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Biomedical subjects

J B Reed

Publications and source records attributed to J B Reed.

At least 19 recordsLinked to original sources
PubMed2001

Highly active antiretroviral therapy-associated regression of cytomegalovirus retinitis: long-Term results in a small case series.

PURPOSE: To report the stability of acquired immunodeficiency syndrome (AIDS)-associated cytomegalovirus (CMV) retinitis lesions that have undergone regression in the absence of specific anti-CMV medications owing to highly active antiretroviral therapy (HAART)-generated immune recovery. METHODS: The initial examination revealed HAART-associated regression of CMV retinitis lesions in eight subjects at two institutions. Patients were monitored for recurrences of CMV activity. CD4+ T-lymphocyte counts and human immunodeficiency virus (HIV) loads were measured. RESULTS: All patients had positive initial responses to HAART with an average HIV load decrease of 2.26 log units (range 0.3-5.57). Mean CD4+ T-lymphocyte count at baseline was 45.6 (range 4-107) and increased by an average of 132.5 (range 7-266) within the first 2 to 4 months of HAART. Patients were observed for an average of 15.5 months (range 11-20 months). Six subjects had a vigorous and sustained response to therapy, achieving an average HIV load of 9,400 copies/mL (3.32 log10 decrease) and CD4+ T-lymphocyte count of 158.2 cells/microL. These patients had no CMV retinitis progression. By contrast, two others who attained an average log10 decrease of only 0.48 had modest and short-lived increases in the CD4+ T-lymphocyte count. These patients experienced reactivation of CMV retinitis after 5 and 7 months, respectively. CONCLUSIONS: Regressed CMV retinitis may remain healed for long periods. However, failure of HAART to induce substantial decreases in HIV load may predict poor or unsustainable rises in the CD4+ T-lymphocyte count and presage recurrence of CMV retinitis. Vigilance in ophthalmic examinations is especially mandatory in these subjects.

AIDS-Related Opportunistic Infections↗
PubMed2000

Highly active antiretroviral therapy-related immune recovery in AIDS patients with cytomegalovirus retinitis.

OBJECTIVE: To characterize cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients who demonstrate immune recovery while receiving highly active antiretroviral therapy (HAART). DESIGN: Consecutive, noncomparative case series. PARTICIPANTS: Twenty-two HIV-positive patients, from two institutions, with a history of CMV retinitis, and with elevated CD4 cell counts after HAART. MAIN OUTCOME MEASURES: Duration of healed CMV retinitis without anti-CMV therapy, CD4 cell count, and HIV viral load. INTERVENTION: Discontinuation of anti-CMV therapy after persistent elevation of CD4 cell count over 50 cell/mm3 (median, 161/mm3; range, 85-408/mm3). RESULTS: The median period of healed CMV retinitis without anti-CMV therapy was 72 weeks (range, 33-116 weeks). Nineteen of 22 patients were still healed without anti-CMV therapy at study end. The three patients with CMV retinitis progression simultaneously had HAART, fail with CD4 cell counts of 37, 35, and 47/mm3. CONCLUSIONS: HIV-positive patients with CMV retinitis, who demonstrate a sustained HAART-induced elevation of CD4 cell count on two consecutive counts 3 months apart and whose retinitis remains healed on anti-CMV therapy for greater than 4 months, are likely to remain healed if the anti-CMV therapy is withdrawn. It is important to monitor these patients with indirect ophthalmoscopy because HAART failure may occur and allow CMV retinitis reactivation.

AIDS-Related Opportunistic Infections↗
PubMed2000

Effect of highly active antiretroviral therapy on the incidence of HIV-related cytomegalovirus retinitis and retinal detachment.

Cytomegalovirus retinitis (CMVR) is the most common intraocular infection encountered in ophthalmic practices. To assess the impact of highly active antiretroviral therapy (HAART) on the incidence of CMVR and subsequent retinal detachments, a retrospective review of the HIV+ patients seen at a single university and community-based practice between 1992-1993 (group 1), before the advent of protease inhibitors, was compared with the data obtained from October 1996 to October 1997 (group 2) and October 1997-1998 (group 3), after the widespread use of HAART. The incidence of CMVR and retinal detachment rates for each group was calculated and compared. Twenty five (2.6%) of 974 HIV+ patients in group 1 developed CMVR. Of these, four patients developed retinal detachment (16%). Group 2 had a total of 1084 HIV+ patients, 18 (1.7%) of whom developed CMVR, which indicates a 35% decline of the incidence of CMV retinitis at our institution (p = 0.052, Odds ratio = 0.533, Confidence interval 0.28-1.01) and three patients (20%) developed retinal detachment. Only 1 patient (0.07%) of 1274 patients in group 3 developed CMVR, which represents a 99% reduction since 1993 (p = 0.0000000456). We conclude that the incidence of CMVR at this institution has decreased significantly with the recent use of HAART therapy. This effect may be related to the aggressive use of HAART and associated immune recovery in this population of AIDS patients. In this small series, however, the rate of retinal detachment appeared unchanged, but was only observed in those individuals who were not on HAART or who had just recently started.

