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Biomedical subjects

S Rosen

Publications and source records attributed to S Rosen.

At least 127 records · Page 7Linked to original sources
PubMed1994

The pathology of nephrotoxic injury: a reappraisal.

The class of nephrotoxins which are directly tubulotoxic in animal studies (cis-platinum, gentamicin, and cephaloridine) produce minimal histological changes in the human kidney. Such alterations do not correlate with the degree of organ dysfunction and fall into the broad category of what has been called 'acute tubular necrosis'. Some nephrotoxins (cyclosporine and amphotericin), acutely and chronically diminish renal perfusion, causing injury to renal parenchymal zones known to have limited oxygen a availability (medullary ray and inner stripe). In cyclosporine toxicity, the human and animal models appear equivalent. This is less clear with amphotericin where there appears to be a tubulotoxic component. Other nephrotoxic substances (contrast, nonsteroidal anti-inflammatory drugs) acutely alter renal perfusion, particularly affecting the medulla. In animal models of renal failure induced by these substances, there is an excellent correlation between medullary thick ascending limb injury and renal failure. Documentation of this phenomenon in human biopsies/autopsies is lacking, probably because of the lack of biopsy material and problems in defining medullary injury. Finally, in toxicological screening programs for nephrotoxic substances, there are groups of reactions which cannot be predicted and are thought to be mediated by immune mechanisms, i.e., immune complex glomerular disease, nil disease and interstitial nephritis.

Acute Kidney Injury↗
PubMed1994

Activation of bovine factor IX by the reaction product of bovine factor VII and human tissue factor.

A study was carried out on the alternate activation of factor IX (FIX) by bovine FVII and human tissue factor (TF) rather than by activated factor XI (FXIa). The reaction product of bovine FVII and human TF functioned as a FIX activator in the assay system used. Published studies suggest that in the presence of Ca2+ ions, the complex of human FVII-TF readily activates both human FIX and human FX, and at low TF concentrations, FIX appears to be the preferred substrate for the reaction product of FVII and TF. This may explain the discrepancy between the mild bleeding of hereditary FXI deficiency and the severe bleeding of hereditary FIX deficiency. The results obtained with bovine FVII and a crude human TF preparation confirm that at low TF concentrations, bovine FIX is the preferred substrate rather than FX. At higher TF concentrations, bovine FX was rapidly activated.

Animals↗
PubMed1993

Effects of ioversol versus iothalamate on endothelin release and radiocontrast nephropathy.

RATIONALE AND OBJECTIVES: Certain radiocontrast agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated. METHODS: Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop radiocontrast nephropathy. RESULTS: In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided. CONCLUSIONS: These results strengthen the hypothesis that endothelin release induced by radiocontrast agents is correlated with their renal toxicity and therefore, may play a role in radiocontrast nephropathy.

Animals↗
PubMed1993

Production of less chronic nephrotoxicity by cyclosporine G than cyclosporine A in a low-salt rat model.

Chronic tubulointerstitial nephropathy during long-term cyclosporine A (CsA) use has led to a search for equally effective but safer analogues. In this study we evaluated one of these analogues, cyclosporine G (CsG), in a rat model of chronic cyclosporine nephrotoxicity. CsG has immunosuppressive effects equivalent to CsA when dosed on a weight basis. Pair-fed Sprague-Dawley rats kept on a low-salt rice diet were given CsA 15 mg/kg, CsG 15 mg/kg, CsG 25 mg/kg, or vehicle subcutaneously. After 21 days, CsA animals had a lower glomerular filtration rate, measured by inulin clearance (0.16 +/- 0.04 ml/min/100 g) and higher serum creatinine (0.94 +/- 0.06 mg/dl) than CsG 15 mg/kg (GFR: 0.41 +/- 0.10 ml/min/100 g and serum creatinine: 0.68 +/- 0.09 mg/dl), CsG 25 mg/kg (GFR: 0.39 +/- 0.16 ml/min/100 g) or control rats (GFR: 0.62 +/- 0.06 ml/min/100 g; serum creatinine: 0.56 +/- 0.03 mg/dl), respectively (P < 0.05). The CsA group had considerable cortical and medullary injury (interstitial fibrosis and tubular atrophy), whereas both groups of CsG animals had more limited changes. Despite the same or larger doses of CsG on a weight basis, cyclosporine blood levels were significantly lower in CsG than CsA rats. We conclude that CsG, an analogue of cyclosporine with immunosuppressive activity equivalent to that of CsA, produced less nephrotoxicity in a model of chronic renal injury in rats, using both functional and structural parameters.

Animals↗
PubMed1993

Uncomodulated glimpsing in "checkerboard" noise.

