p53 in U937 cells. This p53 induction lags behind the TNF-alpha induction of PKR by 1 h. By cell viability determination, ultrastructural studies, apoptotic DNA laddering, and antisense techniques, it was shown that inhibition of p53 expression in PKR-overexpressing U937 cells abrogates the TNF-alpha-induced apoptosis in these cells. Conversely, overexpressing wild type p53 in PKR-deficient U937 cells confers the susceptibility of these cells to TNF-alpha-induced apoptosis. This latter result indicates that p53 induction is an event downstream of TNF-alpha-induced up-regulation of PKR, thereby further establishing the critical role of p53 in TNF-alpha-induced apoptosis in U937 cells. PKR-overexpressing U937 cells were found to possess a constitutively higher level of p53, which partly explains why these cells spontaneously undergo apoptosis even without TNF-alpha treatment. Finally, a model is presented on the interplay between PKR and p53 in effecting TNF-alpha-induced apoptosis in U937 cells.

Inhibition of HIV-1 gp120-induced apoptosis in neuroblastoma SK-N-SH cells by an antisense oligodeoxynucleotide against p53.

OBJECTIVES: This study examines the cytotoxicity potential and the mechanism of toxicity of the HIV-1 gp120 on human neuroblastoma cells. DESIGN: Previous data from our group have suggested that the HIV-1 envelope protein gp120 promotes the secretion of tumor necrosis factor-alpha and other factors by astrocytes and microglial cells present in primary human brain cell cultures, thereby contributing to the injury of neurons in these cultures. This study investigates the cytotoxicity potential and the mechanism of toxicity of gp120 on human neuroblastoma cells. METHODS: SK-N-SH cells were treated with HIV-1 gp120, and was followed by in situ DNA fragmentation staining and small molecular weight DNA extraction studies to ascertain the induction of apoptosis by gp120 in these cells. To evaluate a potential role of the growth suppressor gene p53, gp120-treated SK-N-SH cells were subjected to reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses for the induction of p53. An antisense oligodeoxynucleotide against p53 was used to investigate the role of p53 in the gp120-induced apoptosis in these cells. RESULTS: Data from T7 DNA polymerase staining and small molecular weight DNA extraction studies demonstrated that gp120-induced DNA breakage in SK-N-SH cells with fragmentation patterns characteristic of apoptosis. RT-PCR and Western blot analyses revealed that the gp120-mediated induction of apoptosis was dependent on a gp120-induced and gp120-sustained upregulation of p53. The induction of p53 by gp120 was specific, since an antibody against gp120 prevented both the induction of p53 and subsequent apoptosis in SK-N-SH cells. The critical role of p53 was further illustrated by the effectiveness of a p53 antisense oligodeoxynucleotide to inhibit the gp120-induced apoptosis. As a control, the apoptosis-inducing potential of gp120 on SK-N-SH cells was not seen in the HIV-1 Gag proteins even when used at up to 5 nM. CONCLUSIONS: These results established that HIV-1 gp120 is potentially cytotoxic to human neuronal cells through the induction of p53, which may eventually lead to induction of apoptosis.

An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells.

Tumor necrosis factor alpha (TNF-alpha) is well-characterized for its necrotic action against tumor cells; however, it has been increasingly associated with an apoptosis-inducing potential on target cells. While the signaling events and the actual cytolytic mechanism(s) for both TNF-alpha-induced necrosis and apoptosis remain to be fully elucidated, we report here on (i) the ability of TNF-alpha to induce apoptosis in the promonocytic U937 cells, (ii) the discovery of a cross-talk between the TNF-alpha and the interferon signaling pathways, and (iii) the pivotal role of interferon-inducible, double-stranded RNA-activated protein kinase (PKR) in the induction of apoptosis by TNF-alpha. Our data from microscopy studies, trypan blue exclusion staining, and apoptotic DNA ladder electrophoresis revealed that a subclone derived from U937 and carrying a PKR antisense expression vector was resistant to TNF-alpha-induced apoptosis. Further, TNF-alpha initiated a generalized RNA degradation process in which the participation of PKR was required. Finally, the PKR gene is a candidate "death gene" since overexpression of this gene could bring about apoptosis in U937 cells.

Biology and therapeutic uses of myeloid hematopoietic growth factors and interferons.

Recent advances in basic science and clinical trials have demonstrated that IFNs and myeloid hematopoietins play crucial roles in host defense against pathogens and immune surveillance. Here we have reviewed the biologic functions of GM-CSF, G-CSF, IFN-alpha and IFN-gamma. For patients with neutropenia resulting from cytotoxic chemotherapy, bone marrow transplantation, congenital agranulocytosis and cyclic neutropenia, therapeutic uses of GM-CSF and G-CSF were reviewed. Application of these growth factors to patient management represents a major contribution of biotechnology to a difficult area of therapeutics in febrile, neutropenic patients. Because IFN-alpha plays crucial roles in antiviral responses, its clinical applications in hepatitis B and C, human papilloma virus, HIV infection and malignancy were discussed. The use of IFN-gamma in bacterial prophylaxis in patients with chronic granulomatous disease was also presented. Advances in clinical applications of IFNs and hematopoietic growth factors serve as a paradigm for further development to investigate the use of other important cytokines in modern therapeutics.