AIDS-Related Opportunistic Infections↗
PubMed2000

Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients.

INTRODUCTION: Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity. AIM: To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families. METHODS: Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene. RESULTS: The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region. CONCLUSION: Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.

Cathepsin C↗
PubMed1999

Bartonella henselae infection associated with peripapillary angioma, branch retinal artery occlusion, and severe vision loss.

PURPOSE: To report atypical clinical features of Bartonella henselae neuroretinitis treated with combination antibiotics. METHOD: Case report. RESULTS: A 20-year-old man with a positive B. henselae titer developed a unilateral neuroretinitis, a large peripapillary angiomatous lesion, branch artery occlusion with ischemic maculopathy, and vision loss that failed to improve with clindamycin. Treatment with doxycycline and rifampin led to rapid clinical improvement. The severe vision loss in this case is atypical. CONCLUSIONS: Ocular findings associated with B. henselae infection may include retinal angiomatous lesion and branch retinal artery occlusion. Doxycycline and rifampin were successful in treating the infection.

Adult↗
PubMed1998

High-dose intravenous pulse methylprednisolone hemisuccinate in acute Behçet retinitis.

PURPOSE: To report the response of acute Behçet retinitis to high-dose corticosteroids. METHOD: Case report. A 58-year-old man with Behçet disease and severe bilateral glaucoma experienced a sudden decrease of visual acuity to counting fingers in his (better-seeing) left eye. Examination disclosed hypopyon uveitis and an infiltrative retinitis threatening the fovea. He received intravenous methylprednisolone hemisuccinate, 1 gram per hour on each of 3 successive days, followed by oral prednisone and cyclosporine. RESULTS: The retinal infiltrate disappeared within 24 hours. Visual acuity improved to LE, 20/400 by day 5 and returned to LE, 20/30 after 3 months. A visual field demonstrated a scotoma corresponding to the location of the previous retinitis. CONCLUSION: High-dose intravenous methylprednisolone can reverse severe vision loss in acute Behçet retinitis.

Acute Disease↗
PubMed1998

Bartonella henselae neuroretinitis in cat scratch disease. Diagnosis, management, and sequelae.

OBJECTIVE: This study aimed to report the long-term outcomes of patients treated with an antibiotic drug combination for Bartonella henselae neuroretinitis. DESIGN: The study design was a retrospective case series. PARTICIPANTS: Seven consecutive patients with neuroretinitis and cat scratch disease participated. INTERVENTIONS: Patients underwent medical and ophthalmic evaluations. Blood cultures were obtained, and B. henselae antibody titers were measured. Tuberculosis, Lyme, toxoplasmosis, syphilis, and sarcoidosis were excluded. Patients received oral doxycycline 100 mg and rifampin 300 mg twice daily for 4 to 6 weeks and were observed for an average of 16 months (range, 10-24 months). Formal electrophysiologic testing was performed in three patients after resolution of neuroretinitis. MAIN OUTCOME MEASURES: The changes in ocular inflammation and visual function associated with treatment were recorded. Follow-up examinations and electrophysiologic testing documented sequelae. RESULTS: Patients presented following cat exposure with fever, malaise, and blurred vision. Decreased visual acuity (ranging from 20/40 to counting fingers) frequently was associated with dyschromatopsia and afferent pupillary defects. Ophthalmoscopic analysis showed signs of neuroretinitis, including nerve fiber layer hemorrhages, cotton-wool spots, multiple discrete lesions in the deep retina, and stellate macular exudates. B. henselae infection was confirmed with positive blood cultures or elevated immunofluorescent antibody titers or both. Therapy appeared to promote resolution of neuroretinitis, restoration of visual acuity, and clearance of bacteremia. After 1 to 2 years, two eyes had residual disc pallor, afferent pupillary defects, retinal pigmentary changes, and mildly decreased visual acuity. Electrophysiologic studies showed that when compared to the fellow eye, affected eyes had subnormal contrast sensitivity, abnormal color vision, and abnormal visually evoked potentials. Conversely, electroretinograms were normal in all subjects. CONCLUSIONS: B. henselae is a cause of neuroretinitis in cat scratch disease. Compared to historic cases, doxycycline and rifampin appeared to shorten the course of disease and hasten visual recovery. Long-term prognosis is good, but some individuals may acquire a mild postinfectious optic neuropathy.

Adult↗
PubMed1998

Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy.

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).

AIDS-Related Opportunistic Infections↗
PubMed1998

CMV retinitis and the controversies associated with highly active antiretroviral therapy and the immune recovery hypothesis.