The ability of listeners to "glimpse" acoustic cues during the quieter sections of an interrupted noise has primarily been studied using maskers with interruptions occurring simultaneously across the entire frequency range of the masker--broadband comodulated interruptions. Here, the possibility of uncomodulated glimpsing (the glimpsing of acoustic cues separated both in time and frequency) was investigated. To achieve this, speech reception thresholds for a set of intervocalic consonants were adaptively measured in 100-Hz to 10-kHz pink noise divided into a varying number of frequency bands of equal energy. In uncomodulated noise conditions, the odd and even numbered bands were switched on and off alternately at a rate of 10 Hz. The spectrograms of such noises (on log frequency scales), resemble portions of a checkerboard. Glimpsing in "checkerboard" noise was found with maskers divided into two and four bands, but not into eight bands or more. Further investigations showed that, in the two-band case, this release from masking was indeed due to uncomodulated glimpsing, and not simply attributable to glimpsing in one of the modulated bands. In the four-band case, the release from masking in checkerboard noise can be accounted for without recourse to uncomodulated glimpsing. Interestingly, conditions which allowed glimpsing resulted in greater intersubject variability. The implications of these results for quantitative analyses of masker fluctuations are discussed.

Acoustic Stimulation↗
PubMed1993

Chronic amphotericin nephropathy: morphometric, electron microscopic, and functional studies.

The two major hypotheses for the pathogenesis of amphotericin nephrotoxicity are direct interaction with epithelial cell membranes and vasoconstriction. Studies indicating the special vulnerability of the medullary ray and medulla to hypoxia led to a reexamination of amphotericin nephrotoxicity. Twenty-four rats were divided into four groups: amphotericin injection (5 mg/kg daily for 3 wk), amphotericin plus salt depletion, vehicle, and salt depletion and vehicle. The amphotericin group had polyuria (P < 0.01) but normal serum creatinine. In contrast, amphotericin plus salt depletion rats exhibited renal failure (creatinine of 1.49 +/- 0.05 versus amphotericin alone 0.98 +/- 0.01; P < 0.01). Semiquantitative histologic analysis of cortical and medullary injury correlated with functional impairment. Cortical changes in the amphotericin group were largely restricted to the medullary ray, where focal rupture and calcification of thick ascending limbs were noted. The S2/S3 tubules in the medullary rays showed focally diminished cell complexity with histiocytic/lymphocytic infiltration. However, calcification was also seen in the area of the macula densa. Morphometry revealed that the thick ascending limbs in the medulla were hypertrophied (1,420 +/- 63 versus 1,195 +/- 48 microns 2 for vehicle; P < 0.05). In contrast, in the amphotericin and salt depletion group, the changes in the medullary ray extended to the labyrinth and the thick ascending limbs in the inner stripe showed atrophic changes (772 +/- 23 microns 2; P < 0.01 versus vehicle). Thus, changes as a result of amphotericin toxicity take place both in areas known to be most vulnerable to hypoxia (medullary ray and medulla), and in areas rich in oxygen (adjacent to glomerulus). Salt depletion potentiates the cortical changes and converts medullary hypertrophy to atrophy. These findings support a dual pathogenesis for amphotericin nephropathy (direct toxicity and vasoconstriction).

Amphotericin B↗
PubMed1993

Dissociation of glomerular filtration rate from tubulointerstitial fibrosis in experimental chronic cyclosporine nephropathy: role of sodium intake.

In addition to its well-recognized ability to provoke acute renal dysfunction by promoting intense renal vasoconstriction, cyclosporine produces a chronic tubulointerstitial nephropathy characterized by striped interstitial fibrosis in humans. With a model of chronic cyclosporine nephropathy in which striped fibrosis develops in the uninephrectomized salt-depleted rat, the relationship between renal functional impairment and structural changes was studied during cyclosporine treatment and after its withdrawal in order to ascertain the natural history of this lesion. Groups of uninephrectomized rats maintained on a salt-depleted (-NaCl) or salt-replete (+NaCl) diet were treated with cyclosporine, 15 mg/kg per day, or vehicle by sc injection. GFR and morphology were assessed at 14 and 28 days of treatment and at intervals up to 28 days after drug withdrawal. Although GFR was similarly depressed in cyclosporine-treated animals on either diet (P < 0.001 versus vehicle), tubulointerstitial injury was largely confined to cyclosporine-treated rats on the -NaCl diet (P < 0.001 versus cyclosporine/+NaCl and vehicle). At 28 days after the withdrawal of cyclosporine, there was a marked discordance between renal structure and function in the cyclosporine/-NaCl group as GFR returned toward normal (P > 0.05 versus cyclosporine/+NaCl) but prominent tubulointerstitial injury persisted and, in some instances, even progressed (P < 0.001 versus cyclosporine/+NaCl and vehicle). Thus, sodium intake emerges as an important determinant of structural tubulointerstitial changes, whereas reductions in GFR during cyclosporine therapy are equivalent in sodium-depleted or sodium-replete animals.

