Oxandrolone in AIDS-wasting myopathy.

OBJECTIVE: To evaluate oxandrolone, an oral anabolic steroid with potent anabolic activity and minimal androgenic effects, for the treatment of AIDS-associated myopathy and wasting. METHODS: In a multicenter, double-blind study, 63 HIV-seropositive men with > 10% loss of body weight were randomized to receive either placebo, 5 mg/day oxandrolone, or 15 mg/day oxandrolone for 16 weeks. Body weight, neuromuscular evaluation, and measures of well-being were repeatedly assessed. RESULTS: Patients who received 15 mg/day oxandrolone showed weight gain throughout the 16-week treatment period. Overall, the 5 mg/day oxandrolone group maintained their weight gain over the 16-week period, whereas the placebo group showed continual weight loss. At week 16, significantly more patients in the 15 mg/day dose group reported increases in appetite and activity than those receiving placebo. There were no consistent, dose-related, statistically significant differences from baseline in laboratory values or adverse events. CONCLUSION: Oxandrolone, at a dose of either 5 mg/day or 15 mg/day, in contrast to placebo, had a positive impact on the weight and well-being of HIV-seropositive patients suffering from wasting and weakness. Measurable improvement in muscle strength was not noted at the doses employed in this study. Oxandrolone was well tolerated in all the patients who were enrolled in the study. Based on the results reported here, additional studies using higher doses of oxandrolone seem warranted.

Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium study team.

OBJECTIVE: In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTIs), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. DESIGN: Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. SETTING: Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites. PATIENTS: Adult HIV-infected patients (n = 1313) with CD4 counts < 50 x 10(6) cells/l. INTERVENTIONS: Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. MAIN OUTCOME MEASURES: Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. RESULTS: Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P < 0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P < 0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. CONCLUSIONS: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.

Implications of self-reported cognitive and motor dysfunction in HIV-positive patients.

OBJECTIVE: The authors examined HIV-positive subjects to determine the relationship of patient complaints of cognitive and motor dysfunction to psychiatric status and performance on established cognitive and motor function tests. METHOD: HIV-positive volunteers (N = 77) were evaluated at entry into a longitudinal neurological study. Forty were asymptomatic, 29 had AIDS-related complex, and eight had AIDS. The subjects were not selected for the presence or absence of cognitive or motor complaints. Complaints of cognitive and motor dysfunction were assessed with items from the AIDS Clinical Trials Group Macro Neurologic Exam. Current depression and anxiety were assessed with the Profile of Mood States. Psychiatric status was assessed with the NIMH Diagnostic Interview Schedule, a structured interview that provides DSM-III psychiatric diagnoses. Actual cognitive and motor performance was measured with standard neuropsychological tests known to be sensitive to the effects of HIV. RESULTS: Cognitive complaints were found in 38 (49%) of the subjects. These complaints were associated with psychiatric symptoms but not with cognitive performance. Motor complaints, found in 12 (16%) of the subjects, were associated with poorer motor performance but not with psychiatric symptoms. The overall frequency of psychiatric diagnosis was high. CONCLUSIONS: Self-reports of cognitive and motor dysfunction were common in this unselected group and are of concern to health care providers. Potentially treatable psychiatric conditions were also common, particularly in subjects with cognitive complaints, and appropriate treatment referrals are indicated. Patients who report motor dysfunction should be neurologically evaluated for treatable causes.

Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection.

OBJECTIVE: Previous research has documented a possible relation of stress and depression to cell-mediated immunity. The authors examined how stressful events and depression may affect key parameters of cellular immunity in subjects with and without HIV infection. METHOD: Data were collected on 99 asymptomatic HIV-positive and 65 HIV-negative homosexual men as part of an ongoing, longitudinal study. Criticisms of previous studies of psychoimmunity were addressed by 1) using a comprehensive, semistructured interview to measure the objective context of stressful events, 2) double labeling of lymphocytes with monoclonal antibodies to measure subsets of cytotoxic/suppressor T lymphocytes and natural killer (NK) cells, and 3) controlling for circadian effects and methodological factors. RESULTS: In the HIV-positive men, severe stress was significantly associated with reductions in NK cell populations and a subset of T cells thought to represent cytotoxic T effector cells, particularly the CD8+ T cells expressing the CD57 antigen. In the HIV-negative men, no clear and consistent relation between stress and immune system measures was found. Depression was not correlated with any variables in either of the groups, perhaps due to the low levels of depressive symptoms. CONCLUSIONS: The findings suggest that stress is associated with reductions in killer lymphocytes (decreased NK cell and cytotoxic T lymphocyte phenotypes). The data provide evidence that stress may alter cell populations that provide cytotoxic defense against infection in HIV-positive men and indicate that the clinical significance of stress-related changes in cytotoxic T lymphocytes and NK cells in HIV infection warrants further study.

