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Biomedical subjects

B Berman

Publications and source records attributed to B Berman.

At least 19 recordsLinked to original sources
PubMed1998

Stroke prevention trial in sickle cell anemia.

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.

Adolescent↗
PubMed1998

Is the incidence of appendicitis reduced in patients with sickle cell disease?

BACKGROUND: Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributable to vasoocclusion. Experience at a single institution suggested that appendicitis was a rare cause of abdominal symptoms in this population. OBJECTIVE: We sought to determine whether the incidence of appendicitis was significantly lower in patients with SCD than in the population at large. METHODS: A 17-year retrospective chart review was performed at Rainbow Babies and Children's Hospital, Cleveland, OH, to determine the approximate incidence of acute appendicitis (AA) in patients with SCD. In addition, we performed a statistical analysis comparing the incidence of AA among SCD patients enrolled in the Cooperative Study of Sickle Cell Disease with that in the general population. RESULTS: Only two patients with SCD with pathologically confirmed AA were identified among approximately 200 patients followed at our institution during a 17-year period ( approximately 3500 patient-years), yielding an incidence rate of 5.7 cases per 10 000 patient-years. Among 3765 patients with SCD enrolled in the Cooperative Study of Sickle Cell Disease followed for a mean of 5.3 years (19 886 patient-years), a maximum of 9 cases of AA were identified, yielding an incidence rate of 4.5 cases per 10 000 patient-years. Based on data from the National Hospital Discharge Survey of 1978 to 1981, the incidence rate of AA in the general population (0 to 44 years of age) is approximately 16 per 10 000 patient-years. Paired t test analysis demonstrated a highly significant difference (P < .001) when comparing the incidence of AA among patients enrolled in the Cooperative Study of Sickle Cell Disease and the population at large. CONCLUSION: AA is an unusual event in patients with SCD. The likelihood of developing appendicitis in SCD patients is less than one third of that for the population at large. Conservative therapy is warranted in the large majority of patients with SCD who present with acute abdominal pain. Surgical exploration is best limited to patients with clear evidence of potential surgical pathology or progressive findings during a period of observation. The biologic basis of our findings remains unknown.

Acute Disease↗
PubMed1997

Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance.

BACKGROUND: The classic, first-generation histamine1-receptor antagonists used to treat allergic disorders frequently cause sedation. In contrast, sedation is reduced or absent after administration of recommended doses of second-generation histamine1-receptor antagonists. We measured the initial and steady-state effects of diphenhydramine, a first-generation antihistamine, and loratadine, a second-generation antihistamine, by means of a comprehensive battery of psychometric tests that mirror real-world tasks. METHODS: Healthy volunteers (N = 98) were randomly assigned in a double-blind fashion to receive loratadine (n = 33), diphenhydramine (n = 32), or placebo (n = 33). A computerized test battery was administered at baseline, on day 1 after administration of the initial dose, and on days 3 and 5. RESULTS: After the initial dose, subjects taking diphenhydramine demonstrated poorer cognitive performance than subjects taking loratadine or placebo on tasks of divided attention, working memory, speed, and vigilance. Subjects taking diphenhydramine also reported greater fatigue and sleepiness and lower levels of motivation, and rated the quality of their performance as lower than subjects taking loratadine or placebo. On day 3, subjects taking diphenhydramine continued to show more fatigue and lower motivation, and rated the quality of their test performance as poorer than subjects taking loratadine or placebo. There were no differences between loratadine and placebo after the initial dose or steady-state (day 5) dosing for any measure of cognitive or psychomotor test performance, mood, or sedation. CONCLUSIONS: Patients taking diphenhydramine may be at risk of lapses and significant errors that may lead to potential hazards and decreased work productivity.

Adult↗
PubMed1997

Identification of glypican as a dual modulator of the biological activity of fibroblast growth factors.

