Biomedical subjects

K Nishi

Publications and source records attributed to K Nishi.

At least 109 records · Page 6Linked to original sources

PubMed1998

Population genetic data on four STR loci in a Hungarian Romany population.

A population study of Hungarian Romanies was carried out on the STR loci HumLPL, HumF13B, HumFES and HumF1301. There was little evidence for association of alleles within/between the four STR systems. Allele frequency distributions were significantly different between the Romany and the previously reported Central Hungarian population databases. Population differentiation was estimated by computing F- and phi-statistics as well as frequency estimate differences of individual phenotypes for these two population samples. The results suggest that the population structure may have an effect on the interpretation of forensic DNA evidence in Hungary. Phylogenetic tree reconstruction with six populations from three major ethnic groups revealed a relatively distant genetic relationship of the Baranya Romanies with other Caucasian populations.

Alleles↗

PubMed1998

Tfo1: an Ac-like transposon from the plant pathogenic fungus Fusarium oxysporum.

A transposable element from a plant pathogenic fungus, Fusarium oxrysporum, was isolated and characterized. Four clones carrying moderately repetitive DNA were selected from a genomic library of the strain MAFF305118 of F. oxysporum f. sp. lagenariae, which causes wilt of bottle gourd. One the four clones was found to include a transposable element, which we have named Tfo1. This element is 2763 bp in size and appears to contain a long ORF that can encode a polypeptide of 777 amino acids. The amino acid sequence shows significant similarity to transposases from the hAT family of transposons, such as the maize transposon Activator (Ac). The element has 15-bp terminal inverted repeats and causes an 8-bp target site duplication upon insertion, as expected for an hAT-family transposon. Northern analysis detected a transcript, which hybridized to the putative transposase-encoding region of Tfo1. The size of this transcript (about 2.3 kb) corresponds to that of the ORF. A Southern analysis using pulsed-field gel electrophoresis showed that multiple chromosomal bands carry Tfo1 elements. PCR amplification of the Tfo1 elements with a 15-base inverted repeat primer produced a single DNA fragment of about 2.8 kb in all bottle gourd-infecting strains used. The element was found in multiple copies in the genome of all these strains and also in strains from other formae speciales tested. The sequence similarity of the Tfo1 element to other transposons, together with its transcriptional expression and genomic distribution, strongly suggests that Tfo1 is a member of the hAT transposon family.

Amino Acid Sequence↗

PubMed1998

Capsular bag distention syndrome noted 5 years after intraocular lens implantation.

PURPOSE: To describe a case of capsular bag distention syndrome with opaque contents noted 5 years after intraocular lens implantation. METHODS: A 66-year-old man underwent phacoemulsification after circular capsulorhexis and intraocular lens implantation in the left eye. Five years later, the posterior capsule was vaulted far posteriorly, the capsular opening was apparently sealed by the lens optic, and the bag contents were slightly opacified. Two years later, the contents of the hyperdistended capsular bag showed intensified opacity, causing definite blurred vision. RESULTS: The opacified medium was emptied from the capsular bag posteriorly into the vitreous after Nd:YAG laser capsulotomy, and the distended capsule was restored. CONCLUSIONS: Our findings suggest that the contents were collagens produced by residual lens epithelial cells or necrotic and/or apoptotic autolyzed lens epithelial cells.

Aged↗

PubMed1998

Lens refilling with injectable silicone in rabbit eyes.