Neurobehavioral functioning in a nonconfounded group of asymptomatic HIV-seropositive homosexual men.

Neurobehavioral functioning was tested in 34 asymptomatic HIV-seropositive and 43 HIV-seronegative male homosexual subjects without substance abuse and CNS disorders. The HIV-positive subjects exhibited mild motor slowing compared to the seronegative subjects. These differences remained after controlling for potential cofactors. Early neurobehavioral impairment in HIV infection seems limited to subclinical motor deficits and attributable to HIV rather than possible confounding factors.

Severe life stress as a predictor of early disease progression in HIV infection.

OBJECTIVE: Although there is evidence that stress is associated with alterations in immunity, the role of emotional factors in the onset and course of immune-based diseases such as cancer and AIDS has not been established. This prospective study was designed to test the hypothesis that stressful life events accelerate the course of HIV disease. METHOD: Ninety-three HIV-positive homosexual men who were without clinical symptoms at the time of entry into the study were studied for up to 42 months. Subjects received comprehensive medical, neurological, neuropsychological, and psychiatric assessments every 6 months, including assessment of stressful life events during the preceding 6-month interval. Several statistical approaches were used to assess the relation between stress and disease progression. RESULTS: The time of the first disease progression was analyzed with a proportional hazard survival method, which demonstrated that the more severe the life stress experienced, the greater the risk of early HIV disease progression. Specifically, for every one severe stress per 6-month study interval, the risk of early disease progression was doubled. Among a subset of 66 subjects who had been in the study for at least 24 months, logistic regression analyses showed that higher severe life stress increased the odds of developing HIV disease progression nearly fourfold. the degree of disease progression was also predicted by severe life stress when a proportional odds logistic regression model was used for analysis. CONCLUSIONS: This report presents the first evidence from a prospective research study that severe life event stress is associated with an increased rate of early HIV disease progression.

Congenital monomelic hypertrophy with progressive myopathy.

We describe a patient with congenital monomelic hypertrophy who later developed progressive footdrop due to a degenerative myopathy. The clinical, electrophysiologic, and pathologic features of the case are described and compared with those of a previously reported case.

Event-related potentials in human immunodeficiency virus infection. A prospective study.

P3 event-related evoked potentials (ERP) were recorded from 47 human immunodeficiency virus (HIV)-positive subjects examined twice and 29 HIV-positive subjects examined three times at 6-month intervals. The P3 latency significantly increased over time for asymptomatic subjects and subjects with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. N2 latency was prolonged relative to control values in both HIV-positive groups but did not increase with time. The P3 latency correlated with neuropsychologic measures of motor control and speed of mental processing. Confounding factors (active or previous substance abuse, developmental disabilities, and history of closed head injury or epilepsy) did not significantly affect ERP latencies. Endogenous ERP components are frequently abnormal in HIV-positive subjects and the P3 latency progressively increases over time. Continued follow-up is required to determine the clinical utility of ERP studies in the HIV-positive population.

Peripheral neuropathy in a cohort of human immunodeficiency virus-infected patients. Incidence and relationship to other nervous system dysfunction.

A cohort of 94 patients infected with human immunodeficiency virus was evaluated clinically and electrophysiologically for the presence of peripheral neuropathy, and the results were compared with evaluations of central nervous system function. Thirty-two (34%) had some degree of peripheral neuropathy; 18 (19%) (six [12%] of the 49 asymptomatic patients, five [45%] of the 11 patients with acquired immunodeficiency syndrome [AIDS], and seven [21%] of the 34 patients with AIDS-related complex) had neuropathy on clinical examination; and 21 (23%) (eight [16%] asymptomatic, four [36%] AIDS, and nine [26%] AIDS-related complex) had neuropathy on electrophysiologic evaluation. There was a significant correlation between the presence of neuropathy and evidence of central nervous system dysfunction.