The aggressive multidrug regimen of highly active antiretroviral therapy (HAART) has offered some degree of promise of immune reconstitution in AIDS patients, a phenomenon that theoretically would impact positively on the incidence and severity of opportunistic infections. Some studies already have noted complete regression of cytomegalovirus (CMV) retinitis without specific use of anti-CMV agents in patients undergoing HAART. However, the role of HAART in CMV retinitis remains controversial among investigators. This review of the salient details regarding the controversies associated with CMV retinitis and the immune recovery hypothesis is meant to shed light on current and future therapeutic issues concerns. Early data seem to predict a decline in CMV retinitis. However, some investigators have noted that increased CD4 T-lymphocyte counts may not protect against CMV retinitis; therefore, the diagnosis cannot be excluded based on count alone. There is also the question of whether CMV retinitis progression in any way represents failure of HAART in those patients receiving this type of combination therapy. HAART is seen as an encouraging development in the treatment of AIDS and opportunistic infection, but its more specific therapeutic effect on CMV retinitis requires further research with controlled prospective clinical trials.

AIDS-Related Opportunistic Infections↗
PubMed1998

Vitreomacular traction syndrome following highly active antiretroviral therapy in AIDS patients with cytomegalovirus retinitis.

PURPOSE: To report the development of vitreomacular traction syndrome (VMT) following highly active antiretroviral therapy (HAART) in AIDS patients with cytomegalovirus retinitis (CMV-R). METHODS: We identified two AIDS patients with evidence of CMV-R who later developed VMT following HAART-associated immune recovery vitritis. RESULTS: The CD4+ T-lymphocyte count increased from 5 to 190 cells/microL in Patient 1 and from 26 to 713 cells/microL in Patient 2. HIV-RNA copies/mL decreased from 341,000 to less than 400 in Patient 1 and from 43,900 to less than 400 in Patient 2. Increased vitreous inflammation occurred during this period of immune recovery. After resolution of vitritis, VMT developed in both patients and was confirmed by B-scan ultrasound and fluorescein angiography. In both patients, CMV-R was clinically inactive at the time of VMT development. Both patients underwent pars plana vitrectomy with peeling of the posterior hyaloid, which confirmed VMT intraoperatively. CONCLUSIONS: VMT appears to be a sequelae of HAART-associated immune recovery vitritis in AIDS-related CMV-R. Changes in immune status may permit an inflammatory response that can lead to VMT. As advances in pharmacologic intervention continue, clinical manifestations and ocular sequelae in CMV-R will change, as will the approach and management of this disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

Regression of cytomegalovirus retinitis associated with protease-inhibitor treatment in patients with AIDS.

PURPOSE: To report the observation that anti-retroviral therapy that includes a protease inhibitor can induce the regression of cytomegalovirus retinitis without requiring specific anticytomegalovirus drug therapy. METHODS: We examined the fundi of four patients with advanced acquired immunodeficiency syndrome (AIDS) who were placed on highly active antiretroviral therapy consisting of two nucleoside analogs and a protease inhibitor. The combined medications resulted in increased CD4+ T-lymphocyte counts and decreased load of human immunodeficiency virus (HIV-1). A prospective evaluation of the effect of these medications on an active cytomegalovirus retinitis lesion was conducted in one patient. Retinal lesions were documented with fundus photography. RESULTS: None of these patients received specific anticytomegalovirus medications. The average baseline CD4+ T-lymphocyte count was 33 cells per microliter (range, 4 to 88 cells per microliter) and increased an average of 118.5 cells per microliter (range, 66 to 185 cells per microliter). Average baseline plasma HIV-1 viral loads (HIV-1-RNA copies per ml) decreased 1.46 log units (range, 0.65 to 2.93 log units). In one patient, posterior progression (border advancement toward the posterior pole) of a cytomegalovirus retinitis lesion decelerated over time and stopped. Three other patients on initial examination had areas of retinal scarring consistent with healed cytomegalovirus retinitis. CONCLUSIONS: The addition of an HIV-1 protease inhibitor in the treatment of AIDS may lead to complete regression of cytomegalovirus retinitis without specific anticytomegalovirus medications. This effect may be related to reduced HIV-1 loads, a possible direct drug effect, an increase in CD4+ T-lymphocyte counts, or other associated changes in immune status.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Default in the outpatient treatment of tuberculosis in two hospitals in Northern India.

