The meaning of screening: detection of brain metastasis in the adjuvant setting for stage III melanoma.

BACKGROUND: The incidence of melanoma is increasing and 37% of patients with metastatic melanoma eventually have brain metastasis (BM). Currently, there is no consensus on screening for BM in patients with resected stage III melanoma. However, given the high incidence of BM, routine screening magnetic resonance imaging (MRI) of the brain is considered in patients with completely resected stage III melanoma before the start of adjuvant treatment. The aim of this study was to assess the yield of screening for BM in these patients. MATERIALS AND METHODS: A single-center cohort study was carried out in the Erasmus MC, Rotterdam, The Netherlands, a large tertiary referral center for patients with melanoma. Eligible patients with complete resection of stage III melanoma and a screening MRI of the brain, made within 12 weeks after resection and before adjuvant treatment (programmed cell death protein 1 inhibitors, dabrafenib-trametinib), available between 1 August 2018 and 1 January 2021, were included. RESULTS: A total of 202 patients were included. Eighteen (8.9%) of 202 patients had extracranial metastasis at screening. Two (1.1%) of the remaining 184 patients had BM at screening, resulting in a switch from adjuvant treatment to ipilimumab-nivolumab. At a median follow-up of 21.2 months, BM was detected in another 4 (2.4%) of 166 patients who started with adjuvant treatment. CONCLUSIONS: The yield of screening MRI of the brain is low after complete resection of stage III melanoma, before the start of adjuvant treatment. Therefore, routine screening MRI is not recommended in this setting.

Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer.

Breast cancers related to BRCA mutations are associated with particular biological features. Here we report the clinical and pathological characteristics of breast cancer in Chinese women with and without BRCA mutations and of carriers of BRCA1 mutations compared to BRCA2 mutations. Two hundred and 26 high-risk Hong Kong Chinese women were tested for BRCA mutations, medical information was obtained from medical records, and risk and demographic information was obtained from personal interviews. In this cohort, 28 (12.4%) women were BRCA mutation carriers and among these carriers, 39.3% were BRCA1 and 60.7% were BRCA2 mutations. Mutation carriers were more likely to have a familial history of breast and ovarian cancer, high-grade cancers, and triple negative (TN) cancers. Prevalence of TN was 48.3% in BRCA carriers and 25.6% in non-carriers and was 67.7% in BRCA1 and 35.3% in BRCA2 carriers. Estrogen receptor (ER) negative cancer was significantly associated with BRCA1 mutations, especially in those under 40 years of age. BRCA-related breast cancer in this Chinese population is associated with family history and adverse pathological/prognostic features, with BRCA2 mutations being more prevalent but BRCA1 carriers having more aggressive and TN cancers. Compared to Caucasian populations, prevalence of BRCA2 mutations and TN cancer in BRCA2 mutation carriers in Chinese population are elevated.

An evaluation of SARS and droplet infection control practices in acute and rehabilitation hospitals in Hong Kong.

1. This study has demonstrated that great efforts have been made by the Hospital Authority and the studied hospital cluster to contain and prevent infection, and that high levels of vigilance have been enforced in anticipation of future outbreaks of SARS and other droplet infections. 2. Most health care workers and support workers have good hospital infection control and isolation precaution knowledge levels. 3. Compliance with infection control guidelines is satisfactory and has increased compared with previous studies. 4. Most participants had positive perceptions of the guidelines and found the training programmes useful. 5. This study has identified several structures and infection control practice areas that need strengthening, including improving the clarity of some guidelines and minimising barriers to their implementation.

Process evaluation of a multi-institutional community-based program for diabetes prevention among First Nations.

Epidemic rates of diabetes among Native North Americans demand novel solutions. Zhiiwaapenewin Akino'maagewin: Teaching to Prevent Diabetes was a community-based diabetes prevention program based in schools, food stores and health offices in seven First Nations in northwestern Ontario, Canada. Program interventions in these three institutions included implementation of Grades 3 and 4 healthy lifestyles curricula; stocking and labeling of healthier foods and healthy recipes cooking demonstrations and taste tests; and mass media efforts and community events held by health agencies. Qualitative and quantitative process data collected through surveys, logs and interviews assessed fidelity, dose, reach and context of the intervention to evaluate implementation and explain impact findings. School curricula implementation had moderate fidelity with 63% delivered as planned. Store activities had moderate fidelity: availability of all promoted foods was 70%, and appropriate shelf labels were posted 60% of the time. Cooking demonstrations were performed with 71% fidelity and high dose. A total of 156 posters were placed in community locations; radio, cable TV and newsletters were utilized. Interviews revealed that the program was culturally acceptable and relevant, and suggestions for improvement were made. These findings will be used to plan an expanded trial in several Native North American communities.

