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Biomedical subjects

A R Cohen

Publications and source records attributed to A R Cohen.

At least 19 recordsLinked to original sources
PubMed1996

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study.

OBJECTIVE: To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. DESIGN: Epidemiologic cohort study. SETTING: Five hemophilia treatment centers in the United States. SUBJECTS: A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. METHODS: The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. RESULTS: The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12069 copies/mL) (P = .02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100,000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n = 9), 52% among subjects with 10,000 to 99,999 copies/mL (n = 55), 22% among subjects with 1000 to 9,999 copies/mL (n = 82), and 0% among subjects with fewer than 1000 copies/mL (n = 19) (P < .001). The age-adjusted relative hazard for AIDS for subjects with 10,000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL. CONCLUSIONS: The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low levels define persons with a high probability of long-term AIDS-free survival.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The changing profile of homozygous beta-thalassemia: demography, ethnicity, and age distribution of current North American patients and changes in two decades.

BACKGROUND: The age of patients with homozygous beta-thalassemia is increasing because of better treatment and decreased births. A countering influence is immigration of ethnic groups with a high prevalence of thalassemia. METHODS: a questionnaire sent to 48 North American centers requested information about current patients with homozygous beta-thalassemia: age, clinical severity, and ethnicity. An 83% response was obtained. Twelve reference hospitals that participated in similar surveys in 1972 and 1984 were included. RESULTS: Five hundred eighteen patients with homozygous beta-thalassemia represent most North American patients. Four hundred forty-three (86%) of these had transfusion-dependent thalassemia major (TM); 75 (14%) had thalassemia intermedia (TI). Sixty-two percent were of Greek and Italian ancestry. There were approximately equal numbers of patients with TM in 5-year intervals between 0 and 25 years of age. Thereafter, the numbers of patients fell sharply. The mean age (+/- SD) of the patients with TM was 16.1 +/- 9.2 years. Striking differences were seen in Italian and Greek patients compared with those of other ancestries. Sixty-six percent of the 271 Italian and Greek patients with TM were older than 16 years of age, whereas 77% of the 172 patients of other ethnic groups with TM were younger than 15 years of age. The mean age of the 75 patients with TI was greater than that of the patients with TM. Seventy-three percent of African-American patients had TI, compared with 0% of Southeastern Asian patients. Comparisons of patients with TM from the 12 reference hospitals for two decades show increasing mean ages of TM patients (1973, 11.4 +/- 6.7 years; 1985, 14/2 +/- 7.3 years; and 1993, 16.1 +/- 9.2 years). CONCLUSIONS: There are probably only 750 to 1000 patients with homozygous beta-thalassemia in North America. Only about 15 to 20 new cases are diagnosed each year. The increasing mean age and age distribution indicate that modern therapies are effective, but immigration of non-Mediterranean ethnic groups with thalassemia has resulted in more, younger patients. TM is increasingly becoming a disease of young adults.

Adolescent↗
PubMed1995

The use of capnography for recognition of esophageal intubation in the neonatal intensive care unit.

Failure to recognize esophageal intubation can result in severe hypoxia and permanent neurologic injury. Capnography is a standard monitoring modality in the operating room but has not been utilized fully in other environments. We used capnography at the time of endotracheal intubation in the neonatal intensive care unit (NICU) to determine whether capnography could more quickly and accurately identify endotracheal tube position than other clinical indicators of endotracheal tube position. One hundred intubation episodes were studied in 55 neonates. Capnograms were obtained 15 and 120 sec following tube placement. Intubating personnel were blinded to the capnographic data and determined endotracheal tube location (trachea vs. esophagus) by clinical criteria only. The sensitivity and specificity of capnography and clinical examination for identification of tube position were analyzed, and the time required for establishing by clinical confirmation whether the tube was in the trachea or not was compared to that required for capnography. Forty of 100 intubation attempts resulted in esophageal intubation. Capnography correctly identified these errant tube placements in 39 of 40 instances and did so in 1.6 sec (SD +/- 2.4). Capnography failed to identify successful endotracheal intubation on only one occasion. Clinical indicators of tube position required 97.1 sec (SD +/- 92.6) to identify an esophageal intubation and failed to identify successful endotracheal intubation in 5 of 60 cases. We conclude that capnography is a valuable adjunct to clinical examination to demonstrate whether an endotracheal tube is placed correctly in the trachea of neonates in the NICU.

