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S Steinberg

Publications and source records attributed to S Steinberg.

At least 19 recordsLinked to original sources
PubMed1992

Decreased mesenteric blood flow in experimental multiple organ failure.

Disorders of mucosal blood flow may contribute to gut barrier dysfunction in multiple organ failure (MOF). We evaluated alterations of mesenteric microcirculation in a rat model of MOF. Male Wistar rats received 1 mg/g body weight of zymosan A in 4 ml of mineral oil by intraperitoneal injection and were studied on Days 1, 3, and 5 following injection. A control group received no zymosan. The experimental group also received a fluid resuscitation regimen of 0.9 N saline subcutaneously equal to 0.1 ml/g body weight on the day of zymosan injection and 0.05 ml/g body weight daily thereafter. Day 1 animals tended toward a statistically significantly lower mean arterial pressure versus controls (86.6 +/- 8 mm Hg versus 106 +/- 5 mm Hg, F = 0.09 by ANOVA). Significant arteriolar vasoconstriction occurred on Days 1 and 3 versus control (70 +/- 4 microns and 57 +/- 8 microns versus 96 +/- 3 microns, F = 0.0002). Laser doppler velocity, indicating red blood cell velocity, expressed as a percentage of control paralleled this vasoconstriction (70 +/- 9 and 72 +/- 7%, respectively). We conclude that mesenteric arteriolar vasoconstriction occurs accompanied by decreased red blood velocity. We believe that this is indicative of decreased mesenteric perfusion in this zymosan model of MOF and that survival to Day 5 is associated with a reversal of these microcirculatory changes.

Animals↗
PubMed1992

Acyclovir treatment of varicella in otherwise healthy adolescents. The Collaborative Acyclovir Varicella Study Group.

STUDY OBJECTIVE: To determine whether orally administered acyclovir is of therapeutic benefit for varicella in otherwise healthy adolescents, and to compare the severity of the disease in adolescents with that in younger children. DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial. SETTING: Patients' homes and university hospital clinics. PATIENTS: Sixty-eight adolescents between 13 and 18 years of age with varicella entered the study. Of the 62 adolescents with laboratory-confirmed varicella who were included in the final analysis, 31 received acyclovir and 31 received placebo. INTERVENTIONS: Placebo or an 800 mg acyclovir tablet was given orally four times daily for 5 days, beginning within 24 hours of onset of rash. MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients had significant reductions in times to cessation of new lesion formation (p less than 0.001), maximum number of lesions (p = 0.019), and defervescence (p = 0.045). Mean constitutional illness score was significantly reduced on day 4 (0.5 vs 1.5, p = 0.05), as was the mean number of residual hypopigmented lesions present on 28-day follow-up examination (22.7 vs 92.7, p = 0.018). Two complications, both bacterial superinfections, occurred in placebo recipients. Adverse experiences and varicella-zoster virus antibody titers measured 28 days after enrollment were similar in both treatment groups. Comparison of placebo recipients with children 2 to 12 years of age participating in a companion study indicated that varicella is more severe in adolescents: mean maximum total lesions (421 vs 347, p = 0.003), mean maximum constitutional illness score (3.1 vs 2.2, p = 0.032), and mean number of residual lesions (92.7 vs 33.2, p = 0.01) were all greater in the adolescent population. CONCLUSIONS: Oral acyclovir therapy is safe and effective for treatment of varicella in otherwise healthy adolescents; this may be an appropriate subgroup for treatment with antiviral drugs because the disease is more severe in them than in younger children.

Acyclovir↗
PubMed1992

Varicella vaccine: the American experience.

Live attenuated varicella vaccine is safe and effective in preventing chickenpox. The best immune responses occur in healthy children. Leukemic children have a 50% incidence of mild-to-moderate adverse effects but have a high degree of protection once immune reactions to varicella-zoster virus (VZV) have developed. Adult vaccinees have a lower degree of protection (70%) than children. Vaccinees who develop breakthrough varicella usually have a modified infection. Another significant advantage of vaccination is that in leukemic children it leads to a lower incidence of zoster than after natural chickenpox. It is possible to differentiate between vaccine-type and wild-type VZV using a combination of polymerase chain reaction and restriction endonuclease digestion. A new assay for antibodies to VZV measured by latex agglutination reveals that 8-10 years after vaccination antibodies are detectable in greater than 90% of leukemic children who have not had breakthrough varicella.

