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Biomedical subjects

S Rothenberg

Publications and source records attributed to S Rothenberg.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of an automated culture system for detecting bacterial contamination of platelets: an analysis with 15 contaminating organisms.

BACKGROUND: Approximately 1 in 2000 platelet components are bacterially contaminated. The time to detection of 15 seeded organisms in platelets recovered from an automated culture system was studied. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Bacillus subtilis, Candida albicans, Clostridium perfringens, Corynebacterium species, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus pyogenes, and Streptococcus viridans were inoculated into Day 2 apheresis platelet components to obtain a final concentration of approximately 10 and 100 CFU per mL (2 units/organism). Each bag was sampled 10 times (20 mL/sample). Four mL of each sample was inoculated into standard aerobic and anaerobic bottles and into aerobic and anaerobic bottles containing charcoal; 2 mL was inoculated into pediatric aerobic bottles (so as to maintain a 1:10 ratio of sample to media) and 1 mL into thioglycollate broth. RESULTS: With the exception of P. acnes, all organisms were detected in a mean of 9.2 to 25.6 hours. A range of 10 serial dilutions in inoculating concentrations was associated with an overall 10.1-percent difference in detection time. A mean of 74.4 and 86.2 hours (100 and 10 CFU/mL inocula, respectively) was required for the detection of P. acnes in anaerobic bottles. CONCLUSION: Bacteria thought to be clinically significant platelet contaminants can be detected in 9.2 to 25.6 hours when the starting concentration is approximately 10 to 100 CFU per mL. P. acnes required considerably longer incubation times for detection (in either aerobic or anaerobic bottles). However, P. acnes is of questionable clinical significance. Such a detection system could be used in either a blood collection center or a transfusion service to screen platelet concentrates for bacterial contamination. Such testing (with sterile sampling performed so as to maintain a closed-bag system) would be expected to save lives and might allow an extension of platelet storage.

Bacteria↗
PubMed2000

Severe lead-induced peripheral neuropathy in a dialysis patient.

Toxic neuropathy caused by lead (manifested as wrist drop) was a frequent phenomenon before 1925. In modern times, it is a distinct rarity. We report herein a Hispanic woman who developed end-stage renal failure, followed by wrist drop, in whom the maximal total blood lead was 69 microg/dL. Measurements of lead in her tibia and calcaneus by K-x-ray fluorescence, however, showed markedly elevated values. The wrist drop cleared after four treatments with intravenous calcium sodium edetate (Ca EDTA). In vitro studies of (210)Pb uptake by red blood cells (RBC) after incubation with normal or uremic plasma indicated that (210)Pb uptake was inhibited by uremic plasma. These studies suggest the presence of a transport inhibitor in uremia that modifies the distribution of lead between plasma and RBC, leading to lower overall blood values.

Adult↗
PubMed2000

Improvements in chronic diseases with a comprehensive natural medicine approach: a review and case series.

Approximately 40% of the US population report using complementary and alternative medicine, including Maharishi Vedic Medicine (MVM), a traditional, comprehensive system of natural medicine, for relief from chronic and other disorders. Although many reports suggest health benefits from individual MVM techniques, reports on integrated holistic approaches are rare. This case series, designed to investigate the effectiveness of an integrated, multimodality MVM program in an ideal clinical setting, describes the outcomes in four patients: one with sarcoidosis; one with Parkinson's disease; a third with renal hypertension; and a fourth with diabetes/essential hypertension/anxiety disorder. Standard symptom reports and objective markers of disease were evaluated before, during, and after the treatment period. Results suggested substantial improvements as indicated by reductions in major signs, symptoms, and use of conventional medications in the four patients during the 3-week in-residence treatment phase and continuing through the home follow-up program.

Chronic Disease↗
PubMed1998

Thoracoscopic anterior spinal procedures in children.

