Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy.

Little is known of the changes in human immunodeficiency virus type 1 (HIV-1)-specific effector cytotoxic T lymphocytes (CTL) after potent antiretroviral therapy. Using HLA/peptide tetrameric complexes, we show that after starting treatment, there are early rapid fluctuations in the HIV-1-specific CTL response which last 1 to 2 weeks. These fluctuations are followed by an exponential decay (median half-life, 45 days) of HIV-1-specific CTL which continues while viremia remains undetectable.

HIV-1 antigen-specific and -nonspecific B cell responses are sensitive to combination antiretroviral therapy.

We studied how combination antiviral therapy affects B cell abnormalities associated with HIV-1 infection, namely elevated circulating immunoglobulin (Ig)G antibody-secreting cell (ASC) frequencies and hypergammaglobulinemia. Within a few weeks of starting antiviral therapy, there is a marked decline in IgG-ASC frequency in both acutely and chronically infected people, whereas the hypergammaglobulinemia often present during chronic infection is more gradually resolved. These reductions are sustained while HIV-1 replication is suppressed.

A preliminary evaluation of nelfinavir mesylate, an inhibitor of human immunodeficiency virus (HIV)-1 protease, to treat HIV infection.

A phase I/II dose-ranging open-label 28-day monotherapy study of the safety, pharmacokinetics, and antiviral activity of nelfinavir mesylate (Viracept), an inhibitor of human immunodeficiency virus (HIV)-1 protease, was done in 65 HIV-1-infected subjects. After 28 days, 54 responding subjects entered an open-label extension that allowed for the addition of nucleoside inhibitors of reverse transcriptase and dose escalation to maintain durability. The drug was well-tolerated and demonstrated robust antiviral activity, with demonstrable superiority of the 750 mg and 1000 mg three times daily regimens.

Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.

Although cytotoxic T lymphocytes (CTLs) are thought to be involved in the control of human immunodeficiency virus-type 1 (HIV-1) infection, it has not been possible to demonstrate a direct relation between CTL activity and plasma RNA viral load. Human leukocyte antigen-peptide tetrameric complexes offer a specific means to directly quantitate circulating CTLs ex vivo. With the use of the tetrameric complexes, a significant inverse correlation was observed between HIV-specific CTL frequency and plasma RNA viral load.

Reversing click polarity may uncover auditory neuropathy in infants.

Objective: To identify patients with primary auditory neuropathies whose cochlear potentials to a 100 microsec click persist after click cessation and simulate synchronous auditory brain stem responses (ABRs) at high intensities.

Design: ABRs to condensation and rarefaction clicks, as well as Maximum Length Sequence ABRs and one transtympanic electrocochleogram (ECochG), were collected from five infants with absent middle ear muscle reflexes and normal or near normal otoacoustic emissions. These infants failed ALGO screens, which used alternating polarity clicks, and/or failed full ABRs done elsewhere with alternating polarity clicks.

Glutamate modulation of dopamine measured in vivo with positron emission tomography (PET) and 11C-raclopride in normal human subjects.

Subanesthetic doses of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine exacerbate psychosis in schizophrenic patients, and ketamine has significant abuse liability. These observations indicate that a secondary effect of ketamine may be to increase dopamine concentrations. The present study was undertaken using positron emission tomography (PET) and the dopamine (D2) radiotracer 11C-raclopride to determine whether ketamine would decrease D2 receptor availability, indicative of an increase in dopamine concentrations.

The effects of self-esteem and source credibility on self-denying prophecies.

Self-fulfilling prophecies are a well-studied phenomenon. The study of self-denying prophecies, however, is rare. Self-denying prophecies shift people's behavior in the direction opposite to the prophecy.

Decay characteristics of HIV-1-infected compartments during combination therapy.

Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops by approximately 99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t1/2) of < or =6 hours and loss of productively infected cells with a t1/2 of 1.6 days.

Serotonergic modulation of dopamine measured with [11C]raclopride and PET in normal human subjects.

Objective: This study was undertaken to measure serotonergic modulation of dopamine in vivo by using positron emission tomography (PET), a radiotracer for the striatal dopamine D2 receptor ([11C]raclopride), and a pharmacologic challenge of the serotonin system (d,l-fenfluramine).