STUDY OBJECTIVE: The purpose of the study was to examine default rates in tuberculosis treatment in two hospitals in north India with different follow up arrangements. DESIGN: The study was a retrospective cohort study. SETTING: Two hospitals were involved. One was the District Tuberculosis Centre for the Kulu Valley area of Himachal Pradesh. The other was a private mission hospital serving the same area. PATIENTS: The study involved 321 patients at the tuberculosis centre and 381 at the mission hospital, being all those newly diagnosed with tuberculosis from October 1982 to September 1983; follow-up to October 1984. Patients at the mission hospital were more affluent and had travelled much further to seek treatment; only one reminder was sent to defaulters from treatment. The government hospital had a more active response if the patients missed an appointment, with a home visit by a health worker. RESULTS: Rates of permanent default were similar in each hospital and were very high: approximately 40% at 6 months, 60% at 12 months, and 65% at 18 months of treatment. CONCLUSIONS: Default was a major problem irrespective of the follow up procedures employed. Recommendations are made concerning treatment and follow up, including better communication about the disease and its treatment, active follow up of defaulters, and review of treatment policies.

Adolescent↗
PubMed1989

Electrical pacemakers of canine proximal colon are functionally innervated by inhibitory motor neurons.

Pacemaker activity in the canine proximal colon occurs at the submucosal and myenteric borders of the circular layer [Am. J. Physiol. 252 (Cell Physiol. 21): C215-C224 and C290-C299, 1987]. The present study investigated the neural regulation of rhythmic electrical activity. Spontaneous inhibitory junction potentials (IJPs) were observed in intracellular recordings from circular muscle cells near the myenteric border. The amplitudes of these events decayed with distance through the circular layer. Stimulation at the myenteric plexus surface evoked IJPs that mimicked the spontaneous events. Stimulation at the submucosal surface evoked IJPs in adjacent cells that were of shorter duration and of different waveform than myenteric IJPs. Amplitudes of IJPs evoked by stimulation near either surface decayed with distance from the site of stimulation. The decay functions for IJPs were essentially identical to the decay of spontaneous slow waves or myenteric potential oscillations. Spontaneous and evoked IJPs affected the amplitudes, durations, and patterns of ongoing rhythmic electrical activity. The data suggest that myenteric and submucosal pacemaker populations may be innervated by different populations of inhibitory nerve fibers. Innervation appears to be heterogeneous with dense populations of inhibitory nerve fibers predominantly located in the pacemaker regions. Neural regulations of pacemaker activity influences rhythmic electrical activity throughout the muscularis.

Animals↗
PubMed1989

Gradient in the effects of ethyl alcohol on canine gastric antral circular muscles.

The effects of ethyl alcohol on the electrical and mechanical activities of canine gastric antral circular muscle were studied. Recently it has been reported that the circular layer of the antrum is not homogenous in its electrical activity. Therefore, circular muscles from the regions adjacent to the myenteric and submucosal borders of the circular layer were studied separately to compare the actions of ethyl alcohol through the thickness of the circular layer. In the first series of experiments concentration-response data were collected to describe the effects of ethyl alcohol on the contractile activities of myenteric and submucosal muscles. The data show that ethyl alcohol is more effective as an inhibitor of myenteric contractions than submucosal contractions. Next, experiments were performed to determine the electrical mechanism responsible for the contractile effects. Circular cells of submucosal and myenteric regions were impaled, and the muscles were exposed to several concentrations of ethyl alcohol ranging from 0.1 to 1.5%. Slow wave activity was reduced in frequency and amplitude in both regions. The inhibitory effect of ethyl alcohol on electrical activity was greater in submucosal muscles, but mechanical activity was less affected in these muscles because excitation-contraction coupling occurs at more polarized levels in the submucosal portion of the circular layer.

Acetylcholine↗
PubMed1988

Role of sodium pump in membrane potential gradient of canine proximal colon.

A large gradient in membrane potential exists through the thickness of the circular layer in canine colonic muscles. This study tested the effects of several experimental manipulations known to block electrogenic sodium pumping on the resting potentials of colonic muscles. Membrane potentials were recorded with microelectrodes from cells through the circular muscle layer. In cells adjacent to the submucosal surface of the circular layer, application of ouabain (10(-6) to 10(-5) M) caused an average membrane depolarization of 36 mV. Removal of the external K+ resulted in depolarizations similar to the effect of ouabain. Readmission of K+ (5.9 mM) produced repolarization and an additional hyperpolarization that averaged 13 mV beyond the resting potential. When exposed to 15 mM K+, cells hyperpolarized well beyond the estimated potassium equilibrium potential (EK). Ouabain blocked the repolarization in response to reintroduction of external K+. Lowering the bath temperature to 20 degrees C rapidly depolarized membrane potential; rewarming repolarized cells. Ouabain and K+-free solutions blocked the repolarization response to rewarming. Cells also depolarized when exposed to solutions in which the NaCl was replaced with LiCl. Membrane potentials of cells within the bulk of the circular layer decreased as a function of distance from the submucosal border. Cells at the myenteric border of the circular muscle were not significantly affected by ouabain and K+-free solution, but these treatments abolished the gradient in membrane potential across the circular layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