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Biomedical subjects

R M Levy

Publications and source records attributed to R M Levy.

At least 73 records · Page 4Linked to original sources
PubMed1990

The efficacy and clinical impact of brain imaging in neurologically symptomatic AIDS patients: a prospective CT/MRI study.

The relative efficacies of cranial magnetic resonance imaging (MRI) and computed tomography (CT) brain scans for the detection of intracranial pathology in patients with the acquired immune deficiency syndrome (AIDS) were evaluated prospectively. Fifty homosexual or bisexual men with AIDS and neurologic symptoms were evaluated using both modalities. In 24 patients, MR images and CT scans provided the same diagnostic information (within normal limits in 16, cerebral atrophy only in 6, and similar lesions in 2 patients). In only one instance did CT show the presence of a lesion not seen on MRI. In the 25 remaining patients, MRI was the more sensitive modality. MRI also reflected more consistently the histopathologically documented extent and distribution of central nervous system disease. The greater sensitivity of MRI suggested significant alterations in the diagnostic evaluation and therapeutic management of 20 patients. Thus, MRI was as good or better than CT for the detection of intracranial pathology in 49 of 50 neurologically symptomatic AIDS patients and significantly affected the diagnosis and treatment of 40% of these patients. Although MRI does not appear to be more specific than other modalities in the differentiation of human immunodeficiency virus (HIV)-related neurologic diseases, its greater sensitivity suggests that MRI may be the best neuroimaging procedure for the initial radiologic evaluation of AIDS patients with neurologic illness.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Solution structures of proteins from NMR data and modeling: alternative folds for neutrophil peptide 5.

The structure of neutrophil peptide 5 in solution has recently been reported (Pardi et al., 1988). The structure determination was accomplished by using a distance geometry algorithm and 107 interproton distance constraints obtained from 2D NMR data. In each of the eight independent solutions to the distance geometry equations, the overall fold of the polypeptide backbone was identical and the root mean square (rms) deviation between backbone atoms of the superimposed structures was small (approximately 2.4 A). In this paper we report additional NP-5 structures obtained by using a new structure generation algorithm: a Monte Carlo search in torsion angle space. These structures have a large rms backbone deviation from the distance geometry structures (approximately 5.0 A). The backbone topologies differ in significant respects from the distance geometry structures and from each other. Structures are found that are pseudo mirror images of part or all of the fold corresponding to that first obtained with the distance geometry procedure. For small proteins, the problem of distinguishing the correct structure among pseudo mirror images is likely to be greater than previously recognized. When a set of test distance constraints constructed from a novel Monte Carlo structure is used as input in the distance geometry algorithm, the fold of the resulting structure does not correspond to that of the target. The results also demonstrate that the previously accepted criteria (the magnitude of the rms deviation between multiple solutions of the distance geometry equations) for defining the accuracy and precision of a peptide structure generated from NMR data are inadequate. An energetic analysis of structures corresponding to the different folding topologies has been carried out. The molecular mechanics energies obtained by minimization and molecular dynamics refinement provide sufficient information to eliminate certain alternative structures. On the basis of a careful comparison of the different trial structures with the experimental data, it is concluded that the NP-5 peptide fold which was originally reported is most consistent with the data. An alternative fold corresponding to structures with low energies and small total distance violations is ruled out because for this fold predicted NOEs are not observed experimentally.

Blood Proteins↗
PubMed1989

Central nervous system disorders in AIDS.

