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Biomedical subjects

R Zimmerman

Publications and source records attributed to R Zimmerman.

At least 19 recordsLinked to original sources
PubMed2003

Upregulation of vascular endothelial growth factor (VEGF) in the retinas of transgenic mice overexpressing interleukin-1beta (IL-1beta) in the lens and mice undergoing retinal degeneration.

IL-1beta is a pro-inflammatory agent associated with angiogenesis and increased vascular permeability. To determine whether IL-1beta elicits these responses through an upregulation of VEGF, transgenic mice that overexpress IL-1beta in the lens were evaluated at various time points for the localization of VEGF, the location and extent of blood-retinal barrier (BRB) breakdown, and the origin and extent of neovascularization (NV). In homozygous and heterozygous transgenic mice, but not controls, intense VEGF immunoreactivity was scattered throughout the retina at postnatal days 5-7 (P5-7), just after the onset of inflammatory cell infiltration. VEGF staining in the retina remained widespread, but weak from P9-15. Beginning at P15, the intensity of VEGF immunoreactivity achieved a second peak, which it maintained through adulthood. This peak coincided with significant retinal destruction due to massive inflammation. The onset of BRB breakdown coincided with the upregulation of VEGF (P5-7) and widespread BRB breakdown was demonstrated from about P9. From P9-12, aggregates of cells positive for Griffonia simplicifolia isolectin-B4, a marker for vascular endothelial cells, formed on the retinal surface. These cells migrated into the retina at P12-15 with the more superficial cells forming a network of vessels and the deeper cells remaining in small clusters, thus demonstrating that NV occurs much later than BRB breakdown. Non-transgenic FVB/N mice, which undergo retinal degeneration beginning at about P9, also demonstrate the latter peak of VEGF upregulation and the accompanying BRB breakdown, but not the early upregulation. VEGF immunostaining of transgenic and non-transgenic mouse retinas was eliminated by pre-incubation of the VEGF antibodies with VEGF peptide. The data suggest that the early peak of VEGF upregulation (P5-7) and its accompanying BRB breakdown is due to IL-1beta expression and is likely to be dependent on inflammatory cell infiltration. The latter peak appears to be related to retinal destruction.

Animals↗
PubMed2002

Human granulocytic ehrlichiosis in a renal allograft recipient: review of the clinical spectrum of disease in solid organ transplant patients.

BACKGROUND: Ehrlichiosis is a recently described zoonotic infection with two major expressions: human granulocytic ehrlichiosis (HGE) and human monocytic ehrlichiosis (HME). The organisms associated with HGE and HME have been detected in a tick vector in several regions of United States and cases of ehrlichiosis have been reported in the general population. METHODS: We report a case of HGE in a renal allograft recipient and review the clinical spectrum of disease in solid organ transplant recipients and the epidemiological basis for risk. RESULTS: Our patient demonstrated the typical epidemiological, clinical and laboratory features of human granulocytic ehrlichiosis and responded to treatment with doxycycline. CONCLUSIONS: Human ehrlichiosis should be considered in the differential diagnosis of patients with solid organ transplants, who present with fever and thrombocytopenia. The incidence of ehrlichiosis in the solid organ transplant population is similar to that in the United States general population. As reported in immunocompetent patients, prompt diagnosis and treatment results in the rapid resolution of symptoms in transplanted individuals.

Aged↗
PubMed2002

Stage 3 Kienböck's disease: reconstruction of the fractured lunate using a free vascularized iliac bone graft and external fixation.

Eighteen patients with stage 3 Kienböck's disease were treated by débridement of the necrotic core of the lunate and implantation of a free vascularized corticocancellous iliac bone. The wrist was stabilized with an external fixator during healing. The efficiency of the procedure for restoring the structure of the fractured lunate, preventing carpal collapse and improving the clinical outcome was assessed at a mean follow-up of 5 years. The graft became incorporated in the lunate in 16 of the 18 patients and no fracture of the reconstructed lunate or carpal collapse occurred in these cases. The graft did not integrate and was resorbed in the other two patients.

Adolescent↗
PubMed2001

A capillary-based supersonic jet inlet system for resonance-enhanced laser ionization mass spectrometry: principle and first on-line process analytical applications.

