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D Finkelstein

Publications and source records attributed to D Finkelstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Analysis of MHC class II DP, DQ and DR alleles in Crohn's disease.

BACKGROUND: Although inflammation in Crohn's disease is believed to be mediated by activated T cells, genotyping of all MHC class II alleles in white people with this disease has not been reported. AIMS: To perform a detailed molecular analysis of HLA DPB, DQB, and DRB genes in white patients with Crohn's disease and controls in order to determine if the inheritance of any class II genes confers susceptibility or resistance to this disease. METHODS: Complete molecular typing of HLA class II DPB, DQB, and DRB alleles was performed in 58 white patients with Crohn's disease and 93 healthy controls using a polymerase chain reaction-sequence specific oligonucleotide based approach. RESULTS: No significant association with any DPB or DQB alleles was noted in patients with Crohn's disease. Since our previous studies had shown a strong association of an HLA DRB3*0301/DRB1*1302 haplotype with Crohn's disease, we re-examined this association using more stringent genotyping criteria. This haplotype was present in 20.7% of patients and 5.4% of controls (p = 0.0066; relative risk = 4.59). CONCLUSIONS: The DRB3*0301/DRB1*1302 haplotype is the only significant MHC class II association noted in white people with Crohn's disease and represents the strongest association of any MHC or non-MHC locus with this disease.

Adult↗
PubMed1997

Brainstem tolerance to conformal radiotherapy of skull base tumors.

PURPOSE: The aim of this study was to analyze the long-term incidence of brainstem toxicity in patients treated for skull base tumors with high dose conformal radiotherapy. METHODS AND MATERIALS: Between 1974 and 1995, 367 patients with chordomas (n = 195) and chondrosarcomas (n = 172) of the base of skull have been treated with combined megavoltage photon and 160 MeV proton radiotherapy. Following 3D treatment planning with delineation of target volumes and critical nontarget structures dose distributions and dose-volume histograms were calculated. Radiotherapy was given an 1.8 Gy or CGE (=Cobalt Gray Equivalent) dose per fraction, with prescribed target doses ranging from 63 CGE to 79.2 CGE (mean = 67.8 CGE). Doses to the brainstem surface were limited to < or = 64 CGE and to the brainstem center to < or = 53 CGE. RESULTS: Follow-up time ranged from 6 months to 21.4 years (mean = 42.5 months). Brainstem toxicity was observed in 17 of 367 patients attributable to treatment, resulting in death of three patients. Actuarial rates of 5 and 10-year high-grade toxicity-free survival were 94 and 88%, respectively. Increased risk of brainstem toxicity was significantly associated with maximum dose to brainstem, volume of brainstem receiving > or = 50 CGE, > or = 55 CGE, and > or = 60 CGE, number of surgical procedures, and prevalence of diabetes or high blood pressure. Multivariate analysis identified three independent factors as important prognosticators: number of surgical procedures (p < 0.001), volume of the brainstem receiving 60 CGE (p < 0.001), and prevalence of diabetes (p < 0.01). CONCLUSIONS: Tolerance of brainstem to fractionated radiotherapy appears to be a steep function of tissue volume included in high dose regions rather than the maximum dose of brainstem alone. In addition, presence of predisposing factors as well as extent of surgical manipulation can significantly lower brainstem tolerance in the individual patient.

Adolescent↗
PubMed1997

FGF plays a subtle role in oligodendrocyte maintenance in vivo.

Numerous in vitro studies indicate that fibroblast growth factors (FGFs) play a role in both the development and maintenance of oligodendrocytes. Addition of FGF to mature oligodendrocytes in culture was reported to downregulate the expression of genes encoding proteins of the myelin sheath and to induce a loss of myelin compaction. In this study, a model was developed to functionally block FGF signaling in oligodendrocytes in vivo, by generating transgenic mice expressing a dominant-negative FGF receptor (FGFR1), under the control of the myelin basic protein (MBP) promoter. To demonstrate the effectiveness of this model, truncated FGFR1 was first overexpressed in an FGF-responsive cell line in vitro. It was confirmed that FGF-signalling was blocked in these cells. Subsequently, five independent transgenic lines ("MBP-FRD") were generated. Three lines expressing the highest level of the transgene were further studied. Initial investigation by Western blot and light microscopic analyses revealed no apparent alterations in myelination of the MBP-FRD mouse brains. However, ultrastructural analysis of myelinated optic nerve fibres from two independent MBP-FRD lines revealed a significant increase in myelin thickness as a function of fibre diameter for both transgenic lines (13% and 16% increase). This increase in myelin thickness was not accompanied by alterations in myelin compaction. These results support the idea that FGF signaling in oligodendrocytes plays a role in the modulation of axon myelination in vivo.

Animals↗
PubMed1997

Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle.