Animals↗
PubMed1993

Lip-reading the BKB sentence lists: corrections for list and practice effects.

Two groups of 21 adult subjects with normal hearing viewed the video recordings of the Bamford-Kowal-Bench standard sentence lists issued by the EPI Group in 1986. Each subject viewed all of the 21 lists and attempted to write down the words contained in each sentence. One group lip-read the lists with no sound (the LR:alone condition). The other group also heard a sequence of acoustic pulses which were synchronized to the moments when the talker's vocal folds closed (the LR&Lx condition). Performance was assessed both by loose (KW(L)) and by tight (KW(T)) keyword scoring methods. Both scoring methods produced the same pattern of results: performance was better in the LR&Lx condition; performance in both conditions improved linearly with the logarithm of the list presentation order number; subjects who produced higher overall scores also improved more with experience of the lists. The data were described well by a logistic regression model which provided a formula which can be used to compensate for practice effects and for differences in difficulty between lists. Two simpler, but less accurate, methods for compensating for variation in inter-list difficulty are also described. A figure is provided which can be used to assess the significance of the difference between a pair of scores obtained from a single subject in any pair of presentation conditions.

Adolescent↗
PubMed1993

Six case studies depicting the deliberate self-harm syndrome.

This article comprises information on self-mutilation (and specifically on the Deliberate Self-harm Syndrome) which obtained from a study of mainly American and British literature. Included is data obtained from interviews conducted with a sample of South Africans suffering from the syndrome. Etiology was explained from both a psychological and biological perspective. The former highlighted deficiencies in coping and communication skills while the latter highlighted the compulsive and pain-killer role that endorphines play. From case studies and literature it was possible to clearly distinguish the Deliberate Self-harm Syndrome as a distinct disorder-a syndrome consisting of deliberate, repetitive and private acts of self-harm in the form of cutting, burning and banging oneself. This culminates in extreme tension release.

Adult↗
PubMed1992

Temporal information in speech: acoustic, auditory and linguistic aspects.

The temporal properties of speech appear to play a more important role in linguistic contrasts than has hitherto been appreciated. Therefore, a new framework for describing the acoustic structure of speech based purely on temporal aspects has been developed. From this point of view, speech can be said to be comprised of three main temporal features, based on dominant fluctuation rates: envelope, periodicity, and fine-structure. Each feature has distinct acoustic manifestations, auditory and perceptual correlates, and roles in linguistic contrasts. The applicability of this three-featured temporal system is discussed in relation to hearing-impaired and normal listeners.

Auditory Perception↗
PubMed1992

Cyclosporine nephropathy: morphometric analysis of the medullary thick ascending limb.

The effects of cyclosporine A (CsA) (12.5 mg/kg/d) on the medullary thick ascending limb (mTAL) were studied in five experimental groups: vehicle-treated control (C), salt depletion (SD), cyclosporine (CsA), and the combination of both salt depletion and cyclosporine for 3 (CsA-SD:S) and 8 (CsA-SD:L) weeks. Evaluation was performed on 1-micron plastic horizontal sections. mTALs were classified as either atrophic or nonatrophic by assessing mitochondrial density. The mean cross-sectional area of atrophic mTALs was found to be significantly smaller than the mean of nonatrophic mTALs in all treatment groups. The percentage of atrophic tubules was found to be significantly increased in both CsA-SD groups as compared with the other three treatment groups (P less than 0.01). Regression analysis indicated a rectangular hyperbolic relationship between the percentage of atrophic tubules and mean nonatrophic tubule cross-sectional area (P less than 0.0001). Thus, low levels of injury are associated with a rapid increase in cross-sectional tubular area (hypertrophy), and this response plateaued with increasing degrees of injury. Terminal plasma creatinine correlated with nonatrophic tubular cross-section area (r = 0.52, P less than 0.003). These studies indicate that CsA induces mTAL atrophy, which is more extensive with salt depletion. With limited injury, hypertrophy develops. However, the hypertrophic response cannot be sustained with increasing degrees of injury. The phenomenon of mTAL atrophy and hypertrophy is particularly important, since hypertrophy itself is a known risk factor for mTAL injury.

Animals↗
PubMed1992

Effect of glycine and hypertrophy on renal outer medullary hypoxic injury in ischemia reflow and contrast nephropathy.

Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% +/- 6% to 41% +/- 9% or 55% +/- 7% with glycine infusion of 75 or 135 minutes, respectively (mean +/- SE, P less than 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% +/- 0% to 12% +/- 6% (P less than 0.05) and from 8% +/- 5% to 49% +/- 8% (P less than 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P less than 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