Development of an integrated diabetes prevention program with First Nations in Canada.

Type 2 diabetes mellitus is a major cause of morbidity and mortality among First Nations in Canada. We used multiple research methods to develop an integrated multi-institutional diabetes prevention program based on the successful Sandy Lake Health and Diabetes Project and Apache Healthy Stores programs. In-depth interviews, a structured survey, demonstration and feedback sessions, group activities, and meetings with key stakeholders were used to generate knowledge about the needs and resources for each community, and to obtain feedback on SLHDP interventions. First Nations communities were eager to address the increasing epidemic of diabetes. Educating children through a school prevention program was the most popular proposed intervention. Remote communities had poorer access to healthy foods and more on-reserve media and services than the smaller semi-remote reserves. While the reserves shared similar risk factors for diabetes, variations in health beliefs and attitudes and environmental conditions required tailoring of programs to each reserve. In addition, it was necessary to balance community input with proven health promotion strategies. This study demonstrates the importance of formative research in developing integrated health promotion programs for multiple communities based on previously evaluated studies.

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains.

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca2+ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca2+ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721deltaC and T7721deltaN cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721deltaC cells, but not affected in T7721deltaN cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca2+ mobilization although each domain may play different roles.

Preliminary results of using a commercial fibrin sealant in the treatment of fistula-in-ano.

A prospective non-randomised study fibrin sealant injection to manage patients with fistula-in-ano, with magnetic resonance imaging (MRI) monitoring, was performed during the period 5/6/1999 to 28/2/2000. The aim was to determine whether a fibrin sealant could be used as a treatment modality for anorectal fistula and the usefulness of MRI perineum to monitor the disease activity. Ten patients were included in the study. Mean age was 47 years (range 7 months to 70 years). Male: female ratio was 9:1. Mean follow-up duration was 26.4 weeks. The overall success rate was 60%. The success rate of different fistula types were different (60%, 0%, 100% for intersphincteric, transphincteric, subcutaneous, respectively). Variable decrease in signal on STIR images and contrast enhancement was noted in the patients with successful and failure of fibrin sealant injection. In conclusion, fibrin sealant injection is a useful alternative treatment in the management of fistula-in-ano. MRI is helpful in delineating the anatomy of fistula-in-ano but not a useful tool to follow-up disease activity.

The involvement of HAb18G/CD147 in regulation of store-operated calcium entry and metastasis of human hepatoma cells.

The present study examined the effect of hepatoma-associated antigen HAb18G (homologous to CD147) expression on the NO/cGMP-regulated Ca(2+) mobilization and metastatic process of human hepatoma cells. HAb18G/CD147 cDNA was transfected into human 7721 hepatoma cells to obtain a cell line stably expressing HAb18G/CD147, T7721, as demonstrated by Northern blot and immunocytochemical studies. 8-Bromo-cGMP (cGMP) inhibited the thapsigargin-induced Ca(2+) entry in a concentration-dependent manner in 7721 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 (1 microm). However, expression of HAb18G/CD147 in T7721 cells decreased the inhibitory response to cGMP. A similar concentration-dependent inhibitory effect on the Ca(2+) entry was observed in 7721 cells in response to a NO donor, (+/-)-S-nitroso-N-acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin-induced Ca(2+) entry was significantly reduced in HAb18G/CD147-expressing T7721 cells, indicating a role for HAb18G/CD147 in NO/cGMP-regulated Ca(2+) entry. Experiments investigating metastatic potentials demonstrated that HAb18G/CD147-expressing T7721 cells attached to the Matrigel-coated culture plates and invaded through Matrigel-coated permeable filters at the rate significantly greater than that observed in 7721 cells. Both the attachment and invasion rates could be suppressed by SNAP, and the inhibitory effect of SNAP could be reversed by NO inhibitor, N(G)-nitro-l-arginine methyl ester. The sensitivity of the attachment and invasion rates to cGMP was significantly reduced in T7721 cells as compared with 7721 cells when cells were pretreated with thapsigargin. The difference in the sensitivity between the two cells could be abolished by a Ca(2+) channel blocker, Ni(2+) (3 mm). These results suggest that HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca(2+) entry by NO/cGMP.

Health care funding and delivery in Hong Kong: what should be done?