METHODS: From February 1996 through July 1997, 20 patients were determined to be appropriate for a thoracoscopic approach for the anterior portion of their spinal surgery. Ages ranged from 8 to 17 years of age and weight from 20 to 70 kg. The diagnosis included severe idiopathic and neurogenic scoliosis or kyphosis (n = 20) and congenital hemivertebra (n = 4). The procedures performed included diskectomy and anterior release from two to nine vertebral levels, hemivertebrectomy, and epiphysiodesis. Four patients also had an open lumbar exposure and all had a posterior fusion. RESULTS: All procedures were completed successfully endoscopically. Surgical times for the thoracoscopic portion of the procedure averaged 106 minutes and total procedure times were comparable with the standard open technique. Three patients were extubated at the end of the procedure with the majority extubated on postoperative day 1. Average intensive care unit stay was 1.8 days, and chest tubes were removed between postoperative day 1 and 5 (average, 2.2 days). In follow-up, surgical correction was deemed to be acceptable and equivalent to open techniques in all cases. CONCLUSION: This technique has proven to be safe and effective in children and appears to be associated with less pain and morbidity as evidenced by earlier extubation and chest tube removal and shorter ICU stay.

Adolescent↗
PubMed1993

In vivo gene therapy of hemophilia B: sustained partial correction in factor IX-deficient dogs.

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

Animals↗
PubMed1993

Development of a clinical protocol for hepatic gene transfer: lessons learned in preclinical studies.

Strategies for hepatic gene therapy have been proposed that involve isolation of primary hepatocytes and introduction of recombinant genes into these cells in culture, followed by autologous hepatocellular transplantation (HCT). Consideration of clinical applications requires data suggesting that HCT can be performed safely in human subjects in addition to data indicating that recombinant gene expression can reverse a disease process. This report describes preclinical studies that underlie a clinical trial of HCT in which hepatocytes would be labeled with a marker gene to facilitate assessment of engraftment in the recipient. Human hepatocytes were harvested from liver segments preserved in Belzar's solution and transduced with an amphotropic retroviral vector carrying a recombinant marker gene (neomycin phosphotransferase II). Human hepatocytes were recovered from monolayer culture, stained with the fluorescent dye 1,1'-dioctadecyl-3,3,3,3'-tetra-methylindo-carbocyanine perchlorate (DiI) and transplanted into severe combined immunodeficient mice by splenic injection. Engrafted hepatocytes were identified in the liver and spleen of severe combined immunodeficient mice but not immunocompetent controls. Two large animal models of HCT are described. In a dog model, neomycin phosphotransferase II-containing hepatocytes were identified in the liver 7 wk after transplantation. In a baboon model, autologous HCT with DiI-stained cells demonstrated that transplanted cells assume a normal morphology and constitute up to 5% of hepatocytes. These data demonstrate transduction and transplantation of human hepatocytes and the feasibility of HCT in large animals. On the basis of these studies, the proposed clinical trial for gene transfer and transplantation in human subjects has been approved by the National Institutes of Health and the Food and Drug Administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.

The liver represents an excellent organ for gene therapy since many genetic disorders result from the deficiency of liver-specific gene products. We have previously demonstrated that transgenic mouse hepatocytes can be heterologously transplanted into congenic recipients where they survived indefinitely and continued to function as hepatocytes. Here we demonstrate the autologous transplantation of retrovirally transduced canine hepatocytes. At least 1 x 10(9) hepatocytes or 5% of the liver mass can be transplanted by the portal vasculature. In two animals we have transplanted hepatocytes transduced with a retroviral vector containing the human alpha 1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. Both animals had significant human alpha 1-antitrypsin in the serum for 1 month. Although the serum levels of human alpha 1-antitrypsin eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of transduced hepatocytes migrated to the liver and continued to survive in vivo. The results suggest that gene therapy of hepatic deficiencies may be achieved by hepatocellular transplantation after genetic reconstitution with the use of promoters of cellular genes that are active in the normal liver.

Animals↗
PubMed1991

Suppression of the pituitary-gonadal axis in children with central precocious puberty: effects on growth, growth hormone, insulin-like growth factor-I, and prolactin secretion.

