Cyclical changes in endogenous levels of oestrogen modulate the induction of LTD and LTP in the hippocampal CA1 region

The present study investigated the effects of naturally fluctuating endogenous levels of oestrogen on the induction and maintenance of long-term potentiation (LTP) and long-term depression (LTD) in the CA1 region of the hippocampus. Using an anaesthetized in vivo preparation, the results showed that the induction of LTP was augmented during the pro-oestrous stage of the oestrous cycle. In contrast to LTP, however, the induction of paired-pulse LTD was severely attenuated during pro-oestrous, but was clearly manifested by rats during met/dioestrous and oestrous stages of the cycle. These findings are discussed with reference to: (i) the modulatory effects of oestrogen on N-methyl-D-aspartate (NMDA) receptor function and gamma-aminobutyric acid (GABA) neurotransmission in the hippocampus; and (ii) the functional implications that such cyclical changes in synaptic plasticity have for learning and memory processes supported by the hippocampus.     

The role of oral etoposide in non-small cell lung cancer

Oral etoposide has been tested alone and in combination in a number of tumour types since the late 1980s because of its mild toxicity, high response rates, ease of administration, and comparatively low cost. Encouraging early results with protracted oral etoposide therapy in small cell lung cancer have not been borne out in non-small cell lung cancer (NSCLC), particularly in the advanced-disease setting. However, in stage IV NSCLC, oral etoposide does appear to be as compatible with most of the newer agents as it has been with platinum compounds; these combinations continue to be explored, although they have not penetrated into standard usage. In stage III NSCLC, large combined-modality studies are ongoing. Other investigations examining protracted administration in combination with radiation 'sensitisers' are planned. It is possible that by exploiting the 'radiosensitising effect' of prolonged low dose oral etoposide, combined with that of other proven radiosensitisers such as paclitaxel, gemcitabine, and topotecan, we may identify a niche for oral etoposide in the future.     

Contrast enhancement of the cerebrospinal fluid on MRI in two cases of spirochaetal meningitis

We report two patients with meningitis due to spirochaetal infection, both of whom showed diffusely enhancing meninges around the brain and spinal cord. In addition, there was enhancement of the cerebrospinal fluid after intravenous administration of Gd-DTPA. Received: 1 March 1998/Accepted: 21 August 1999     

Historic Landmarks in Clinical Transplantation: Conclusions from the Consensus Conference at the University of California, Los Angeles

The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three-decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contributions of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here in six tables and annotated with references.     

Low-dose outpatient chemobiotherapy with temozolomide, granulocyte-macrophage colony stimulating factor, interferon-alpha2b, and recombinant interleukin-2 for the treatment of metastatic melanoma.

PURPOSE: The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). RESULTS: Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. CONCLUSION: This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases.     

Unirhinal Norms for the University of Pennsylvania Smell Identification Test

Adult normative data are presented for unirhinal administration of the University of Pennsylvania Smell Identification Test (UPSIT). Two-hundred and seventy healthy adults, aged 15-64, were administered half of the UPSIT (20 items) to each nostril. The main findings were: (1) unirhinal and birhinal performance are not equivalent necessitating the use of unirhinal norms, rather than prorated birhinal norms, (2) unirhinal performance does not differ according to nostril of presentation, (3) unirhinal performance does not differ according to sex, (4) within the age ranges studied, age accounted for only a minor proportion of the variability, and (5) being a current smoker and having lower levels of formal education contributed to reduced unirhinal UPSIT scores. Correction factors are suggested for the education and smoking variables. Unirhinal evaluation may assist in further delineating the structural integrity of specific ipsilateral brain regions and potentially aid in differential diagnosis for a number of disorders.     

Early psychosis in Indonesia: reflections on illness and treatment

Abstract

This paper provides an overview of more than 22?years of research conducted in the central Javanese province of Yogyakarta, Indonesia, by teams of researchers associated with Gadjah Mada University and Harvard University, led by the authors of this essay. This work is placed in the context of the very limited literature on early psychosis and mental health services in Indonesia. It provides an overview of mental health services in Indonesia and of this team’s research trajectory, then addresses four key domains: the cultural phenomenology of early experiences of psychotic illness; patterns of onset, with a particular focus on extremely rapid onset psychoses; patterns of care-seeking for first episode illness; and mental health services and patterns of utilization. It then discusses the importance of rapid onset psychosis for research on early psychosis, and the question of whether collinearity of rapidity of onset and rapidity of care-seeking raises questions about the long-standing finding that a short duration of untreated psychosis leads to better outcomes. It concludes by discussing difficulties of prioritizing early intervention models in settings with very low mental health resources.