AIDS is no longer a rare disease affecting only a small segment of our population. It has now been observed throughout the United States and most other countries in the world. As the current data demonstrate, the effect of AIDS on the nervous system is profound and widespread. About 10% of all AIDS patients will first present with a neurological complaint. Evaluation of this complaint will then lead to the diagnosis of AIDS. Nearly 40% of all AIDS patients will develop major neurological symptoms during their lifetime; these symptoms may be related to primary HIV infection or secondarily to any of a number of opportunistic processes. At autopsy, 75% of AIDS patients will have neuropathological abnormalities. The AIDS-related central neurological syndromes are many and varied, as are their associated signs and symptoms. As with radiologic and serologic examination, the findings resulting from clinical examination of the AIDS patient with neurological illness are nonspecific. While there are clinical findings that are suggestive of one or another class of AIDS-related neurological illness, there is such overlap in their presentations as to make specific CNS diagnosis on the basis of clinical examination virtually impossible. The differential diagnosis of AIDS-related neurological illness is made even more difficult by the frequent observation of multiple CNS pathological processes in the same AIDS patient. Nearly one-third of all histologically examined AIDS cases had multiple intracranial pathologies. Multiple treatable pathological abnormalities have been identified both within the same intracranial lesion and within different lesions, and both simultaneously and sequentially. Thus, the evaluation and treatment of the AIDS patient with central neurological illness is a difficult challenge. Close attention must be paid to subtle neurological complaints, and careful neurological examination is warranted in all AIDS patients. Once the patient complains of neurological dysfunction or a neurological abnormality is identified on clinical examination, a careful workup including MRI or CT brain scanning and cerebrospinal fluid examination is indicated. Specific diagnosis must then be made on the basis of CSF findings, response to empiric therapy or biopsy. Therapy for AIDS-related CNS diseases in not unlike that for the same disease in other patient populations. (see Chapters 18 and 19). There is no cure for HIV encephalitis; azidothymidine (AZT) appears to cross the blood-brain barrier, and trials of AZT for the treatment of HIV encephalitis show early promise.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Dementia Complex↗
PubMed1988

Opportunistic central nervous system pathology in patients with AIDS.

Central nervous system disease related to the acquired immunodeficiency syndrome (AIDS) includes both those illnesses arising from primary human immunodeficiency virus infection and those secondary to opportunistic processes. Ten percent of AIDS patients present with neurological illness; nearly 40% have significant neurological symptoms and 75% have neuropathological abnormalities on autopsy. The frequency of multiple central nervous system pathological processes in the neurologically symptomatic AIDS patient may approach 30%, making the diagnosis and follow-up of these patients extremely difficult. Specific AIDS-related opportunistic infections of the central nervous system are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Primary central nervous system lymphomas in patients with AIDS.

Primary central nervous system non-Hodgkin's lymphomas are observed in approximately 1.9% of all patients with acquired immunodeficiency syndrome (AIDS). The yearly incidence of AIDS-associated tumors has surpassed the yearly incidence from all other causes and could become as frequent as low-grade astrocytomas by 1991. Patients' signs, symptoms, and radiographic studies are not specific for this lesion; brain biopsy usually is necessary to make a definitive diagnosis. Most tumors are high-grade lymphomas and are pathologically similar to the primary central nervous system lymphomas observed before the AIDS epidemic. AIDS-associated tumors respond readily to radiation therapy. However, patient survival remains limited owing to other manifestations of the syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pain control with laser-produced dorsal root entry zone lesions.

Pain relief was evaluated in 40 patients with various types of deafferentation pain that were treated with dorsal root entry zone (DREZ) lesions produced with microsurgical lasers. Good long-term pain relief was evident in some paraplegics and in all patients with brachial plexus avulsion. Several other small subgroups of patients benefited from laser DREZ lesions as well. Pain associated with arachnoiditis and peripheral nerve injury or neuropathy did not respond to laser DREZ lesioning. Based upon the smaller lesion dimensions produced with the lasers, it is proposed that interruption of impulses in the tract of Lissauer may be a mechanism of pain control in patients that responded to laser DREZ lesions.

Humans↗
PubMed1988

The neurology of human immunodeficiency virus infection.

HIV-infected patients are at markedly increased risk for neurological dysfunction, which may occur at any level of the neuraxis (see Table 1). The most common syndromes--AIDS dementia complex, vacuolar myelopathy, and possibly distal symmetric peripheral neuropathy--appear to be related to HIV infection within the nervous system, rather than due to the immunoincompetence caused by HIV. However, the mechanism(s) by which HIV causes these syndromes, e.g., infecting neurons or oligodendroglia directly, interfering with neurotrophic factors, effecting toxic monokine production, etc., is unknown. Early, albeit incomplete, success with azidothymidine is encouraging. Less commonly, neurological syndromes may be secondary to the immunoincompetence produced by HIV. Many different etiologies--most of which are treatable--have been encountered, but a few of these (cerebral toxoplasmosis, cryptococcal meningitis, primary CNS lymphoma, and progressive multifocal leukoencephalopathy) are responsible for most of the opportunistic complications. Marked differences in symptoms and signs between AIDS patients and immunologically normal patients may complicate recognition of some of these diseases (e.g., herpes simplex encephalitis). Finally, some HIV-associated syndromes, e.g., inflammatory demyelinating polyradiculoneuropathy and retinal microvasculopathy, are of unknown etiology.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Central nervous system dysfunction in acquired immunodeficiency syndrome.

