Cardiac transplantation: first-year experience in a community hospital

The issue of decentralizing heart transplant services, formerly restricted to a few large medical centers, is currently under review by federal and state governments. We present the results of the first year of cardiac transplantation at a 385-bed community hospital. Twelve patients were selected according to generally accepted criteria from a pool of 24 referrals, all from within 75 miles of our institution. All patients were in New York Heart Association Class IV preoperatively. The one-year survival rate was found to be 82%, which is equivalent to that reported by established centers. All surviving patients were fully rehabilitated. Rates of infection and rejection were lower than expected, and costs were about half the national average. This series, in all likelihood, tests the limits to which the decentralization of cardiac transplant services can be taken. We conclude that cardiac transplantation can be accomplished at a community hospital with results, even for the first patients undergoing transplantation, comparable to those obtained by established programs at major medical centers.     

Detection of new respiratory viruses in hospitalized infants with bronchiolitis: a three‐year prospective study

Aim: We have designed a study with the objective of describing the clinical impact of other viruses different from the respiratory syncytial virus (RSV) in hospitalized infants with bronchiolitis. Methods: A 3 year prospective study was conducted on infants admitted to the Paediatrics Department of the Severo Ochoa Hospital (Spain). We studied the frequency of 16 respiratory viruses. Clinical characteristics of RSV‐only infections were compared with other single agent viral infections. Results: Positive results were confirmed in 275 (86.5%) of the 318 children studied. A single virus was detected in 196 patients and 79 were dual or multiple viral infections. RSV was detected in 61.3% of total bronchiolitis. Rhinovirus (RV) was 17.4% of the identified virus, followed by human bocavirus (HBoV), adenovirus and metapneumovirus (hMPV). Only RV, HBoV and hMPV were significant as single infections. RSV patients were younger than HBoV (p > 0.0001) and hMPV (p = 0.025). Seasonality was clearly different between them. Children with RSV infection needed treatment in the intensive care unit more frequently than others. Conclusions: In hospitalized infants, RSV was the most frequent agent in bronchiolitis in winter, but other viruses were present in 47% of the patients. RV, HBoV and hMPV had a significant proportion of single infections. Clinical characteristics were similar amongst them, but seasonality was clearly different.     

Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer.

An improved formulation of the photosensitizer chlorin e6 (Ce6) in combination with the hydrophilic polymer polyvinylpyrrolidone (PVP) was investigated for its potential clinical applications in fluorescence diagnosis and photodynamic therapy (PDT) of cancer. This study reports the comparative preclinical biodistribution and efficacy of Ce6 delivered with or without PVP versus dimethyl sulfoxide (DMSO). The safety and fluorescence pharmacokinetics of Ce6-PVP in humans was also accessed. Biodistribution results showed that Ce6-PVP had higher tumor to normal tissue ratio compared to the other formulations. The sensitivity and specificity derived from the area under the receiver operating characteristics curves showed that the formulations were able to discriminate tumor from peritumoral muscle in the following order: Ce6-PVP>Ce6>Ce6-DMSO. In vitro PDT results showed that Ce6-PVP was found to induce selective phototoxicity in leukemic cells compared to peripheral mononuclear blood cells. In addition, in vivo light irradiation at 1h after Ce6-PVP was found to induce greater tumor necrosis without causing animal toxicity. In patients, preferential accumulation of Ce6-PVP was observed in angiosarcoma lesions compared to normal skin following intravenous administration. In conclusion, PVP significantly enhanced the Ce6 concentration in tumors compared with Ce6 alone and increased the therapeutic index of PDT without any side effects in animal model. No serious adverse events were observed in human as well.     

The many epidemiological faces of AIDS with special reference to Hong Kong and implications for prevention and control