PURPOSE: To evaluate the technique of refilling the lens capsule with injectable silicone and assess the postoperative findings. SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS: The lens capsules in the eyes of 16 rabbits weighing 1.5 to 2.0 kg were refilled with 0.2 mL of silicone polymer (about 66% bag volume) after endocapsular phacoemulsification through an upper minicircular capsulorhexis 1.5 to 1.8 mm in diameter. The capsule opening was sealed with a silicone plug to prevent leakage of the injected silicone. Main outcome measures were surgical success rate, inflammation, endothelial cell loss, refractive change after pilocarpine 4% instillation, and capsule opacification. RESULTS: The lens capsule could be refilled in 10 eyes. The failures were caused by capsule rupture during phacoemulsification (n = 3) and profuse leakage of the injected silicone. Silicone that leaked minimally during surgery was easily washed away. Silicone that leaked and polymerized in the anterior chamber postoperatively (n = 3) was easily removed by surgery the following day. Mean endothelial cell loss was 10.2% 1 month after surgery. Aqueous flare intensity was significantly lower on days 2 and 4 than after conventional intraocular lens implantation in a control group. The respective mean preoperative and postoperative refractions were 0.7 diopters (D) +/- 1.0 (SD) and 19.1 +/- 1.0 D and the mean change (difference between the refractions before and after topical application of pilocarpine 4%), -0.4 +/- 0.6 and 1.1 +/- 0.4 D (P < .01). Posterior capsule opacification (PCO) was noted after 3 weeks in all eyes. CONCLUSIONS: Lens capsule refilling and capsular plug use to prevent silicone leakage was shown to be feasible and avoided complications caused by leakage. Refractive changes suggest that the procedure could yield accommodation in primates> Although neodymium: YAG laser capsulotomy did not cause herniation of the injected silicone, PCO prevention is an essential issue in lens refilling because the capsulotomy may annul the attained accommodation.

Animals↗

PubMed1998

Inhibition of sodium current by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in guinea pig cardiac ventricular cells.

The effects of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a potent anion transport blocker, on transmembrane action potentials (APs) and the sodium current (I[Na]) of guinea pig ventricular myocytes were examined by using conventional microelectrode and whole-cell patch-clamp recording techniques. In papillary muscle preparations, DIDS (> or =0.1 mM) suppressed the maximal upstroke velocity (.v[max]) of the AP without significant changes in other AP parameters. Extracellular application of DIDS on single cardiomyocytes isolated from the guinea pig ventricle markedly reduced the peak amplitude of the tetrodotoxin (TTX)-sensitive and voltage-activated sodium current. The concentration-dependent block of DIDS could be expressed by the Hill equation with a Hill coefficient of 0.97 and a dissociation constant of 0.15 mM at a holding potential of (VH) -120 mV. DIDS (0.1 mM) shifted the steady-state inactivation curve for I(Na) toward more negative potentials by 6.0 +/- 0.5 mV and the activation curve to more positive potentials by 5.0 +/- 1.0 mV, although the slope factors were unaffected. With repetitive depolarizing pulses from -120 mV, DIDS produced a use-dependent block on the I(Na). Recovery of I(Na) from inactivation was slowed (time constant = 245 ms, compared with 10 ms of control) in the presence of 0.1 mM DIDS. In the two-pulse experiments, DIDS produced two distinct phases of development of I(Na) block, the rapid phase (tau = 5 ms) caused by an open channel block, and the slower phase (tau = 382 ms) induced by an inactivated channel block. These results suggest that the Cl- transport blocker DIDS has a direct inhibitory effect on the cardiac sodium channel. DIDS-induced use dependence of I(Na) block may result from the interaction of the drug with sodium channels in both the open and inactivated channel states.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1998

Pharmacologic actions of temiverine (p-INN) and its active metabolite, RCC-36, on isolated human urinary bladder muscle.

BACKGROUND: Temiverine (p-INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC-36, on isolated human bladder. METHODS: Effects of temiverine and RCC-36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric field stimulation were evaluated using the muscle-bath technique, and compared with the effects of atropine and oxybutynin. RESULTS: Atropine (10(-9) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of the concentration-response curves to acetylcholine stimulation. The rank order of pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)-induced contractile responses. Rank order of maximum inhibition was RCC-36 = temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent inhibition of electric field-induced contraction with or without 10(-6) mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were significantly greater than that of oxybutynin. CONCLUSION: Atropine, oxybutynin, temiverine, and RCC-36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the atropine-resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.

Acetylcholine↗

PubMed1998

Comparison of 2 toothbrushing methods for efficacy in supragingival plaque removal. The Toothpick method and the Bass method.