This paper outlines a taxonomy of alternative health care funding avenues and the implications of these alternatives. The current approach to health care funding in Sweden is highlighted and a similar proposal outlined to meet the Hong Kong situation. The benefits of the proposed combination of tax-funded and capped voluntary payments, supplemented by 'moral hazard neutral' fees are presented, in terms of expenditure containment, universal access to health care, and optimal resource allocation.

Market reforms and China's health care system.

This paper provides an overview of the medical care system in the People's Republic of China, and assesses the impact of market reforms on the evolution of the medical care system. There is clear indication that China is moving towards a 'prepaid' system closely related to the HMO of the west. Decentralization of the medical care system administration has paved the way for a diversity of local experiments with different ways of reform, but the main direction is towards a integration of decisions over medical services and the insurance function. It is argued that reforms in this direction, while retaining a degree of socialization, will improve the efficiency and equity aspects of the Chinese medical care system.

Splanchnic uptake of haloperidol and release of reduced haloperidol in vivo in the guinea pig.

Splanchnic uptake of haloperidol (HAL) and release of reduced haloperidol (RHAL) were studied in vivo in guinea pigs. Anesthetized animals with implanted cannulae in the aorta, the hepatic vein and the inferior vena cava were infused intravenously with HAL at a rate of 9.6 micrograms/min/animal for 90 min. Plasma HAL and RHAL in samples taken from the arterial and hepatic venous cannulae were measured by HPLC with an electrochemical detector. Contamination of the hepatic venous samples by blood from the inferior vena cava was ruled out by the validation method of tritiated water washout [Huang MT, J Appl Physiol 71: 359-364, 1991]. HAL concentrations plateaued at 70-80 ng/mL in the aorta and 5-7 ng/mL in the hepatic vein during the final 30 min of infusion. Splanchnic extraction of HAL was 91%. Hepatic blood flow was estimated to be 1.95 +/- 0.40 (SD) mL/min/g. If assuming that splanchnic uptake of HAL took place in the liver, a rate of uptake of HAL in the liver of 79.2 +/- 18.6 (SD) ng/min/g could be calculated by the Fick principle. The uptake in the whole liver accounted for 14% of the rate of HAL infusion into the animal. Plasma RHAL in the aorta, 6.4 +/- 6.6 (SD) ng/mL at 60 min and 9.4 +/- 4.6 (SD) ng/mL at the end of HAL infusion, was about 10-12-fold less than aortic HAL. The concentrations of RHAL in the hepatic vein were not significantly different from those in the aorta, indicating that splanchnic tissues including the liver are not responsible for plasma RHAL secretion. The highly efficient uptake of HAL as well as the ketone reductases found previously in vitro in liver microsomes of guinea pigs were probably involved only in biliary excretion of HAL.

Stability and reproducibility of the biologic activity of premixed short-acting and intermediate-acting insulins.

Mixtures of short-acting and intermediate-acting insulins often represent an effective regimen to achieve near-normal blood glucose values, yet controversy exists concerning the stability and predictability of such mixtures. In a study of diabetic patients, the biologic activity of a specific intermediate-acting insulin (insulatard) and a short-acting insulin (Velosulin) premixed in a 70:30 ratio was reproducible at three intervals and was stable for a period of up to three months. The serum levels of free insulin and the rate of onset and extent of the blood glucose lowering effects were not altered, showed two distinct peaks, and were comparable to those experienced with separate injections of equivalent doses of the intermediate-acting and short-acting insulins.

Regulation of plasma arginine vasopressin in patients with chronic renal failure maintained on hemodialysis.

Plasma arginine vasopressin (PAVP) was studied in patients before and after hemodialysis. The levels of PAVP were higher before and reverted to normal range after dialysis (5.7 vs. 2.7 pg/ml). Sequential chemical dialysis showed that vasopressin was removed during the chemical dialysis phase. Data obtained during a simulation experiment were also consistent with the view that vasopressin was removed during the chemical dialysis phase.

Controlled release effect of insecticide microcapsules and their results in common household insect pest control.

Since 1978 we have prepared microencapsulated insecticides by complex coacervation and interfacial polymerization for household insect pest control, fenthion being the main core element. A series of tests have been conducted against mosquitoes (Culex pipiens quinquefasciatus), cockroaches (Periplaneta americana) and bedbugs (Cimex lectularius), and the results indicate that microencapsulation can prolong persistent effects by 2-12 times, enhance safety and subdue offensive odour. Furthermore, the production cost is comparatively low.