Optimal therapy of malignant pleural effusions

A randomized phase III trial of bleomycin, tetracycline and talc following chest tube drainage and a meta-analysis of relative benefit of bleomycin and tetracycline as sclerosing agents were performed to determine the optimal approach to malignant pleural effusion (MPE). Fifty patients were randomized to receive bleomycin (n=16), tetracycline (n=19) or talc (n=16) following chest tube drainage. Treatment groups were balanced for pretreatment characteristics. The study was ended prematurely because of the removal of parenteral tetracycline from the market. Overall, 52% of randomized patients had successful control of effusion 30 days after sclerosis. There were no differences between any of the three treatment groups in terms of 30 day control of effusion, overall survival (6 months), resclerosis rate, pain with sclerosis, fever, or duration of hospitalization (6 days). A meta-analysis was performed using the four previously reported trials of tetracycline vs. bleomycin and revealed a 20.6% advantage to the use of bleomycin (95% C.I. 7.9%-33.3%) (p=0.002). This phase III failed to demonstrate a significant difference between the three agents in terms of control of MPE at 30 days, side effects or survival. However, because of small sample size, this study lacks sufficient power to observe potentially clinically important differences between treatment groups. Inclusion of data from four previous trials in a meta-analysis showed that bleomycin may be superior. The median duration of hospitalization and the overall success rate of all three sclerosing agents in this study argue convincingly that new approaches to palliate MPE are needed.     

Antiapoptotic activity of bovine papilloma virus

Transformed fibroblasts have been recently shown to be sensitive for induction of apoptosis by TGF-beta-treated neighbouring untransformed cells. Cells transformed by a variety of different transformation principles were regularly sensitive for intercellular induction of apoptosis, but fibroblasts transformed by bovine papillomavirus (BPV) represented a striking exception. In contrast to chemically transformed C127 cells, BPV-transformed C127 cells showed resistance against intercellular induction of apoptosis. In addition, BPV-transformed cells were resistant against induction of apoptosis by ROS in glutathione depleted cells. The antiapoptotic function of papillomaviruses may be of central importance for papillomavirus-induced tumor formation as it can protect transformed cells from intercellular control of oncogenesis.     

Quality of health care, survival and health outcomes in Ghana

This paper analyzes the effect of quality and accessibility of health services and other public infrastructure on the health of children in Ghana. We focus on child survival, child height and weight using data from the Ghana Living Standards Survey. The results suggest an important role for public health policy in eliminating the rural-urban disparities in health status and particularly in improving the health status of rural children and reducing their mortality rates. Increased availability of birth services and other related child programs, as well as Improved water and sanitation infrastructure would have an immediate payoff.     

99mTc-labeled nucleotides as tumor-seeking radiodiagnostic agents.

Several lines of human tumor cells in monolayer and soft agar cultures allow permeation of low levels of adenine nucleotides through their plasma membranes, while, in general, untransformed cells do not incorporate adenine nucleotides into their cellular pools without prior degradation of the nucleotides to adenosine. This study determined the uptake of 99mTc-radiolabeled chelated forms of adenine nucleotides, 99mTc-Ap4A (diadenosine 5',5"',P1,P4-tetraphosphate) and 99mTc-ATP chelates as radiodiagnostic agents suitable for the in vivo detection of tumors by radionuclide imaging. Biodistribution studies revealed that Ap4A accumulated preferentially in RT-24 tumors implanted in rats and that V2 carcinoma implanted in rabbits could be readily visualized by in vivo imaging. The biodistribution at various time points showed increased tumor-to-muscle ratios after 99mTc-Ap4A or 99mTc-ATP injections when compared with a nonspecific marker of the extracellular fluid space, 99mTc-labeled diethylenetriaminepentaacetic acid and with an agent known to localize in some tumors, 67Ga-labeled citrate. Studies of ectoenzymatic activities of virus-transformed animal cells and their untransformed counterparts in monolayer cultures showed marked decreases in the ectoenzymatic activities that degrade Ap4A in the transformed cells. Incorporation of en bloc [3H, 32P]Ap4A into cellular acid-soluble nucleotide pools of certain transformed cells was observed. Normal untransformed cells incorporated the radioactive label only by prior degradation to [3H]adenosine and 32Pi.     

Why is the Doppler pressure gradient higher than the one measured by catheter?]

Hemodynamic assessment of aorto-iliac occlusive disease is necessary for successful arterial reconstruction of the legs. Various methods have been proposed and the "pull-through" intra-arterial pressure measurement method is accepted as the best standard. The pressure readings, however, seemed to depend on the intraluminal position of the catheter. To explain these observations and make a comparison between the Doppler method and the "pull-through" method, we have studied center-line velocity changes at the stenosis throat by Doppler ultrasound, and axial and lateral pressure gradients using pressure transducers, mounted 10 mm and 40 mm downstream of short (4 mm) and long (40 mm) axisymmetric sharp-edged model stenoses having cross sectional reduced areas of 64%, 84%, 91%, and 96%. Axial manometric pressures measured 10 mm after the throat of 84% stenosis were more than twice as high as the lateral pressures. There was no significant difference between axial and lateral pressures measured 40 mm downstream from throat. This pressure distribution has important clinical relevance. Mean and peak pressure gradients for both the Doppler method and manometric measurements were compared. Measurements with Doppler method and manometric measurements, indicated that mean pressure gradients (r = 0.98; SEE = +/- -2.4 mmHg) correlate better than peak pressure gradients (r = 0.90; SEE = +/- 16.5 mmHg). Doppler gradients were higher than manometer gradients. Overestimation was 13% for mean pressure gradients, and ranging from 10% to 150% for peak pressure gradients. Explanation for the difference between mean Doppler and catheter gradient may be the pressure recovery occurring in the relaminarized poststenotic regions.     

Awareness of illness in schizophrenia

This article reviews the literature on "poor insight" or unawareness of illness in schizophrenia. A large body of knowledge representing several different perspectives on insight has developed. This work can be divided into three broad categories, suggesting an important role for insight in the phenomenology, pathophysiology, and treatment of schizophrenia. The argument is made here that many of the self-awareness deficits observed in schizophrenia are of diagnostic significance, are neurally based, and are indispensable in guiding treatment decisions. In addition, this article proposes guidelines for assessing unawareness of illness in schizophrenia and discusses the relevance of such deficits to the diagnosis of schizophrenia.     

Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis]-I-125 or I-125 PA. Tissue distribution studies in mice (N=16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 PA and Tc-99^m MDP. Chronic loss of the I-125 PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99^m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 PA can be utilized to measure acute bone formation and chronic resorption.     

Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line

The Raji human lymphoma line is able to remove O⁶-methylguanine(O⁶MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitroso-guanidine(MNNG). The reaction has a rapid phase in which 40% of theO⁶MeG is removed in the first 10 min. The capacity of cellsfor rapid O⁶MeG removal is limited and is saturated at concentrationsof MNNG which do not saturate the systems removing 3-methyladenine.Pretreatment of cells with MNNG inhibits their ability to removeO⁶MeG produced by a subsequent dose given after 2 h. Treatmentwith N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) is effectivein diminishing cellular capacity for O⁶MeG removal, and cellsunable to remove O⁶MeG and sensitive to the cytotoxic effectsof MNNG are also more sensitive to ENNG than their removal competentcounterparts. Regeneration of the ability to remove O⁶MeG requiresincubation of cells for periods > 24 h. The O⁶MeG removalsystem is similar to that found in adapted Escherichia colialthough the capacity of the Raji lymphoma line is much lowerthan that of the induced bacteria per unit of DNA.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (α-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3–5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.