Adult↗
PubMed1992

Suramin: a novel growth factor antagonist with activity in hormone-refractory metastatic prostate cancer.

PURPOSE: Suramin is known to inhibit the growth of malignant prostate carcinoma cells in vitro. This led us to evaluate the effectiveness of suramin in the treatment of 38 patients with prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS: Suramin was administered by continuous infusion at a rate designed to reach a peak of 300 micrograms/mL at the end of 14 days. Patients were given 8 weeks to recover from any toxicity before beginning the second cycle. Subsequent cycles were administered in the same manner except the starting dose rate was 280 mg/m2. RESULTS: In 17 patients with measurable soft tissue disease, three had complete disappearance of soft tissue disease for 4, 5, and 11 months, whereas three patients had a greater than or equal to 50% decrease in the sum of the products of the diameters of all measurable disease for greater than or equal to 1 month. Of these 17 patients, pretreatment prostate-specific antigen (PSA) decreased by 75% or more in five (29%) and normalized in one (6%). The remaining 21 patients had disease limited to bone, and only one of these experienced resolution of more than 50% of all lesions on bone scan. Of these 21 patients, pretreatment PSA decreased by 75% or more in eight (38%) and normalized in five (25%). Median time to progression for all patients was 26.3 weeks, and median survival was 42.3 weeks. Patients with bone involvement alone exhibited a better survival than patients with soft tissue involvement (P2 = .02). Survival was strongly correlated (P2 = .0001) with a decline in the pretreatment PSA of greater than or equal to 75% by the eighth week on therapy, with nearly an 85% survival at 1 year compared with a 20% survival for those whose pretreatment PSA did not decline by that amount. CONCLUSION: We conclude that suramin is an active agent in hormone-refractory prostate carcinoma.

Aged↗
PubMed1992

Mesenteric microcirculatory changes in nonlethal hemorrhagic shock: the role of resuscitation with balanced electrolyte or hypertonic saline/dextran.

Class I and II hemorrhage has been routinely treated clinically with 2-2.5 times the volume of shed blood as balanced electrolyte solution. Although this regimen has been shown to adequately restore arterial pressure in trauma patients, it is not clear that it uniformly restores regional perfusion. Since it is becoming apparent that the gut plays a major role in the development of the posttraumatic septic state, we studied the effects of graded doses of balanced electrolyte resuscitation on the mesenteric microcirculation. Regimens consisting of one (1 x LR), two (2 x LR), or three (3 x LR) times the volume of shed blood as lactated Ringer's (LR) solution or 7.5% hypertonic saline and 6% dextran (HSD) equal to one seventh the volume of shed blood were given to groups of anesthetized (urethane-chloralose) male Sprague-Dawley rats after 30 minutes of hemorrhage to 50% of baseline mean arterial blood pressure. The microcirculation of the distal ileum was observed using an in vivo video microscope. Mean arterial pressure and ileal A1 diameters returned to baseline values with HSD within 20 minutes following this moderate hemorrhage. Additionally, A1 diameters returned to baseline in the 2 x LR and 3 x LR groups. A1 vessels remained significantly constricted in the 1 x LR group. Mean arterial pressure remained significantly lower than the baseline value in all of the LR groups. We conclude that in this model, HSD is superior to LR for restoration of blood pressure. In restoring A1 diameters, LR is equivalent to HSD only when volumes of balanced electrolyte two and three times shed blood volume are given.

Animals↗
PubMed1992

Melkersson-Rosenthal syndrome: clinical, pathologic, and therapeutic considerations.