Plaque removing efficacy was compared between a new toothbrushing method named the Toothpick method and the Bass method. 20 male university dental students participated in the study, which consisted of 2 experiments. Prior to each experiment, all subjects were asked to abstain from all oral hygiene procedures for 48 h. In Exp. I, plaque-removing efficacy was assessed after each participant's mouth had been professionally brushed by a dentist. In this experiment, 2 quadrants were brushed professionally using the Toothpick method, and the remaining 2 quadrants were brushed using the Bass method. The brushing time amounted to a total of 2 min per mouth. In Exp. II, the subjects brushed their own teeth after receiving toothbrushing instruction. A blind examiner assessed dental plaque using a modification of the Quigley and Hein index at 6 sites around each tooth. Toothbrushing using the Toothpick method was found to remove significantly more plaque from proximal tooth surfaces than brushing using the Bass method.

Adult↗

PubMed1998

Intracellular chloride activity increases in guinea pig ventricular muscle during simulated ischemia.

We investigated the effects of simulated ischemia on intracellular Cl- activity ([Cl-]i) in isolated guinea pig ventricular papillary muscles using ion-selective microelectrode techniques. Simulated ischemia in ventricular muscles was produced by stopping the flow of superfusion and immersing preparations in mineral oil as previously described [B. Vanheel, L. Leybaert, A. De Hemptinne, and I. Leusen. Am. J. Physiol. 257 (Cell Physiol. 26): C365-C379, 1989; Z. F. Lai, J. Liu, and K. Nishi. Jpn. J. Pharmacol. 72: 161-174, 1996]. When preparations were exposed to paraffin oil for 15 min, [Cl-]i markedly increased and the peak magnitude of [Cl-]i reached 55.3 +/- 2.5 mM from 18.7 +/- 3.5 mM, whereas membrane potentials (Vm) depolarized from -82.5 +/- 1.1 to -54.7 +/- 2.4 mV (n = 6 muscles from 6 animals). SITS (0.5 mM), a known blocker of the Cl-/HCO-3 exchanger, suppressed the ischemia-induced depolarization of Vm and delayed the onset of the ischemia-induced increase in [Cl-]i but did not suppress the magnitude of the increase of [Cl-]i. Under Cl--free conditions created by replacing Cl- with equimolar gluconate, the increase in [Cl-]i during ischemia was transient and suppressed by >60% compared with that in normal-Cl- conditions (peak value was 20. 3 +/- 1.7 mM, n = 6 muscles from 6 animals). The present results provide direct evidence that [Cl-]i in ventricular muscle increases in ischemic conditions in quiescent guinea pig ventricular muscle, suggesting that activation of the Cl-/HCO-3 exchanger by ischemia would partially contribute to the elevation of [Cl-]i during the initial stage of ischemia.

Animals↗

PubMed1998

Properties of alpha-1-adrenergic receptors in the rat prostate: effect of experimental diabetes.

We studied the effects of 8 weeks of streptozotocin (STZ)-induced diabetes on the density and the pharmacological properties of alpha1-adrenoceptors in the rat prostate using receptor-binding experiments with [125I]iodo-2[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone [125I]HEAT. Saturation experiments showed the presence of specific [125I]HEAT-binding sites in the control and diabetic rat prostate and that the induction of diabetes significantly decreased the density of [125I]HEAT-binding sites in the rat prostate. [125I]HEAT-binding sites in the prostate of both groups were inhibited by prazosin (nonselective), spiperone (alpha1B-selective), WB4101 and 5-methylurapidil (alpha1A-selective) and BMY7378 (alpha1D-selective) with the following rank order of Ki values: prazosin < WB4101 < 5-methylurapidil < spiperone < BMY7378, indicating a similar pharmacological profile of alpha1-adrenoceptor in the 2 groups. Comparing the Ki values of the rat prostate with those obtained from the rat submaxillary gland (alpha1A), rat spleen (alpha1B), rat vas deferens (alpha1A + alpha1B) and those reported for cloned alpha1D, indicates the predominance of the alpha1A + alpha1B or the alpha1A subtype in the rat prostate. The present study demonstrates that STZ-induced diabetes downregulates the expression of alpha1-adrenoceptor in the rat prostate, without significantly affecting the receptor subtype specificity.

Adrenergic alpha-Antagonists↗

PubMed1998

Isolation and characterization of an alanyl aminopeptidase from rat liver cytosol as a puromycin-sensitive enkephalin-degrading aminopeptidase.

