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Biomedical subjects

S Steinberg

Publications and source records attributed to S Steinberg.

At least 73 records · Page 4Linked to original sources

Detection of antibodies to varicella-zoster virus using a latex agglutination assay.

BACKGROUND: There is a clinical need to have a rapid and sensitive means to identify persons with immunity to varicella-zoster virus (VZV). OBJECTIVES: We evaluated a simple-to-perform assay for detecting antibodies to VZV using a commercial latex agglutination (LA) test, in which dilutions of test sera were added to latex particles that had been coated with VZV glycoprotein antigens. STUDY DESIGN: Sera obtained from patients, including recipients of varicella vaccine, whose clinical immune status to VZV was known, were tested by LA and the results compared to those obtained by a standard indirect immunofluorescence assay (FAMA). Using the LA test, long-term persistence of antibodies in leukemic and adult recipients of varicella vaccine were determined. RESULTS: The LA test compared favorably with FAMA in varicella susceptibles and immunes. 741 acute sera were negative and 741 convalescent varicella sera were positive by LA. Antibodies to VZV were found to persist for as long as 11 years in most recipients of varicella vaccine (n = 145). Geometric mean titers were higher by LA than FAMA. Prozone phenomena were noted in about 5% of antibody-positive sera. Results from this test are available in less than an hour, and no special equipment is required. CONCLUSIONS: This assay is rapid, simple to perform, and inexpensive. It is particularly useful for identifying individuals who are immune to varicella, including those who have been immunized in the distant past. The main problem associated with the test is that prozone phenomena can occur; these may be avoided by testing sera at various dilutions.

Journal Article↗

Transmission of varicella-zoster virus from a vaccinee with leukemia, demonstrated by polymerase chain reaction.

A 5-year-old white boy in remission from acute lymphoblastic leukemia who was receiving maintenance anticancer chemotherapy had approximately 200 vesicular skin lesions 1 month after receiving live attenuated varicella vaccine. About 2 to 3 weeks later, a mild illness resembling varicella occurred in his susceptible siblings and in three of his classmates. Vaccine-type varicella-zoster virus was demonstrated by polymerase chain reaction in swab specimens from vesicular lesions in his two siblings, in whom antibody to varicella-zoster virus also developed.

Chickenpox↗

Phase I and pharmacokinetic study of recombinant human granulocyte-macrophage colony-stimulating factor given in combination with fluorouracil plus calcium leucovorin in metastatic gastrointestinal adenocarcinoma.

PURPOSE: To determine the toxicities and potential for dose escalation of intravenous (IV) bolus fluorouracil (5-FU) given with 500 mg/m2/d leucovorin (LCV) and granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS: Thirty-seven patients received escalating doses of 5-FU/LCV on days 1 to 5 with subcutaneous GM-CSF either 5 or 10 micrograms/kg/d starting on day 6 or 3 micrograms/kg/d starting on day 1. 5-FU was escalated from 370 mg/m2/d by 15% increments between patient cohorts and within patients according to tolerance. RESULTS: With GM-CSF starting on day 6, dose-limiting toxicity occurred during cycle no. 1 in all three patients entered at 5-FU 490 mg/m2/d. However, individual patients tolerated 5-FU doses up to 644 mg/m2/d. When all cycles were analyzed, grade 3 to 4 mucositis and grade 4 granulocytopenia complicated < or = 15% and < or = 6% of cycles with 5-FU doses < or = 560 mg/m2/d (115 cycles). With GM-CSF starting on day 1, dose-limiting granulocytopenia occurred during cycle no. 1 in five of 10 patients entered at 5-FU 490 mg/m2/d. Although the granulocyte nadirs were significantly lower at each 5-FU dose level with the concurrent GM-CSF schedule (eg, 490 mg/m2/d: median, 879/microL v3,286/microL; two-tailed P [P2] < .001), dose-limiting granulocytopenia complicated < or = 16% of cycles with 5-FU < or = 560 mg/m2/d (99 cycles); > or = grade 3 mucositis occurred in < or = 20% of cycles. Grade 3 to 4 diarrhea was unusual with either GM-CSF schedule. Most patients treated with GM-CSF > or = 5 micrograms/kg/d required dose reductions for constitutional toxicity; 3.0 to 3.8 micrograms/kg/d was better tolerated. Venous thrombosis occurred in 17% of patients (concurrent v sequential GM-CSF, 29% v 5%; P2 = .08). The median delivered 5-FU dose-intensity for GM-CSF starting either on day 6 or on day 1 was 615 and 647 mg/m2/wk (P2 = .41), respectively. Pharmacologic exposure to 5-FU increased with higher doses of 5-FU, and concurrent GM-CSF administration did not affect 5-FU clearance. CONCLUSION: A starting dose of 425 mg/m2/d of 5-FU with LCV on days 1 to 5 could be safely combined with GM-CSF starting either on day 1 or day 6, with further 5-FU dose escalation according to individual tolerance.

