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Biomedical subjects

R Zuckerman

Publications and source records attributed to R Zuckerman.

18 recordsLinked to original sources

The effects of pneumoperitoneum and patient position on hemodynamics during laparoscopic cholecystectomy.

BACKGROUND: The purpose of this study was to prospectively examine the combined effects of pneumoperitoneum and the reverse Trendelenberg position on cardiac hemodynamics during laparoscopic cholecystectomy. METHODS: Thirty-nine patients undergoing laparoscopic cholecystectomy as performed by a single surgeon were enrolled in the study. Hemodynamic data were collected continuously using a transthoracic bioimpedance monitor. All patients were subjected to insufflation pressures of 15 mmHg. Data were examined using mixed analysis of variance (ANOVA). RESULTS: Cardiac index fell 11% with induction of anesthesia (p < 0.05), with stroke volume decreasing 7.2% (p < 0.05). Insufflation caused significant decreases in stroke volume (SV) left ventricular end diastolic volume (LVEDV) but not cardiac index (CI). Placing the patients in the reverse Trendelenberg position caused no significant changes in these parameters. There were no significant differences between ASA (American Society of Anesthesiologists) classes I and II patients when compared to ASA III patients. CONCLUSIONS: Patients undergoing laparoscopic cholecystectomy experience significant hemodynamic depression. The effect of general anesthesia is the most profound. Insufflation of the abdomen caused more mild hemodynamic effects in our study. The addition of a reverse Trendelenberg position did not alter the patient's hemodynamic status.

Adult↗

Abdominal-wall pseudohernia secondary to herpes zoster.

We present a case of a 78-year-old woman with abdominal-wall muscle paralysis following cutaneous herpes zoster in the T12-L1 dermatomes. An EMG confirmed paralysis, and a CT scan ruled out fascial defect. The paralysis had completely resolved 1 year later. A review of the literature regarding these unusual sequelae of herpes zoster is presented.

Aged↗

Pediatric melanoma: confirming the diagnosis with sentinel node biopsy.

Many pediatric melanoma lesions present at a more advanced stage than those in the adult population. Clinical and histological melanoma mimics, including a subset of Spitz nevi, are difficult to discriminate from melanoma. When dealing with a childhood melanoma, the clinician is likely to be faced with a thick lesion, and one in which the actual diagnosis may even be in doubt. There is a paucity of data to guide the physician in his management of melanoma in this age group, particularly with respect to node status and adjuvant therapy. The authors present two cases of pediatric melanoma in which the novel use of sentinel node biopsy helped confirm the diagnosis of melanoma, determined the need for full lymph node dissection, and guided the use of adjuvant interferon therapy.

Adolescent↗

Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy.

To date, in utero bone marrow transplantation (BMT) has had limited success, largely because of poor donor engraftment. The poor engraftment is probably the result of performing the procedure late in gestation after significant fetal immunocompetence has developed and/or transplanting insufficient numbers of donor hematopoietic stem cells for competing successfully with ongoing fetal hematopoiesis. To overcome these problems, we performed in utero BMT on a fetus with globoid cell leukodystrophy during the first trimester of gestation using selected paternal bone marrow stem (CD34+) cells. CD34 selection allowed a substantially greater number of stem cells to be transplanted. Although the fetus died 7 weeks after the procedure (during the 20th week of gestation), full donor engraftment was established. Moreover, the cause of death appeared to be overwhelming donor engraftment and leukostasis with paternal myeloid cells infiltrating most tissues. The ability of in utero BMT to produce this degree of engraftment provides great promise for the use of this approach in the treatment of a variety of inherited disorders that can be diagnosed prenatally.

Bone Marrow Transplantation↗

An international collaborative study of the effects of coinfection with human T-lymphotropic virus type II on human immunodeficiency virus type 1 disease progression in injection drug users.

To determine whether human T-lymphotropic virus (HTLV) type II coinfection affects progression of human immunodeficiency virus type 1 (HIV) infection, longitudinal data on 370 HIV-infected injection drug users (IDUs) with known HIV seroconversion dates from four cohort studies were pooled. HTLV infection was determined by EIA and confirmed and typed by Western blot. Proportional hazards models were used to determine whether HTLV-II infection was associated with AIDS or AIDS-related mortality. Regression analyses were used to compare declines in CD4 cell percents in singly and dually infected persons. Of 370 IDUs, 61 (16%) were HTLV-II-coinfected. During follow-up, 43 (12%) developed and 24 (6%) died of AIDS. HTLV-II coinfection was not associated with progression to AIDS (relative hazard [RH], .82; 95% confidence interval [CI], 0.34-1.94]) or AIDS mortality (RH, 1.69; 95% CI, 0.62-4.60). Rates of decline in CD4 cell percent were similar in singly and dually infected IDUs. These results suggest that HTLV-II does not affect the progression of HIV infection.

Acquired Immunodeficiency Syndrome↗

Optical mapping of inner retinal tissue PO2.