Blood Gas Monitoring, Transcutaneous↗
PubMed1995

Loss of detectable antibody to hepatitis B surface antigen in immunized patients with hemophilia but without human immunodeficiency virus infection.

We investigated the loss of detectable antibody directed against the hepatitis B surface antigen after immunization with hepatitis B vaccine in 55 patients who were seronegative for the human immunodeficiency virus and had hemophilia. Twenty percent of patients lost detectable antibody at a mean of 4.6 years after completion of immunization. Monitoring of hepatitis B serostatus or routine revaccination may be necessary.

Child↗
PubMed1995

Human immunodeficiency virus (HIV) type 1 infection status and in vitro susceptibility to HIV infection among high-risk HIV-1-seronegative hemophiliacs.

Blood samples were obtained from 16 hemophiliacs who had a 50%-94% defined risk of human immunodeficiency virus (HIV) type 1 infection on the basis of treatment history and from 14 controls not at risk for HIV infection. HIV-1 was not detected in any of 12 patient samples by cocultivation nor in 14 patient samples by the polymerase chain reaction. Peripheral blood cells from 7 seronegative hemophiliacs at highest risk of seroconversion (94%) were less susceptible to HIV-1 infection in vitro than were cells from healthy controls (P < .025, one-tailed Wilcoxon rank sum test). In contrast, the susceptibility to HIV-1 infection of lymphocytes from 6 seronegative hemophiliacs at moderate risk (50%-56%) of seroconversion did not differ from that of cells from controls or from high-risk hemophiliacs. Therefore, prolonged periods of seronegative HIV-1 infection are not common in this high-risk population. In addition, among hemophiliacs there may exist heterogeneity in susceptibility to HIV-1 infection in vitro and in vivo.

Adult↗
PubMed1995

Endoscope-assisted craniotomy: approach to the rostral brain stem.

We describe a surgical technique to improve visualization of deep brain structures during craniotomy. The technique, developed in a cadaveric model, combines the use of an operating microscope and a solid-rod lens endoscope. Addition of the endoscope during craniotomy allows the operator to visualize structures that otherwise might not have been seen. An approach to the brain stem is demonstrated.

Brain Stem↗
PubMed1995

Caudal agenesis and associated caudal spinal cord malformations.

Caudal agenesis is a rare congenital anomaly resulting from an insult to the structures of the caudal eminence. It may be associated with anomalies of other structures derived from the caudal eminence: the hindgut and the urogenital system. Patients are more likely to present first to the pediatric surgeon (for evaluation of gastrointestinal anomalies), the urologist (for urogenital malformation or dysfunction), or the orthopedic surgeon (for lower extremity abnormalities), than to the neurosurgeon. Characteristic external features of the buttocks, hips, and lower extremities may suggest the diagnosis. MR imaging is the diagnostic modality of choice and should be used in all patients with suggestive external features or other caudal anomalies. The level of bone anomaly corresponds well to the level of weakness but not sensory loss. Sensation is usually relatively preserved. The caudal spinal cord is often truncated in cases of high bone lesions and tethered, with occasional association with a dysraphic lesion, in cases of low bone lesions. Early neurosurgical intervention is preferred in all cases of recognized occult spinal dysraphism. Progressive neurologic deficits may develop later in life in patients with unrecognized tethered cord or dural stenosis and require neurosurgical repair on diagnosis. A better understanding of the embryology of the caudal region and investigation of the teratogens that may interfere with this stage of development should lead to more effective treatment and prevention of caudal agenesis and the associated caudal anomalies.

Abnormalities, Multiple↗
PubMed1994

Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate. Multicenter Hemophilia Cohort Study.

