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Biomedical subjects

S Goldman

Publications and source records attributed to S Goldman.

At least 109 records · Page 6Linked to original sources
PubMed1998

Assessment of coronary flow reserve by transesophageal echocardiography in cardiac transplant recipients.

This study investigated the feasibility of dipyridamole Doppler transesophageal echocardiography to assess coronary flow reserve in 26 patients with orthotopic heart transplantation and compared it with positron emission tomography. We found an 85% success rate in obtaining Doppler flow signals in the proximal left anterior descending coronary artery. Our data also showed that the correlation between transesophageal echocardiography and dipyridamole N-13 ammonia positron emission tomography increases when respective resting rate-pressure products are taken into account. However, comparison between the two methods should be made with caution because coronary flow reserve derived from transesophageal echocardiography tends to be higher than that obtained with positron emission tomography.

Adult↗
PubMed1998

Cerebral glucose metabolism and centrotemporal spikes.

The pathophysiology of regional glucose hypometabolism often associated with refractory, lesion-related, epilepsy is not well understood. In particular, the role of interictal spiking is controversial since animal models of partial epilepsy have shown that interictal spiking increases glucose metabolism. We addressed this question by studying with positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) the regional cerebral metabolism in children with focal spiking unrelated to a brain lesion. Patients (11 children with benign childhood epilepsy with centrotemporal spikes (BCECS) and two children without seizures) had on EEG centrotemporal spikes which were either strictly unilateral (ten cases) or strongly predominant on one side (three cases). We looked for an asymmetry in the distribution of cerebral glucose metabolism in our group of patients using statistical parametric mapping (SPM). After spatial normalization, a reversed copy of the 13 scans was obtained, resulting in 26 scans which were assigned to two groups: a group with left-sided centrotemporal spikes and a group with right-sided centrotemporal spikes. Regional glucose metabolism was not statistically different in the two groups. This suggests that metabolic changes associated with interictal spiking cannot be demonstrated by PET with FDG in BCECS, and that this technique could be helpful for the differentiation between idiopathic and symptomatic cases of partial epilepsy in children.

Brain↗
PubMed1998

High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine brain stem tumors. Children's Cancer Group.

PURPOSE: Diffuse pontine tumors are highly lethal, and there are few long-term survivors with the standard treatment of external beam irradiation. We investigated the effectiveness of high-dose thiotepa and etoposide-based chemotherapy regimens with autologous bone marrow rescue (ABMR) in children with pontine tumors. PATIENTS AND METHODS: Sixteen children with diffuse pontine tumors were treated. Ten had resistant or recurrent tumors. All ten had previously received irradiation; five had also received chemotherapy and one, beta-interferon. Three high-dose chemotherapy regimens were employed. Six patients received three days of thiotepa (300 mg/m2/day) and etoposide (250-500 mg/m2/day) (TE); two received three days of carmustine (BCNU) (200 mg/m2/day divided every 12 hours) followed by TE (BTE); and two received three days of carboplatin (500 mg/m2/day) followed by TE (CTE). Six other patients had newly-diagnosed tumors and had not received any prior treatment. They all received the BTE regimen and subsequently were treated with hyperfractionated irradiation (7200-7800 cGy) beginning approximately six weeks post-ABMR. RESULTS: There were two toxic deaths (13%), both in previously treated patients, due to multiorgan system failure and Candida septicemia in one case each. Median survival of the patients with resistant or recurrent disease was 4.7 months (range 0.1-18.7) from time of ABMR. Median survival of the newly-diagnosed patients was 11.4 months (range 7.6-17.1) from the time of ABMR. CONCLUSION: High-dose chemotherapy utilizing these regimens followed by ABMR did not appear to prolong survival compared to conventional therapy in these children with pontine tumors. Alternative strategies need to be developed for this highly lethal disease.

Adolescent↗
PubMed1998

Survival following intensive chemotherapy with bone marrow reconstitution for children with recurrent intracranial ependymoma--a report of the Children's Cancer Group.

Recurrent intracranial ependymoma is rarely cured by surgery, radiotherapy, and chemotherapy in conventional doses. This study was designed to determine the toxicity, radiographic response rate and outcome following intensive chemotherapy with ThioTEPA, etoposide, carboplatinum and autologous bone marrow rescue (ABMR) for young children with recurrent central nervous system ependymoma. ThioTEPA 300 mg/m2/day (total 900 mg/m2) and etoposide 250 to 500 mg/m2/day (total 750 to 1500 mg/m2) were administered for three consecutive days with or without the addition of carboplatinum 500 mg/m2/day (total 1500 mg/m2) for an additional three consecutive days, and autologous bone marrow was reinfused 72 hours following chemotherapy. Eligibility criteria required adequate renal, hepatic and pulmonary function, and no tumor infiltration of bone marrow. Fifteen children with recurrent intracranial ependymoma, aged 5 months to 12 years (median 22 months), were treated. Five patients died of treatment related toxicities within 62 days of marrow reinfusion. Eight have expired from progressive disease a median of six months post-ABMR, and one has died from unrelated causes. One child remains alive 25 months post-ABMR, following further disease recurrence. No partial or complete responses were observed. This regimen of high-dose ThioTEPA and etoposide with or without additional carboplatinum with ABMR is not an effective strategy for retrieving heavily pre-treated children with recurrent ependymoma.