Alanyl aminopeptidase (AAP-S) was purified to homogeneity from rat liver cytosol. The molecular weight of the purified enzyme was calculated to be approximately 100,000 on Sephacryl S-200 HR and to be 90,000 on SDS-PAGE in the presence of beta-mercaptoethanol. These findings suggested that the enzyme exists as a monomeric form in rat liver cytosol. The enzyme rapidly hydrolyzed the substrates Ala-, Tyr- and Met-MCAs, and moderately hydrolyzed Arg-, Lys-, Leu-, Phe- and Lys-Ala-MCAs at pHs ranging from 7.5to 8.0. The enzyme also hydrolyzed several amino acid 4-methyl-coumaryl-7-amide (MCA) substrates. The order for k(cat)/Km values of AAP-S at the optimal pH (pH 7.5) was Lys->Met->Arg->Ala->Leu->Phe->Tyr->Lys-Ala-MCAs. It was strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1, 10-phenanthroline, PCMBS, Zn2+, Cd2+, Co2+, Cu2+ and Hg2+, and puromycin. The amino acid sequence of the first 43 residues of the enzyme was determined as Pro1-Glu-Lys-Arg-Pro5-Phe-Glu-Arg-Leu-Pro10-Thr-Glu-Val-Ser-Pro 15-Ile-Asn-Tyr-Ser-Leu20-(Cys)-Leu-Lys-Pro-Asp25-Leu-Leu- Asp-Phe-Thr30-Phe-Glu-Gly-Lys-Leu35-Glu-Ala-Ala-Ala-Gln40 -Val-Arg-Gln-. This N-terminal amino acid sequence is almost identical with those of puromycin-sensitive enkephalin-degrading aminopeptidases in rat and human brains, and the mouse neuroblastoma cell line Neuro2A. These findings suggest that the AAP-S from rat liver cytosol is a puromycin-sensitive aminopeptidase. Furthermore, with immunohistochemistry the enzyme was strongly stained in the cytosol of the rat liver cells.

Amino Acid Sequence↗

PubMed1998

Hyperperfusion syndrome after extracranial-intracranial bypass in a patient with moyamoya disease--case report.

A 47-year-old female developed hyperperfusion syndrome after superficial temporal artery-middle cerebral artery (STA-MCA) bypass for moyamoya disease. She presented with right hemiparesis and motor aphasia due to left cerebral infarction. She underwent left STA-MCA bypass. One day after surgery, she manifested neurological deterioration. Magnetic resonance (MR) imaging 4 days after the operation indicated regional edema in the territory supplied by the bypass, and single photon emission computed tomography 17 days after the operation demonstrated hyperperfusion in that area. Symptoms improved within 1 week after surgery, and MR imaging showed disappearance of edema and return to the preoperative appearance. Such events are rare, but hyperperfusion syndrome may occur after STA-MCA bypass for moyamoya disease.

Brain Edema↗

PubMed1998

[Surgical management of pulmonary metastases].

The results of surgical resection for pulmonary metastases from colorectal, breast, and renal cell carcinomas, soft tissue sarcoma, and osteosarcoma are reviewed. The number of pulmonary metastases, the presence of hilar or mediastinal involvement, and extrapulmonary foci are discussed in terms of surgical treatment. The size of pulmonary tumors or tumor doubling time has no significant effect on survival, while the number of metastatic foci does. Although a slight survival advantage has been noted for patients without hepatic metastases from colorectal cancer before pulmonary metastases occur, the difference in survival rates among patients with and without hepatic metastases is not significant. The role of surgery is less clear in breast cancer patients, and therefore further prospective study is considered essential. Higher relapse rates have been reported in patients with soft tissue sarcoma and osteosarcoma, although patients with these metastases can achieve long-term survival after a second metastasectomy. VATS is not be recommended for metastatic cancer surgery, because intraoperative identification of metastatic foci is often difficult.

Breast Neoplasms↗

PubMed1998

The inhibition of lens epithelial cell migration by a discontinuous capsular bend created by a band-shaped circular loop or a capsule-bending ring.