Melkersson-Rosenthal syndrome (MRS) has been described as a rare disease. Localized swelling (usually of the lips) with noncaseating epithelioid granuloma is necessary for diagnosis. We report 11 patients with biopsy-proven MRS. Mean age was 28 years (range 12-47 years). Mean duration of lesions was 4.4 years. Lip biopsy confirmed typical sarcoid-like granuloma. Five additional patients with typical symptoms are awaiting or refused lip biopsy. Clinically all patients presented with localized swelling of the lips. Treatment with clofazimine (100 mg 4 times weekly for 3-11 months) was associated with complete remission in 5/10 patients and clinical improvement in 3/10 patients with moderate constant swelling. Two patients (one severe and one moderate swelling) failed to respond to treatment. Rebiopsy in four patients confirmed improvement with disappearance or decreased granulomatous inflammation in 3/4. Complete spontaneous remission was also seen in three untreated patients. We conclude MRS is not uncommon, clofazimine may be effective treatment in moderate lesions and spontaneous remissions can occur.

Adolescent↗
PubMed1992

Results of the National Cancer Institute early breast cancer trial.

In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in-breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy.

Actuarial Analysis↗
PubMed1991

The treatment of late luteal phase dysphoric disorder.

This mini-review provides a comprehensive discussion of the management of the late luteal phase dysphoric disorder (LLPDD). The various treatments will be described with particular attention to their efficacy and the nature of side effects. These include: psychoactive drugs (lithium, anxiolytics, antidepressants), nutritional agents (L-tryptophan, Vitamin B6, prostaglandins precursors and inhibitors), dopamine agonists, diuretics, antihypertensives, hormonal interventions (gonadotrophin releasing hormone analogues, oestradiol, tamoxifen, progesterone, danazol, and oral contraceptives). Less attention has been given to non-pharmacologic approaches such as diet, exercise and psychotherapy. The availability of an operational definition of LLPDD in the DSM-III-R and the improvement in research methodology has provided a clearer direction for clinical management and for future investigations.

Exercise↗
PubMed1991

Multifactorial assessment of bulimia nervosa.

We investigated a multifactorial approach to the assessment of bulimia nervosa by means of hierarchical factor analysis. Two hundred forty-five bulimia nervosa patients and 68 patients with either anorexia nervosa or eating disorders not otherwise specified were administered a self-report battery that was organized into 21 dimensions relevant to eating disorder patients. When dimensions from this battery were subjected to hierarchical factor analysis, support for bulimia nervosa as a unique diagnostic category was obtained. However, the emergence of 3 secondary factors and 6 primary factors suggests that bulimia nervosa can also be described more complexly. The emergence of a multifactorial model of bulimia nervosa that incorporates several existing undimensional models suggests the potential for both divergent and complicated clinical presentation in bulimia nervosa patients.

Bulimia↗
PubMed1990

Detection of primary colorectal cancer with indium 111 monoclonal antibody B72.3.

B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.

Adenocarcinoma↗
PubMed1990

Definitive control of mortality from severe pelvic fracture.

Within a group of 271 patients with pelvic fracture, 69 patients met criteria for severe hemorrhage. Sixty consecutive patients were treated by a combined multispecialty musculoskeletal trauma service using a protocol designed to control bleeding, rapidly diagnose and control associated injuries, as well as to prepare the patient for open reduction of the pelvic fracture, if appropriate. The pneumatic antishock garment, external fixation, and angiography were selectively used to control bleeding. Abdominal injuries were diagnosed using clinical examination and diagnostic peritoneal lavage. When lavage aspirate was grossly bloody, patients had no negative explorations. Microscopically positive lavages were associated with a 50% false-negative rate. Using the protocol, the mortality rate was 5%. Overall mortality rate was 10%. The combination of a trauma team approach and a specifically designed protocol reduces the number of deaths from pelvic fracture.

Adult↗
PubMed1990

Persistent arteriolar constriction in microcirculation of the terminal ileum following moderate hemorrhagic hypovolemia and volume restoration.

