Biomedical subjects
Publications and source records attributed to J B Martin.
We present a rare case of intraorbital ophthalmic artery aneurysm found incidentally, together with a ruptured aneurysm of the tip of the basilar artery. The intraorbital aneurysm was asymptomatic, and no treatment was offered. Angiographic control was recommended to detect any progression. Treatment may be indicated for documented enlargement or significant mass effect of the aneurysm.
We evaluated the performance of long straight coils (Detach-18 J-shaped coils) in large and giant in-vitro aneurysms. The coils consisted of a distal semicircular part 7 or 15 mm in diameter and a proximal 70 cm straight part having three types of stiffness: soft, standard, and stiff. We first investigated the ease of passage through a microcatheter in a realistic cerebral vessel model. Second, we made silicone models simulating lateral-type aneurysms of various spherical dome diameters (12, 15, 20 and 30 mm) and neck sizes (3-10 mm; dome-to-neck ratio approximately 3:1) and connected them to a pulsating circulatory pump. We evaluated the anchoring and folding patterns of the coils, stability of the microcatheter and coils in the aneurysm, and smoothness of delivery and retrieval of coils. Third, we compared the conformability of a coil in a large, irregular aneurysm with that of a spiral coil. The long J-shaped coils were easily advanced and retrieved through a microcatheter in a tortuous vessel model. In 12 mm spherical aneurysms, each coil made a complex framework, and knot formation or damage to the coil during withdrawal was often observed. In 15 mm aneurysms, the coils were all easily delivered and retrieved; standard-stiffness coils adapted best to this size. In 20 mm aneurysms, frameworks were less complex but still good with a standard or stiff coil, but those with soft coil were unstable and changed significantly within 3 min of detachment due to gravity and pulsatile flow. In 30 mm aneurysms, soft coils filled only the lower part during introduction, whereas a stiff coil still made a favourable framework. Conformability of a long J-shaped coil was superior to that of a spiral coil in a large, irregular aneurysm. Long J-shaped coils conform well to various configurations of large and giant aneurysms and can shorten procedures since a larger implant volume can be delivered with a single coil. Their principle of action may promote more favourable occlusion of irregular and large aneurysms by improved conformability and stability.
A measurement system is proposed to evaluate reconstructive effects of carotid stents on the geometry of the carotid bifurcation and the course of the internal carotid artery. To describe deviations of the stenotic internal carotid artery (ICA) from the extended axis of the common carotid artery (CCA) the CCA-ICA angle is measured between the CCA midaxis and the midaxis of the stenotic ICA segment. Maximal extensions of ICA tortuosities perpendicular to the course of the CCA axis are defined as ICA offset. The measurements were applied to DSA images of 224 carotid stenoses to evaluate variation and correlation between the two parameters. Comparative pre- and post-stent evaluation was performed in two series of 55 and 31 carotid stenoses treated with Wallstents and in a historic control group of 35 stenoses treated with Strecker stents. Straight course of the ICA was associated with low angle and low offset values, whereas tortuous course of the ICA showed larger angle and offset. A moderate linear correlation between the two parameters was found. Corresponding to a straightening of the stented segment, Wallstents reduced mean angle and offset values significantly. In five cases of the second series of Wallstents, transferrals of curves above the distal stent end associated with kinks were observed, and offset remained constant or increased. Strecker stent implantation caused no significant changes of bifurcational geometry. The proposed parameters corresponded to visual aspects of ICA tortuosity and detected reconstructive effects of self-expanding Wallstents on the ICA course. The measurement system may provide a basis for geometric evaluation of different stent types or implantation concepts with the aim: to optimize anatomic recanalization results in tortuous high angle-high offset bifurcations.
Transcranial Doppler (TCD) sonography is a new imaging technique allowing for non-invasive evaluation of the intracranial vascular anatomy and cerebral hemodynamics. The recent introduction of echographic contrast agents has significantly increased the sensitivity of TCD for the diagnosis of intracranial vascular lesions. We report a case of giant AComA aneurysm, undetected by color and power TCD, which became visible after echographic contrast administration as a delayed and persistent area of contrast enhancement. Knowledge of atypical or contrast-specific lesion appearances will become important if contrast-enhanced TCD is to be used routinely in the diagnosis of intracranial aneurysms.
BACKGROUND: Dictyostelium cells exhibit an unusual response to hyperosmolarity that is distinct from the response in other organisms investigated: instead of accumulating compatible osmolytes as it has been described for a wide range of organisms, Dictyostelium cells rearrange their cytoskeleton and thereby build up a rigid network which is believed to constitute the major osmoprotective mechanism in this organism. To gain more insight into the osmoregulation of this amoeba, we investigated physiological processes affected under hyperosmotic conditions in Dictyostelium. RESULTS: We determined pH changes in response to hyperosmotic stress using FACS or 31P-NMR. Hyperosmolarity was found to acidify the cytosol from pH 7.5 to 6.8 within 5 minutes, whereas the pH of the endo-lysosomal compartment remained constant. Fluid-phase endocytosis was identified as a possible target of cytosolic acidification, as the inhibition of endocytosis observed under hypertonic conditions can be fully attributed to cytosolic acidification. In addition, a deceleration of vesicle mobility and a decrease in the NTP pool was observed. CONCLUSION: Together, these results indicate that hyperosmotic stress triggers pleiotropic effects, which are partially mediated by a pH signal and which all contribute to the downregulation of cellular activity. The comparison of our results with the effect of hyperosmolarity and intracellular acidification on receptor-mediated endocytosis in mammalian cells reveals striking similarities, suggesting the hypothesis of the same mechanism of inhibition by low internal pH.
