The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity

PURPOSE: To determine whether the uniform field and pattern ERGs that are reduced in macaque eyes with experimental glaucoma have the same inner-retinal origins. METHODS: ERGs were recorded from 14 anesthetized adult macaques using DTL electrodes. Six monkeys had laser-induced experimental glaucoma, and two others received intravitreal injections of tetrodotoxin (TTX, 6 microM) to block spiking activity of inner-retinal neurons. The remaining 6 animals were normal. Uniform fields and grating patterns (0.1-3 cpd) were square-wave modulated at 1.7 Hz (transient) and 8 Hz (steady state). The test field (42 degrees x 32 degrees) had a mean luminance of 44 cd/m2 and a contrast of 10% to 82%. RESULTS: In normal eyes transient ERGs to uniform fields contained photopic negative responses (PhNR) after the b-wave and after the d-wave. Transient pattern electroretinograms (PERGs) at each contrast reversal showed positive (P50) potentials followed by negative (N95) potentials of time course similar to that of the PhNR. The PhNR and N95 were greatly reduced or eliminated by experimental glaucoma and by TTX. Summing responses to luminance increments and decrements of the uniform field could simulate the PERG to low spatial frequency stimuli. Further, the PERG responses to high spatial frequencies were similar to the simulation in shape but slightly delayed in time. Experimental glaucoma and TTX had similar effects on the N95 of the simulated PERG as to those on the actual PERG. However, P50 was more reduced by experimental glaucoma than by TTX, indicating a nonspiking contribution to P50. For the steady state condition, the uniform field ERG, the simulated PERG, and the actual PERG all were affected by experimental glaucoma and TTX, indicating that they contained contributions from the spiking activity of ganglion cells. CONCLUSIONS: The changes in the uniform field and PERG responses produced by experimental glaucoma are related and are largely a consequence of reduced spiking activity of ganglion cells and their axons. These findings raise the possibility that the uniform field ERG could serve as a useful alternative to the PERG in the assessment of clinical glaucomatous neuropathy.     

Mycobacterial infections in organ transplant recipients

Tuberculosis has a major adverse impact on solid organ transplant recipients; this article attempts to define this fact. The prevalence of posttransplant tuberculosis is increasing globally and currently is 13.7% at our center. The transplant surgery divides the continuum of pretransplant tuberculosis and posttransplant tuberculosis; immunosuppression accounts for a greater severity of the latter. Cyclosporin and tacrolimus are associated with an earlier onset of tuberculosis when compared with prednisolone and azathioprine immunosuppression. Disseminated disease is more common in nonrenal transplants. The risk for developing posttransplant tuberculosis in renal transplant recipients increased 2.25 times independently with cytomegalovirus (CMV) and twice with chronic liver disease; OKT3 treatment enhances the risk 1.8-fold. Tuberculosis occurring after 2 years of transplantation, diabetes mellitus, posttransplant diabetes mellitus, chronic liver disease, CMV, and deep mycoses each independently confer a risk, 1.5-times or higher, for death. Disseminated disease entails a 2-fold risk. Treatment with or without rifampicin is possible; the former is associated with a higher risk for allograft rejection. Isoniazid prophylaxis is recommended for high-risk patients with apparent clinical efficacy. However, in endemic areas, attendant liver disease makes it a difficult goal.     

Nocardiosis in tropical renal transplant recipients

BACKGROUND: The epidemiology of nocardiosis in the tropics among renal transplant recipients has not been reported. METHODS: An evaluation of nocardiosis for 30 yr in one of the large transplant centres in South Asian region. RESULTS: Of the 1968 patients who received primary renal allografts at Christian Medical College & Hospital, 27 patients developed nocardiosis over 30 yr. Early nocardiosis (2 yr). Seventeen patients (63%) had two or more associated post-transplant infections, of whom 10 had tuberculosis. Mortality in these patients was associated with chronic liver disease. CONCLUSIONS: Nocardiosis manifests earlier (<2 yr) in CsA treated patients who have chronic liver disease. Among renal transplant recipients of the tropics nocardiosis is a marker of a high susceptibility to tuberculosis and other infections, the association with tuberculosis is stronger in those developing early nocardiosis (<2 yr). Chronic liver disease is a risk factor for death in patients with nocardiosis especially when associated with tuberculosis. This report constitutes the largest single centre experience among renal transplant recipients.     

