Surgical starting time in the morning versus the afternoon: propensity score matched analysis of operative outcomes following laparoscopic colectomy for colorectal cancer.

BACKGROUND: The number of colorectal cancer cases is increasing, and so the number of laparoscopic colectomy procedures being performed is also increasing, leading to an increased workload for surgeons. However, operating for prolonged time periods may cause surgeons to lose their concentration and develop fatigue. We hypothesized that there is a time-of-day variation in outcome for patients with colorectal cancer who undergo laparoscopic colectomy. The present study aimed to compare the operative outcome between laparoscopic colectomy for colorectal cancer performed in the morning versus the afternoon. METHODS: This was a single-center, retrospective study. All 1961 consecutive patients who underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were included; 1006 of these patients underwent morning surgery, while 955 underwent afternoon surgery. These patients were analyzed using propensity score matching, giving 791 patients in each group. The short- and long-term outcomes in both groups were compared. RESULTS: Before propensity score matching, the morning group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P = 0.0035). After matching, the two groups did not significantly differ in any patient characteristics. Compared with the afternoon group, the morning group had a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%; P = 0.027), and a significantly greater incidence of post-operative abdominal abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and morbidities were similar in both groups. The median operative time in the morning group (201 min) was significantly longer than that in the afternoon group (193 min; P = 0.0124). The two groups did not differ in 5-year overall survival rates and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical start times are correlated with surgical outcomes. Our data will help to ensure the safest possible surgeries.

Administration of platelet concentrates suspended in bicarbonated Ringer's solution in children who had platelet transfusion reactions.

BACKGROUND AND OBJECTIVES: Adverse reactions to platelet transfusions are a problem. Children with primary haematological and malignant diseases may experience allergic transfusion reactions (ATRs) to platelet concentrates (PCs), which can be prevented by giving washed PCs. A new platelet additive solution, using bicarbonated Ringer's solution and acid-citrate-dextrose formula A (BRS-A), may be better for platelet washing and storage, but clinical data are scarce. MATERIALS AND METHODS: A retrospective cohort study for consecutive cases was performed between 2013 and 2017. For 24 months, we transfused washed PCs containing BRS-A to children with primary haematological and malignant diseases and previous adverse reactions. Patients transfused with conventional PCs (containing residual plasma) were assigned as controls, and results were compared in terms of frequency of ATRs, corrected count increment (CCI) and occurrence of bleeding. We also studied children transfused with PCs washed by a different system as historical controls. RESULTS: Thirty-two patients received 377 conventional PC transfusions. ATRs occurred in 12 (37·5%) patients from transfused with 18 (4·8%) bags. Thirteen patients, who experienced reactions to regular PCs in plasma, then received 119 transfusion bags of washed PCs containing BRS-A, and none had ATRs to washed PCs containing BRS-A. Before study period, six patients transfused 137 classical washed PCs with different platelet additive solution, under same indication, ATRs occurred in one (16·7%) patient from transfused with one (0·7%) bags. CCIs (24 h) in were lower with classical washed PCs (1·26 ± 0·54) compared to regular PCs in plasma (2·07 ± 0·76) (P < 0·001), but there was no difference between washed PCs containing BRS-A (2·14 ± 0·77) and regular PCs (2·21 ± 0·79) (P = 0·769), and we saw no post-transfusion bleeding. CONCLUSION: Washed PCs containing BRS-A appear to prevent ATRs without loss of transfusion efficacy in children with primary haematological and malignant diseases. Their efficacy should be further evaluated through larger prospective clinical trials.

Donor Left-Sided Heptectomy by Use of the Real-Time Moving Windows Method With 8-Centimeter Transverse Skin Incision.

