Enumeration of T-cells in peripheral blood as well as in joint fluid from patients with rheumatoid arthritis (RA) and the effect of cyclophosphamide

Gradient centrifugation was quite useful in obtaining "mononuclear" cell fractions from synovial fluids derived from patients with rheumatoid arthritis. The ratio of lymphocytes to monocytoid cells was similar to that seen in peripheral blood. Prior treatment of the fluid with hyaluronidase was found to be necessary to obtain a satisfactory yield of the cells. Sheep erythrocyte rosette-forming lymphocytes (T-cells) were studied in 18 paired samples of synovial fluid and blood in RA and 15 control blood samples from normal persons were also examined. In the paired synovial fluid and blood samples from the RA patients, the mean percentages of the T-cells were 56.6 and 47.1 respectively and the difference was statistically significant (0.01<p<0.05). There was no significant difference between T-cell percentages in rheumatoid and control peripheral blood. In two RA patients receiving cyclophosphamide over an average period of 20 weeks, sequential studies of T-cells were performed on both the blood and synovial fluid. By the tenth week of treatment, they were markedly reduced in both synovial fluid and peripheral blood. By the 12th to the 15th week, however, at a time when the cumulative dose of cyclophosphamide was 5,000 mg, a rebound increase in T-cells was observed in the synovial effusion. The numbers of the T-cells in the blood concomitantly showed only a minimal rebound

Normal chemotactic activity of granulocytes obtained by filtration leucapheresis

The chemotactic activity of granulocytes obtained by the Terumo Filtration Leucapheresis System (F.L.) was examined by the method of Boyden's chamber. The number of cells migrating through the Millipore filter was expressed as the chemotactic activity. The mean values were 117 for the F.L. and 122 in a control, in which cells were collected from the same donor blood using dextran sedimentation. The results suggested that the in vitro chemotactic function of granulocytes obtained by F.L. was within normal limits.</p

Circulatory changes in rheumatoid fingers as estimated by thermography and photoelectric plethysmography

In an attempt to evaluate circulatory changes in patients with rheumatoid arthritis (RA), 20 patients with classical or definite RA as determined by ARA criteria and twenty healthy volunteers serving as control were randomly selected. None of the patients showed the clinical signs suggesting Raynaud's phenomenon. Thermograms as well as photoelectric plethysmograms were obtained solely from the right middle finger tip of each examinee. The whole hand was then immersed in the cold (10℃) water and kept there for one minute. After wiping away the wet hand with a dry towel very gently, we followed the sequential changes of the tempe· rature of the third finger tip and the period of time necessary for the tip to return to the original temperature prior to the cold water immersion was measured and expressed as 'return time' in minute. Before exposure to the cold, the mean values of temperature of the finger tips between the two groups were not significantly different. As opposed to the normal pattern in which one can find the warmest point at the finger tip and which was more frequently found in the control group of the current study, a type in which the distal part of the finger was much cooler than the proximal area (so-called 'distal cold type') was observed in 8 RA patients, whereas only four demonstrated this pattern in the control group. After brief exposure to the cold, eight out of 20 rheumatoid patients showed much prolonged return time (longer than 20 minutes), while only three of 20 controls remained with prolonged cool periphery, The difference between the two, however, was not statistically significant. Studies of the digital plethysmograph revealed that 70% of all the rheumatoids showed abnormal patterns: sclerotic and monophasic waves were discovered in 55% of the patients. In contrast, seventy percent of the normal control demonstra· ted normal wave pattern. Although the significant difference was not noted, the mean height of the systolic peak of the plethysmograph derived from the rheumatoid group tended to be much reduced, suggesting the reduced blood volume at the finger tips. Six RA patients and 13 normals who showed normal plethysmographic pattern before immersion in the cold water, demonstrated rapid return to the original temperature. Only in one normal control with a normal wave pattern, prolonged return time was observed, although the height of the systolic peak of the plethysmogram in this particular case was well within normal limit. Digital circulatory disturbance, however, was strongly suspected in eight RA patients with severely prolonged return time, They all showed abnormal wave patterns of the plethysmogram, including 2 cases with peripheral plateau wave, Markedly reduced heights of the systolic peaks were also demonstrated in all. Further elaborate studies including digital arteriography were indicated to implicate any organic change in the digital vessels, such as digital arteritis in RA first reported by Bywaters in 1957

Two cases of bile duct anomalies

We reported two cases of biIe duct anomalies detected by percutaneons transhepatic cholangiography. The first case was a 53-years-old woman who had a long cystic duct running paralleI to, and apparently adhered to a common hepatic duct distally, thus forming one large duct separated by a thin membrane within. Stenosis of the lower bile duct and subsequent dilatation of the proximal part of the duct were also demonstrated. In the second case, 5-years-old girl, the most conspicuous findings include stenosis of the extrahepatic duct with the resultant dilatation of the proximal par t of the common hepatic duct and bilateral hepatic ducts. Distally displaced opening of the common biIe duct to the duodenum and aberrant run of the duodenum were also disrcovered radiographically

Treatment of refractory acute leukemia with aclacinomycin-A.

