Effect of D-glucose on intestinal permeability and its passive absorption in human small intestine in vivo

BACKGROUND: Based on studies in animals, it has been proposed that carrier-mediated D-glucose absorption markedly enhances passive permeability of the jejunal mucosa, allowing the majority of D-glucose absorption to proceed passively. In this study, we evaluated this hypothesis in the human jejunum in vivo. METHODS: Using the constant perfusion, nonabsorbable marker technique, permeability of jejunal mucosa was assessed by measuring the ratio of diffusion rates of urea/L-xylose and mannitol/L-xylose. Passive D-glucose absorption was quantitated using L-glucose and mannitol as probes for D-glucose. RESULTS: Addition of D-glucose to perfused solutions did not change the diffusion ratios, indicating that D-glucose has no effect on the size of channels for passive diffusion across the jejunal mucosa. The fraction of total D-glucose absorption that could be attributed to a passive mechanism averaged 5%. In the human ileum in vivo, we detected no evidence of passive D-glucose absorption. CONCLUSIONS: Carrier-mediated D-glucose absorption does not increase passive permeability of human jejunal mucosa to solutes with molecular radii between 2.6 and 4.0 A. The amount of D-glucose absorbed passively from the human jejunum is trivial compared with the overwhelmingly dominant mechanism, carrier-mediated transport. Our results do not support the concept that sodium-dependent nutrient transport increases tight junction permeability.     

The mini-mental state examination in screening of cognitive dysfunction and dementia

The mini-mental state examination (MMSE) is one of the most widely used screening instruments for the detection of cognitive impairments, used primarily in connection with screening for dementia. The intent of this review is to describe the original purpose of the MMSE and how it is currently used in clinical practice and in research. Advantages and limitations of the MMSE in providing a valid diagnosis of cognitive impairments (dementia) are discussed including sensitivity and specificity, the issues of the relationship of the MMSE scores to sociodemographic variables and examinations of factor structures of the MMSE. It is concluded that the MMSE provides a valid diagnosis of cognitive impairments among people with moderate and severe dementia in general populations. However, MMSE is not recommended as a screening instrument for the detection of early stages of dementia. Studies are needed to extend the present knowledge about how or whether the MMSE can be used in the clinical diagnostic evaluation of dementia and how demented patients treated with medications should be monitored.     

Effect of topical anesthetic use on initial patient satisfaction and overall success with rigid gas permeable contact lenses

BACKGROUND: Rigid gas permeable (RGP) contact lenses have numerous benefits; however, RGP lens use is not increasing in the United States. An important factor for this trend has been initial comfort. Studies have demonstrated that how RGPs are presented to patients, in addition to lens design, can play an important role in the initial comfort process. Another important factor could be the use of a topical anesthetic during the fitting and dispensing visits. The purpose of this study was to use a multicenter format to determine if topical anesthetic use increased the likelihood of patient satisfaction and success. METHODS: A total of 80 subjects, with no previous rigid lens wear experience, was entered into this 1-month study, including 20 subjects from each of 4 institutions. Subjects were randomly divided into the following two groups: (A) anesthetic or (B) placebo, with the former group receiving one drop of a topical anesthetic before lens insertion at both the diagnostic fitting and dispensing visits, whereas the latter group received a placebo. Subjects completed a questionnaire on their perception of rigid lens wear both immediately before fitting and at the 1-month visit. After diagnostic fitting with rigid lenses, subjects completed an adaptation questionnaire after 15 min, 1 week, 2 weeks, and 1 month of lens wear. RESULTS: Seventy of the 80 subjects completed the study and, of the 10 subjects who discontinued, 8 were in the placebo group. In all categories evaluated, the anesthetic group experienced a more optimum adaptation experience at each visit vs. the placebo group. Specifically, overall comfort was rated significantly higher at both dispensing and 2 weeks. In addition, the anesthetic group exhibited significantly greater overall satisfaction with rigid lens wear at 2 and 4 weeks. Also, the anesthetic group perceived their adaptation, sensitivity, and adaptation time to be significantly better at the 1-month visit. There was no significant difference in corneal staining between these two groups at each visit, with the exception of a greater amount of staining in the central quadrant for the placebo group at the 1-month visit. CONCLUSIONS: The use of a topical anesthetic at the fitting and dispensing visits for first-time wearers of RGP lenses resulted in significantly fewer dropouts, improved initial comfort, an enhanced perception of the adaptation process, and greater overall satisfaction after 1 month of lens wear as compared to the use of a nonanesthetizing placebo at those visits. This result, in combination with both presenting RGP lenses in a nonthreatening manner and optimizing the lens design and fitting relationship, should result in a positive adaptation process and successful wear of RGP contact lenses.     

Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment

Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100-300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to optimize delivery of these agents. Here we analyze the functional limits of transvascular transport and its modulation by the microenvironment. One human and five murine tumors including mammary and colorectal carcinomas, hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or cranial window, and the pore cutoff size, a functional measure of transvascular gap size, was determined. The microenvironment was modulated: (i) spatially, by growing tumors in subcutaneous or cranial locations and (ii) temporally, by inducing vascular regression in hormone-dependent tumors. Tumors grown subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 1.2 microm. This pore cutoff size was reduced in tumors grown in the cranium or in regressing tumors after hormone withdrawal. Vessels induced in basic fibroblast growth factor-containing gels had a pore cutoff size of 200 nm. Albumin permeability was independent of pore cutoff size. These results have three major implications for the delivery of therapeutic agents: (i) delivery may be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery may be reduced during tumor regression induced by hormonal ablation, and (iii) permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter.     

Ethics of resource allocation in developing countries: the case of Sri Lanka

The issues of prioritization of health care services and allocation of resources have recently received increasing attention and discussion. Several reports have been published by governments in different countries and the issues are discussed in many recent books and papers. In this paper the focus is on the problems faced by a developing country when allocation of health care resources is considered. We consider these issues under three headings and exemplify the situation in a developing country by taking Sri Lanka as an example. Firstly the evidence to formulate an ethical basis for the existing health care system in Sri Lanka is discussed, in particular the problem of defining a minimum quality of health care for the population. Secondly, we consider the issues which arise when we want to formulate the ethical basis for health sector reform. In particular, we examine current World Bank proposals. We shall argue that there are a number of important conceptual and ethical issues that have not been properly addressed in the various policy documents. Finally, we introduce our own alternative ethical framework for policy reform.     

Comparison of the structures and the crystal contacts of trypanosomal triosephosphate isomerase in four different crystal forms

Triosephosphate isomerase (TIM) is a dimeric enzyme consisting of 2 identical subunits. Trypanosomal TIM can be crystallized in 4 different spacegroups: P2(1)2(1)2(1), C2(big cell), C2(small cell), and P1. The P1 crystal form only grows in the presence of 1.4 M DMSO; there are 2 DMSO binding sites per subunit. The structures have been refined at a resolution of 1.83 A, 2.10 A, 2.13 A, and 1.80 A, respectively. In the 4 different spacegroups the TIM subunit can be observed in the context of 7 different crystallographic environments. In the C2 cells, the dimer 2-fold axis coincides with a crystallographic 2-fold axis. The similarities and differences of the 7 subunits are discussed. In 6 subunits the flexible loop (loop 6) is open, whereas in the P2(1)2(1)2(1) cell, the flexible loop of subunit 2 is in an almost closed conformation. The crystal contacts in the 4 different crystal forms are predominantly generated by polar residues in loops. A statistical analysis of the residues involved in crystal contacts shows that, in particular, serines are frequently involved in these interactions; 19% of the exposed serines are involved in crystal contacts.     

Solitary plasmacytoma of bone--a rare disorder with an unusual evolution

A 40 year old woman presented with a spinal epidural tumour, which on histology was shown to be a plasmacytoma. At that time she had no evidence of multiple myeloma. Ten months later, she developed a second isolated plasmacytoma in the spleen, for which she underwent splenectomy. Two years after her initial presentation she had another recurrence in the liver, followed by a full-blown picture of multiple myeloma. The myeloma was progressive and resistant to all forms of chemotherapy. She finally died of a massive gastrointestinal haemorrhage. The clinical features, natural evolution and management of solitary plasmacytomas are discussed.