BACKGROUND: In this study, we demonstrated our new device for open donor liver surgery with left-sided heptectomy by use of the real-time moving windows (RTMW) method with 8-cm transverse skin incision for living donors from the viewpoints of cosmetic, economic, and safety procedures. METHODS: After the upper abdominal 8-cm transverse skin incision was made, the subcutaneous area was exfoliated and the reverse T-shaped-abdominal incision was made, as in open surgery. After that, the 2 Kent hooks for the upper region and the 2 surgical arms for the lower region were placed. The operative fields of hepatic vein, hepatic hilus, and common hepatic artery were explored, respectively, by use of the RTMW method with the use of the 4 surgical hooks. Hepatic parenchymal dissection was carried out with the use of CUSA and laparosonic coagulating shears. Manipulations of 3 hepatic vessels and the hepatic duct were done by the usual procedure of open surgery. RESULTS: This operative procedure could be performed without laparoscopic techniques. The operative time was 7 hours, without blood transfusion. The operative course was uneventful, and the patient was discharged on postoperative day 11. CONCLUSIONS: Our RTMW method for donor left-sided hepatectomy is considered to be a useful operative procedure from the viewpoints of donor safety, cosmetic advantage, and cost performance.

Factors related to allergic transfusion reactions and febrile non-haemolytic transfusion reactions in children.

BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are the two major types of transfusion-related adverse reactions (TRARs). Although prestorage leucocyte reduction and diversion of the first aliquot of blood (LR/D) could reduce FNHTRs and bacterial contamination in adult transfusion, ATRs are still problematic. In addition, there is little information about TRARs in paediatric population. MATERIALS AND METHODS: We conducted a single-centre retrospective analysis of all transfusions, except washing products, and TRARs for 153 months to evaluate related factors such as delivery of treatment and the characteristics of recipients. RESULTS: Most TRARs were FNHTRs and/or ATRs in children. In delivering blood products with LR/D, the frequencies of not only FNHTRs but also ATRs were significantly reduced with both platelet concentrates (PCs) and red cell concentrates (RCCs). TRARs of fresh-frozen plasma were infrequent in children. In addition, even after the introduction of LR/D, ATRs were significantly more frequent in patients with primary haematological and malignant diseases who received PCs and RCCs, older patients who received PCs and patients who received frequent RCCs. CONCLUSION: These results suggest that leucocytes or mediators from leucocytes are underlying cause of ATRs in addition to FNHTRs in children. Furthermore, particular characteristics of patients would be other risk factors for ATRs.

First case of bacteremia due to chromosome-encoded CfxA3-beta-lactamase-producing Capnocytophaga sputigena in a pediatric patient with acute erythroblastic leukemia.

Bacteremia due to Capnocytophaga sputigena occurred in a 4-year and 9-month-old Japanese girl patient with acute erythroblastic leukemia in Shinshu University Hospital, Japan. On her admission to the hospital, she had a temperature of 38.2 degrees C with canker sore. Prior to the commencement of chemotherapy, peripheral blood culture was carried out with the BacT/Alert 3D System ver. 4.00D (bioMerieux Japan Ltd., Tokyo, Japan) using both the PF and the SN bottles. At 48 hrs of incubation, the System showed the positive sign only in the anaerobic SN bottle for bacterial growth. The strain isolated from the SN bottle was morphologically, biochemically, and genetically characterized, and finally identified as Capnocytophaga sputigena. The causative Capnocytophaga sputigena isolate was found to be a beta-lactamase-producer demonstrating to possess cfxA3 gene. The gene responsible for the production of CfxA3-beta-lactamase was proved to be chromosome-encoded, by means of southern hybridization analysis. This was the first case of bacteremia caused by chromosome-encoded CfxA3-beta-lactamase-producing Capnocytophaga sputigena.

Chromosomal change during 6-mercaptopurine (6-MP) therapy in juvenile myelomonocytic leukemia: the growth of a 6-MP-refractory clone that already exists at onset.

Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease.

Virtual histology of colorectal lesions using laser-scanning confocal microscopy.