Antineoplastic Agents↗
PubMed1998

Gap-junction-mediated propagation and amplification of cell injury.

Gap junctions are conductive channels that connect the interiors of coupled cells. We determined whether gap junctions propagate transcellular signals during metabolic stress and whether such signaling exacerbates cell injury. Although overexpression of the human proto-oncogene bcl2 in C6 glioma cells normally increased their resistance to injury, the relative resistance of bcl2+ cells to calcium overload, oxidative stress and metabolic inhibition was compromised when they formed gap junctions with more vulnerable cells. The likelihood of death was in direct proportion to the number and density of gap junctions with their less resistant neighbors. Thus, dying glia killed neighboring cells that would otherwise have escaped injury. This process of glial 'fratricide' may provide a basis for the secondary propagation of brain injury in cerebral ischemia.

Animals↗
PubMed1998

The Swedish National Care Programme for Anal Carcinoma--implementation and overall results.

The Swedish National Care Programme for Anal Carcinoma (SNCPAC) was instituted in order to create a uniform handling policy for anal cancer and thus to accrue a population-based material allowing unbiased analyses. This study evaluates the degree of implementation of the SNCPAC guidelines, and presents overall treatment results in a total of 356 patients with epidermoid cancer of the anus and the perianal region diagnosed in Sweden between 1985 and 1989. Primary treatment according to the guidelines was irradiation up to 40 Gy, Bleomycin was administered intramuscularly before the first 18 fractions. After a 3-week pause, radiotherapy was to be continued up to a dose of 60-64 Gy, if at least an almost complete response was achieved. Otherwise, the patient was recommended surgery within a week. The guidelines were applied in 90%, of cases where such treatment was possible. The 5-year tumour-specific survival rate was 72%. The survival rate was more favourable in perianal tumours (90%) than in anal canal tumours (68%, p < 0.01). The 5-year probability of having a preserved anus was 64% (anal canal/perianal 58%/91%, p < 0.001). Bleomycin did not appear to have any effect on treatment results. The care programme has had a rapid and almost complete nation-wide penetration, and h as created the desired uniformity allowing proper analyses. The treatment results also appear comparable with specialised referral centres.

Adult↗
PubMed1998

Perisylvian dysgenesis. Clinical, EEG, MRI and glucose metabolism features in 10 patients.

We studied 10 patients who had neurological disorders with a MRI-based diagnosis of perisylvian dysgenesis based on the fact that the parasagittal and centrifugal extremity of the sylvian fissure was abnormally mesial. This abnormality was bilateral in seven cases; in the other three patients, the contralateral sylvian fissure appeared either normal (two cases) or enlarged (open operculum). The perisylvian cortex had a polymicrogyric appearance in most patients. Potential aetiopathogenic factors were determined in four patients. In two of them, ischaemia at mid-gestation was ascribed to death of a co-twin in a context of monozygotic twinning. In the other two patients, who were siblings, genetic factors were suspected. Pseudobulbar palsy was found in eight patients and epilepsy in five patients. We used PET with [18F]fluorodeoxyglucose to test the hypothesis that, despite this clinical and MRI heterogeneity, regional cerebral glucose distribution could have common features in these patients. The analysis of PET data was performed by visual inspection in two cases and by using statistical parametric mapping (SPM) in eight patients compared with a control group. Segmented grey matter MRIs of seven out these patients were also analysed using SPM. We found that the abnormal perisylvian cortex had normal grey matter activity in eight patients and in the other two there was a heterogeneous pattern with areas of preserved metabolism and of decreased metabolism. Metabolic changes were also detected outside the polymicrogyric-like cortex; three patients had hypometabolic areas in cortical regions where the MRI appeared normal and had a normal intensity. When polymicrogyria extended into the white matter, this ectopic dysgenetic cortex was associated with a grey matter pattern within the white matter territory, and was detected by SPM as areas of PET hypermetabolism and MRI hyperintensity. In order to detect possible metabolic changes undetected by the individual analyses, the group of patients was compared with the control group. This comparison revealed bilateral hypometabolism in the frontal opercular cortex. We propose that these PET data be considered in light of the presumed cyto-architectonic pattern of perisylvian dysgenesis, i.e. polymicrogyria. In this malformation, two dense cell layers are separated by a necrotic sparse cell layer. We speculate that the amount of synaptic activity preserved in these dense cell layers depends on the importance and timing of the necrotic process; this hypothesis accounts for the large range of metabolic patterns found, from profoundly decreased glucose metabolism to nearly normal activity.