To assess further the relationship between gonadal sex steroids and PRL, GH, and insulin-like growth factor-I (IGF-I) secretion and to help clarify the mechanism underlying the pubertal growth spurt, we studied 11 children (10 girls) with central precocious puberty before and during gonadal suppression with the GnRH agonist (GnRH-a) leuprolide acetate. Nocturnal sampling for plasma levels of GH and PRL, GH response to GH-releasing factor-(1-44), and plasma IGF-I levels were determined before and 3-6 months after pituitary-gonadal suppression. Treatment caused a significant decrease in the LH and FSH responses to GnRH (P less than 0.01) and the plasma concentration of estradiol (P less than 0.05). The patients' mean height velocity SD score for chronological age, initially 3.8 +/- 1.9, decreased significantly to 0.9 +/- 0.9 with treatment (P less than 0.005). Nocturnal GH secretion (mean GH concentration, sum of GH pulse areas, sum of GH pulse amplitudes, and GH pulse frequency) and mean IGF-I levels (1.38 +/- 0.6 vs. 1.72 +/- 0.34 U/mL) were not significantly altered by treatment. However, the mean peak GH response to GH-releasing factor-(1-44) was 29.2 +/- 6.8 micrograms/L before treatment and declined significantly to 17.7 +/- 3.4 micrograms/L after gonadal suppression (P less than 0.05). PRL secretion was similar before and after GnRH-a-induced suppression. These results indicate that the decrease in height velocity noted during GnRH-a treatment occurred independently of changes in nocturnal GH secretion and IGF-I levels. These data are consistent with the premise that sex steroids can modulate growth by a direct action on skeletal growth.

Antineoplastic Agents↗
PubMed1989

Acromegaly in an infant.

Serial hormonal studies were carried out in a girl with a growth hormone-secreting pituitary adenoma and hyperprolactinemia diagnosed at 21 months of age, the youngest verified case of acromegaly. The child had progressive macrocephaly, noted at 6 months of age, which preceded the rapid acceleration of linear growth by nearly 1 year. At 21 months of age, the girl's head circumference measured 55 cm (+5.5 SD) and her height was 97.6 cm (+4.4 SD). Preoperative serum growth hormone level was 135 ng/mL, somatomedin C was 1,540 ng/mL (normal for bone age 18 to 97 ng/mL), and prolactin was 370 ng/mL (normal less than 20 ng/mL). Following total resection of a large adenoma, immunohistochemical staining of the tumor showed growth hormone but not prolactin. With longitudinal monitoring of the child for 2 years postoperatively, persistently low growth hormone levels were demonstrated and normal growth velocity (6 cm/yr). Peak serum growth hormone levels ranged from 2.8 to 4.1 ng/mL after stimulation tests with insulin, arginine, and L-dopa. Maximum sleep-entrained growth hormone level was 3.4 ng/mL. At the same time, serum somatomedin C levels measured serially were normal (29 to 111 ng/mL), whereas simultaneous prolactin levels were moderately increased (30 to 147 ng/mL). The data support the hypothesis that hyperprolactinemia may have contributed to stimulating somatomedin C and sustaining the normal growth rate in this child.

Acromegaly↗
PubMed1987

Selective management of blunt abdominal trauma in children--the triage role of peritoneal lavage.

The evolution of selective laparotomy in children sustaining blunt abdominal trauma has been highly controversial. This report describes our experience and policy change during this transitional period. Emergency laparotomies performed in the pediatric age group (less than 14 yr) between 1980 and 1984, based on peritoneal lavage, were reviewed. Of 16 such patients, six (37.5%) had injuries identified at laparotomy necessitating operation, (four greater than Grade III spleen, one hepatic vein, one small bowel). The remaining ten patients (67.5%) had injuries which probably could have been managed nonoperatively (eight less than or equal to Grade II spleen, two less than or equal to Grade II liver). We additionally reviewed 46 peritoneal lavages done in children during 1984, and noted a 100% sensitivity but 86% specificity when considering essential laparotomies. Based on these data, we established a selective management protocol and initiated a prospective study in January 1985. The protocol consisted of: 1) routine peritoneal lavage (DPL) in children at high risk for abdominal injury, 2) immediate laparotomy for DPL positive for blood in conjunction with hemodynamic instability, 3) selective laparotomy for DPL positive for blood in a stable child, additionally evaluated by abdominal CT scan (major mechanism) or liver/spleen scan (minor mechanism), and 4) mandatory laparotomy for DPL effluent positive by criteria other than blood. This policy reduced unnecessary laparotomy, otherwise warranted by DPL, to 18% (2/11); both patients had Grade II splenic injuries. Five children sustaining low-energy trauma were managed nonoperatively following peritoneal aspiration of gross blood with L-S scan confirming minor solid visceral injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗
PubMed1985

Use of the afterloading technique for intraoral radiation carriers.