Vitamin B12 deficiency and nervous system disease in HIV infection.

BACKGROUND: Vitamin B12 deficiency may result in a number of neurological and neuropsychiatric disorders. Patients with human immunodeficiency virus type 1 (HIV-1) infection may have a high rate of vitamin B12 deficiency and nervous system disease. Vitamin B12 deficiency may contribute to neurological disease in HIV-1-infected individuals. OBJECTIVE: To evaluate the possible contribution of vitamin B12 deficiency to neurological disease in HIV-1-infected individuals. MAIN OUTCOME MEASURES: Comparison of serum vitamin B12 levels with neurological, neuropsychological, and mood state abnormalities in 153 HIV-1-positive subjects and 57 high-risk seronegative controls. A subgroup of 67 subjects underwent additional extensive clinical neurophysiological, cerebrospinal fluid, and magnetic resonance imaging evaluations. RESULTS: No statistically significant relationships were noted between vitamin B12 levels and abnormalities on any of the measures examined. CONCLUSIONS: This study does not indicate an important role for vitamin B12 deficiency in the neurological disease of HIV-1 infection.

The importance of confounding factors in the evaluation of neuropsychological changes in patients infected with human immunodeficiency virus.

There are conflicting reports on the early effects of human immunodeficiency virus (HIV) infection on the nervous system. Some studies have suggested that there may be early cognitive impairment, while others have refuted this. We describe the results of extensive neuropsychological testing in a group of 40 infected subjects. These indicate that the degree of impairment is closely related to confounding factors other than the infection itself. Our conclusion is that the early stages of HIV disease are not associated with a high frequency of cognitive impairment if these confounding variables are taken into consideration.

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

Age-related changes in rate and magnitude of ankle torque development: implications for balance control.

BACKGROUND: One of the key components of postural control is the motor system's ability to produce appropriate torques to counteract perturbations that may lead to a loss of balance. Evidence exists to show that there is an age-related decline in absolute strength and in the ability to rapidly produce torque. The relationship between age-related decreases in these voluntary torque production capabilities and the ability to rapidly produce torques in a reactive balance task has not been studied. Thus, the purpose of this study was to examine the magnitude and rate of torque production in younger and older adults under reactive balance conditions. METHODS: Older (OA) and younger (YA) adults received forward and backward support surface translations of varying amplitudes and velocities. Maximum ankle muscle torque (maxMa) and rate of change of ankle muscle torque (Ma) following a perturbation were calculated. RESULTS: Two balance responses emerged: a no-step and a step response. With increasing perturbation difficulty, YA and OA used different responses. The no-step and step responses were examined for age-group differences in the force characteristics. No significant age-group differences were found for maxMa or rate of change of Ma within either no-step or step responses. CONCLUSION: The results of this study suggest that neither the magnitude nor rate of ankle muscle torque production, as produced during the initial balance response in this set of reactive balance control tasks, determines the different balance responses seen in younger versus older adults.

Progressive multifocal leukoencephalopathy in AIDS: are there any MR findings useful to patient management and predictive of patient survival? AIDS Clinical Trials Group, 243 Team.

BACKGROUND AND PURPOSE: While MR findings in progressive multifocal leukoencephalopathy (PML) have been described previously, usually in retrospective studies with limited sample size, what has not been well addressed is whether any are predictive of longer survival. Our participation in a large prospective clinical trial of AIDS patients with biopsy-proved PML and MR correlation allowed us to test our hypothesis that certain MR features could be found favorable to patient survival. METHODS: The patient cohort derived from a randomized multicenter clinical trial of cytosine arabinoside for PML. Pretreatment T1- and T2-weighted noncontrast images (n = 48) and T1-weighted contrast-enhanced images (n = 45) of 48 HIV-positive patients with a PML tissue diagnosis as well as the follow-up images in 15 patients were reviewed to determine signal abnormalities, lesion location and size, and the presence or absence of mass effect, contrast enhancement, and atrophy, and to ascertain the frequency of these findings. A statistical analysis was performed to determine if any MR abnormalities, either at baseline or at follow-up, were predictive of patient survival. RESULTS: No MR abnormalities either on univariate or multivariate analysis significantly correlated with patient survival, with the exception of mass effect, which was significantly associated with shorter survival. The mass effect, however, always minimal, was infrequent (five of 48). More severe degrees of cortical atrophy and ventricular dilatation, lesion location and size, and other MR variables were not predictive of outcome. CONCLUSION: Except for mass effect, we found no MR findings predictive of the risk of death in patients with PML. The mass effect, however, was so infrequent and minimal that it was not a useful MR prognostic sign.