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We studied the anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé in 57 consecutive angiograms. Patients with pathology in intracranial venous structures or with inadequate image quality of the venous system were excluded. Arachnoid granulations were found in 12 of the 57 patients (21.1%), always at the junction of the vein of Labbé and the transverse sinus; the vein of Labbé was present in 55 patients (96.5%), most often without associated arachnoid granulations; the latter, however, were not observed in the absence of a vein of Labbé. This study confirms the close, constant anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé. This observation may help to differentiate arachnoid granulations from pathologic conditions involving the transverse sinus such as dural sinus thrombosis. The constant character of this relationship suggests a developmental role of afferent veins in the formation of arachnoid granulations.
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RATIONALE AND OBJECTIVES: The purpose of this in vitro study was to evaluate and quantify the benefit of the balloon protection device, to identify the most effective sequence of irrigation or flushing, and to determine the most effective catheter position to remove the maximum number of emboli or debris beneath the flow-arrest balloon. MATERIALS AND METHODS: Silicone models of the neurovasculature were attached to a systodiastolic pump. Stents were placed in carotid stenoses by using the distal flow protection technique. Embolic material was released within the stent. The effectiveness of different irrigation techniques was evaluated. RESULTS: Aspiration under the balloon through the guiding catheter with a 60-mL syringe followed by one power injection at 40 mL injected at 2 mL/sec will result in removal of about 98% of potential emboli from the internal carotid artery [corrected]. CONCLUSION: In vitro evaluation of the distal flow protection technique indicates that it should reduce stroke risk during carotid stent placement.
Harvard University, the oldest university in the United States, established its medical school in 1782. Harvard Medical School led the way in reform of medical education and in medical research. Since the school's earliest days, Harvard physicians and scientists have demonstrated that treatments are often found beyond the boundaries of prevailing medical practice. In 1802, Professor Benjamin Waterhouse, having learned of Edward Jenner's pioneering work, introduced the smallpox vaccine to America. Later in the nineteenth century, Dr. Oliver Wendell Holmes promoted new standards of sanitary practice, despite the skepticism of many fellow physicians. In 1847, Dr. John Collins Warren first publicly demonstrated the use of clinical anesthesia with ether. This tradition of inquiry and innovation has continued into the present century, as attested by the 15 Nobel prizes awarded to Harvard Medical School scientists. It is in this spirit of open-minded inquiry and rigorous scientific standards that Harvard Medical School now looks into complementary and alternative medicine. The popularity of complementary and alternative treatments has grown enormously in recent years. Physicians must understand what therapies our patients are using and how these therapies work. We must ask if these therapies interact with medicines we prescribe. We must recognize that medical care is both science, and a connection between patient and healer. And we must be open to the likelihood that, as in the past, some therapies that are now considered alternative will be standard practice in the future.
BACKGROUND AND PURPOSE: We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures. METHODS: Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group. RESULTS: The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 microm; 115 to 8697 in number) and lipoid masses (7 to 600 microm; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (P:=0.017). CONCLUSIONS: Blood samples collected during stent implantation procedures contain a large quantity of atheromatous plaque debris. This emphasizes the role of distal protection techniques in avoiding migration of this plaque material into the cerebral circulation.
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Remarkable advances in modern biology have enhanced our understanding of disease, permitting us to define-and potentially to treat-illness at the cellular and molecular level. The challenge we now face as physicians and physician-scientists is ensuring that these advances find expression in clinical practice. Thus far, the distance from the bench to the bedside has been surprisingly difficult to span, reflecting the need to develop broader, more integrative approaches to understanding how component molecules and physiologic systems function in the context of the whole person. Although there appears to be a consensus about the need to pursue such integrative, patient-oriented research, a mechanism for training future investigators in this discipline is less well established. In this essay, we present and develop the rationale for a set of underlying principles for patient-oriented research that can be used to guide appropriate training in this field. We also describe briefly a recently established prototype program-the Harvard initiative in Patient-Associated Science: Training, Education, Understanding, and Research (PASTEUR)-that we hope will help cultivate patient-oriented investigators and catalyze the evolution of patient-oriented research into a fully realized academic discipline.