Nearly 40% of AIDS patients develop neurological complications during the course of their illness, and about 10% experience neurological symptoms as the initial manifestations of AIDS. The most common neurological complication (14% of AIDS patients) is human immunodeficiency virus (HIV) encephalopathy, but opportunistic viral and nonviral infections and neoplasms are also quite common; the most frequent among these are cryptococcal meningitis, toxoplasmosis, primary central nervous system (CNS) lymphoma, progressive multifocal leukoencephalopathy, and herpesvirus infections. Most of the nonviral infections and neoplasms are potentially treatable. Neurological syndromes include diffuse and regional encephalopathies, myelopathy, meningitis, intraaxial cranial neuropathies, and retinopathy. About 10% of AIDS patients develop a CNS mass lesion; the chief causes of these lesions are toxoplasmosis and primary CNS lymphoma. Since the clinical profiles of the various diseases overlap to a great extent, differential diagnosis requires a thorough workup, including magnetic resonance imaging or computed tomography brain scanning, examination of the cerebrospinal fluid, and, frequently, brain biopsy. Because AIDS patients have a high incidence of multiple intracranial pathologies, the diagnostic workup may have to be repeated to identify all of the diseases present.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Neuroepidemiology of acquired immunodeficiency syndrome.

Data from the Centers for Disease Control (CDC) and from the hospitals affiliated with the University of California, San Francisco show a significant incidence of neurological complications in AIDS patients and suggest that patients from different risk groups and geographic regions are at different relative risk for specific neurological complications. CDC national surveillance data show that Haitian-born AIDS patients are 3.7 times more likely to have neurological complications than are patients in other risk groups; neurological illness is also reported more often in intravenous drug abusers and black AIDS patients. Cryptococcal meningitis is most prevalent among intravenous drug abusers, Haitians, and blacks, and is most commonly reported in New Jersey, a state with a large proportion of AIDS patients in these three groups. Cerebral toxoplasmosis is reported much more often in Haitians than in other risk groups and is most prevalent in Florida among both Haitians and non-Haitians, probably because of greater exposure to Toxoplasma gondii organisms in the semitropical climate of Florida. The prevalence rates for progressive multifocal leukoencephalopathy (PML) and primary central nervous system lymphoma are similar throughout various risk groups and regions of the United States.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Contralateral intracerebral hemorrhage as a complication of tumor biopsy.

The authors report two cases of contralateral intratumoral hemorrhage after tumor biopsy in patients with bilateral glioblastoma multiforme. There was no evidence of systemic hypertension during either procedure. The occurrence of hemorrhage distant to the site of biopsy may be related to some aspect of the surgical procedure and should be recognized as a possible complication of brain tumor biopsy procedures.

Aged↗
PubMed1987

Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature.

Since the senior author's (J.E.A.) first report in 1972 of the use of deep brain stimulation (DBS) to control chronic pain, electrodes for DBS have been implanted in 141 patients. Of reported series, this one has the largest number of patients and the longest period of follow-up. The mean age of patients in this study was 51.2 years. The mean length of follow-up was 80 months. Patients had experienced pain for a mean period of 65 months before DBS was attempted; all patients had exhausted other medical and surgical therapies. For the purposes of this study, pain states were characterized as being either nociceptive or deafferentation in nature. Nociceptive pain was treated primarily by stimulation of the periaqueductal or periventricular gray, and deafferentation pain was treated primarily by stimulation of the sensory thalamus. Eighty-four patients were treated for deafferentation pain, which included the thalamic pain syndrome (25 cases), peripheral neuropathic pain (16 cases), anesthesia dolorosa (12 cases), paraplegia pain (11 cases), postcordotomy dyesthesia (5 cases), phantom limb pain (5 cases), thoracic neuralgia (4 cases), and miscellaneous pain states (6 cases). We treated 57 patients with nociceptive pain states, 51 for low back and skeletal pain and 6 for pain from the invasion of cancer. Initial relief of pain was obtained by 83 patients (59%). After the mean follow-up period of 80 months, 42 patients (31%) continued to obtain significant pain relief with DBS. Some pain states, particularly anesthesia dolorosa and paraplegia pain, did not seem to respond to DBS. Major complications of therapy included wound infection (12%) and intracranial hemorrhage (3.5%); there was one death in the series (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1986

Temperature-dependent molecular dynamics and restrained X-ray refinement simulations of a Z-DNA hexamer.

