Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

Role for Raf in the entry of viruses associated with AIDS (review)

The biology of acquired immune deficiency (AIDS) is yet to be completely understood partly because it is complicated by the manifestation of various viral infections and associated pathogenesis. Virus entry into target cells is a key step in the virus replication cycle which is characterized by intricate and complex interactions between virus and host cells. Analyses of virus entry are always hampered to some extent due to the inability to mimic in vivo conditions. Emphasis has been placed on understanding what the virus does during the entry process; for example the signaling it mediates during entry, or identifying the cellular receptors with which the virus interact. Often, the role of the cellular environment that is critical for the complex process of virus uptake has taken a back stage. Interestingly, most of the viruses associated with AIDS cause tumors. In a recently concluded study, we identified a role for intracellular oncogenic (Raf) signaling in human herpesvirus-8 (HHV-8/KSHV) infection of target cells. In this review we present an update on entry of various viruses commonly associated with AIDS and yet another novel way of analyzing virus entry.     

Rod photoreceptor function predicts blood vessel abnormality in retinopathy of prematurity

PURPOSE: To test the hypothesis that early rod dysfunction predicts the blood vessel abnormalities that are the clinical hallmark of retinopathy of prematurity (ROP). METHODS: Two rat models of ROP, induced by exposure to alternating 50%/10% oxygen (50/10 model) from postnatal day (P) 0 to P14, or exposure to 75% oxygen (75 model) from P7 to P14, and controls reared in room air were studied. In a longitudinal design, electroretinographic (ERG) records and digital fundus images were obtained at P20 +/- 1, P30 +/- 1, and P60 +/- 1. Rod sensitivity was derived from the ERG a-wave. Integrated curvature for the arterioles was calculated using Retinal Image multi-Scale Analysis (RISA) software. RESULTS: In both ROP models, rod sensitivity was low at P20. Sensitivity improved by P60 in the 50/10 model, but remained low in the 75 model. Integrated curvature was high at P20 in both ROP models, decreased nearly to normal by P30 in the 50/10 model, but remained high in the 75 model, even at P60. At P20, rod sensitivity correlated with integrated vessel curvature. Furthermore, low rod sensitivity at P20 predicted abnormal retinal vasculature--that is, high integrated curvature--at P30 and P60. In contrast, vessel curvature at P20 did not predict sensitivity at P30 or P60. CONCLUSIONS: The rods may instigate the vascular abnormalities that are the clinical hallmark of ROP.     

The retinal vasculature and function of the neural retina in a rat model of retinopathy of prematurity

PURPOSE: In a rat model of retinopathy of prematurity (ROP), the retinal vasculature and function of the neural retina were studied longitudinally. Vascular and neural parameters were evaluated for significant relationships. METHODS: Retinopathy was induced by exposing newborn rats to alternating 50% and 10% oxygen until age 14 days. To evaluate the function of the neural retina, electroretinographic (ERG) responses to full-field stimuli were recorded from dark-adapted rats at ages 18 and 31 days. Sensitivity and saturated amplitude of photoreceptor and postreceptor activity were derived from ERG a- and b- waves. To evaluate the retinal vasculature, digital fundus photographs were obtained at the same ages, and the tortuosity indices of the arterioles (TIA) and venules (TIV) were calculated. ROP rats and room-air-raised control animals were compared. Vascular and response parameters were evaluated for significant relationships. RESULTS: In ROP rats, TIA was high at 18 days and decreased in every rat to nearly normal levels by 31 days. TIV was less affected by ROP or age. Deficits in all receptor and post-receptor response parameters were present in 18-day-old ROP rats. Post-receptor sensitivity recovered completely by 31 days. Deficits in other response parameters persisted. No significant correlations between vascular and ERG parameters were found in 18-day-old ROP rats. CONCLUSIONS: Noninvasive, longitudinal measures in this model of ROP showed significant abnormalities in both the retinal vasculature and function of the neural retina that were most marked at age 18 days. However, vascular and neural abnormalities did not correlate.     