We have reexamined the structure of inositol phosphates present in trophozoites of the parasitic amoeba Entamoeba histolytica and show here that, rather than being myo-inositol derivatives (Martin, J.-B., Bakker-Grunwald, T., and Klein, G. (1993) Eur. J. Biochem. 214, 711-718), these compounds belong to a new class of inositol phosphates in which the cyclitol isomer is neo-inositol. The structures of neo-inositol hexakisphosphate, 2-diphospho-neo-inositol pentakisphosphate, and 2, 5-bisdiphospho-neo-inositol tetrakisphosphate, which are present in E. histolytica at concentrations of 0.08-0.36 mM, were solved by two-dimensional (31)P-(1)H NMR spectroscopy. No evidence for the co-existence of their myo-inositol counterparts has been found. These neo-inositol compounds were not substrates of 6-diphospho-inositol pentakisphosphate 5-kinase, an enzyme purified from Dictyostelium discoideum that phosphorylates 6-diphospho-myo-inositol pentakisphosphate and more slowly also myo-inositol hexakisphosphate, specifically on position 5. Because preliminary data indicate that large amounts of the same neo-inositol phosphate and diphosphate esters are also present in another primitive amoeba, Phreatamoeba balamuthi, the occurrence of high concentrations of neo-inositol polyphosphates may be much more general than previously thought.
The effects of supplementation with docosahexaenoic acid (DHA) on DHA levels in serum, seminal plasma, and sperm of asthenozoospermic men as well as on sperm motility were examined in a randomized, double-blind, placebo-controlled manner. Asthenozoospermic men (n = 28; < or =50% motility) were supplemented with 0, 400, or 800 mg DHA/d for 3 mon. Sperm motility and the fatty acid composition of serum, seminal plasma, and sperm phospholipid were determined before and after supplementation. In serum, DHA supplementation resulted in decreases in 22:4n-6 (-30% in the 800-mg DHA group only) and total n-6 (-6 and -12% in the 400- and 800-mg DHA groups, respectively) fatty acids. Increases were noted in DHA (71 and 131% in the 400- and 800-mg DHA groups, respectively), total n-3 fatty acids (42 and 67% in the 400- and 800-mg DHA groups, respectively), and the n-3/n-6 ratio (50 and 93% in the 400- and 800-mg DHA groups, respectively). In seminal plasma, DHA supplementation resulted in a decrease in 22:4n-6 (-31% in the 800-mg DHA group only) and an increase in the ratio of n-3 to n-6 (35 and 33% in the 400- and 800-mg DHA groups, respectively). There were insignificant increases in DHA and total n-3 fatty acids. In sperm, decreases were noted in 22:4n-6 (-37 and -31% in the 400- and 800-mg DHA groups, respectively). There were no other changes. There was no effect of DHA supplementation on sperm motility. The results show that dietary DHA supplementation results in increased serum--and possibly seminal plasma--phospholipid DHA levels, without affecting the incorporation of DHA into the spermatozoa phospholipid in asthenozoospermic men. This inability of DHA to be incorporated into sperm phospholipid is most likely responsible for the observed lack of effect of DHA supplementation on sperm motility.
The treatment of a bleeding carotid artery pseudoaneurysm in a patient using endovascular repair is described. Vein-covered stents were successfully employed. There were no neurological complications and no recurrent bleeding during 8 months follow up and carotid artery continuity was achieved. Stents covered with saphenous vein may be considered a treatment option for endovascular repair of pseudoaneurysm of the carotid artery.
The scholarship of integration is concerned with making connections across scientific disciplines, placing the work of individual investigators and their specialty fields into a larger context, and educating nonspecialists. The authors focus their comments on the biomedical sciences, but observe that closer integration of the biomedical and behavioral sciences will be particularly crucial to advance understanding of the human brain. They observe that as biomedical sciences become more technologically sophisticated, progress is increasingly dependent on sciences such as physics, chemistry, engineering, and related fields. However, the scholarship of integration has been slower than other forms of scholarship to gain acceptance as an integral activity of the professoriate. The isolation of disciplines from one another, particularly at large universities, and the perception of interdisciplinary work as risky and professionally unrewarding are among the forces that may discourage integrative scholarship. In addition, a troubling disconnect exists between the scientific community and the larger public in the understanding of science. Leaders in academic medicine and science must develop strategies to move interdisciplinary work from the margins into the mainstream of academia. Solutions that have been proposed include creating new research entities and funding mechanisms dedicated to interdisciplinary work; reinvigorating the integrative role of the physician-scientist; and training specialists in translational research. The scientific community must also work to develop more effective means of communicating the importance of its work to the public.
The authors evaluated a mechanically detachable platinum coil system intended for neurovascular use. The introduction characteristics, ease of delivery, ease of retrieval, and detachability were studied with fluoroscopic guidance with in vitro silicone models. All the coils passed easily through the microcatheter. The detachment maneuver occurred within 20 seconds with 20 or fewer rotations of the pusher wire. One of 229 coils detached prematurely but only after deliberate and extreme manipulation. The detachment system is safe, reliable, and consistent and will be useful for interventional neuroradiologists.