A high resolution optical mapping procedure was developed to visualize oxygen concentration levels topographically within the tissue of the inner retina in vivo. The novel optical mapping procedure has the potential for describing oxygen metabolism in retinal and other body tissues and elucidating the coupling of metabolism to function. The method is based upon the fluorescence quenching by molecular oxygen of a lipid soluble probe substance which accumulates within the lipid bilayers of tissue cells. The optical mapping system can provide more than 300,000 values of tissue PO2 in space with millisecond time resolution. Optical maps of inner retinal tissue PO2 were imaged under conditions of normoxia, hyperoxia, and for a retina which received restricted panretinal photocoagulation. Moreover, the effects of transient increases in intraocular pressure were also investigated. An O2 consumption rate of 5.48 +/- 0.50 (SEM) x 10(-3) ml O2/ml tissue/min for the light-adapted rat inner retina was estimated from the application of a Krogh cylinder diffusion model to tissue PO2 gradients measured in the capillary-free zone around arterioles. Similarly, arterioles oxygenated a surrounding cylinder of tissue with a mean radius of 144.73 +/- 5.52 (SEM) microns. Histograms of PO2 values within inner retinal tissue (mean PO2 = 25.03 mm Hg, median = 24.58 mm Hg) showed remarkable correspondence to those determined invasively in brain by others, using O2 microcathodes, possibly suggesting a similarity in the underlying capillary architectures of the two neural tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term antimicrobial therapy in the prevention of recurrent soft-tissue infections.

Thirty-six patients who had suffered two or more episodes of erysipelas or cellulitis during the previous year were randomly divided into two equal groups; one group received erythromycin base 250 mg b.i.d. for 18 months, while the other group received no prophylaxis for a similar period. No patients in the treated group developed infection during the 18 months' follow-up but eight of the control group (50%) relapsed and required antibiotic treatment. Prolonged antimicrobial prophylaxis is effective and safe in preventing recurrent episodes of soft-tissue infections.

Cellulitis↗

Sites of arrestin action during the quench phenomenon in retinal rods.

The target proteins for arrestin (48 kDa protein) action during the quench of cGMP phosphodiesterase (PDE) activation in retinal rod disk membranes were identified by the use of a cross-linking reagent. A heterobifunctional, cleavable, photo-activatable cross-linker (sulfo-SADP) was coupled to purified arrestin. Under precise weak visible light bleach and nucleotide conditions of quench, the cross-linker was UV flash-activated at a time when quench was well established. The target proteins covalently linked to arrestin by cross-linker activation were identified by immunoblotting. In the presence of ATP arrestin cross-linked to both PDE and rhodopsin during the quench phenomenon. Removal of ATP from the reaction mixture essentially abolished the cross-link with PDE, just as ATP omission abolishes quench, but significantly increased the cross-link to rhodopsin. The absence of a cross-link to the plentiful beta-subunit of transductin, as well as the results of competition studies employing arrestin without attached cross-linker, suggest that the observed cross-links are specific and reflect true binding interactions of arrestin during quench. The data are consistent with a model of quench in which photolyzed rhodopsin (R*) catalyzes the formation of an activated form of arrestin, which dissociates from R* in the presence of ATP, and binds to PDEs, thereby deactivating them.

3',5'-Cyclic-GMP Phosphodiesterases↗

A 48 kDa protein arrests cGMP phosphodiesterase activation in retinal rod disk membranes.

Photolyzed rhodopsin (R) catalyzes GTP-binding to alpha-transducins (T alpha); T alpha X GTPs then activate cGMP phosphodiesterase (PDE). PDE activation is arrested by ATP in two ways: (i) initial velocity is suppressed, and (ii) PDE velocity rapidly returns to preactivation levels (turnoff). Arrestin (a 48 kDa protein) markedly enhances turnoff while not affecting initial velocity. Arrestin in the presence of ATP achieves rapid turnoff by directly inhibiting activated PDE, as indicated by its ability to inhibit the direct activation of PDE by T alpha X GMP--PNP (guanylyl-imidodiphosphate). Double reciprocal plots reveal a competition between arrestins and activated transducins for sites on PDE. Blocking R phosphorylation blocks initial velocity suppression but does not disturb rapid turnoff. Our data suggest a 2-fold mechanism for PDE deactivation: (i) formation of T alpha X GTPs is suppressed by R phosphorylation, while (ii) activation of PDE by T alpha X GTPs is competitively inhibited by arrestins when ATP is present.

3',5'-Cyclic-GMP Phosphodiesterases↗

Response of human retinal blood flow to light and dark.

The laser Doppler technique was used to measure alterations in retinal blood flow in human subjects under dark-adapted conditions compared to light-adapted conditions. Retinal blood flow increased 40 to 70% after the transition from light to dark. We show quantitatively that the measured increases in retinal blood flow provide the appropriate increases of available oxygen for the inner retinal tissue necessary to compensate for increased oxygen consumption in the dark by the photoreceptor-RPE complex. In addition, we show that measured increases or decreases in human retinal blood flow are quantitatively linked to two intrinsic characteristics of the rod photoreceptor: its metabolic response to known, graded light levels, and its rhodopsin-mediated wavelength-dependent light-absorption properties. We also discuss how light-activated blood flow changes may provide a physiologic test for the autoregulatory capacity of the retinal vasculature.