Adolescent↗
PubMed1998

Monoclonal antibodies against epidermal growth factor prevent outgrowth of mouse embryos in vitro.

The necessity of epidermal growth factor (EGF) in the process of mouse embryo development and outgrowth in vitro was studied. Mouse 4-cell stage embryos were cultured up to spreading stage (outgrowth) in human tubal fluid (HTF) medium alone (control) or with 10 ng/ml EGF and 1:250 diluted monoclonal antibodies against EGF (study groups). Hatching and outgrowth were significantly increased up to 60.9 and 52.4% respectively, while in the control only 33.7 and 20.4% reached hatching and outgrowth respectively. Moreover monoclonal antibodies against EGF significantly inhibited embryo development (P < 0.01). Only 5.8% of the embryos reached the hatching stage and none of them reached the spreading stage. Our results show that EGF is probably involved in the modulation of early embryonic growth and in the initiation of implantation.

Animals↗
PubMed1998

Does glucose affect fertilization, development and pregnancy rates of human in-vitro fertilized oocytes?

The study was conducted to examine whether the presence of glucose in the incubation medium affects fertilization, development and implantation rates of human oocytes of patients who were attending our in-vitro fertilization programme. Harvested oocytes were transferred into one of four different media: human tubal fluid (HTF), P1, M3 and IVF-Universal (IVF-Med). Three of these contained glucose; the fourth (P1), contained no glucose or phosphate ions. In an independent preliminary study, some of the oocytes of each patient were incubated in IVF-Med, which lacks phosphate ions, but not glucose. Comparisons of fertilization rates between media pairs showed differences among all pairs except HTF and M3. When comparing the four study groups, no difference was noticed in embryo development or embryo quality 48 h post-ovum retrieval. A higher development rate was demonstrated in embryos incubated in M3 medium, in comparison with the P1 and IVF-Med embryos after incubation for 72 h. No difference in pregnancy rate was found after embryo transfers of preimplantation embryos which were incubated in one of the following media: HTF, M3 and IVF-Med (seven out of 22, 18 of 54 and 32 of 69 treatment cycles respectively). A lower incidence of pregnancies occurred following transfers of embryos which were incubated in P1 medium (seven pregnancies out of 37 cycles). We suggest that the presence of glucose in the incubation medium enhances implantation potential of in-vitro-developing preimplantation embryos.

Adult↗
PubMed1998

Hearing results of intratympanic steroid treatment of endolymphatic hydrops.

OBJECTIVES/HYPOTHESIS: This study evaluated the effectiveness of a single application of steroids to the open middle ear in improving short-term hearing in patients with Meniere's disease and cochlear hydrops. STUDY DESIGN: Retrospective study in which each patient's pretreatment hearing served as the control compared with posttreatment hearing. METHODS: Patients were treated with a single application of dexamethasone, 8 mg, in hyaluronan. Following tympanotomy and lysis of round window adhesions, steroids were placed in the round window niche with absorbable gelatin sponge and the remainder of the middle ear was then filled with the steroid solution. Systemic steroids were not administered. Audiograms were performed within 1 month before surgery and at least 1 month after surgery. RESULTS: Between September 1996 and July 1997, 21 ears in 19 patients underwent intratympanic steroid treatment. The criterion for hearing change was a 10-dB or greater change in pure-tone average (PTA), or a 15% change in speech discrimination score (SDS). Of the 15 ears meeting inclusion criteria for this study, five (33%) demonstrated hearing improvement and three (20%) demonstrated hearing deterioration. Maximum improvement was a 38-dB improvement in PTA and a 32% improvement in SDS. CONCLUSION: A single application of intratympanic dexamethasone/hyaluronan solution directly to the round window did not produce dramatic short-term hearing improvement in patients with endolymphatic hydrops. Although the theoretical basis for intratympanic steroid treatment of endolymphatic hydrops is appealing, we urge close evaluation of the results of specific protocols of intratympanic steroid administration before widespread utilization of this treatment. The choice of steroid, route of administration, frequency of application, and need for simultaneous systemic administration require standardization to adequately assess the efficacy of this treatment.

Adjuvants, Immunologic↗
PubMed1998

Potential use of granulocyte colon-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates.