A stable in vivo preparation of moderate hypovolemia with prompt volume restoration was produced in anesthetized rats. The microcirculation of the terminal ileum was observed in vivo videomicroscopy, and changes in mean arterial pressure (MAP) as well as arteriolar diameters were recorded after a 30-min period in which the MAP was reduced by 50% by bleeding. Volume was restored with shed blood alone (control); dextran 70 alone (dextran); or dextran + hypertonic (7.5%) saline (dextran + HS). A final group of rats was pretreated with allopurinol 5 mg/kg and then treated identically to the control group to assess the role of the xanthine oxidase system in microcirculation changes following hemorrhage. MAP was restored to normal by return of shed blood in control animals, but inflow arterioles (A1) remained significantly constricted. MAP was significantly higher and A1 arteriolar dilation was observed in the dextran + HS group. Responses in allopurinol-pretreated animals were not different from the responses seen in control animals. We conclude that persistent arteriolar constriction is produced by moderate hypovolemia and this effect is ameliorated by volume restoration with dextran + HS.

Allopurinol↗
PubMed1990

Once-daily intramuscular ceftriaxone in the outpatient treatment of severe community-acquired pneumonia in children.

Ceftriaxone, a broad spectrum third-generation cephalosporin with a half-life of six to eight hours, was evaluated prospectively in 147 children with severe community-acquired bacterial pneumonia during the period 11/15/88-5/15/89. Thirty-nine of the children had been unsuccessfully treated with vanous oral antibiotics prior to admission [corrected]. All the patients were initially hospitalized and started on once a day intramuscular ceftriaxone. Mean duration of ceftriaxone therapy was five days. Pathogens were recovered from blood cultures of 17 (11.6%) patients and included S. pneumoniae (13 patients), H. influenzae (three, all resistant to ampicillin) and S. viridans (1) [corrected]. All isolates were sensitive to ceftriaxone. An additional patient had L. pneumophila diagnosed by serology. Cure was achieved in 142 (96.6%) patients; improvement was usually observed within 24-48 hours. After 48 hours, 121 (82.2%) children could be discharged and continued the therapy on ambulatory basis. Based on previous experience we estimated that 383 hospitalization days were saved. No serious side effects were observed. Five patients were considered therapeutic failures; two of them developed empyema and one of them required repeated drainage procedures. A third patient experienced a relapse of pneumonia shortly after completion of therapy. The other two remained febrile for more than seven days; their subsequent improvement was unrelated to the antibiotic therapy, suggesting a viral or mycoplasmal syndrome. Our data suggest that once daily intramuscular ceftriaxone can be successfully used for the outpatient treatment of most community-acquired severe bacterial pneumonias in children. In our opinion it represents the treatment of choice for patients who failed treatment with other antimicrobials and are clinically stable enough not to require hospitalization.

Adolescent↗
PubMed1989

Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins.

Endothelium is an important target of tumor necrosis factor/cachectin (TNF), a central mediator of the host response in endotoxemia and Gram-negative sepsis. In this report, TNF is shown to increase the permeability of endothelial cell monolayers to macromolecules and lower molecular weight solutes by a mechanism involving a pertussis toxin-sensitive regulatory G protein. Within 1-3 h of exposure to TNF (5 nM), changes in cell shape/cytoskeleton occurred that led to disruption of monolayer continuity with the formation of intercellular gaps. Correlated with these structural changes was an increase in endothelial permeability to macromolecular and lower molecular weight tracers; time-dependent, reversible increases in passage of these tracers, evident by 1-3 h, were observed after addition of TNF to cultures. Perturbation of barrier function by TNF also depended on the dose of TNF added being half-maximal by approximately 0.4 nM. Only a brief exposure (15 min) of TNF to endothelium was required to induce an increase in permeability, and this was not prevented by the presence of cycloheximide or actinomycin D. Preincubation of monolayers with pertussis toxin blocked in parallel TNF-induced increased passage of solutes and cell shape/cytoskeletal perturbation, indicating the close correlation between these changes in endothelial cell function. In contrast, pertussis toxin did not alter TNF-induced modulation of two endothelial cell coagulant properties. These data provide evidence for two intracellular pathways of TNF action that are distinguishable by pertussis toxin and provide insight into a mechanism underlying loss of solute from the intravascular space mediated by TNF: alteration in endothelial cell barrier function.