A new supersonic jet inlet system for resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (REMPI-TOFMS), based on a fused-silica capillary with an integral nozzle has been developed. The new jet inlet system generates a supersonic molecular beam that originates in the center of the ion source of the time-of-flight mass spectrometer. Because of the design of the inlet system, high spatial overlap of sample and laser beam (i.e., increased detection sensitivity) and excellent jet beam qualities are achieved with good adiabatic cooling properties of analyte molecules (i.e., considerably enhanced optical selectivity of the REMPI process). Furthermore, the inlet is very robust and chemically inert and contains no moving parts. As a result of these properties, the new inlet is perfectly suited for field applications of jet-REMPI. A first field application of a mobile supersonic jet-REMPI mass spectrometer equipped with the novel inlet technique is reported; namely, the concentration of monochlorobenzene, which is an indicator for the formation and emission of toxic polychlorinated dibenzo-p-dioxins/furans, PCDD/F) was measured on-line in the flue gas of a waste incineration plant.

Journal Article↗
PubMed2001

Bone formation and inflammation in cardiac valves.

BACKGROUND: For nearly a century, the mechanical failure of calcified heart valves was attributed to a passive degenerative process. Recently, several case reports described bone formation in surgically excised heart valves and suggested an unexpected process of tissue repair. METHODS AND RESULTS: We studied the prevalence and pathology of heterotopic ossification in 347 surgically excised heart valves (256 aortic, 91 mitral) in 324 consecutive patients (182 men, 142 women; mean age 68 years) who underwent cardiac valve replacement surgery between 1994 and 1998. The valves were examined microscopically to determine the prevalence and features of bone formation and remodeling. Two hundred eighty-eight valves (83%) had dystrophic calcification. Mature lamellar bone with hematopoietic elements and active bone remodeling were present in 36 valves (13%) with dystrophic calcification. Endochondral bone formation, similar to that seen in normal fracture repair, was identified in 4 valves. Microfractures were present in 92% of all valves with ossification. Neoangiogenesis was found in all valves with ossification. Bone morphogenetic proteins 2 and 4 (BMP 2/4), potent osteogenic morphogens, were expressed by myofibroblasts and preosteoblasts in areas adjacent to B- and T-lymphocyte infiltration in valves where ossification was identified. Mast cells were present in calcified and ossified valves and were especially prominent in atheromatous regions. CONCLUSIONS: Heterotopic ossification consisting of mature lamellar bone formation and active bone remodeling is a relatively common and unexpected finding in end-stage valvular heart disease and may be associated with repair of pathological microfractures in calcified cardiac valves.

Adult↗
PubMed2001

Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study.

BACKGROUND: Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS: 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS: In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION: The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.

Adult↗
PubMed2001

Neuropsychologic performance in school-aged children with sickle cell disease: a report from the Cooperative Study of Sickle Cell Disease.

OBJECTIVES: To compare the results of serial neuropsychologic testing in children with sickle cell disease with the results of serial magnetic resonance imaging (MRI) examinations, particularly to evaluate neuropsychologic function in the absence of overt stroke. STUDY DESIGN: In the Cooperative Study of Sickle Cell Disease, serial neuropsychologic and MRI tests were performed in 373 patients (255 with hemoglobin SS and 118 with hemoglobin SC), 6 to 18 years of age. MRI of the brain and a neuropsychologic battery that included the Wechsler Intelligence Scale for Children (WISC-R or WISC-III) and the Woodcock-Johnson Math and Reading Achievement Tests were performed concurrently and repeated every 2 to 3 years. A silent infarct was defined as an MRI finding of increased signal intensity on T(2) imaging in a patient without a history of stroke. RESULTS: Twenty-seven patients, all with hemoglobin SS, had overt strokes and 62 had silent infarcts (52 with hemoglobin SS). Patients with hemoglobin SS and silent infarcts had significantly lower scores for math and reading achievement, Full-Scale IQ, Verbal IQ, and Performance IQ, when compared with those with normal MRI findings. In children with hemoglobin SS and normal MRI findings, the scores for Verbal IQ, math achievement, and coding (a subscale of Performance IQ) declined with increasing age. CONCLUSIONS: School-aged children with sickle cell disease had compromised neuropsychologic function in the presence of silent infarcts. In addition, they had declines in performance in certain areas of function over time. Therapeutic interventions that prevent or lessen cognitive impairment are needed before school entry for children with sickle cell disease.

Anemia, Sickle Cell↗
PubMed2001

Advances in the treatment of lupus nephritis.

Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic for the disease. Different forms of glomerulonephritis can occur in patients with SLE and can contribute significantly to the associated morbidity and, ultimately, mortality from the disease. Over the past two decades, there have been significant strides in our understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal damage and end-stage renal disease. In this chapter, we review the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and discuss the experimental and human data regarding some of the potential newer forms of therapy. We discuss data regarding the use of steroids, azathioprine, cyclophosphamide, cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis, LJP 394, flaxseed oil, bindarit, anti-CD40 ligand, and CTLA4Ig.