Heparan sulfate moieties of cell-surface proteoglycans modulate the biological responses to fibroblast growth factors (FGFs). We have reported previously that cell-associated heparan sulfates inhibit the binding of the keratinocyte growth factor (KGF), but enhance the binding of acidic FGF to the KGF receptor, both in keratinocytes, which naturally express this receptor, and in rat myoblasts, which ectopically express it (Reich-Slotky, R., Bonneh-Barkay, D., Shaoul, E., Berman, B., Svahn, C. M., and Ron, D. (1994) J. Biol. Chem. 269, 32279-32285). The proteoglycan bearing these modulatory heparan sulfates was purified to homogeneity from salt extracts of rat myoblasts by anion-exchange and FGF affinity chromatography and was identified as rat glypican. Affinity-purified glypican augmented the binding of acidic FGF and basic FGF to human FGF receptor-1 in a cell-free system. This effect was abolished following digestion of glypican by heparinase. Addition of purified soluble glypican effectively replaced heparin in supporting basic FGF-induced cellular proliferation of heparan sulfate-negative cells expressing recombinant FGF receptor-1. In keratinocytes, glypican strongly inhibited the mitogenic response to KGF while enhancing the response to acidic FGF. Taken together, these findings demonstrate that glypican plays an important role in regulating the biological activity of fibroblast growth factors and that, for different growth factors, glypican can either enhance or suppress cellular responsiveness.

Animals↗
PubMed1997

Recurrence rates of excised keloids treated with postoperative triamcinolone acetonide injections or interferon alfa-2b injections.

BACKGROUND: Keloids that are surgically removed commonly recur within the excision sites. OBJECTIVE: Our purpose was to determine whether postsurgical adjunctive therapy reduces such recurrences. METHODS: We determined the rate of recurrence after excision alone (n = 43) and postoperative injection with triamcinolone acetonide (TAC; n = 65) or interferon alfa-2b (IFN-alpha 2b; n = 16). RESULTS: Of lesions excised without postoperative injections, 51.1% (22 of 43) recurred; 58.4% of TAC-treated lesions (38 of 65) recurred and 18.7% of IFN-alpha 2b-treated lesions (3 of 16) recurred (p = 0.025). CONCLUSION: Postoperative TAC injections do not reduce the number of keloid recurrences. However, injection of keloid excision sites with IFN-alpha 2b offers a therapeutic advantage over keloid excision.

Adolescent↗
PubMed1997

Cutaneous disseminated histoplasmosis in AIDS patients in south Florida.

BACKGROUND: Histoplasma capsulatum is a dimorphic pathogenic fungus endemic to the Mississippi and Ohio river valleys. In the immunocompetent it causes a self-limited disease, but in the immunocompromised may lead to disseminated disease (disseminated histoplasmosis (DH)). It is one of the opportunistic infections which defines the acquired immunodeficiency syndrome (AIDS) and is rarely encountered outside endemic regions. METHODS: Clinical, laboratory, and histologic information concerning seven patients with DH and AIDS in South Florida was recorded. RESULTS: We report seven cases of DH with mucocutaneous lesions in patients infected with the human immunodeficiency virus (HIV). All patients had markedly depressed CD4 counts of less than 40 cells/mm3, and only two had traveled to endemic areas. Two out of the seven patients were diagnosed with HIV/AIDS at the time DH was identified. All of our patients had mucocutaneous lesions at the time of diagnosis, which clinically presented as a generalized papular eruption, ulcers, and erythematous scaly plaques. CONCLUSIONS: Even in non-endemic regions, HIV-positive patients presenting with fever, chills, weight loss, hepatosplenomegaly, anemia, cough, lymphadenopathy, and mucocutaneous lesions should have an early skin biopsy specimen taken for mycologic tissue culture and histopathologic evaluation for disseminated fungal infections.

AIDS-Related Opportunistic Infections↗
PubMed1997

Teledermatology.

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Confidentiality↗
PubMed1997

Teledermatology and underserved populations.

BACKGROUND: The dermatologic needs of many communities in the United States and worldwide are underserved. Telemedicine enables physicians and non-physician primary care providers to use modern telecommunications devices to gain access to specialist consultations promptly and with much less travel. The independently developed telemedicine programs described herein support 3 traditionally underserved populations: Pacific Islanders, migrant farmworkers, and prison inmates. OBSERVATIONS: In 3 independently designed telemedicine programs, dermatology emerged as the specialty most used by remote practitioners. Patients were presented for both diagnosis and treatment and in the setting of initial evaluation and as part of follow-up care. CONCLUSION: Teledermatology is a useful way to provide dermatologic support to remote or underserved communities.

Dermatology↗
PubMed1997

Timing of the expression of enamel gene products during mouse tooth development.