In HIV-infected subjects with haemophilia, CD4 counts seem to fall more slowly in those on high-purity factor VIII (FVIII) than on intermediate-purity product. We evaluated whether risks for AIDS or death were associated with either product among 411 HIV-infected individuals. The relative hazard of AIDS was slightly elevated for both current (1.34) [corrected] and cumulative (1.01 per month) use of high-purity products (neither significant). The corresponding hazards for death were 1.49 and 1.03 (neither significant). Thus we found no evidence that high-purity FVIII concentrates retard the development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Survival in medically treated patients with homozygous beta-thalassemia.

BACKGROUND: The prognosis of patients with homozygous beta-thalassemia (thalassemia major) has been improved by transfusion and iron-chelation therapy. We analyzed outcome and prognostic factors among patients receiving transfusions and chelation therapy who had reached the age at which iron-induced cardiac disease, the most common cause of death, usually occurs. METHODS: Using the duration of life without the need for either inotropic or antiarrhythmic drugs as a measure of survival without cardiac disease, we studied 97 patients born before 1976 who were treated with regular transfusions and chelation therapy. We used Cox proportional-hazards analysis to assess the effect of prognostic factors and life-table analysis to estimate freedom from cardiac disease over time. RESULTS: Of the 97 patients, 59 (61 percent) had no cardiac disease; 36 (37 percent) had cardiac disease, and 18 of them had died. Univariate analysis demonstrated that factors affecting cardiac disease-free survival were age at the start of chelation therapy (P < 0.001), the natural log of the serum ferritin concentration before chelation therapy began (P = 0.01), the mean ferritin concentration (P < 0.001), and the proportion of ferritin measurements exceeding 2500 ng per milliliter (P < 0.001). With stepwise Cox modeling, only the proportion of ferritin measurements exceeding 2500 ng per milliliter affected cardiac disease-free survival (P < 0.001). Patients in whom less than 33 percent of the serum ferritin values exceeded 2500 ng per milliliter had estimated rates of survival without cardiac disease of 100 percent after 10 years of chelation therapy and 91 percent after 15 years. CONCLUSIONS: The prognosis for survival without cardiac disease is excellent for patients with thalassemia major who receive regular transfusions and whose serum ferritin concentrations remain below 2500 ng per milliliter with chelation therapy.

Adult↗
PubMed1994

Erythrocytapheresis therapy to reduce iron overload in chronically transfused patients with sickle cell disease.

Chelation therapy with deferoxamine is effective in preventing the risk of transfusional iron overload, but treatment failure is common because of noncompliance. To reduce the transfusional iron load, we have evaluated longterm erythrocytapheresis in 14 subjects with sickle cell disease and stroke (11) or other complications (3) as an alternative to simple transfusion. Subjects were treated with erythrocytapheresis using the Haemonetics V50 (Haemonetics Corp, Braintree, MA) to maintain the target pretransfusion hemoglobin S (Hb S) level less than 50% for 6 to 71 months. The transfusional iron load and the donor blood usage were analyzed for a 6- to 36-month study period and were compared with similar data from a subset of 7 subjects previously treated with conventional (target Hb S < 30%) and modified (target Hb S < 50%) simple transfusion protocols. The effect of erythrocytapheresis on iron accumulation was determined by assessment of serum ferritin levels in the absence of iron chelation. The mean transfusional iron load and donor blood usage with erythrocytapheresis were 19 +/- 14 mg iron/kg/yr (range, 6 to 50) and 188.4 +/- 55.2 mL packed-red blood cells (RBC)/kg/yr (range, 107 to 281), respectively. Of 6 subjects receiving no iron chelation therapy, 5 maintained normal or nearly normal serum ferritin levels during 11 to 36 months of erythrocytapheresis. In comparison with conventional simple transfusion and modified simple transfusion, erythrocytapheresis reduced iron loading by 87% (P < .01) and 82% (P < .01), respectively, but increased donor blood usage by 23% and 73%, respectively. Subjects with pre-erythrocytapheresis Hb levels > or = 8.0 g/dL had lower iron accumulation (P < .001) and less donor blood usage (P < .005) than subjects with Hb levels < or = 8.0 g/dL. Although donor blood usage is increased in comparison with simple transfusion, long-term erythrocytapheresis markedly reduces or prevents iron accumulation. This form of transfusion therapy allows the cessation of iron chelation in well-chelated subjects and, if used as the initial form of transfusion therapy, may prevent long-term complications of sickle cell disease without risk of iron overload and the need for chelation therapy.