Indigoferabietone,a novel abietane diterpenoid from Indigofera longeracemosa with potential antituberculous and antibacterial activity

From the stems of Indigofera longeracemosa, a novel abietane diterpenoid, indigoferabietone was isolated. The structure was established by spectral techniques. The inhibitory activity of indigoferabietone (1) tested against Mycobacterium tuberculosis and Candida albicans, and the antibacterial activity tested against Staphylococcus aureus, Proteus vulgaris, and Escherichia coli were found to be significant.     

Multifocal pattern electroretinogram: cellular origins and clinical implications.

PURPOSES: The purposes of this article are to gain insight into the cellular origins of the multifocal pattern electroretinogram (mPERG) and evaluate its potential for clinical use. METHODS: mPERGs were recorded from four anesthetized monkeys before and after pharmacologic blockade of light-driven activity of inner-retinal neurons and from 55 normal human subjects (19-91 years) and six patients with glaucoma (43-77 years of age). Stimuli consisted of counterphase-modulated black and white triangles organized in 61-scaled hexagons with mean luminance 100 cd/m2 and 100% contrast. The stimulus array subtended 31 degrees vertically and 37 degrees horizontally at 48 cm. The amplifier cutoff frequencies were 3 and 100 Hz. Responses were grouped as quadrants and the first slice of the second-order kernel was analyzed. RESULTS: The mPERG responses of monkeys and humans were similar. In the monkey responses, there was an early positive potential (P1) around 25 ms and a later positive potential (P2) found selectively in the nasal field quadrants around 31 ms. These responses were seen around 22 and 36 ms in the human responses. After blockade of inner-retinal activity in monkeys, P1 amplitude was greatly reduced at all retinal locations and P2 was eliminated. P1 and P2 amplitudes were significantly reduced in the glaucomatous eyes relative to amplitudes of age-matched controls. Reductions in the amplitudes of P1 and P2 could easily discriminate between glaucomatous visual field quadrants with and without behavioral sensitivity losses. However, these alterations are likely to reflect diffuse losses. CONCLUSIONS: mPERG responses contain prominent contributions from inner-retinal neurons that can be reduced in glaucomatous eyes. These findings raise the possibility that the mPERG could be potentially useful in the objective estimation of neural damage in glaucoma. However, further refinement of recording techniques will be required if the mPERG is to be used to detect focal damage.     

Unintentional injuries in the home in the United States Part I: mortality

BACKGROUND: Unintentional injuries are a leading cause of death in the United States. It is unclear, however, what proportion of these injuries occur in the home. The purpose of this paper is to quantify and describe fatal unintentional injuries that take place in the home environment. METHODS: Data from the National Vital Statistics System (NVSS) were used to calculate average annual rates for unintentional home injury deaths, with 95% confidence intervals from 1992 to 1999 for the United States overall, and by mechanism of injury, gender, and age group. RESULTS: From 1992 to 1999, an average of 18,048 unintentional home injury deaths occurred annually in the United States (6.83 deaths per 100,000). Home injury deaths varied by age and gender, with males having higher rates of home injury death than females (8.78 vs 4.97 per 100,000), and older adults (>/=70 years) having higher rates than all other age groups. Falls (2.25 per 100,000), poisoning (1.83 per 100,000), and fire/burn injuries (1.29 per 100,000) were the leading causes of home injury death. Rates of fall death were highest for older adults, poisoning deaths were highest among middle-aged adults, and fire/burn death rates were highest among children. Inhalation/suffocation and drowning deaths were important injury issues for young children. CONCLUSIONS: Unintentional injury in the home is a significant problem. Specific home injury issues include falls among older adults, poisonings among middle-aged adults, fire/burn injuries among older adults and children, and inhalation/suffocation and drowning among young children. In addition, recommendations are presented for improvements to the NVSS.