In order to understand the mechanisms involved in tooth development it is important to define the timing for tissue-specific gene expression. A consequence of ameloblast cell differentiation is the sequential expression of tissue-specific genes whose products form the enamel extracellular matrix. The ameloblast phenotype has been characterized as consisting of two major classes of proteins: amelogenins and non-amelogenin proteins such as anionic enamel proteins (enamelins, tuft proteins, tuftelin, sulfated proteins) and enamel proteases. The postulated functions for the anionic enamel proteins are as nucleators for hydroxyapatite crystal formation while amelogenins control the crystal size, growth and orientation. While the amelogenins have been well characterized, detailed knowledge for anionic enamel proteins has been sparse. In the present study, we designed experiments to characterize one of the anionic enamel proteins from mouse molars, tuftelin, and to determine the timing of expression of this protein during molar tooth development. Our results showed the initial detection of tuftelin transcripts within proliferating inner enamel epithelial cells at very early stages of tooth development (13 days of embryonic development equivalent to the bud stage of tooth development). These data provide direct evidence that invalidates previous dogmas that enamel proteins were synthesized by polarized, non-dividing, fully differentiated ameloblast cells. In addition, tuftelin was found to be synthesized also by dental papilla mesenchyme cells suggesting that this protein is not enamel-specific. These data taken together open the possibility that the tuftelin present in the dentino-enamel junction could be secreted by both, preodontoblast cells and preameloblast cells. It might also suggest a possible different role for tuftelin than nucleator of hydroxyapatite crystals.

Amelogenin↗
PubMed1996

Adjunct therapies to surgical management of keloids.

BACKGROUND: The literature describing surgical treatments, with or without supplementary nonsurgical treatments for keloids, offers a confusing picture of widely variable "success" rates, recurrence rates, patient populations, and follow-up periods. OBJECTIVE: A review of the surgical treatment of keloids with emphasis on surgery combined with nonsurgical therapies is presented. RESULTS: Surgery alone leads to recurrence rates ranging from 45 to 100%. When surgery is combined with intradermal corticosteroids the recurrence rate in the majority of studies falls below 50%. Surgery combined with button compression therapy on earlobes led to no recurrences. External radiation following excision, often combined with other therapies, has been associated with recurrence rates of less than 10%. Various lasers have been used in the treatment of keloids with great variability in the recurrence rate but in general result in similar recurrence rates as conventional surgery. As with cryodestruction, laser ablation recurrence rates often are improved when combined with other treatments. Inferon-alpha 2b injected after keloid excision demonstrated, in a small series of patients an 8% recurrence rate. CONCLUSION: Presently, it appears that a combined therapeutic approach offers the most propitious possibility for preventing keloid recurrence.

Combined Modality Therapy↗
PubMed1995

Chimeric molecules between keratinocyte growth factor and basic fibroblast growth factor define domains that confer receptor binding specificities.

Basic fibroblast growth factor (FGF) and keratinocyte growth factor (KGF) are structurally related fibroblast growth factors, yet they exhibit distinct receptor binding specificity. Basic FGF binds with high affinity to FGFR1, FGFR2, and FGFR4, whereas KGF does not interact with these receptors and can only bind an isoform of FGFR2 known as the KGFR. Basic GFG binds KGFR but with lower affinity than KGF. In order to identify domains that confer this specificity, four reciprocal chimeras were generated between the two growth factors and were analyzed for receptor recognition and biological activity. The chimeras are designated BK1 (bFGF1-54:KGF91-194), BK2 (bFGF1-74:KGF111-194), KB1 (KGF31-90:bFGF55-155), and KB2 (KGF31-110:bFGF75-155). The two BK chimera similarly interacted with FGFR1 and FGFR4 but differed from each other with respect to KGFR recognition. BK1 displayed a slightly better affinity for KGFR than BK2 and induced a higher level of DNA synthesis in keratinocytes compared with bFGF and BK2. A neutralizing monoclonal antibody directed against bFGF specifically neutralized the biological activity of the BK chimeras. The reciprocal chimeras, KB1 and KB2, exhibited KGF-like receptor binding and activation properties. However, KB2 displayed higher affinity for KGFR and was significantly more potent mitogen that KB1. Altogether, our results suggest that the amino-terminal part of KGF and bFGF plays an important role in determining their receptor binding specificity. In addition, the results point to the contribution of a segment from the middle part of KGF (residues 91-110) for recognition and activation of the KGFR, as the two chimeras containing these residues (BK1 and KB2) displayed an enhanced interaction with the KGFR.

3T3 Cells↗