Clinical and pathological features of an autosomal recessive neuropathy.

Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN.

Sciatic entrapment neuropathy. Case report.

A case of sciatic entrapment neuropathy is discussed. When evaluating patients with unilateral leg pain and paresthesias, one should consider the possibility of entrapment of peripheral nerve. Electrodiagnostic studies are helpful in establishing the diagnosis.

The Burch procedure: a comprehensive review.

The purpose of this review is to provide the obstetrician/gynecologist with a comprehensive review of the open Burch procedure including operative technique and modifications, complications, and success rates. A computerized search of English-language articles was performed on the MEDLINE database. Additional sources were identified through cross-referencing. All identified articles were reviewed with particular attention to operative technique, complication, and success rates. Each reference was reviewed; operative technique and modifications are cited, and all complications are reported here. Overall success rates by length of follow-up are tabulated. Several comparative studies are cited. The Burch procedure via laparotomy has undergone minimal modification since its initial description in 1961. Complications including voiding dysfunction, detrusor instability, and urinary tract infection occur in up to 41 percent of patients, but more serious sequelae such as urinary tract injury, hemorrhage, or venous thromboembolism are rare. Long-term success rates of the Burch procedure range from 61 to 100 percent, which are as good or better than any other incontinence procedure.

Cerebrospinal fluid analysis in human immunodeficiency virus infection.

Cerebrospinal fluid (CSF) analytes were evaluated in 59 human immunodeficiency virus (HIV+) individuals to assess neurological involvement. Glucose, total protein, cell counts, p24 antigen, CSF: serum albumin/IgG ratios, and oligoclonal bands were measured. Eighty percent of samples showed abnormalities in one or more analyte. In some patients samples, these abnormalities could mimic those of secondary opportunistic infection when none was present. The presence of oligoclonal banding in CSF (31 percent) and disturbances in CSF: serum albumin/IgG ratio (30 percent) were related to decreases in serum CD4+ lymphocytes. Disturbances in CSF: Serum albumin/IgG ratio were also related to severity of non-neurological HIV disease staging. Cerebrospinal fluid oligoclonal bands were distinct from that found in serum in the same subjects. Since immune complexes between immunoglobulins and enzymes are observed in these same patients, these oligoclonal bands may result in artifactually elevated enzyme results secondary to decreased clearance leading to erroneous clinical decisions. There was no significant relationship between any abnormalities and the presence of neurologic disease as established by a wide variety of other studies. It is important to recognize the limits of CSF interpretation in this patient group.

Transoral-transclival clipping of a giant lower basilar artery aneurysm.

The authors discuss the choice of the transoral-transclival approach for the repair of a lower basilar artery aneurysm in a 32-year-old sickle-cell patient. Efficiency of approach and minimization of damage to vital structures support the use of this technique. The risks of cerebrospinal fluid fistula and meningitis are considered. One year after operation, the patient is neurologically intact.

Porous hydroxyapatite as an onlay bone-graft substitute for maxillofacial surgery.

This paper chronicles 3 years of a continuing study comparing porous hydroxyapatite to autogenous bone grafts as onlays in maxillofacial surgery. Twenty-five patients, seen from June of 1984 to May of 1985, underwent onlay augmentation on various maxillary and mandibular locations. A total of 68 onlay augmentation sites comparing Interpore porous hydroxyapatite and autogenous bone were followed for 2 years or more. This long-term study compares these substances in radiologic longevity, histologic incorporation, clinical function, and aesthetic appearance.