Animals↗
PubMed1989

Development of a bacteria-independent model of the multiple organ failure syndrome.

Criteria that allow definition of the multiple organ failure syndrome include pulmonary, hepatic, renal, and gut barrier dysfunction along with characteristic histopathologic changes. It has been difficult to study multiple organ failure due to lack of a satisfactory experimental model that would reproduce the pathophysiologic and histopathologic characteristics, would be stable enough to allow study over several days, and would be free of exogenous primary bacterial infection. We have studied pathophysiologic and histopathologic alterations in a potential model of multiple organ failure. Wistar rats received one of the following solutions by intraperitoneal injection: 4 mL of saline, 4 mL of mineral oil, or 1 mg per gram of body weight of zymosan A in 4 mL of mineral oil. Animals that received zymosan developed hypoxia, decreased creatinine clearance, and changes in hepatic microsomal cytochrome P450 content and aniline hydroxylase activity. Bacterial translocation occurred in the zymosan group. The lungs, liver, and kidneys of the animals that received zymosan exhibited histopathologic changes. We conclude that this model fulfills our criteria for a model of multiple organ failure.

Animals↗
PubMed1989

Electrophysiological assessment of putative antagonists of 5-hydroxytryptamine receptors: a single-cell study in the rat dorsal raphe nucleus.

The intravenous administration of low doses of lysergic acid diethylamide (LSD) or of the selective 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) depresses the firing activity of dorsal raphe 5-HT-containing neurons, presumably via the activation of 5-HT1A receptors. The present studies were undertaken to determine the effect of different types of 5-HT receptor antagonists on this effect of LSD and 8-OH-DPAT. (-)-Propranolol (2 mg/kg i.v.), methiothepin (2 mg/kg i.p., twice daily for 4 days followed by an additional dose of 2 mg/kg i.p., prior to the experiment), pelanserine (0.5 mg/kg i.v.), and indorenate (125 micrograms/kg i.v.) failed to block the effects of either LSD or 8-OH-DPAT on the firing activity of 5-HT neurons of the dorsal raphe nucleus. However, spiperone (1 mg/kg i.v.) significantly reduced the effect of both LSD and 8-OH-DPAT. These results indicate that, among the five putative 5-HT receptor antagonists tested, only spiperone can antagonize the suppressant effect of 5-HT receptor agonists on the firing of dorsal raphe 5-HT neurons.

5-Methoxytryptamine↗
PubMed1989

Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer.

We performed an escalating dose study of the combined administration of interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) in 94 patients with metastatic cancer. Patients received alpha-IFN at a dose of 3 x 10(6) U/m2 in conjunction with IL-2 at doses of either 1 x 10(6) U/m2 (six patients), 3 x 10(6) U/m2 (32 patients), or 4.5 x 10(6) U/m2 (26 patients). Thirty patients received alpha-IFN at 6 x 10(6) U/m2 plus IL-2 at 4.5 x 10(6) U/m2. Patients each received cytokine as an intravenous bolus infusion every 8 hours for up to 5 consecutive days and after a 10-day rest received a second cycle of combination cytokines. Of the 91 patients evaluable for response, seven patients had a complete regression of cancer, and 18 had a partial regression. At the four increasing dose levels used in patients with renal cell cancer (35 patients) or melanoma (39 patients), objective responses were seen in 17% (of six patients), 24% (of 25 patients), 38% (of 16 patients), and 41% (of 27 patients), respectively. Of the 25 total responding patients, 16 are still responding 5 to 14 months after treatment. The toxicities associated with the combined administration of IL-2 and alpha-IFN were similar to those expected from each agent alone. There was one treatment-related death in the 94 patients treated in this study. Thus, using increasing doses of the combination of IL-2 and alpha-IFN, it appears that response rates may be related to the doses of the cytokines used, and that at the highest doses of these combination cytokines, response rates may be higher than those for either cytokine alone. A prospective randomized trial comparing the cytokine combinations with each cytokine administered alone is necessary as is the extension of this combination cytokine treatment to patients with other types of solid cancer.

Adult↗