Subclavian artery pseudoaneurysm in type IV Ehlers-Danlos syndrome

We report case of a subclavian artery pseudoaneurysm in a patient with type IV Ehlers-Danlos Syndrome. A 16-year-old boy underwent successful repair of a subclavian artery pseudoaneurysm that occurred after a cervical hyperextension injury. Subsequent workup included skin biopsy and fibroblast culture, which were consistent with a diagnosis of type IV Ehlers-Danlos Syndrome. This condition is a dominantly inherited connective tissue disorder, which in this patient was found to be caused by a spontaneous point mutation in the COL3A1 gene that encodes the chains of type III procollagen. The clinical, genetic, and molecular characteristics of type IV Ehlers-Danlos Syndrome are briefly reviewed.     

Synthesis and glutathione S-transferase structure-affinity relationships of nonpeptide and peptidase-stable glutathione analogues

A series of nonpeptidic glutathione analogues where the peptide bonds were replaced by simple carbon-carbon bonds or isosteric E double bonds were prepared. The optimal length for the two alkyl chains on either side of the mercaptomethyl group was evaluated using structure-affinity relationships. Affinities of the analogues 14a-f, 23, and 25 were evaluated for a recombinant GST enzyme using a new affinity chromatography method previously developed in our laboratory. Analysis of these analogues gives an additional understanding for GST affinity requirements: (a) the carbon skeleton must conserve that of glutathione since analogue 14a showed the best affinity (IC50 = 5.2 microM); (b) the GST G site is not able to accommodate a chain length elongation of one methylene group (no affinity for analogues 14c,f); (c) a one-methylene group chain length reduction is tolerated, much more for the "Glu side" (14d, IC50 = 10.1 microM) than for the "Gly side" (14b, IC50 = 1800 microM); (d) the mercaptomethyl group must remain at position 5 as shown from the null affinity of the 6-mercaptomethyl analogue 14e; (e) the additional peptide isosteric E double bond (25) or hydroxyl derivative (23) in 14e did not help to retrieve affinity. This work reveals useful information for the design of new selective nonpeptidic and peptidase-stable glutathione analogues.     

Neurobiological correlates of the antidepressant action of electroconvulsive therapy

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.     

The immunology of corneal graft rejection

Corneal transplantation is the most successful of organ transplants due to the fact that the eye is an immunologically privileged site, and the cornea is an immunologically privileged tissue. The factors responsible for this include presence of the blood-aqueous barrier, the avascularity of the cornea, the absence of classic antigen-presenting cells (APCs) in the central cornea, inhibitory factors in the aqueous humor, the phenomenon known as anterior chamber-associated immune deviation (ACAID), and the intraocular expression of Fas ligand. Loss of ocular immune privilege can occur with breaching of the blood-ocular barrier, corneal neovascularization, migration of classic APCs to the center of the cornea, loss of inhibitory factors in aqueous humor, abrogation of ACAID, and loss of Fas ligand expression within the anterior chamber. The purpose of this review is to analyze these events and how they relate to corneal graft rejection. A discussion on future research and therapeutic modalities is provided.     

Supportive care: some definitions and principles

Supportive care is defined as the totality of medical, nursing, psychosocial and rehabilitative support from the onset of the disease until possible fatal outcome, including all active therapeutic phases. This concept is thus quite large and heterogeneous. The term palliative care is reserved for the approach to the terminal patient. Hospital "Palliative Medicine" should be considered as a subspecialty of Internal Medicine and Medical Oncology. In palliative medicine, symptom control, and no longer prolongation of survival, takes a preponderant place to finally become the only goal to reach. In our mind, a Palliative Care Unit is not necessarily the final stay of a patient where spiritual support will be preponderant. One of our essential goals is always that the patient can come back in his family in collaboration with the family doctor, even for a short time. The ideal situation consists in short stays in the Unit to treat an acute complication before the patient is sent back home or to his Residency. Along this line, a very close collaboration with the family doctor is absolutely essential.     

