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Biomedical subjects

A R Cohen

Publications and source records attributed to A R Cohen.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1992

A modified transfusion program for prevention of stroke in sickle cell disease.

Regular red blood cell transfusions reduce the rate of recurrent cerebral infarction in sickle cell disease but lead to accumulation of excessive iron. We studied the effect on the prevention of recurrent stroke and the volume of blood transfused of a modified transfusion program in which the pretransfusion percentage of hemoglobin S (HbS) was maintained at 50%, rather than the conventional 30%. Fifteen patients with sickle cell disease and cerebral infarction who had been free of recurrent stroke for at least 4 years during which the pretransfusion HbS was maintained below 30% were assigned to a transfusion program in which the HbS was allowed to increase to 50%. Transfusion regimens included simple transfusion and manual and automated partial exchange transfusion. The duration of follow-up was 14 to 130 months with a median duration of 84 months. None of the 15 patients had a recurrent cerebral infarction during 1,023 patient-months in which the target pretransfusion HbS was 50%. Analysis of this finding, using a binomial distribution, indicates that there is less than a 5% chance that the risk per patient of recurrent stroke in the first year of the modified transfusion program is greater than 18%. One 23-year-old patient had a fatal intraventricular hemorrhage when the HbS was 30% and a 21-year-old patient had a fatal subarachnoid hemorrhage in the 40th week of pregnancy when the HbS was 29%. Blood requirements with simple transfusions decreased by 17% to 48% (mean 31%) when the target pretransfusion HbS level was increased from 30% to 50% (P less than .001). Manual or automated partial exchange transfusions and a target HbS level of 50% in eight patients reduced blood requirements by 33% to 99% (mean 67%) in comparison with simple transfusion and a target HbS level of 30% (P less than .001). This study offers evidence that a target pretransfusion HbS level of 50% affords a continuing high rate of protection against recurrent cerebral infarction in sickle cell disease after 4 years of a conventional transfusion program. Increasing the target HbS level from 30% to 50% provides a major reduction in blood requirements and lowers the rate of iron accumulation.

Adolescent↗
PubMed1992

Low recovery in vivo of highly purified factor VIII in patients with hemophilia.

To assess whether the response and recovery of highly purified factor VIII products approach the levels predicted by use of manufacturers' suggestions, we studied response in vivo and percentage of recovery in boys and men with hemophilia after infusion of 50 IU of an immunoaffinity-purified factor VIII preparation (Hemofil M) per kilogram of body weight. We also studied dose response and percentage of recovery in the same boys after infusion of a factor VII concentrate prepared by solvent detergent treatment and gel filtration (Koate-HP). For boys the difference between mean peak factor VIII response with Hemofil M (1.02% +/- 0.07%) and the response with Koate-HP (1.21% +/- 0.10%) was not significant (p = 0.10), but the response of both products was considerably less than the predicted response of 2.0%. The response to Hemofil M in men (1.38% +/- 0.12%) was significantly better than the response in boys (p = 0.004) but, again, fell short of the anticipated response of 2.0%. In boys the percentage of recovery of Hemofil M was 38.4% +/- 2.1%, compared with Koate-HP recovery, which was 47.0% +/- 3.6% (p = 0.034). The percentage of recovery in men was 47.5% +/- 2.8%. The better response observed in men appears to be, in part, a function of larger body size. We conclude that peak factor VIII response and recovery in boys and men who receive highly purified factor VIII concentrates are lower than those predicted by use of current prescribing recommendations.

Adult↗
PubMed1992

Neurologic events after partial exchange transfusion for priapism in sickle cell disease.

We describe six boys with homozygous sickle cell disease, aged 7 to 13 years, in whom acute, severe neurologic abnormalities developed 1 to 11 days after partial exchange transfusion was performed to treat priapism that was unresponsive to more conservative therapy. Hemoglobin levels were 10.5 to 13.4 gm/dl (mean 12.1 gm/dl), and hemoglobin S levels were 18% to 33% (mean 27%) before the onset of neurologic complications. Severe headache was the initial finding in five patients, four of whom had increased intracranial pressure and three of whom required tracheal intubation and hyperventilation. Four patients had seizures; three had focal neurologic deficits for more than 24 hours. Cerebral arteriography demonstrated vascular abnormalities, including irregularity, stenosis, and complete occlusion of vessels. Patients treated with regular erythrocyte transfusions had no recurrence of neurologic signs or symptoms when hemoglobin S levels were kept at 30% to 50%. The occurrence of serious neurologic complications after partial exchange transfusion in patients with homozygous sickle cell disease from three centers indicates the possibility of a causal relationship between the events. Early and thorough investigation of neurologic symptoms, especially severe headache, is warranted in this clinical setting.

Anemia, Sickle Cell↗
PubMed1992

Preoperative history and coagulation screening in children undergoing tonsillectomy.