By 1987, only 3 cases of acquired immunodeficiency syndrome (AIDS) had been reported in Hong Kong. All 3 involved males who had been infected through sexual contact with a European or North American. In 2 cases, the sexual contact was homosexual; the 3rd case involved a man who had frequent sexual contact in New York and Miami with female prostitutes. The Government of Hong Kong moved rapidly to establish an AIDS Expert Advisory Committee to carry out a public educational campaign and formulated clear guidelines for health workers. In recognition of the need for epidemiologic data, a seroprevalence program was initiated in 1985 to define risk groups and the prevalence of infection. During a 21-month surveillance period, 38,312 individuals were screened for antibodies to human immunodeficiency virus (HIV), 72 (0.2%) of whom were confirmed to be seropositive. Of the 61 individuals for whom a history was available, 12 (20%) were homosexual or bisexual men, 46 (75%) had a history of transfusions of blood or blood products (largely for hemophilia), and 3 reported sexual contact with female prostitutes outside of Hong Kong. Only 2 of the 72 positive tests involved women. None of the sera from the 1123 intravenous drug abusers and 1360 prostitutes screened contained antibodies to HIV. Consistent with a lack of documented local heterosexual spread of HIV infection is the absence of cases among infants and children. To reduce the risk of parenterally spread infection, universal blood donor unit screening for HIV antibody and the introduction of heat-treated Factor VIII have been implemented. In addition, an AIDS Education and Publicity Committee was established in 1986 to heighten public awareness of the risk factors involved in HIV infection.     

Inpatient admissions for interventional radiology: philosophy of patient management

As an alternative to performing interventional radiology on inpatients under the care of internists and surgeons, the authors have established a cardiovascular radiology admitting service for well-screened, elective patients. The patients are admitted under the care of a cardiovascular radiology fellow and a staff physician. From April 1982 to December 1983, 133 patients were admitted to the service. Patients are cared for in a surgical ward or in an intermediate unit, as determined by the clinical situation. Advantages of this approach include a broader patient referral base, improved rapport with clinical colleagues and patients, improved follow-up data, and rapid evaluation and treatment, resulting in short hospital stays. The major disadvantages involve the commitment of time and staff necessary to provide quality care. The concept of the interventional radiologist in the role of admitting physician has important implications in terms of negotiations for additional financial compensation, commensurate with the skill and time required for performing these procedures and caring for the patient.     

Dynamic and static phantoms for evaluation of digital subtraction angiographic systems

Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings.     

7-Ethynylcoumarins: selective inhibitors of human cytochrome P450s 1A1 and 1A2

To discover new selective mechanism-based P450 inhibitors, eight 7-ethynylcoumarin derivatives were prepared through a facile two-step synthetic route. Cytochrome P450 activity assays indicated that introduction of functional groups in the backbone of coumarin could enhance the inhibition activities toward P450s 1A1 and 1A2, providing good selectivity against P450s 2A6 and 2B1. The most potent product 7-ethynyl-3,4,8-trimethylcoumarin (7ETMC) showed IC(50) values of 0.46 μM and 0.50 μM for P450s 1A1 and 1A2 in the first six minutes, respectively, and did not show any inhibition activity for P450s 2A6 and 2B1 even at the dose of 50 μM. All of the inhibitors except 7-ethynyl-3-methyl-4-phenylcoumarin (7E3M4PC) showed mechanism-based inhibition of P450s 1A1 and 1A2. In order to explain this mechanistic difference in inhibitory activities, X-ray crystallography data were used to study the difference in conformation between 7E3M4PC and the other compounds studied. Docking simulations indicated that the binding orientations and affinities resulted in different behaviors of the inhibitors on P450 1A2. Specifically, 7E3M4PC with its two-plane structure fits into the P450 1A2's active site cavity with an orientation leading to no reactive binding, causing it to act as a competitive inhibitor.     

抗真菌药物的研究II.C-端含氧代赖氨酸二肽的合成及抗白念珠菌活性

引用违法传递概念设计合成了11个C-末端含氧代赖氨酸二肽,进行抗深部致病菌-白念珠菌活性试验,体外实验结果显示极强的抑菌活性,MIC在12.5～0.8μg/disk之间,较母体氧化赖氨酸大50～135倍(克分子比。     

The Role of Liver-Directed Therapy in Metastatic Colorectal Cancer

Purpose of Review

Colorectal cancer liver metastasis is a major clinical problem, and surgical resection is the only potentially curative treatment. We seek to discuss various liver-directed therapy modalities and explore their roles in the evolving realm of treatment strategies for metastatic colorectal cancer.

Recent Findings

Clinical outcomes for patients with colorectal cancer liver metastases have improved as more patients undergo potentially curative resection and as the armamentarium of systemic treatment and liver-directed therapies continues to expand. Liver-directed therapies have been developed as adjuncts to improve resectability, employed in the adjuvant setting to potentially reduce local recurrence rates, and utilized in the palliative setting with the aim to improve overall survival.

Summary

Ongoing research is expected to validate the role of these evolving therapeutic options, and determine how best to sequence and when to apply these therapies.