BACKGROUND AND STUDY AIMS: Histological examination of gastrointestinal lesions is currently based on light-microscopic examination of thin-slice specimens, with hematoxylin and eosin staining. A study of the use of laser-scanning confocal microscopy (LCM) to obtain immediate microscopic images of untreated specimens for examining colorectal lesions was carried out. A probe-type LCM prototype endomicroscope that can be passed through the working channel of an endoscope has also been developed. MATERIALS AND METHODS: The study materials consisted of colorectal lesions resected either endoscopically or surgically at Showa University Northern Yokohama Hospital. One hundred untreated specimens were examined using LCM. The histopathological findings in the lesions were seven cases of normal colonic mucosa, five hyperplastic polyps, 68 adenomas with low-grade dysplasia, 10 adenomas with high-grade dysplasia, and 10 adenocarcinomas. An argon laser beam with a wavelength of 488 nm was used for the LCM study. Observation of the resected normal colonic mucosa (in vitro) and the rectal mucosa of a healthy volunteer (in vivo) was possible using the endomicroscope. The LCM images for each specimen were compared with the hematoxylin-eosin-stained histopathological cross-sections. RESULTS: The LCM images corresponded well with the conventional hematoxylin-eosin light-microscopic images. The nuclei were not visualized in normal mucosa or hyperplastic polyps. In adenomas with high-grade dysplasia and carcinomas, nuclei were more often visible than in adenomas with low-grade dysplasia. The rate of visualization of nuclei was significantly different ( P < 0.01) between these two groups (60.0 % vs. 10.3 %). In LCM images using endomicroscope, it was possible to recognize the orifices of the colonic glands and goblet cells both in vitro and in vivo. CONCLUSIONS: Laser-scanning confocal microscopy provides immediate images that correspond well with those of hematoxylin-eosin staining. An improved probe-type LCM endomicroscope is being developed which should provide better histological images of colorectal lesions in vivo.

Development of virtual histology and virtual biopsy using laser-scanning confocal microscopy.

The aim of this project is to acquire a direct image of histology from in vivo gastrointestinal mucosa. In other words, the task of 'endo-microscope' is to observe the cellular architecture of tissue in vivo during routine endoscopic examination. As the first step to completing this study, resected fresh specimens from the oesophagus. stomach and colon were examined by laser-scanning confocal microscopy (LCM) (Fluoview, Olympus, Tokyo). Fresh untreated mucosal specimens obtained by endoscopic pinch biopsy, polypectomy or endoscopic mucosal resection were collected and placed in normal saline and examined by LCM, collecting the reflective light of a 488-nm wavelength argon laser beam. As the second step, a probe-type LCM 'endo-microscope' was designed and applied to observe the human oral-cavity mucosa. The probe has 4.5-mm outer diameter and 20-cm length, which enables easy access to oral cavity mucosa. The estimated special resolution of the probe is 1-5 microm. A real-time microscopic image directly from ex vivo fresh specimens was acquired. The acquired LCM images corresponded well with the conventional H-E light microscopic images. Cell wall, nucleus and cytoplasm were simultaneously visualized by LCM scanning. This novel method enables serial imaginary microscopic sections on fresh specimens. In addition, a probe-type LCM 'endo-microscope' was designed and was applied to observe human oral cavity mucosa. Virtual histological images from the living oral squamous cell were successfully obtained. LCM images from ex vivo fresh specimens demonstrated the features of the H-E staining histological image. In the next step to accomplish our project, we developed a LCM probe with 4.5-mm outer diameter to obtain a virtual image of human oral cavity mucosa.

A case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus.

We report a very rare case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus. An 83 year old woman was referred to our hospital in June 1999 for further examination and treatment of oesophageal tumour. Although a physical examination and laboratory data showed no significant abnormalities, endoscopic observation revealed two slightly elevated submucosal tumour-like lesions of the oesophagus. Tissue specimens were obtained by endoscopic mucosal resection of the oesophagus using a cap fitted panendoscope. The lesions were composed of diffuse small atypical lymphoid cells--that is, centrocyte-like cells--which were stained with CD20, L26, BCL-2, and kappa, but not with CD3, CD5, CD10, or cyclin D1. Monoclonality was detected by polymerase chain reaction analysis using the primer for CDR-3 of immunoglobulin H and diagnosed as low grade MALT lymphoma of the oesophagus. The tumours were considered to be completely resected and therefore additional treatment was not administered. The patient is alive and well 22 months after treatment and diagnosis.