Adolescent↗
PubMed1994

Automated tracing and volume measurements of neurons from 3-D confocal fluorescence microscopy data.

Three-dimensional (3-D) image analysis algorithms and experimental results that demonstrate the feasibility of fully automated tracing of neurons from fluorescence confocal microscopy data are presented. The input to the automated analysis is a set of successive optical slices that have been acquired using a confocal scanning laser microscope. The output of the system is a labelled graph representation of the neuronal topology that is spatially aligned with the 3-D image data. A variety of topological and metric analyses can be carried out using this representation. For instance, precise measurements of volumes, lengths, diameters and tortuosities can be made over specific portions of the neuron that are specified in terms of the graph representation. The effectiveness of the method is demonstrated for a set of sample fields featuring selectively stained neurons. Additional work will be needed to refine the method for unsupervised use with complex data involving multiple intertwined neurons and extremely fine dendritic structures.

Algorithms↗
PubMed1994

Chiari I malformations: assessment with phase-contrast velocity MR.

PURPOSE: To assess movement of the medulla, tonsils, and upper cervical cord as well as that of the posterior fossa cerebrospinal fluid pathways in both normal subjects and those with Chiari I malformations. METHODS: Nine healthy volunteers and eight patients with Chiari I malformations were examined with phase-contrast cine MR. With a region-of-interest cursor, the directions and intensities of the brain and cerebrospinal fluid were assessed and intensity-versus-time graphs generated. RESULTS: Cerebrospinal fluid flow patterns of the patients with Chiari I malformations were normal except for absence of valleculla flow. In addition, increased velocities (10 times normal) of the tonsils of all patients with Chiari I malformations together with posterior movement of the medulla (rather than the expected anterior movement seen in volunteers) occurred. CONCLUSIONS: Increased velocities of the tonsils may be the result of the carotid systolic pulse being delivered to a structure (the tonsil) without the normal surrounding cerebrospinal fluid, resulting in impact of the tonsils in the confined foramen magnum and a consequent caudocranial recoil. An alternative explanation would include the Bernoulli effect caused by the confined location of the tonsils. There may be a decrease in the peak tonsillar velocities after surgery.

Adolescent↗
PubMed1993

Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major.

To examine the relationship between hepatic iron stores and plasma ferritin concentration in individuals treated with red cell transfusion and iron chelation therapy, 37 patients with sickle cell anemia and 74 patients with thalassemia major were studied. In each patient, hepatic iron stores were measured by an independently validated noninvasive magnetic method, and plasma ferritin was determined by immunoassay. The correlation between hepatic iron and plasma ferritin was significant both in patients with sickle cell anemia (R = 0.75, P < 0.0001) and in those with thalassemia major (R = 0.76, P < 0.0001). Regression analysis showed no significant difference between the two groups in the linear relationships between hepatic iron stores and plasma ferritin. Considering all 111 transfused patients as a group, the coefficient of correlation between hepatic iron stores and plasma ferritin was highly significant (R = 0.76, P < 0.0001). Regression analysis found that variation in body iron stores, as assessed by magnetic determinations of hepatic iron, accounted for only approximately 57% of the variation in plasma ferritin, suggesting that the remainder was the result of other factors, such as hemolysis, ineffective erythropoiesis, ascorbate deficiency, inflammation, and liver disease. The 95% prediction intervals for hepatic iron concentration, given the plasma ferritin, were so broad as to make a single determination of plasma ferritin an unreliable predictor of body iron stores. Variability resulting from factors other than iron status limits the clinical usefulness of the plasma ferritin concentration as a predictor of body iron stores.

Adolescent↗