Method: Two PET studies using [11C]raclopride were performed in 11 normal male subjects before administration of the serotonin-releasing agent and reuptake inhibitor fenfluramine (60 mg p.o.

Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS).

We describe the clinical effects of cholesterol supplementation in 6 children with the RSH-"Smith-Lemli-Opitz" syndrome (SLOS). The children ranged in age from birth to 11 years at the onset of therapy, with pretreatment cholesterol levels ranging from 8 to 62 mg/dl. Clinical benefits of therapy were seen in all patients, irrespective of age at onset of treatment, or severity of cholesterol defect.

Physical status and complications in patients with Alzheimer disease: implications for outcome studies.

Physical illnesses commonly coexist with dementia of the Alzheimer type (DAT). Their presence complicates DAT research because it represents a confounding variable. Furthermore, some illnesses or their symptoms also may be used as outcome measures.

Contralateral suppression of transient-evoked otoacoustic emissions in humans: intensity effects.

Transient evoked otoacoustic emissions (TEOAEs) were recorded to clicks presented at peak sound pressures of 50, 55, 60, 65 and 70 dB while continuous contralateral white noise was varied from 10 dB below to 10 dB above the click level. Suppression increased predictably with suppressor noise level for any given click level. However, when the suppressor noise level was held constant, suppression was greater for lower click levels.

The Misdiagnosis of Hallucinations and Delusions in Persons with Mental Retardation: A Neurodevelopmental Perspective.

The identification of psychotic features in persons with mental retardation is challenging as the presence of hallucinations and delusions are disclosed through verbal self-report. In persons with mental retardation, self-report data is limited in utility because of the neuropsychological impairments that are uniformly reflected in limited communication and linguistic functions. Two major areas of misdiagnosis occur when interpreting reported hallucinations and delusions.

Use of the Rorschach and Thematic Apperception Test in Persons With Mental Retardation.

The need to access the internal mental life of a patient during the diagnostic process is essential and is ordinarily accomplished through self-report data during the psychiatric diagnostic interview. Because of cognititve and verbal limitations, persons with mental retardation, however, are ill-equipped to fully participate in the psychiatric interview. The ability of projective tests to access the patient's inner mental life provides a very helpful diagnostic aid, especially for persons with mental retardation.

Automated slide preparation system for the clinical laboratory.

An automated device has been developed to prepare a wide variety of cytology preparations. Using the device, cells collected in suspension are mildly dispersed and transferred to a glass slide using filter-transfer technology. The cell density on the slide is controlled by the instrument.

Effect of fever-management strategy on the progression of dementia of the Alzheimer type.

This study was undertaken to determine if the progression of dementia of the Alzheimer type (DAT) is accelerated by an intercurrent infection and if management strategy (aggressive or palliative care) would modify this effect. A prospective cohort study compared the progression of DAT in patients in three 25-bed dementia special care units that provide a hospice option for care. There were three groups of patients, as follows: (a) developed a fever and received aggressive care (FAC, n = 30), (b) developed a fever and received palliative care (FPC, n = 19), and (c) did not develop a fever (NF, n = 46).

A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.

Background: Ritonavir is a potent inhibitor in vitro of human immunodeficiency virus type 1 (HIV-1) protease, which is needed for virions to mature and become infective. We assessed the safety and efficacy of ritonavir in patients with HIV-1 infection.

Methods: We administered ritonavir orally to 62 patients in one of four dosages during a 12-week trial containing a 4-week randomized, placebo-controlled, double-blinded phase followed by an 8-week dose-blinded phase.

Reaching consensus: the process of recommending treatment decisions for Alzheimer's patients.

Observational and interview data obtained from nurse caregivers and family members of patients with late-stage Alzheimer's disease were analyzed to explicate the nursing role in advance proxy planning. A four-phase model, Achieving Consensus: Decision Making to Determine Treatment Options for Patients with Alzheimer's Disease, was developed. Patient decline, family coping, professional development of nursing staff, and nursing unit philosophy were community characteristics found to be important antecedents to the process of reaching consensus.