Twelve patients with refractory acute leukemia (7 patients with acute myelocytic leukemia and 5 patients with acute lymphocytic leukemia) were treated with a new anthracycline antibiotic, aclacinomycin-A (ACM). ACM was administrated by intravenous drip infusion at a dose of 20 mg/day for 7 or 14 days and this was repeated after at least 7 days. Four of 12 patients (33.3%) achieved a complete remission; 3 of 7 acute myelocytic leukemia (42.8%) and 1 of 5 acute lymphocytic leukemia (20.0%). The days required for achieving the complete remission ranged from 23 to 78 days (median: 61) and the total doses of ACM used from 180 to 500 mg (median: 310), and the durations of complete remission from 11 to 28+ weeks (median: 21+). The untoward effects on digestive organs, such as nausea, vomiting and anorexia, and hematological toxicities were frequently seen; however, they were controlled by supportive treatment. Alopecia was not observed. Arrythmia was recognized in one patient at the initiation of ACM infusion with complete remission without withdrawal of ACM. These results suggest that ACM is a potentially effective anthracycline antibiotic in the clinical management of acute leukemia.</p

Treatment of refractory acute leukemia with aclacinomycin-A.

Twelve patients with refractory acute leukemia (7 patients with acute myelocytic leukemia and 5 patients with acute lymphocytic leukemia) were treated with a new anthracycline antibiotic, aclacinomycin-A (ACM). ACM was administrated by intravenous drip infusion at a dose of 20 mg/day for 7 or 14 days and this was repeated after at least 7 days. Four of 12 patients (33.3%) achieved a complete remission; 3 of 7 acute myelocytic leukemia (42.8%) and 1 of 5 acute lymphocytic leukemia (20.0%). The days required for achieving the complete remission ranged from 23 to 78 days (median: 61) and the total doses of ACM used from 180 to 500 mg (median: 310), and the durations of complete remission from 11 to 28+ weeks (median: 21+). The untoward effects on digestive organs, such as nausea, vomiting and anorexia, and hematological toxicities were frequently seen; however, they were controlled by supportive treatment. Alopecia was not observed. Arrythmia was recognized in one patient at the initiation of ACM infusion with complete remission without withdrawal of ACM. These results suggest that ACM is a potentially effective anthracycline antibiotic in the clinical management of acute leukemia.</p

A case of hand mirror cell variant of acute lymphoblastic leukemia.

A 30 year old female patient diagnosed as acute lymphoblastic leukemia (ALL) with hand mirror like configuration of lymphoblastic-lymphocytic cells is reported. Although the leukemia was resistant to conventional chemotherapeutic regimens, the patient always looked well and survived for more than 20 months. Surface marker analysis showed that the cell was non-T, non-B, and not reactive to antiserum against common ALL antigen. A cytogenetic study of all the analyzable metaphases of the direct bone marrow preparation had a normal female karyotype. The clinical and hematological course is described. The immunological significance and the influence of hand mirror cell on chemosensitivity and prognosis are discussed.</p

Treatment of relapsed acute myelocytic leukemia with a combination of aclarubicin and cytosine arabinoside.

Relapses in nine patients with acute myelocytic leukemia were treated with a combination of aclarubicin (ACR) and cytosine arabinoside (ara-C). ACR, 40 mg/m2/day, was administered daily by intravenous injection from day 1 to day 3 and ara-C, 60-80 mg/m2/day, divided into 2 doses, was given every 12 h by intravenous infusion from day 1 to day 7. Depending on the state of the bone marrow, ACR-ara-C regimen was modified in administration period and repeated after the resting periods of at least 7 days. Complete remission was obtained in 7 of 9 patients (77.8%). The time required for achieving the complete remission varied from 20 to 55 days with a median of 39 days. The duration of complete remission was from 8 to 52 weeks with a median of 22 weeks. Side effects on digestive system such as nausea, vomiting and anorexia, were seen in all patients, although they were managed by symptomatic treatment. The results indicate the effectiveness of this ACR-ara-C regimen in the clinical management of acute nonlymphocytic leukemia.</p

Induction chemotherapy for acute leukemia Part 1. Clinical trial of NCMP two-step regimen for treatment of acute non-lymphocytic leukemia