Adenocarcinoma↗

Selecting antibiotics for nosocomial bacterial infections in patients requiring neonatal intensive care.

Nosocomial infections increase neonates' morbidity, hospital costs, and mortality. These infections occur most commonly in very low birth weight infants, who frequently required plastic intravascular catheters and parenteral nutrition. Diagnosis often relies on a combination of laboratory tests and nonspecific clinical signs. Criteria for diagnosing nosocomial infections have been published by the Centers for Disease Control (CDC) and should be used to standardize the identification of cases. Initial antibiotic therapy depends on (1) the bacterial species most likely to cause infection, (2) antibiotic resistance patterns in one's own hospital, (3) the patient's clinical condition, and (4) previous antibiotic therapy. Antibiotic coverage of both gram-positive and gram-negative bacteria is necessary. Following laboratory identification of the infecting organism and the antibiotic susceptibility results, the patient should be reevaluated and definitive therapy prescribed. Multiple antibiotics may be needed as definitive therapy if (1) the infecting organism is likely to develop resistant mutants during therapy (e.g., Pseudomonas species), (2) higher bactericidal serum activity is required than can usually be achieved with a single agent (e.g., enterococci, Listeria), (3) the patient is neutropenic or otherwise severely immunocompromised, or (4) blood cultures are persistently positive for bacteria despite appropriate therapy with a single agent. Attempts to prevent nosocomial bacteremias by routinely administering prophylactic vancomycin may hasten the development of vancomycin-resistant, coagulase-negative staphylococci or enterococci and should be avoided.

Anti-Bacterial Agents↗

Tryptophan in the treatment of late luteal phase dysphoric disorder: a pilot study.

Thirteen patients diagnosed during two menstrual cycles as suffering from late luteal phase dysphoric disorder were then followed in an open pilot study for a further three cycles. During one complete cycle, baseline levels of symptoms were obtained. During the next three cycles, the patients were treated with L-tryptophan, six grams per day. L-tryptophan treatment was associated with a significant amelioration of symptoms with only mild side effects. These data suggest that L-tryptophan should be tested at a dose of six grams of L-tryptophan per day in a placebo-controlled study in patients with late luteal phase dysphoric disorder who suffer from symptoms such as depression, irritability, insomnia and carbohydrate craving, which may respond to potentiation of serotonin function.

Adult↗

Dose-dependent inhibition of aspartate carbamoyltransferase in peripheral blood mononuclear cells in patients receiving N-(phosphonacetyl)-L-aspartate.

Forty-eight patients with adenocarcinoma of the gastrointestinal tract were treated on this trial. The MTD of 5-FU given as a 72 hour infusion with high-dose leucovorin was initially determined to be 2000 mg/m2/d. Patients were treated at PALA dose levels ranging from 250 to 2848 mg/m2. Biochemical assessment of target enzyme activity was performed at each PALA dose level. We conclude that compared to each patient's own baseline, PALA at 250 mg/m2 failed to appreciably inhibit ACTase activity at 24 hours in most patients. More consistent inhibition of ACTase activity was seen with PALA at or above 1266 mg/m2, but toxicity was prohibitive with 2848 mg/m2 PALA. Even with the highest PALA doses, ACTase activity was back to baseline by 96 hours in most patients. PALA at 1266 mg/m2 given 24 hours prior to the start of 72 hour infusional 5-FU plus high-dose leucovorin was associated with acceptable toxicity and did not appear to compromise 5-FU dose-intensity. Finally, because of interpatient variability in the degree of ACTase inhibition following PALA, biochemical monitoring of target enzyme activity may permit more rational adjustment of the PALA dose in individual patients.

Antineoplastic Agents↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