Analysis of the immunologic heterogeneity of HIV-1: I. "Arginine-glutamine trigger" in the fourth position of the central tetrapeptide of the V3 loop of gp120

This article reviews the existing knowledge base concerning the biology of spinal fusion, with the understanding that the focus is weighted toward posterolateral lumbar spinal fusion because of a relative paucity of biologic information on healing of other types of fusions. The discussion focuses first on the basic science of spinal fusion healing from the standpoint of animal modeling. Next, the discussion centers on the multitude of local factors that can affect fusion healing. Finally, the numerous systemic factors known to affect fusion healing are discussed.     

Radial tunnel syndrome: diagnosis and management

PURPOSE: To present the first documentation of iris retraction syndrome in eyes with nonrhegmatogenous retinal detachment. PATIENTS AND METHODS: One patient with age-related macular degeneration and another with panuveitis developed exudative retinal detachment with iris retraction configuration. Ultrasound biomicroscopy was performed to investigate the anatomic relationship of structures in the anterior segment of the eye. RESULTS: Ultrasound biomicroscopy demonstrated a severe backward bowing of the peripheral iris with irido-ciliary body and irido-zonular contact as well as broad iris lens touch. The iris retraction syndrome resolved after pupil dilation and disruption of the pupillary adhesions in both cases. The retinal detachment resolved several months later, without surgery. CONCLUSION: Iris retraction syndrome appears not to be exclusive to rhegmatogenous retinal detachment but can present in eyes with exudative - nonrhegmatogenous retinal detachment. Thus, when the configuration of the iris shows bowing in patients with retinal detachment, iris retraction syndrome should be considered and prompt pupil dilation should be carried out.     

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.     

Long-term progression in chronic manganism: ten years of follow-up

We studied the long-term clinical course of five patients with chronic manganese intoxication. The mean scores of the King's College Hospital Rating Scale for Parkinson's disease increased from 15.0 +/- 4.2 in 1987 to 28.3 +/- 6.70 in 1991 and then to 38.1 +/- 12.9 in 1995. The deterioration was most prominent in gait, rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs did not show paramagnetic high-signal intensity on T1-weighted images. The data indicate that clinical progression in patients with manganese parkinsonism continues even 10 years after cessation of exposure.     

T cell vaccination induces T cell receptor Vbeta-specific Qa-1-restricted regulatory CD8(+) T cells

Vaccination of mice with activated autoantigen-reactive CD4(+) T cells (T cell vaccination, TCV) has been shown to induce protection from the subsequent induction of a variety of experimental autoimmune diseases, including experimental allergic encephalomyelitis (EAE). Although the mechanisms involved in TCV-mediated protection are not completely known, there is some evidence that TCV induces CD8(+) regulatory T cells that are specific for pathogenic CD4(+) T cells. Previously, we demonstrated that, after superantigen administration in vivo, CD8(+) T cells emerge that preferentially lyse and regulate activated autologous CD4(+) T cells in a T cell receptor (TCR) Vbeta-specific manner. This TCR Vbeta-specific regulation is not observed in beta2-microglobulin-deficient mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar Vbeta8-specific Qa-1-restricted CD8(+) T cells are also induced by TCV with activated CD4(+) Vbeta8(+) T cells. These CD8(+) T cells specifically lyse murine or human transfectants coexpressing Qa-1 and murine TCR Vbeta8. Further, CD8(+) T cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic protein-specific CD4(+)Vbeta8(+) T cell clone specifically recognize other CD4(+) T cells and T cell tumors that express Vbeta8 and the syngeneic Qa-1(a) but not the allogeneic Qa-1(b) molecule. Thus, Vbeta-specific Qa-1-restricted CD8(+) T cells are induced by activated CD4(+) T cells. We suggest that these CD8(+) T cells may function to specifically regulate activated CD4(+) T cells during immune responses.     

Somatic hypermutation of immunoglobulin genes is independent of the Bloom''s syndrome DNA helicase

The aim of these studies was to examine the effects of imidazoles on testosterone secretion and testicular interstitial fluid (TIF) formation through measurement of serum LH, serum testosterone, TIF testosterone, and TIF volumes. Imidazole, 1-methylimidazole, 4-methylimidazole (4-MI), and ketoconazole, an oral imidazole antifungal agent, caused dose-dependent decreases in testosterone secretion and TIF formation. Imidazole, 2-methylimidazole, and 4-MI decreased LH secretion. 4-MI decreased testosterone secretion 1-6 h after injection, increased testosterone at 8-16 h, decreased LH secretion at 4 h, decreased TIF volumes at 1-8 h, and slightly increased TIF volumes at 24 h. 4-MI blocked the stimulatory effects of hCG on testosterone secretion and prevented an expected increase in LH secretion after the 4-MI-induced decrease in testosterone secretion. 4-MI also reversed the effects of three other stimulants of testosterone secretion that presumably act through three different testicular regulatory systems: N-methyl-D,L-aspartate, an excitatory amino acid; NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor; and naltrexone, an opioid antagonist. These results support the hypothesis that imidazoles inhibit testicular function and male reproductive function through inhibition of testosterone secretion, TIF formation, and LH secretion regulatory systems.     

Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats

Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 micro g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 micro g/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 micro g/h) increased plasma BNP (69 +/- 8 vs. 35 +/- 4 pg/ml, P < 0.05), lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/- 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 +/- 3 vs. 64 +/- 2, P = not significant). Infusion of ANP at 1.4 micro g/h increased plasma ANP in hypoxic rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.     

Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs

The neurotoxicity of dibucaine was compared with that of commercially available local anesthetics in studies using rabbit desheathed cervical vagus nerve preparation. Dibucaine dose-dependently suppressed the evoked action potential of myelinated A beta nerve component and nonmyelinated C nerve component. The potential of A beta nerve component was more strongly suppressed, compared with that of C nerve component. At low concentrations of 0.0001-0.001%, the suppression was reversible and recovery with C nerve component was faster and more complete. At higher concentrations, the suppression was irreversible. The minimum concentrations of irreversible blockade were 0.003% for A beta nerve component and 0.03% for C nerve component. Electron microscopically, marked damages in the myelin layer and intraaxonal structure were observed in nerves treated with 0.03% dibucaine. When the neurotoxic effect of dibucaine was compared, in terms of safety margins (minimum concentration of irreversible blockade/clinically used concentrations), with those of commercially available local anesthetics, the rank order was dibucaine, tetracaine and bupivacaine; dibucaine showing the lowest safety margin.     

Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk of ototoxicity

Patients diagnosed with nodules (NO = 40) in a large university hospital clinic and an age-stratum matched nondiseased group (ND = 200) described adverse outcomes of vocal impairment on work and work-related communications. NOs were significantly more likely than NDs to report symptoms of hoarseness (73% vs. 26%), high-note difficulty (70% vs. 20%), difficulty speaking with a lower voice (53% vs. 13%) and a tired voice (50% vs. 10%), and their greatest source of physical discomfort was associated with scratchiness (61% vs. 3%). The average number of symptoms was four in NOs and less than one in NDs. Nodule patients were most concerned about the effects their voice problem would have on their future career (78% vs. 24%) and 49% of NOS reported their voice problem had an adverse work effect in the past compared with 4% of NDs. Having a voice condition limited current job performance in 39% of the NO group but only in 2% of the ND group. The results suggest that a diagnosis of nodules plays a major role in disrupting careers and work activities and that available educational programs and additional research are needed for improving their functional ability and preventing adverse outcomes in the lives of individuals with voice disorders.