The clinical effectiveness of a new protocol, the NCMP (N:neocarzinostatin C:cytosine arabinoside M:6- mercaptopurine P:prednisolone) two-step regimen was studied in 19 patients with acute non-lymphocytic leukemia (ANLL). All patients were previously untreated and ages ranged from 15 to 75 y.o. (median:54 y.o.). The ratio of male to female was 11 to 8. The doses and administration-routes of antileukemic agents were: N, 1,400u/m(2)/day, was administrated by i.v. drip on day 1, 2, 3 and 4 (Regimen 1) and N, 4,000u/m(2)/day, i.v. drip on day 1 and 2 (Regimen 2). C, 60-100mg/m(2)/day, was administered by i.v. drip and M, 60-100mg/m(2)/day, was given p.o. daily. P, 20-40mg/m(2)/day, was also given p.o. daily. As the first step, antileukemic agents were administrated until peripheral blood cell counts and bone marrow nucleated cell counts decreased to less than 1,200/cmm and 15,000/cmm, respectively. Treatment with or without N as the second step was started about 3-7 days after the first step treatment. Eighteen patients were adequately treated by the NCMP two-step regimen and 12 of 18 patients, 66.7%, obtained complete remission (CR). On the basis of the types of leukemia, CR was achieved in 11 of 16 patients with AML, 68.8%, and 1 of 2 patients with AMoL, 50%. The ratio of CR was higher in younger patients (less than 49 y.o.) than in elderly patients (more than 50 y.o.). These ratios were 85.7% and 54.5%, respectively. On the basis of therapeutic regimens, 8 of 11 patients, 72.7%, achieved CR by Regimen 1 and 4 of 7 patients, 57.1%, by Regimen 2. The duration of CR ranged from 1.0 to 39.5+M (median:11.5 M). The survivals from the diagnosis of leukemia were from 13 to 41+M (median:12.1 M) in all patients and from 4.2 to 41+M (median:16.4 M) in responders. As toxic manifestations, digestive side effects such as anorexia, 68.4%, and nausea and vomiting, 21.1%, were marked, but were tolerable. These results indicate that the NCMP two-step regimen is an effective induction chemotherapy for ANLL

Induction chemotherapy for acute leukemia Part 2. Clinical trial of 5 drug combination chemotherapy (NCDVP, NCyclo-cDVP) for treatment of refractory acute leukemia

In this study, the clinical effectiveness of 5 drugs as combination chemotherapy, NCDVP (N:neocarzinostatin C: cytosine arabinoside D:daunorubicin V:vincrisitine P: prednisolone) and NCyclo-cDVP (Cyclo-c:cyclocytidine), for refractory acute leukemia was evaluated. Twenty patients (12 patients relapsed and 8 patients with the first induction failure) were entered in this study; 14 patients with acute non-lymphocytic leukemia (ANLL) and 6 patients with acute lymphocytic leukemia (ALL). Their ages ranged from 15 y.o. to 73 y.o. (median:39 y.o.) and the ratio of males to females was 15 to 5. Doses and administration methods were: N, 1,400u/m(2)/day, was administered by i.v. drip on day 3, 4, 5 and 6 and C, 40-80mg/m(2)/day, was administered by i.v. drip from day 1 to day 6. D, 20-25mg/m(2)/day, was administered by i.v. bolus on day 3 and 5 and V, 1.4mg/m(2)/day, i.v. bolus on day 2. P, 20-40mg/m(2)/day, was administered by i.v. drip or p.o. from day 1 to day 6. The treatment was repeated with at least a 7 days resting period. All patients were adequatedly treated and 9 of them, 45%, obtained complete remission (CR). One patient showed partial remission. On the basis of types of leukemia, 7 of 14 patients with ANLL, 50%, and 2 of 6 patients with ALL, 33%, achieved CR. In order to obtain CR, one or 2 courses of the treatment were required (median:1.4 courses) and the duration of CR ranged from 2 to 38 weeks (median:6 weeks). In peripheral blood, the nadir of white blood cell counts, neutrophils and thrombocytes was 600/cmm, 200/cmm and 24,000/cmm, respectively and the number of days to this nadir was 12 days for white blood cell counts, 11 days for neutrophils and 13 days for thrombocytes. The nadir of bone marrow nucleated cell counts was 7,800/cmm and the number of days to nadir was 10 days. As toxic manifestations, digestive side effects were marked, but were tolerable. Eight patients showed alopetia and 4 patients complained of pain in the parotid gland. One patient complained of a sense of numbness in the fingers. Toxic effects on liver function were recognized in 5 patients, one of whom died of fulminant hepatitis. The treatment of refractory acute leukemia is one of the major problems in the clinical management of leukemia. The results of the 5 drug combination chemotherapy presented here suggests its effectiveness in refractory acute leukemia in man