BACKGROUND AND OBJECTIVE: This study investigated the inhibitory effect of a discontinuous capsular bend created by an intraocular lens (IOL) with a band-shaped loop or a capsule tension ring on migrating lens epithelial cells (LECs). MATERIALS AND METHODS: To create a sharp bend in the capsule, the round form (shown on cross section) of the open-circular loop of a polymethylmethacrylate IOL was changed to a band-like shape, 1.0 mm wide and 0.2 mm thick. A capsule tension ring of the same shape (on cross section) with a 14-mm diameter was also made. After cataract surgery, this IOL or ring was implanted into the capsular bag in 5 rabbit eyes. The same IOL with an unmodified haptic or conventional capsule tension ring was implanted in the contralateral eye as a control. After 8 weeks, Miyake view and histopathologic examinations were performed. RESULTS: LECs accumulated at the equatorial corner outside the haptic or ring, showing the inhibition of LEC migration. In the control eyes, LECs accumulated inside the haptic or ring, forming a Soemmering's ring cataract, thus showing markedly less inhibition of LEC migration on macroscopic and microscopic observations. CONCLUSIONS: A discontinuous bend in the capsule significantly inhibited LEC migration in rabbit eyes. The creation of a capsular bend through the appropriate design of the IOL-haptic or capsule tension ring might significantly decrease the incidence of posterior capsule opacification for humans.

Animals↗

PubMed1998

Characterization, localization and distribution of alpha1 adrenoceptor subtype in male rabbit urethra.

PURPOSE: The subtype specificity, localization and distribution of urethral alpha1-adrenoceptors were studied in the male rabbit urethra. MATERIALS AND METHODS: The properties of the urethral alpha1-adrenoceptors were investigated using radioligand receptor binding and light microscopic autoradiography with [125I]iodo-2-[b-(4-hydroxyphenyl)-ethylaminomethyl]tetralone (HEAT), and immunohistochemistry with monoclonal anti-alpha smooth muscle actin and anti-alpha sarcomeric actin antibodies. RESULTS: Saturation experiments with [125I]HEAT demonstrated the presence of significant amounts of a single high affinity binding site for alpha1 adrenoceptors in the male rabbit urethra. The pharmacological profile of the alpha1 adrenoceptors in rabbit urethra, determined by inhibition experiments with subtype selective alpha1 adrenoceptor antagonists, was characterized by the following rank order of potency of inhibition constants (Ki values): prazosin < or = WB 4101 < spiperone < 5-methylurapidil < BMY 7378. The pKi values for the rabbit urethra were correlated with the pKi values for rat spleen, submaxillary glands, and vas deferens and for those reported for cloned alpha1d receptors with correlation coefficients of 0.68, 0.929, 0.909, and 0.523, respectively. CONCLUSIONS: The pharmacological characterization demonstrates the predominance of alpha1A or alpha1A + alpha1B adrenoceptor subtype(s) in male rabbit urethral smooth muscle. Furthermore, the autoradiographic and immunohistochemical studies show a heterogeneous distribution of alpha1 adrenoceptors along the longitudinal axis of the urethra, within the smooth muscle fibers, with the receptors being localized more densely in the proximal than in the distal urethra.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1998

Inhibition of migrating lens epithelial cells at the capsular bend created by the rectangular optic edge of a posterior chamber intraocular lens.

BACKGROUND AND OBJECTIVE: To study the mechanism of the reportedly low incidence of posterior capsule opacification (PCO) in eyes treated with a posterior chamber intraocular lens (PC IOL). MATERIALS AND METHODS: Various IOL designs, including the PC IOL, were studied using scanning electron microscopy. Rabbit lens capsules were studied histopathologically 2, 3, and 4 weeks after implantation of a PC IOL in one eye and a biconvex polymethylmethacrylate (PMMA) IOL in the contralateral eye as a control. RESULTS: The optic edge of the PC IOL was sharp and rectangular, whereas that of the biconvex PMMA or silicone IOLs from various manufacturers had been smoothed and rounded by polishing. PCO was significantly reduced in the eye with a PC IOL in all rabbits. The lens capsule wrapped tightly around the optic edge of the PC IOL so that it conformed to the same shape and thereby created a distinct rectangular bend in the capsule or a rectangle between the optic edge and the posterior capsule. Migrating lens epithelial cells (LECs) were obviously inhibited at that site. CONCLUSIONS: A discontinuous capsular bend or rectangle created by the sharp, square optic edge of the PC IOL may have induced contact inhibition to migrating LECs and reduced PCO. How, whether, and to what extent this design-dependent effect is influenced by features of the IOL material needs to be clarified by comparison with results achieved with an IOL made from the same material in a different design and vice versa.

