An Improved Method for Performing Neutrophil Survival Studies

An improved method for doing DFP³² neutrophil survival studies is described that allows quantitative measurement of total circulating neutrophil-associated radioactivity. DFP³² labeled neutrophils are quantitatively trappedon a nylon fiber column and washed free of contaminating radioactivity. Theneutrophil-associated radioactivity is then counted in a liquid scintillationcounter. Data so obtained can then be used to construct both a true neutrophilsurvival curve and a curve for the fall-off of neutrophil specific activity. Leukokinetic data on hematologically normal individuals compare favorably withthe values for normal persons that Athens and his collaborators have published.

Submitted on January 2, 1969 Revised on January 16, 1970 Accepted on January 29, 1970     

Obscure Syncope and the Sick Sinus Syndrome

This report describes a 25-year-old vigorous young man who had a history of eight years of near syncope and syncope of unknown etiology. Repeat in-hospital observation and laboratory electrophysiologic functional testing did not elucidate the origin of the symptoms. Prolonged Holter monitoring finally showed that the syncopal attacks were caused by a sick sinus syndrome (SSS). On electrophysiologic study, a concealed rate-dependent unidirectional antegrade accessory A-V pathway (AP) was found to be present. The AP was an incidental finding and was unrelated to the patient's symptoms. The symptomatic SSS may occur in the young as well as in the elderly. Sinoatrial dysfunction may be intermittent and difficult to detect, may cause severe symptoms, and may even be life-threatening. Prior to definitive therapy (such as the permanent implantation of a pacemaker), the importance of relating symptoms to a rhythm disturbance has been stressed. In cases where the cause of the symptoms is not obvious, this is best accomplished by continuous Holter monitoring.     

Early Identification of Patients Who May Require Electrical Control Treatment

Patients who are at increased risk of sudden death generally have significant underlying organic heart disease, but this is not always the case. The majority of patients at risk include those with the idiopathic long QT syndrome, the Wolff-Parkinson-White disorder, mitral valve prolapse, coronary heart disease, and cardiomyopathy. A history of syncope or presyncope and/or frequent or repetitive runs of ventricular ectopic beats are common prodromal findings in patients with a potentially life-threatening problem. Potential candidates for implantable antiarrhythmic devices include high-risk patients in whom an effective antiarrhythmic agent cannot be identified or those who cannot tolerate indicated antiarrhythmic agents because of adverse side effects.     

Combination Chemotherapy With Nitrogen Mustard, Vincristine, Procarbazine and Prednisone in Previously Treated Patients With Hodgkin's Disease

Combination chemotherapy with fourdrugs—nitrogen mustard, vincristine,procarbazine and prednisone—was usedin 27 previously treated patients withadvanced progressive Hodgkin’s disease.Six 2-week cycles of chemotherapy wereadministered in the following schedule:nitrogen mustard, 6 mg./sq.M. I.V., andvincristine, 1.4 mg./sq.M. I.V., on days1 and 8 of each cycle; procarbazine,100 mg./sq.M. by mouth daily throughout each cycle, and prednisone, 40mg./sq.M. orally each day of cycles 1and 4. Each cycle was followed by a2-week period during which no drug wasgiven. Twenty-two patients had StageIV disease and 17 had systemic symptoms at the time of drug administration.All patients had histories of previoustherapy. Two received chemotherapyalone, 15 had radiotherapy alone and10 had both chemotherapy and radiotherapy. Nineteen out of the 27 patients(70%) had complete responses (total regression of all lesions) to the four drugcombination and five patients (19%) hadpartial responses (50% regression of alllesions). Fourteen out of the 19 whoresponded completely are still in unmaintained remission 1-24 months from therapy completion. Eighteen out of the 19who responded completely are still surviving from 6 to 30 months after thestart of combination chemotherapy.Those patients treated previously withboth radiotherapy and chemotherapy didnot respond as well as patients treatedwith prior radiotherapy alone. In general, therapy was well tolerated, withleukopenia being the major dosage-limiting toxicity. There was a progressivelypoorer tolerance to the drugs with increasing extent of prior radiotherapy.

Submitted on May 12, 1970 Revised on July 20, 1970 Accepted on July 27, 1970     

The Chromatography of Hemins from Normal and Abnormal Human Erythrocytes

1. Erythrocyte hemins, extracted with acid-acetone, exhibited multiplecomponents on two chromatographic systems. However, this heterogeneity canbe explained by various physicochemical properties of hemin in solution anddoes not imply that heme, when attached to globin in the native hemoglobinmolecule, is heterogeneous.

2. The presence of a non-polar fraction may be accounted for by esterification of protohemin as a result of reaction with small amounts of methanol contaminating the acetone and/or the presence of some un-ionized protoheminmolecule in solutions of low pH.

3. The presence of poorly soluble fractions is probably the result of polymerization of the hydroxyhemin molecule into so-called - and -hematins.

4. The formation of mesohemin is considered unlikely, but the formation ofdeuterohemin or hematohemin cannot be excluded.

5. No changes in hemin chromatographic patterns were noted in disease.

6. It is necessary to evaluate reports concerning chromatographic heminheterogeneity in the light of the artifacts described above before attributingphysiologic or pathogenetic significance to the findings.

Submitted on August 6, 1963 Accepted on September 14, 1963     

Pyridoxine-Responsive Anemia

1. Two patients with microcytic hypochromic anemia, hyperferremia, andhemosiderosis have been described .A partial hematologic remission was observed in both patients following the administration of pyridoxine.

2. Interruption of pyridoxine therapy resulted in reticulocytopenia, a decline in the concentration of hemoglobin and a decrease in free erythrocyteprotoporphyrin. Increased excretion of kynurenine and kynurenic acid, butnot xanthurenic acid, was observed in the urine of one of the patients following administration of tryptophane. The excretion of tryptophane metaboliteswas within normal limits in the second patient.

3. Reinstitution of pyridoxine therapy was followed by reticulocytosis, anincrease in free erythrocyte protoporphyrin and an increase in the concentration of hemoglobin. The excretion of tryptophane metabolites in the urinefollowing the administration of tryptophane was within normal limits in bothpatients. However, microcytosis, hypochromia, anemia and hyperferremiapersisted.

4. The administration of brewer’s yeast, Valentine’s liver extract, calciumdisodium ethylenediamine tetra-acetic acid, ethinyl estradiol, pantothenicacid, pyridoxal, pyridoxamine, ascorbic acid, niacin, riboflavin, glutamic acidand tryptophane failed to elicit a further hematologic response.

5. These patients have been compared with the seven other reported casesof "pyridoxine-responsive" anemia.

Submitted on April 20, 1961 Accepted on May 13, 1961