To evaluate the usefulness of preoperative screening for coagulation disorders in children, we prospectively studied laboratory and bleeding histories in 1603 children undergoing tonsillectomy. All patients had preoperative laboratory screening with a complete blood count, prothrombin time, activated partial thromboplastin time, and bleeding time. Persistent abnormalities on repeat testing 1 week later were investigated further by a standardized schema. A subset of 129 patients, including all those who bled perioperatively or had laboratory abnormalities, completed a standard historical questionnaire. Thirteen patients had persistent laboratory abnormalities diagnostic of lupus inhibitor (5), non-lupus inhibitor (6), mild hemophilia A (1), and vonWillebrand disease (1). Two patients had persistently prolonged activated partial thromboplastin times of undefined cause. Fourteen patients (10.8%) interviewed reported positive bleeding histories. Of these, five, including the patient with vonWillebrand disease, had persistent laboratory abnormalities. History alone failed to detect the patient with hemophilia A. For patients with inhibitors or prolonged activated partial thromboplastin times of unknown cause, surgery was delayed until the coagulation abnormalities resolved, and there was no perioperative bleeding. The patient with vonWillebrand disease had severe postoperative bleeding despite treatment with cryoprecipitate. In predicting perioperative bleeding, history and laboratory screening had a high specificity but a very low positive predictive value due to poor sensitivity and a low prevalence of bleeding. Some children with bleeding disorders may be identified first during routine preoperative coagulation testing, and replacement therapy or delay or cancellation of surgery may reduce or prevent perioperative hemorrhage. However, the large number of false positive laboratory tests and bleeding histories, coupled with the relative rarity of inherited and acquired coagulopathies, raises doubts about the overall value of routine screening.

Adolescent↗
PubMed1991

How selective is selective posterior rhizotomy?

Although selective posterior rhizotomy has become an increasingly utilized surgical treatment for spasticity, the procedure is unstandardized and is performed differently at various medical centers. Most surgeons use some form of direct dorsal rootlet stimulation with intraoperative multichannel electromyographic response monitoring. Electrophysiological monitoring offers the theoretical advantage of identifying pathologic reflex circuits for interruption while preserving those pathways that are "normal." However, the monitoring technique most commonly used has not been critically evaluated and, therefore, its value remains uncertain. In 22 selective posterior rhizotomy procedures performed for spastic cerebral palsy, the authors were unable to identify a single electromyographic response that could be called normal by presently accepted criteria. Dorsal rootlets were chosen for division on the basis of relative degrees of abnormality. Intraoperative electromyographic monitoring of a nonspastic patient produced tracings suggestive of spasticity by presently accepted criteria. These discrepancies suggest that current electrophysiological monitoring in selective posterior rhizotomy should be reevaluated.

Adolescent↗
PubMed1991

Diversity of organ site involvement among malignant lymphomas of mucosa-associated tissues.

Fifteen cases of low-grade B-cell lymphoma involving unusual extranodal sites have been studied in comparison to cases reported or observed arising in typical mucosa-associated lymphoid tissues. In every case, histopathologic features conformed to those characteristic for lymphomas of mucosa-associated lymphoid tissues, including the production of lymphoepithelial complexes. Immunoglobulin light chain restriction was demonstrated by immunocytochemistry in 14 cases. Sites of involvement included the breast (6), skin (5), kidney (1), prostate (1), gallbladder (1), and uterine cervix (1). In three cases there was simultaneous or previous lymphoma of mucosa-associated lymphoid tissues identified in a more common mucosal site. It is concluded that the unifying concept of lymphomas of mucosa-associated lymphoid tissues applies to extranodal organs less commonly associated with mucosa-associated lymphoid tissues, as well as to those mucosal organ sites described in earlier series.

Adult↗
PubMed1991

Gonadotropin-secreting pineal teratoma causing precocious puberty.

A case of precocious puberty in a 7-year-old boy with a tumor of the pineal region is reported. Human chorionic gonadotropin levels were elevated in the serum and cerebrospinal fluid. Endocrinological evaluation of the hypothalamic-pituitary axis demonstrated a normal prepubertal response. The tumor was resected and proved to be an immature teratoma. Human chorionic gonadotropin levels were markedly elevated in the tumor cyst fluid. Sexual precocity regressed and human chorionic gonadotropin levels in the serum and cerebrospinal fluid fell to normal after surgery, suggesting that the precocious puberty was secondary to ectopic human chorionic gonadotropin production by the pineal teratoma.

Brain Neoplasms↗
PubMed1991

Endoscopic ventricular fenestration using a "saline torch".

The fiberoptic endoscope has never gained popularity among neurosurgeons although it is ideally suited for navigating within the cerebral ventricles. Recent advances in optics and miniaturization make the application of endoscopy in neurosurgery more practical. The authors report eight children who underwent ventriculoscopic fenestration of symptomatic loculated cerebrospinal fluid (CSF) collections. These CSF collections were either isolated ventricular cysts or trapped lateral ventricles secondary to obstruction at the foramen of Monro. Cyst wall dissection was carried out with a "saline torch" dissector which was introduced through a working channel in the ventriculoscope. The torch was used to coagulate vessels and to sculpt large windows in cyst walls or in the septum pellucidum. Ventriculoscope-guided cyst fenestration can be performed safely and easily under direct vision. The technique may permit simplification of shunt systems in some patients and elimination of shunts in others.

Brain Diseases↗