Development of the electroretinographic oscillatory potentials in normal and ROP rats

PURPOSE: To study the development of the electroretinographic (ERG) oscillatory potentials (OPs) in rats and to compare normal OPs with those in a rat model of retinopathy of prematurity (ROP). METHODS: Following a longitudinal design, ERG responses to a greater than 5 log unit range of full-field stimuli were recorded in dark-adapted rats at postnatal day (P) 18, P31, P47, and P67. The ERG records were digitally filtered (60-235 Hz), and the trough-to-peak amplitudes and implicit times of OP2, OP3, OP4, and OP5 were measured. Additionally, rats with oxygen-induced retinopathy, a model of ROP, were studied at P31. RESULTS: Generally, OP amplitude increased and implicit time decreased with increasing stimulus intensity. The shape of the stimulus-response functions changed with age. The amplitudes of OP2, OP3, and OP4 were largest at P31. OP5 was largest at P47. All OPs were significantly affected in ROP rats; OP5 was least affected by ROP. CONCLUSIONS: A prolonged normal course of OP development, which featured waxing and waning of amplitudes, was observed and might have been consequent to maturation and then to final refinements of inner retinal circuitry. In ROP rats, marked attenuation of early OPs was consistent with persistent dysfunction of photoreceptors, and significant attenuation of the late OP5 was evidence of compromised function of inner retinal circuitry.     

Increased availability of angiotensin AT 1 receptors leads to sustained arterial constriction to angiotensin II in diabetes - role for Rho-kinase activation

BACKGROUND AND PURPOSE

Antagonists of angiotensin AT₁ receptors elicit beneficial vascular effects in diabetes mellitus. We hypothesized that diabetes induces sustained availability of AT₁ receptors, causing enhanced arterial constriction to angiotensin II.

EXPERIMENTAL APPROACH

To assess functional availability of AT₁ receptors, constrictions to successive applications of angiotensin II were measured in isolated skeletal muscle resistance arteries (∼150 µm) of Zucker diabetic fatty (ZDF) rats and of their controls (+/Fa), exposed acutely to high glucose concentrations (HG, 25 mM, 1 h). AT₁ receptors on cell membrane surface were measured by immunofluorescence.

KEY RESULTS

Angiotensin II-induced constrictions to first applications were greater in arteries of ZDF rats (maximum: 82 ± 3% original diameter) than in those from +/Fa rats (61 ± 5%). Constrictions to repeated angiotensin II administration were decreased in +/Fa arteries (20 ± 6%), but were maintained in ZDF arteries (67 ± 4%) and in +/Fa arteries vessels exposed to HG (65 ± 6%). In ZDF arteries and in HG-exposed +/Fa arteries, Rho-kinase activities were enhanced. The Rho-kinase inhibitor, Y27632 inhibited sustained constrictions to angiotensin II in ZDF arteries and in +/Fa arteries exposed to HG. Levels of surface AT₁ receptors on cultured vascular smooth muscle cells (VSMCs) were decreased by angiotensin II but were maintained in VSMCs exposed to HG. In VSMCs exposed to HG and treated with Y27632, angiotensin II decreased surface AT₁ receptors.

CONCLUSIONS AND IMPLICATIONS

In diabetes, elevated glucose concentrations activate Rho-kinase which inhibits internalization or facilitates recycling of AT₁ receptors, leading to increased functional availability of AT₁ receptors and sustained angiotensin II-induced arterial constriction.     

Intralesional immunotherapy with killed Mycobacterium w vaccine for the treatment of ano-genital warts: an open label pilot study

Background  Intralesional immunotherapy with skin test antigens and vaccines has been found to be effective in the management of genital and extragenital warts.
Objective  To evaluate the efficacy and safety of intralesional Mycobacterium w (M w ) vaccine monotherapy for the treatment of ano-genital warts.
Patients and methods  Ten patients clinically diagnosed to have external ano-genital warts, including three with giant ano-genital warts (Buschke Löwenstein tumour), were included in this open-label pilot study. Two patients were human immunodeficiency virus seropositive, and one was on iatrogenic immunosuppression for renal transplantation. M w vaccine (0.1 mL) was initially injected intradermally in the deltoid region on both the sides, followed 2 weeks later by intradermal intralesional injection into the genital warts. Intralesional injections were repeated weekly until either complete clearance or a maximum of 10 injections was achieved.
Results  One patient was lost to follow-up after the first intralesional injection. In 8 out of remaining 9 patients (88.9%), the genital warts cleared completely. In one patient with giant perianal wart, the lesion was reduced to less than 5% of its volume after 10 intralesional injections, which was later electrosurgically excised. The treatment was well tolerated by the majority of the patients. The adverse reactions were noted in four patients, which were reversible. No recurrence was seen after a mean follow-up of 5.1 months.
Conclusion  Intralesional immunotherapy of ano-genital warts with M w vaccine seems to be a promising new approach, which needs to be evaluated in the randomized controlled trials.