Adaptation, Physiological↗

Rhodopsin-to-metarhodopsin II transition triggers amplified changes in cytosol ATP and ADP in intact retinal rod outer segments.

We have observed rapid, light-initiated changes in unbound cytosol ATP and ADP during the rhodopsin-to-metarhodopsin II transition in intact rod outer segments (ROS). Upon illumination of the ROS, ATP is rapidly removed from the unbound phase of ROS, accompanied by the concomitant release of ADP into the cytosol. The exchange process involves decreases of approximately equal to 0.5 mM ATP in ROS cytosol ATP content in response to a saturating flash. At levels of light well below saturation (less than 0.001% bleach), the process is highly amplified, with a decrease in cytosol ATP of approximately equal to 2,000 ATP molecules per absorbed photon per ROS. Rapid time-resolution techniques reveal that cytosol ATP content decreases rapidly, within 250 msec of a saturating flash. Bleaching rhodopsin to metarhodopsin II results in a decrease in cytosol ATP, accompanied by an increase in cytosol ADP, whereas photoreversal of metarhodopsin II by a blue flash reverses the process, increasing ATP concentration to its control level in the dark. The photoreversibility of the ATP decrease during the rhodopsin-to-metarhodopsin II transition establishes a direct link between the state of an early intermediate of photolyzed rhodopsin and the state of a nucleoside triphosphate in intact ROS. The results are consistent with a light-activated exchange of unbound ATP for bound ADP, and we propose, therefore, an ATP/ADP amplification cycle in which metarhodopsin II catalyzes the exchange of ATP for ADP on a nucleotide binding protein.

Adenosine Diphosphate↗

A model for the pathogenesis of retrolental fibroplasia based on the metabolic control of blood vessel development.

We postulate that the pathogenesis of retrolental fibroplasia (RLF) is related to the disruption of the normally coordinated ocular development and maturation in which there is an interplay between function, metabolism, and blood vessel development. The normal retina is avascular until the fourth month of gestation, at which time vascularization proceeds from the optic disk towards the peripheral retina. Until this time, the underlying choroidal circulation provides for full-thickness retinal oxygenation. We hypothesize that the centrifugal maturation of the retina, including the retinal photoreceptors (the major oxygen-consuming cell type of the adult retina), precedes this vascular outgrowth. The maturation of the photoreceptors and the concomitant increased oxygen consumption would make it impossible for the choroid to provide adequate full-thickness retinal oxygenation. The resulting progressive change in the inner retinal metabolism thus provides an orderly, controlled stimulus for the subsequent progression of retinal vascularization from the optic disk to the peripheral retina. Exposure of the premature neonate to abnormal oxygen levels would selectively retard inner retinal blood vessel development while the photoreceptors continue to mature and increase their oxygen consumption. Thus, when the infant is removed from abnormal oxygen, a neovascular proliferative stimulus will develop in direct relation to the mass of non-vascularized but metabolically active retina, initiating uncoordinated vessel growth in the inner retina.

Fetus↗

The influence of the photoreceptor-RPE complex on the inner retina. An explanation for the beneficial effects of photocoagulation.

We have measured oxygen consumption in the various retinal layers and have found that the photoreceptor-retinal pigment epithelial (RPE) complex accounts for two thirds of total oxygen consumption. Hence, this complex substantially influences oxygen transport between the choroid and the inner retina. This finding has significant implications in explaining the beneficial effects of panretinal photocoagulation as well as retinal vasculature changes in outer retinal degenerations.

Adult↗

Ionic analysis of photoreceptor membrane currents.

1. Membrane current was derived from simultaneous measurements of interstitial ;dark' voltages and conductivities along the radial axis of frog photoreceptor cells. Membrane current was subsequently resolved into its component ionic currents or fluxes by means of ionic substitution and by the use of inhibitors of active transport.2. The plasma membrane of the frog rod outer segment was found to be permeable to Na(+) and Cl(-), with a ratio of Na(+) to K(+) permeabilities higher than that found in most neuronal cells. A net inward flux of 1.5 x 10(8) Na(+)/sec.rod flows across the outer segment plasma membrane in the dark.3. The proximal portion of the rod receptor, extending from the proximal region of the inner segment to the synaptic terminal, is mainly permeable to K(+), although some degree of Na(+) permeability is also presumed.4. A hyperpolarizing electrogenic Na pump was localized to the base of the outer segment and inner segment of the cell. The pump transfers at least 10(8) charges/sec out of the cell at this level, the pump current dividing and re-entering the cell at both the outer segment and proximal portion of the photoreceptor including the synaptic terminal.5. These findings have been incorporated into an ionic model of the photoreceptor, and its implications for cellular functioning considered.

Animals↗