Molecular dynamics simulations of the Z-DNA hexamer 5BrdC-dG-5BrdC-dG-5BrdC-dG were performed at several temperatures between 100 K and 300 K. Above 250 K, a strong sequence-dependent flexibility in the nucleic acid is observed, with the guanine sugar and the phosphate of GpC sequences much more mobile than the cytosine sugar and phosphate of CpG sequences. At 300 K, the hexamer is in dynamic equilibrium between several Z forms, including the crystallographically determined ZI and ZII forms. The local base-pair geometry, however, is not very variable, except for the roll of the base-pairs. The hexamer molecular dynamics trajectories have been used to test the restrained parameter crystallographic refinement model for nucleic acids. X-ray diffraction intensities corresponding to observed diffraction data were computed. The average structures obtained from the simulations were then refined against the calculated intensities, using a restrained least-squares program developed for nucleic acids in order to analyse the effects of the refinement model on the derived quantities. In general, the temperature dependence of the atomic fluctuations determined directly from the refined Debye-Waller factors is in reasonably good agreement with the results obtained by calculating the atomic fluctuations directly from the Z-DNA molecular dynamics trajectories. The agreement is best for refinement of temperature factors without restraints. At the highest temperature studied (300 K), the effect of the refinement on the most mobile atoms (phosphates) is to significantly reduce the mean-square atomic fluctuations estimated from the refined Debye-Waller factors below the actual values (less than (delta r)2 greater than congruent to 0.5 A2). Analysis of the temperature-dependence of the mean-square atomic fluctuations provides information concerning the conformational potential within which the atoms move. The calculated temperature-dependence and anharmonicity of the Z-DNA helix are compared with the results observed for proteins. The average structures from the simulations were refined against the experimental X-ray intensities. It is found that low-temperature molecular dynamics simulations provide a useful tool for optimizing the refinement of X-ray structures.

Base Sequence↗
PubMed1986

Effect of anisotropy and anharmonicity on protein crystallographic refinement. An evaluation by molecular dynamics.

Molecular dynamics simulations are employed to determine the errors introduced by anharmonicity and anisotropy in the structure and temperature factors obtained for proteins by refinement of X-ray diffraction data. Simulations (25 ps and 300 ps) of metmyoglobin are used to generate time-averaged diffraction data at 1.5 A resolution. The crystallographic restrained-parameter least-squares refinement program PROLSQ is used to refine models against these simulated data. The resulting atomic positions and isotropic temperature factors are compared with the average structure and fluctuations calculated directly from the simulations. It is found that significant errors in the atomic positions and fluctuations are introduced by the refinement, and that the errors increase with the magnitude of the atomic fluctuations. Of particular interest is the fact that the refinement generally underestimates the atomic motions. Moreover, while the actual fluctuations go up to a mean-square value of about 5 A2, the X-ray results never go above approximately 2 A2. This systematic deviation in the motional parameters appears to be due to the use of a single-site isotropic model for the atomic fluctuations. Many atoms have multiple peaks in their probability distribution functions. For some atoms, the multiple peaks are seen in difference electron density maps and it is possible to include these in the refinement as disordered residues. However, for most atoms the refinement fits only one peak and neglects the rest, leading to the observed errors in position and temperature factor. The use of strict stereochemical restraints is inconsistent with the average dynamical structure; nevertheless, refinement with tight restraints results in structures that are comparable to those obtained with loose restraints and better than those obtained with no restraints. The results support the use of tight stereochemical restraints, but indicate that restraints on the variation of temperature factors are too restrictive.

Amino Acid Sequence↗
PubMed1986

The effect of analgesic doses of morphine on regional cerebral glucose metabolism in pain-related structures.

The effect of morphine on regional cerebral glucose metabolism was measured in rats using high resolution [14C]2-deoxyglucose autoradiography with concurrent confirmation of morphine-induced analgesia measured by tail-flick latency to noxious heat. Within the limits of resolution of this technique, doses of morphine sufficient to inhibit the tail-flick reflex had no significant effect on glucose metabolism in structures implicated in the modulation of pain.

Animals↗