The cytokine leukemia inhibitory factor (LIF) favors the survival and growth of axons in vitro and in vivo. Fibronectin has been shown to enhance nerve regeneration when added in combination with various growth factors including LIF. The goal of this study was to evaluate the effect of LIF plus fibronectin on the regeneration of transected nerve and functional recovery of reinnervated skeletal muscle, in one experimental model of peripheral nerve repair, at two recovery times. The rat sciatic nerve was cut at mid-thigh level and a silicone cuff containing either saline (control), LIF, or LIF plus fibronectin (L+F) was used to bridge the proximal and distal nerve stumps leaving a 1 cm gap between them. Rats were then explored at 6 or 12 weeks following the initial surgery. Regenerating nerves were assessed by measuring the diameter of myelinated axons, conduction velocity, and number of myelinated fibers. Muscle reinnervation was assessed by measuring muscle mass, force of contraction, and histologically for changes in muscle fiber type (type I and type II). In this report we demonstrate that at 6 weeks there were significant increases in 1) nerve conduction velocity, 2) myelinated axon diameter, and 3) number of myelinated axons over that of control (saline-treated) animals. Both LIF groups demonstrated a shift in type II muscle fiber area compared to saline-treated controls, with the L+F group having a significant increase in muscle mass. At 12 weeks there was an improved recovery over and above that demonstrated at 6 weeks. Muscle mass was 65% and 42% greater than control for LIF and L+F, respectively. Force of contraction, conduction velocity, myelinated fiber number, and diameter were also significantly greater for both LIF- and L+F-treated rats than saline-treated rats. These results demonstrate that LIF significantly improves the regeneration of damaged peripheral nerves and the preservation of muscle viability, resulting in greatly enhanced recovery of skeletal muscle function.

Analysis of Variance↗
PubMed1997

Parental involvement in diabetes management tasks: relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus.

OBJECTIVES: The goal of this study was to identify parental behaviors that relate to adherence and metabolic control in a population of young adolescents with insulin-dependent diabetes mellitus (IDDM), and to understand the interrelationships among the variables of parental involvement, adherence to blood glucose monitoring, and glycemic control. STUDY DESIGN: A cross-sectional design was used to investigate parental involvement in diabetes regimen tasks in 89 youth, aged 10 to 15 years, with IDDM. Levels of parental involvement in blood glucose monitoring (BGM) and insulin administration were evaluated through interviews. Assessment of adherence was made by physicians or nurses, independent of patient or parent reports of adherence. Glycemic control was assessed with glycosylated hemoglobin (HbA1c) (reference range, 4% to 6%). RESULTS: There were significant differences in the mean HbA1c values between the older (13 to 15 years of age) (HbA1c = 8.9% +/- 1.03%) and younger (10 to 12 years) patients (HbA1c = 8.4% +/- 1.06%) (p < 0.02). Parental involvement in BGM was significantly related to adherence to BGM (number of blood sugar concentrations checked daily) in both groups of adolescent patients. The younger patients monitored their blood glucose levels more frequently than did the older patients, 39% of the younger patients checked sugar concentrations four or more times daily compared with only 10% of the older group (p < 0.007). In a multivariate model controlling for age, gender, Tanner staging, and duration of diabetes, the frequency of BGM was a significant predictor of glycemic control (R2 = 0.19, p < 0.02). Increased frequency of BGM was associated with lower HbA1c levels. When the frequency of BGM was zero or once a day, the mean HbA1c level was 9.9% +/- 0.44 (SE); when the frequency of BGM was two or three times a day, the mean HbA1c level was 8.7% +/- 0.17; and when the frequency of BGM was four or more times daily, the mean HbA1c level was 8.3% +/- 0.22. CONCLUSIONS: Parental involvement in BGM supports more frequent BGM in 10- to 15-year-old patients with IDDM. This increased adherence to BGM is associated with better metabolic control (i.e., lower HbA1c levels). These findings suggest that encouraging parental involvement in BGM with 10- to 15-year-old patients with IDDM may help to prevent the well-documented deterioration in glycemic control and adherence to treatment that often occurs in later adolescence.

Adolescent↗
PubMed1997

Current concepts in the management of central retinal vein occlusion.

The results of the Central Vein Occlusion Study (CVOS) guide the management of macular edema and neovascularization. This study did not show that grid-pattern laser photocoagulation had a significant beneficial effect for the management of decreased visual acuity caused by perfused macular edema in eyes with central retinal vein occlusion (CRVO). Panretinal laser photocoagulation (PRP) was shown to be beneficial for eyes with at least 2 clock hours of iris neovascularization or any angle neovascularization. PRP has not been advocated as prophylaxis for ischemic eyes before the formation of neovascularization. Although treatment of the ocular consequences of CRVO may be guided by the CVOS data, management of the underlying cause of CRVO-the occluded vein itself-was not addressed in the study. Recently, several reports have suggested restoring venous outflow by 1) creating a laser-induced or surgically induced chorioretinal anastomosis, 2) administering recombinant tissue plasminogen activator (rt-PA), 3) cannulating the retinal vein transvitreally, or 4) transecting the posterior scleral ring.