Abatacept↗
PubMed2001

Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia.

OBJECTIVE: In recent years, the increased prevalence of breastfeeding in conjunction with early discharge practices has increased the risk for marked hyperbilirubinemia in neonates. This has resulted in the potential for bilirubin brain injury in affected infants. The purpose of this study was to identify all infants >/=36 weeks' gestational age with bilirubin levels >25 mg/dL and evaluate them for early and late evidence of bilirubin brain injury. METHODS: We reviewed the charts of all infants (from 1993-1996) >/=36 weeks' gestational age who were readmitted to the hospital during the first week of life with bilirubin levels >25 mg/dL. Readmission records were reviewed for early signs of bilirubin encephalopathy. Magnetic resonance imaging (MRIs) and Brainstem auditory-evoked responses (BAERs) were reviewed for evidence of bilirubin toxicity. At follow-up, study infants had a complete neurodevelopmental examination, repeat MRIs, and behavioral hearing evaluations. RESULTS: From 1993 to 1996, we identified 6 term and near-term infants readmitted to the hospital within the first week of life with peak bilirubin values ranging from 26.4 mg/dL (451 micromol/L) to 36.9 mg/dL (631 micromol/L). Five of 6 infants had bilirubin values >30 mg/dL (513 micromol/L). All were exclusively breastfed or fed a combination of breast and bottle feedings. Five of 6 infants presented with abnormal neurologic signs. Four infants had initial MRIs, 3 of whom had increased signal intensity in the basal ganglia consistent with kernicterus. Two infants had abnormal BAERs; both also had abnormal MRIs. Five of 6 infants received exchange transfusions and all were treated with phototherapy and intravenous fluids. Follow-up examinations between 3 months and 2 years showed resolution of clinical signs in all but 1 infant. Four infants had a subsequent normal MRI and 1 had residual hearing impairment. One infant demonstrated severely abnormal developmental evaluations, as well as both an abnormal initial MRI and BAERs. Follow-up MRI showed evidence of encephalomalacia with changes not characteristic of kernicterus. CONCLUSIONS: We observed transient neurologic abnormalities in 5 of 6 infants readmitted to the hospital during the first week of life with marked hyperbilirubinemia. The abnormalities resolved following aggressive management using hydration, phototherapy, and exchange transfusion and may not correlate with long-term prognosis. Less aggressive therapy may be associated with residual neurologic abnormalities. We speculate that inadequate establishment of breastfeeding coupled with early discharge practices may play a role in the development of marked hyperbilirubinemia in these infants.

Breast Feeding↗
PubMed2000

Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses.

BACKGROUND: Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia. METHODS: We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses. RESULTS: Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent. CONCLUSIONS: In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Blood Flow Velocity↗
PubMed2000

Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology.

OBJECTIVE: To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation. DESIGN: Prospective analysis. SETTING: University IVF program. PATIENT(S): Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12). INTERVENTION(S): Controlled ovarian hyperstimulation and IVF. MAIN OUTCOME MEASURE(S): Serum estradiol, testosterone, and leptin. RESULT(S): Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively). CONCLUSION(S): Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.

Adult↗
PubMed2000

Differences in young adult psychopathology among drug abstainers, experimenters, and frequent users.

Shedler and Block offered the provocative proposal that individuals who experiment with drugs are psychologically healthier than either those who abstain completely or those who are frequent users. Not all studies have come to such conclusions, however. In an effort to specify under what conditions Shedler and Block's conclusions might hold, the present study examined three groups of drug users (abstainers, experimenters, frequent users) classified according to three different criteria: (a) marijuana use at age 20; (b) alcohol use during 10th grade; and (c) alcohol use at age 20. The three groups were compared at age 20 in terms of personality, deviant behavior, and psychopathology. The results revealed that abstainers were never more psychologically impaired, and were occasionally healthier, than experimenters. Frequent users of marijuana were consistently more imparied than both the abstainers and experimenters, in terms of both internalizing and externalizing disorders. Classification according to marijuana use appeared to be more related to psychopathology than did classification according to alcohol use.

Adolescent↗
PubMed2000

Use of mycophenolate mofetil in resistant membranous nephropathy.

Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Optimal therapy for this disease is still debated. We report our experience using mycophenolate mofetil (MMF), an immunosuppressive agent widely used in transplant recipients, to treat 16 nephrotic patients with MN. All patients had biopsy-documented MN; secondary forms were ruled out. Fifteen patients had steroid-resistant disease; cytotoxic agents had failed in 6 patients and cyclosporine therapy had failed in 5 patients. Patients were treated with MMF (dose range, 500 to 2,000 mg) for a mean of 8 months. Six patients experienced a halving of proteinuria, which occurred after a mean duration of 6 months of therapy. Partial remissions occurred in 2 patients. There were no significant changes in mean values for serum creatinine, serum albumin, or proteinuria. Mean cholesterol levels were significantly less. Side effects of MMF were infrequent and generally mild. In summary, MMF appears to reduce proteinuria in some patients with idiopathic MN previously resistant to steroids, cytotoxic agents, or cyclosporine. Further trials with this agent are warranted.

Adolescent↗
PubMed2000

Limited utility of chest radiograph after thoracentesis.

STUDY OBJECTIVE: To assess the utility of chest radiograph (CXR) immediately after routine thoracentesis. DESIGN: Prospective cohort study. SETTING: Multispecialty clinic/teaching hospital. PARTICIPANTS: All outpatients and inpatients undergoing thoracentesis in the procedure area from October 1995 to January 1998. MEASUREMENTS: Immediately after thoracentesis, the physician completed a questionnaire assessing the likelihood of a complication. CXRs were obtained at physician discretion. Patient demographics, indications for thoracentesis, use of ultrasound guidance, level of training, radiographic interpretation, and eventual patient outcome were recorded. RESULTS: Two hundred eighteen patients were enrolled for a total of 278 thoracenteses. Two hundred fifty-one procedures performed on 199 patients could be prospectively evaluated. A complication was suspected in 30 procedures; immediate CXR confirmed such in 9 (30%). There were 221 procedures with no clinical suspicion or indication of a complication. Ninety CXRs were obtained immediately after the procedure; the remaining 131 procedures had no CXR. The complication rates were 3.3% and 2.3%, respectively, for these groups. Four postthoracentesis radiographs demonstrated additional findings regardless of the indication for the radiograph. CONCLUSIONS: In the absence of a clinical indication of a complication, chest radiography is not indicated immediately after routine thoracentesis. Aspiration of air strongly correlates with the occurrence of pneumothorax, whereas pain, hypotension, and dry tap do not. Use of a vacuum bottle to withdraw fluid obscures the appreciation of this finding and was identified as a risk factor for subsequent pneumothorax. Additional radiographic findings are rarely detected and may not contribute to clinical management.

Aged↗
PubMed1999

Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after high-responder rat heart transplantation.

BACKGROUND: Allograft rejection depends on T cell immune responses requiring antigen recognition and costimulatory signals through accessory T cell receptors, including CD28. Inhibition of CD28 signaling with a CTLA-4-immunoglobulin (Ig) fusion protein has resulted in immunosuppression and occasional T cell anergy in mouse transplant models, but not in rats. Because this approach also inhibits a potentially tolerizing signal through CTLA-4, selective blockade of CD28 ligation might induce more profound immunosuppression and transplant tolerance. METHODS: The effects of escalating doses of the rat CD28 monoclonal antibody JJ319 on allograft survival were studied after vascularized heterotopic heart transplantation in a high responder strain combination (DA to Lewis). CD28 antigen modulation and circulating antibody levels were monitored by flow cytometry. RESULTS: CD28 antibody JJ319 markedly prolonged cardiac graft survival compared with untreated controls (7 days, range: 6-8). A strictly dose-dependent increase in median graft survival time was demonstrated with a maximum of 36 days (range: 30-40; p <0.001) after the administration of 8 x 1 mg JJ319 i.p. (days -1 to +6 before/after transplantation). However, indefinite graft survival and tolerance could not be induced by JJ319 treatment. At the maximal dose, flow cytometry showed complete down modulation of the CD28 receptor for 10-14 days without T cell depletion in close temporal relation to antibody presence in serum. In vitro, CD28-modulated T cells showed significantly reduced responses to activation. CONCLUSIONS: CD28 antibody JJ319 induces profound immunosuppression after rat heart transplantation, however without development of transplant tolerance. The underlying mechanism seems to be receptor modulation during primary alloantigen recognition. While still potentially applicable clinically, there are no qualitative or quantitative differences to the treatment with CTLA-4/lg or the blockade of CD2 or LFA-1, as reported elsewhere. Thus, a CD28-modulating approach seems not to allow therapeutic exploitation of a tolerizing signal delivered by CTLA-4 but may still be clinically applicable, especially in combined immune interventions.

Abatacept↗
PubMed1999

Association of diabetes mellitus and chronic hepatitis C virus infection.

While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.

Adult↗