The immaturity of neonatal phagocytic immunity contributes to increased mortality during neonatal sepsis. Neonates have both quantitative and qualitative neutrophil defects with decreased bone marrow neutrophil storage pool (NSP) reserves, an inability to increase neutrophil production, and defective neutrophil functional activity. Neonates respond to overwhelming sepsis with depletion of the NSP and the development of peripheral neutropenia. The myelopoietic cytokines granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been documented to induce neutrophilia in neonatal animals and human infants, increase the NSP, and upregulate neutrophils for improved functional activity. Preclinical studies in neonatal rats demonstrate increased survival with prophylactic G-CSF during experimental group B streptococcal sepsis. In pilot phase I/II human trials, G-CSF and GM-CSF were demonstrated to be both safe and well tolerated and to induce significant increases in absolute neutrophil count and NSP. Prophylactic GM-CSF in the very low birth weight neonate may reduce the incidence of nosocomial infections. Phase III trials are needed to further delineate the clinical usefulness of these myelopoietic cytokines in neonates with a high predisposition to sepsis.

Animals↗
PubMed1998

Cerebello-thalamo-cerebral diaschisis: a case report.

This reports positron emission tomography and [18F]fluorodeoxyglucose (PET-FDG) in a 69-year-old woman who underwent resection of the left cerebellar hemisphere for an acoustic neurinoma 17 years earlier. Functional impairment in cerebral cortical and subcortical structures was evaluated by studying the level of glucose metabolic activity at rest. Relative glucose metabolism was reduced in the prefrontal cortex contralateral to the cerebellar lesion. Contralateral thalamic metabolism was reduced significantly. The results suggest that this phenomenon of "crossed cerebello-thalamo-cerebral diaschisis" is related to a functional depression of the cerebello-thalamo-cortical pathway.

Aged↗
PubMed1998

Large artery remodeling during aging: biaxial passive and active stiffness.

To examine arterial mechanical changes during aging, pressure-radius and axial force-radius curves were measured in vivo in carotid arteries from 6- and 23-month-old Brown Norway X Fischer 344 rats. Incremental passive circumferential stiffness (measured at 50, 100, and 200 mm Hg) was higher (P<0.01) in the 23- compared with the 6-month-old rats (14.02+/-1.23 versus 6.58+/-1.51; 2.68+/-0.56 versus 0.99+/-0.34; 1.10+/-0.24 versus 0.69+/-0.15 dyne/mm2x10(3), respectively). Incremental passive axial stiffness was increased (P<0.01) in the 23- compared with the 6-month-old rats (7.95+/-0.70 versus 4.24+/-0.81; 1.91+/-0.10 versus 0.61+/-0.16; 0.58+/-0.09 versus 0.36+/-0.06 dyne/mm2x10(3), respectively). Active incremental circumferential arterial stiffness at 100 and 200 mm Hg was increased (P<0.01) in the older rats. In 6-month-old rats, activation of vascular smooth muscle enhanced (P<0.01) the incremental circumferential and axial stiffness measured at 200 mm Hg. In 23-month-old rats, only active incremental stiffness was increased (P<0.01) at 200 mm Hg. Aging increased (P<0.05) media thickness, collagen content, and the collagen/elastin ratio by 12%, 21%, and 38%, respectively. Elastin density and the number of smooth muscle cell nuclei were decreased by 20% and 31%, respectively, with aging. Thus, structural alterations that occur with aging are associated with changes in both active and passive stiffness. Vascular smooth muscle tone modulates arterial wall anisotropy differently during aging.

Aging↗
PubMed1998

High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group.

PURPOSE: Medulloblastoma is a highly lethal disease when it recurs. Very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. METHODS: Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/mL x min via Calvert formula) on days -8, -7, and -6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days -5, -4, and -3; followed by ASCR on day 0. In addition to the study-prescribed therapy, 21 patients received other treatment: neurosurgical resection in seven, conventional chemotherapy in 17, and external-beam irradiation in 11 cases. RESULTS: Twenty-three patients with recurrent medulloblastoma, aged two to 44 years (median, 13 years) at ASCR, were treated. Three patients died of treatment-related toxicities within 21 days of ASCR; multiorgan system failure in two, and Aspergillus infection with venoocclusive disease in one. Seven of 23 patients (30%) are event-free survivors at a median of 54 months post-ASCR (range, 24 to 78 months). Kaplan-Meier estimates of event-free (EFS) and overall survival are 34% +/- 10% and 46% +/- 11%, respectively, at 36 months post-ASCR. CONCLUSION: This strategy may provide long-term survival for some patients with recurrent medulloblastoma.

Adolescent↗