A method for fabrication of a radiation carrier with an adaptation of the afterloading technique has been described. The use of the afterloading technique allows for quick and easy placement of multiple radioactive sources; thus time and exposure to the radiotherapist and the patient are minimized during the period of placement and activation of the prosthesis at the time of therapy.

Brachytherapy↗
PubMed1984

Evidence for deficit in interhemispheric transfer of information in dyslexic boys.

Visual thresholds for identification of briefly flashed, lateralized letters were obtained for dyslexics and normal readers, age 11-15 years. Subjects were also tested for ability to localize tactile stimuli on the fingers and transfer information intermanually, a task failed by callosal agenesis patients (Dennis, 1976). Dyslexics differed significantly from normals on both tasks. Half the dyslexics demonstrated high threshold asymmetry across hemifields and many tactile localization errors, a pattern suggesting an "interhemispheric transfer deficit" as a cause of reading failure. Despite equally severe initial handicaps, dyslexics showing low, symmetric thresholds and few tactile errors, showed more reading improvement than did the others.

Adolescent↗
PubMed1980

Specific oculomotor deficit after acute methadone. I. Saccadic eye movements.

Changes in saccadic eye movements before and after up to 10 mg oral methadone were measured electrooculographically in nontolerant nondependent humans. Undershoot of initial saccades increased with increasing size of horizontal target displacement (to 36 degrees) from a central viewing position. Dosage as low as 5 mg caused significant increase in saccade undershoot especially to target displacements greater than 10-15 degrees. Latency from target displacement to onset of initial saccade also increased after methadone. These results, in combination with the lack of significant drug effect on latency between initial saccade and corrective saccade, and on initial saccade duration, maximum velocity, and time to maximum velocity indicate methadone action on specific sensory, rather than motor, components of saccadic response. The similarity of alteration of saccadic response after methadone and after lesion of the upper layers of the superior colliculus in primates, as reported in the literature, suggests that opiate binding sites in the upper layers of the superior colliculus may be physiologically active.

Adult↗
PubMed1980

Specific oculomotor deficit after acute methadone. II. Smooth pursuit eye movements.

Changes in smooth pursuit eye tracking of targets moving sinusoidally in horizontal and vertical planes before and after up to 10 mg oral methadone were measured electrooculographically in nontolerant nondependent humans. Methadone depressed the gain of horizontal tracking movements at most frequencies tested (0.2 - 1.6 Hz) without changing target-eye phase relationships. Lack of change in target-eye cross-correlation functions after methadone and examination of individual records indicate that gain reduction was due to the eye failing to follow the target to the full extent of target excusion (+5 degrees from eyes straight ahead view). Possible mechanisms and the practical consequences of methadone action on smooth pursuit were discussed.

Adult↗
PubMed1979

Methadone depression of visual signal detection performance.

In order to determine the origin of a previously reported slowing of simple visual reaction time in subjects receiving single doses of oral methadone, three well-trained subjects performed. a modified double flash detection task several times after single doses of 5 mg and 10 mg of oral methadone and a placebo. A Theory of Signal Detectability analysis allowed for a clear distinction between drug-induced changes in visual sensitivity and changes in response bias. It was found that methadone reduced visual sensitivity. The peak depression in detection as well as the duration of the depressed performance were dose-related. Depression in performance paralleled the subjective effect of the drug in each subject. Averaged visual evoked potentials showed significant changes at peak drug effect to the onset of each of the pair of stimuli. It was concluded that methadone depresses visual function by acting on the visual parts of the central nervous system. The retina, midbrain and thalamic visual nuclei were discussed as possible sites of action of methadone.

Adult↗
PubMed1979

A model for thyroid hormone--receptor interactions.

Theoretical electronic structure calculations on the thyroid hormones and analogues, as well as model hormone--receptor interactions, have been carried out. These studies (a) support the concept that the 4'-OH group is a H-bond donor to the in vivo nuclear receptor and suggest that at the receptor this OH group is trans to the 3' (distal) substituent; (b) indicate that there is an important intramolecular interaction between 3' and 4' substituents, and those 3' substituents that most favor both 4' OH orientation trans to the 3' group and a more acidic OH group substantially increase binding and biological activity; and (c) support the concept that there is a direct correlation between the conformational free energy of the aromatic rings and biological activity.

Animals↗