Prefrontal and cerebellar abnormalities in major depression: evidence from oculomotor studies

BACKGROUND: Neurobehavioral studies have identified multiple cognitive and motor system disturbances in depressed patients. Neuroimaging studies have identified abnormalities in neocortex, striatum, and cerebellar vermis that are probable causes of these impairments. METHODS: To further clarify the origins of motor and cognitive disturbances in major depression, unmedicated depressed inpatients (n = 29) and an age- and gendermatched healthy comparison group (n = 19) were tested with a battery of oculomotor tasks selected to assess the functional integrity of frontostriatal circuitry and the cerebellar vermis. RESULTS: Depressed patients demonstrated increased rates of response suppression errors on an antisaccade task, less accurate memory for spatial location information in a spatial delayed response task, dysmetric visually guided saccades, and increased rates of saccadic intrusions during visual fixation. CONCLUSIONS: These results provide quantitative documentation of significant disturbances in neurophysiological processes subserved by prefrontal cortex and the cerebellar vermis during episodes of major depression.     

Subunit exchange of lens alpha-crystallin: a fluorescence energy transfer study with the fluorescent labeled alphaA-crystallin mutant W9F as a probe

A chemical study of the common Caribbean sea plume Pseudopterogorgia acerosa from Puerto Rico has produced two previously undescribed secondary metabolites. One of them, 1, is a new representative of the pseudopterane family of diterpenes possessing the uncommon 3,4;5,6 diepoxyfuran moiety. The other metabolite, 2, is a rare norcembranolide diterpene. Their chemical structures, including relative stereochemistry, were established by detailed analysis of the spectral data in addition to NMR spectral comparisons with known pseudopterane and cembrane models.     

A survey of current clinical practice of permanent prostate brachytherapy in the United States

PURPOSE: To help establish standards of care for transperineal interstitial permanent prostate brachytherapy (TIPPB) by obtaining data regarding current clinical practice among the most experienced TIPPB brachytherapists in the United States. METHODS AND MATERIALS: The 70 brachytherapists who performed the greatest number of TIPPB cases in 1995 in the U.S. were surveyed. Each received a comprehensive four page questionnaire that included sections on training and experience, patient and isotope selection criteria, manpower, technique, and follow-up. Thirty-five (50%) surveys were ultimately returned after three mailings and follow-up phone calls. The cumulative experience of the 35 respondents represented approximately 45% of the total TIPPB volume in the U.S. for 1995. Respondents included 29 from the private sector and six from academic programs. RESULTS: The median physician experience with TIPPB was reported as 4.9 years. Each performed an average of 73 TIPPB procedures in 1995 (range 40-300). This represented an increase in volume for most (74%) of the respondents. Sixty-three percent of the respondents attended a formal training course, 54% had TIPPB-specific residency training, and 31% had been proctored (16 had received two or more types of training experience). The most commonly reported selection criteria for implant alone was on Gleason score < or = 7, PSA < 15, < or = Stage T2a, and gland size < or = 60 cc, although no clear consensus was found. Fifty-four percent considered a history of TURP to be a relative contraindication, while 34% considered TURP to have no impact on patient selection. Eighty-six percent of respondents combine brachytherapy with external beam radiation in an average of 32% of their patients. Boosts were given with both 125I prescribed to 120 Gy (75%) or 103Pd to 90 Gy (50%). Sixty percent reported using a Mick applicator, 46% prefer using preloaded needles, and (11%) use both techniques. Real-time imaging was usually performed with ultrasound (94%); most included fluoroscopy (60%). Definitions of PSA control varied widely. CONCLUSIONS: TIPPB clinical practice in the U.S. demonstrates similarities in technique, but differences in patient selection and definitions of biochemical control. It is, therefore, incumbent on those beginning TIPPB programs to carefully review the specific practice details of those institutions with a broad experience.