Animals↗
PubMed1997

When a physician harms a patient by a medical error: ethical, legal, and risk-management considerations.

Errors that harm patients are infrequently brought to the attention of these patients. The full disclosure of such medical errors is in the best interest of patients because it allows them to understand what has occurred, and to gain appropriate compensation for the harm that they have suffered. Physicians have been given little guidance regarding how to conduct a relationship with the patient after such an injury. We argue that the physician must continue to respect the patient, and communicate honestly with him or her throughout their relationship, even after the patient has been injured. It is painful to admit our errors, especially to those who have been harmed by them. Nevertheless, offering an apology for harming a patient should be considered to be one of the ethical responsibilities of the profession of medicine. Monetary compensation alone is not to be offered as a charitable gesture; rather, it should be accompanied by an apology to demonstrate the responsibility of the physician to the trusting patient. Full and honest disclosure of errors is most consistent with the mutual respect and trust patients expect from their physicians. Clearly, physicians' ethical responsibilities sometimes differ from their legal and risk-management responsibilities.

Adult↗
PubMed1996

Primary care involvement among hospitalized children.

OBJECTIVE: To examine relations between characteristics of a child's usual source of primary care and involvement of that source before and during hospitalization. DESIGN: Medical record review of pediatric hospitalizations. SETTING: All hospitals in Boston, Mass; New Haven, Conn; and Rochester, NY admitting children during the calendar years 1988 through 1990. PATIENTS: The study included 1875 randomly selected pediatric hospitalizations for five diagnostic groups (i.e., asthma and other lower respiratory tract disease, abdominal pain [including appendicitis], meningitis [bacterial and viral], toxic ingestions, and head injury). Hospital records selected were limited to children aged between 1 month and 12 years and residing in the three study communities. OUTCOME MEASURES: Whether the primary care source examined the child before admission to the hospital, referred the child to the emergency department, or served as the in-hospital attending physician. RESULTS: Of the medical charts reviewed, 85.7% identified primary care sources. Children in Rochester had higher rates of medical visits before admission (P < .04), referrals (P < .001), and in-hospital care provided by the primary care physician (P < .001, chi 2) than children in Boston and New Haven. Patterns of primary care involvement also varied by source of care within cities, after controlling for income and severity of illness. Compared with children from Rochester community-based private practices, children in Boston receiving care from health centers, hospitals, or community-based private practices generally had 25% to 50% lower likelihood of positive findings on all primary care involvement measures. Children in New Haven receiving care from community-based private or hospital-based practices also had lower rates, but involvement rates were not higher when they received care from health centers. Other children in Rochester and children receiving care from health maintenance organizations in all cities demonstrated almost no significant differences compared with data from Rochester community practices. CONCLUSION: The source of primary care is associated with patterns of prehospital and hospital care among hospitalized children, although specific associations vary by city.

Child↗
PubMed1996

Laser therapy for central retinal vein obstruction.

The Collaborative Central Retinal Vein Occlusion Study has recently reported information on the early natural history of central vein occlusion that includes a 16% conversion of perfusion to nonperfusion within the first 4 months. The Collaborative Central Vein Occlusion Study randomized trial of laser photocoagulation for macular edema and for the management of iris neovascularization suggested that grid laser photocoagulation is not useful for the improvement of visual acuity that is decreased because of perfused macular edema and that iris neovascularization is best managed by applying panretinal photocoagulation after the first appearance of iris neovascularization. A recent report has suggested that chorioretinal venous anastomosis can be achieved in some patients with vein occlusion to permit venous outflow through the choroid, lessen the likelihood of progression to ischemia, and improve visual acuity by lessening macular edema.

Fluorescein Angiography↗
PubMed1996

Antiphospholipid antibodies and retinal vascular disease.