Acrylic Resins↗

PubMed1998

[Assessment of the quality of life (QOL) of prostatic cancer patients under LH-RH analogue treatment].

Assessments of QOL on 53 prostatic cancer patients under LH-RH analogue treatment were evaluated using our own questionnaire. Three months after treatment, the improvement of ADL, appetite, physical symptoms, mental symptoms, sexual life and social life occurred in 24.3%, 51.5%, 44.7%, 29.7%, 7.5% and 35.4% of the patients, respectively. Twelve months after treatment, the improvement of them occurred in 30.9%, 48.4%, 31.7%, 33.7%, 8.3% and 34.4%, respectively. The quality of sexual life for the prostatic cancer patients treated with LH-RH analogue was worse than that of others. LH-RH analogue is effective on QOL in the treatment of prostatic cancer patients.

Antineoplastic Agents, Hormonal↗

PubMed1998

Capsule-bending ring for the prevention of capsular opacification: a preliminary report.

BACKGROUND AND OBJECTIVE: To report the preliminary results of a study on the preventive effect of the capsule-bending ring on anterior and posterior capsule opacification (ACO and PCO, respectively). PATIENTS AND METHODS: The ring is an open, band-shaped, circular polymethylmethacrylate (PMMA) ring measuring 11 mm in diameter with pre-tension (13 mm in diameter when the ring is open), 0.2 mm in thickness, and 0.7 mm in width. To retain sharp edges, the ring is not polished. The sharp edges should create a sharp, discontinuous capsular bend in the fornix, which induces contact inhibition of migrating lens epithelial cells after cataract surgery. This capsule-bending ring is inserted into the capsular fornix following phacoemulsification, prior to the implantation of an intraocular lens (IOL). In a multicenter trial, 100 patients were scheduled to undergo phacoemulsification and IOL implantation in both eyes within 1 month. The procedure was performed with the ring in 1 eye and without the ring in the other eye of each patient. RESULTS: The anterior capsule was prevented from coming into contact with the IOL, and ACO was significantly reduced in the eyes with the ring, rendering the capsular opening larger 3 months after surgery. PCO was obviously reduced on slit-lamp examination in the follow-up period up to 6 months, but needs to be evaluated during a longer period. CONCLUSION: This band-shaped, sharp-edged capsule-bending ring may be useful for cases that need good fundus visualization for photocoagulation or expected vitreoretinal surgery and for the prevention of PCO.

Biocompatible Materials↗

PubMed1998

[Bone marrow relapse in high-risk pediatric patients with acute lymphoblastic leukemia: a comparison of relapse times and initial clinical features of patients on different protocols. Children's Cancer and Leukemia Study group (CCLSG)].

To clarify the efficacy of modern intensive chemotherapy for ALL patients with unfavorable features, we compared the time to failure and initial clinical features of children who relapsed in the bone marrow or combined sites, as documented by early CCLSG studies (H811 and H851; 1981-1987) and later studies (H874 and H/HH911; 1987-1993) concerning high-risk ALL patients. In the later studies patients outcomes with new intensive regimens employing early intensification and reinduction therapy were apparently better than those of patients in the early studies with conventional regimens. When we compared the number of relapsed patients based on duration of first remission, we found that the improved outcomes for patients in the later studies were due to a decrease in the number who relapsed 7-36 months after the start of treatment (intermediate relapse), and that the percentage of those who relapsed within the first 6 months of therapy (early relapse) was higher. Patients with high initial WBC counts tended to relapse much earlier than those with low initial WBC counts. However, in the later studies, patients with high WBC counts often relapsed after the termination of therapy (late relapse). These results suggest that the intensive chemotherapy regimens used in the later studies can prevent the development of drug resistant leukemic clones, except in extremely high-risk patients likely to relapse within the first 6 months of therapy.

Antineoplastic Combined Chemotherapy Protocols↗