Interleukin-12 induces interferon-gamma expression and natural killer cytotoxicity in cord blood mononuclear cells.

Severe viral infection in newborns has been attributed to immaturity of the immune system including a defect in natural killer cytotoxicity (NKC) and decreased production of cytokines that are important for natural killer (NK) function. We investigated the induction of interferon (IFN)-gamma and activation of NK activity in adult and cord blood mononuclear cells (BMC) after IL-12 treatment. The levels of mRNA in these BMC were measured by Northern blot and reverse transcription-polymerase chain reactions using primers specific for IFN-gamma. The levels of IFN-gamma protein were measured by ELISA. In the absence of IL-12, only adult BMC spontaneously produced low levels of IFN-gamma. After IL-12 treatment, induction of IFN-gamma expression was detected as early as 4 h in both cord and adult BMC. Both cord and adult cells showed similar levels of IFN-gamma mRNA and protein expression in response to IL-12 at a concentration as low as 10 U/mL. In contrast, upon phorbol ester and ionomycin treatment, adult BMC produced more IFN-gamma mRNA than cord BMC. In a 51Cr release assay with human immunodeficiency-infected H9 cells as indicators, both cord and adult cells responded to IL-12 induction of NKC. Our findings demonstrate that cord BMC are capable of responding to IL-12 stimulation, competent in synthesizing IFN-gamma, and able to mount NKC. Thus, it appears that the deficiency in IFN-gamma production or NKC in cord cells is not due to an inherent defect in IL-12 response of the cord cells.

The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha.

OBJECTIVE: To investigate the induction of cytokines as a possible mechanism for the neurotoxicity of the HIV-1 envelope protein gp120. DESIGN: The gp120 protein was tested directly on primary human brain cultures to examine its ability to induce cytokines and its neurotoxicity on human neural cells because gp120 is known to be toxic to rodent ganglion cultures, and neural cells such as astrocytes and microglia produce cytokines when stimulated. METHODS: Primary cultures of human brain cell aggregates, astrocytes and macrophages were exposed to HIV-1 recombinant (r) gp120SF2. Induction of cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR); neurotoxicity of rgp120SF2 and interleukin (IL)-6 on human brain cultures was examined by electron microscopy. RESULTS: ELISA and RT-PCR studies revealed that rgp120SF2 induced IL-6 and tumor necrosis factor (TNF)-alpha in brain cultures; IL-6 could also be induced by TNF-alpha added to brain cultures. Both IL-6 and TNF-alpha were upregulated in astrocytes and macrophage cultures on rgp120SF2 treatment. Ultrastructural studies demonstrated that IL-6 treatment for 72 h induced large cytoplasmic vacuoles in neural cells with morphology consistent with neurons; rgp120SF2 treatment for 7 days resulted in chromatin condensation along the inner margins of nuclear envelopes of neural cells. CONCLUSIONS: Our results demonstrated that HIV-1 rgp120SF2 can upregulate at least two known neurotoxic cytokines, IL-6 and TNF-alpha, which may injure neural cells and contribute to the neuropathology observed in AIDS dementia patients.

Cervical disc herniation presenting with chest wall pain.

This report highlights the clinical features of two patients who presented with severe neuropathic chest wall pain caused by herniated C6-7 disc, and speculates on the pathophysiology of this syndrome. Worsening of symptoms with neck movement helped localize the process as cervical spine rather than plexus in origin. Both patients had herniated C6-7 disc material compressing the spinal cord and C7 nerve root, and neurological symptoms resolved promptly following surgery. Neuropathic chest wall pain should alert the clinician to consider the diagnosis of cervical disc herniation and prompt definitive imaging of the cervical spine by myelography or magnetic resonance imaging (MRI).

Skeletal muscle arises as a late event during development of wound sarcomas in v-jun transgenic mice.

Mice carrying an H-2K-v-jun transgene develop malignant sarcomas by a multistage mechanism following wounding. Here we show that these malignancies are often heterogeneous in composition, containing both undifferentiated mesenchymal cells as well as focal areas of skeletal muscle. Such myogenic areas are not detectable in premalignant precursor lesions, suggesting that cells competent for muscle differentiation arise at a late stage of tumorigenesis. Immunohistochemical staining of transgenic sarcomas reveals that levels of v-Jun correlate inversely with muscle-specific gene expression, suggesting that high levels may be inhibitory to myogenesis. Consistent with this idea, we demonstrate that whereas high levels of v-Jun are able to block MyoD-dependent gene expression in vitro, the levels of v-Jun in sarcoma-derived myogenic cells are below the threshold required to produce this effect. The cell of origin of v-jun wound sarcomas, as well as the relationship between myogenic determination and multistage tumorigenesis, are discussed in the light of these results.