BACKGROUND: Antiphospholipid antibody retinopathy is a rare and poorly defined clinical entity in which the proper diagnosis has important ocular and systemic implications. The clinical course of five patients with antiphospholipid antibody retinopathy is described and the role of such antibodies in idiopathic retinal venous occlusive disease is investigated. METHODS: Five case reports are presented highlighting the presentation, course, therapy, associations and outcomes of patients with antiphospholipid antibody retinopathy. In addition, twenty additional patients presenting with idiopathic retinal venous occlusive disease were tested for the presence of antiphospholipid antibodies. RESULTS: All five patients with antiphospholipid antibody retinopathy had diffuse retinal vascular occlusion. All five patients presented with associated rheumatologic disease, including three with lupus or lupus-like disease. Antibodies to antiphospholipid were not detected in any of the twenty patients with idiopathic retinal venous occlusive disease. Prompt panretinal photocoagulation together with varying regimens of corticosteroids, immunosuppressives, or warfarin was partially successful in stabilizing the ocular and systemic disease. CONCLUSION: The diagnosis of antiphospholipid antibody retinopathy should be suspected in patients with diffuse retinal vaso-occlusion, particularly when characterized by involvement of both arteries and veins, neovascularization at presentation, and symptoms of symptoms of systemic rheumatologic disease. Antiphospholipid antibodies do not appear to play an important role in idiopathic retinal vein occlusions.

Adult↗
PubMed1996

Procarbazine, lomustine, and vincristine (PCV) chemotherapy for grade III and grade IV oligoastrocytomas.

The authors provided procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy to 32 patients whose tumors contained varying mixtures of oligodendroglial and astrocytic cells. Twenty-five patients had oligodendroglioma-astrocytoma (oligoastrocytoma) with a histological Grade of III (19 patients) or IV (six patients); seven had anaplastic oligodendroglioma. The PCV therapy was administered every 6 weeks for a total of at least 124 cycles. The median duration of follow-up review from the start of chemotherapy was 19.3 months. Nineteen patients were treated before receiving radiation therapy and 12 after receiving it (one patient received concurrent radiotherapy and chemotherapy). Grade 3 or 4 hematological toxicity was experienced by nine (31%) of 29 patients. Ten patients had delayed treatment due to treatment-related toxicities (34.5%). Ninety-one percent of the 32 patients responded to the therapy. These included 10 patients with a complete response and 19 with a partial response. The median time to progression was 15.4 months for all patients and 23.2 months for those with Grade III tumors. The median time to progression for patients with Grade III oligoastrocytomas was 13.8 months; for those with Grade IV oligoastrocytoma it was 12.4 months and for those with anaplastic oligodendrogliomas it was 63.4 months (p = 0.0348). These patients survived a median of 49.8 months, 16 months, and 76 or more months, respectively, from the start of chemotherapy (p = 0.0154). The PCV therapy provides durable responses in patients with Grade III or IV oligoastrocytomas.

Adult↗
PubMed1996

Does quality of care affect rates of hospitalization for childhood asthma?

BACKGROUND: Hospitalization rates for childhood asthma are three times as high in Boston, Massachusetts, as in Rochester, New York; New Haven, Connecticut, rates are intermediate. We undertook this study to determine how care for children admitted for asthma varies across these communities. METHODS: We performed a community-wide retrospective chart review. We reviewed a random sample of all asthma hospitalizations, from 1988 to 1990, of children 2 to 12 years old living in these communities (n = 614). Abstracted data included demographics, illness severity, and treatment before admission. RESULTS: Compared with Rochester children, Boston children were less likely to have received maintenance preventive therapy (inhaled corticosteroids or cromolyn [odds ratio (OR), 0.4 (0.2, 0.9)]), acute "rescue" therapy (oral corticosteroids [OR, 0.2 (0.1, 0.4)]), or inhaled beta-agonist therapy [OR, 0.5 (0.3, 1.0)]. A larger proportion of admitted asthmatic patients in Boston (34%) were in the least severely ill group-oxygen saturation 95% or above-compared with patients in Rochester (20%). CONCLUSIONS: The quality of ambulatory care, including choice of preventive therapies and thresholds for admission, likely plays a key role in determining community hospitalization rates for chronic conditions such as childhood asthma.

Acute Disease↗
PubMed1996

Choroidal rupture. Clinicopathologic correlation of an unusual case.

BACKGROUND: Choroidal ruptures occurring as a result of blunt ocular injury are uncommon. A 72-year-old woman sustained blunt trauma to the left eye in 1965. In 1986, she was seen at the Wilmer Institute, and posterior choroidal rupture was documented and fluorescein angiography was performed. Absence of fluorescence was seen in the area of the rupture, and the inferotemporal artery and vein dipped into the area and emerged on the other side of the rupture. METHODS: The eyes were obtained postmortem, and histologic examination was performed. RESULTS: Examination of the left eye revealed a horizontal linear white scar inferior to the optic nerve and macula. Stepped-serial sections through the rupture revealed a 0.7-mm wide defect in Bruch's membrane and retina where fibrous tissue containing melanocytes extended into the vitreous cavity for a short distance. CONCLUSION: The clinicopathologic features of an indirect horizontal choroidal rupture is reported.

Aged↗
PubMed1995

A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. METHODS: We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. RESULTS: After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.

AIDS-Related Opportunistic Infections↗