Expression of apoptosis-associated speck-like protein containing a caspase recruitment domain, a pyrin N-terminal homology domain-containing protein, in normal human tissues.

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a pyrin N-terminal homology domain (PYD)- and caspase recruitment domain (CARD)-containing a proapoptotic molecule. This molecule has also been identified as a target of methylation-induced silencing (TMS)-1. We cloned the ASC cDNA by immunoscreening using an anti-ASC monoclonal antibody. In this study, we determined the binding site of the anti-ASC monoclonal antibody on ASC and analyzed the expression of ASC in normal human tissues. ASC expression was observed in anterior horn cells of the spinal cord, trophoblasts of the placental villi, tubule epithelium of the kidney, seminiferous tubules and Leydig cells of the testis, hepatocytes and interlobular bile ducts of the liver, squamous epithelial cells of the tonsil and skin, hair follicle, sebaceous and eccrine glands of the skin, and peripheral blood leukocytes. In the colon, ASC was detected in mature epithelial cells facing the luminal side rather than immature cells located deeper in the crypts. These observations indicate that high levels of ASC are abundantly expressed in epithelial cells and leukocytes, which are involved in host defense against external pathogens and in well-differentiated cells, the proliferation of which is regulated.

Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer.

BACKGROUND AND AIMS: Helicobacter pylori locate not only on the apical surface of surface mucous cells but also in the mucous gel layer covering the gastric mucosa. The present study was undertaken to observe the mucous gel layer itself and any H pylori in this layer at the electron microscopic level, and to determine whether H pylori proliferate in this layer. METHODS: We examined resected human stomachs (five cases, fixed in Carnoy's solution, paraffin embedded) under the light microscope, and gastric biopsy specimens (10 cases, fixed in glutaraldehyde with or without osmium, epoxy embedded) under the electron microscope. We performed histochemical staining for gastric mucins and immunostaining for H pylori, gastric gland mucous type mucins, and intestinal mucins. RESULTS: Under the electron microscope, surface mucous cell type mucins and gland mucous cell type mucins in the mucous gel layer covering gastric mucosa without intestinal metaplasia showed reticular and band like structures, respectively. H pylori were frequently found as small aggregates within the mucous gel layer of surface mucous cell type mucins, and H pylori within these aggregates were seen dividing. H pylori were frequently found in the mucous gel layer of the surface mucous cell type mucins along the border with the layer of gland mucous cell mucins. Occasionally, H pylori were trapped by frayed thin threads of the gland mucous cell type mucins. CONCLUSIONS: The two types of gastric mucins in the mucous gel layer differ in ultrastructure. H pylori preferentially colonise and form microcolonies within the mucous gel layer of surface mucous cell type mucins. Mucins from gland mucous cells may disturb the movement of H pylori within the mucous gel layer.

Characterization of an apolipoprotein E3 variant (Arg 145-->His) associated with mild hypertriglyceridemia.

In a proband (21-yr-old female), we previously identified an apolipoprotein (apo) E variant, apoE3 (Arg 145-->His), with an isoelectric point midway between apoE3 and apoE2. ApoE gene analysis of 4 of the proband's kin indicated that 3 possess the same variant. All 4 had a high concentration of apoE in plasma, while 3 of 4 had hypertriglyceridemia. In the proband (who had no hypertriglyceridemia), most apoE was distributed in slow-alpha lipoproteins (predominantly in the form of apoE-AII heterodimer) and in larger molecules with apparent molecular weights of 80 and 100 kDa. In the proband's brother (with hypertriglyceridemia), however, most apoE was distributed in slow pre-beta lipoproteins, predominantly in the form of monomeric apoE. In each subject, the concentration of apoE3 variant was significantly higher than that of normal apoE3 in the predominant apoE-rich lipoprotein. The apoE3 variant, which displayed a slightly reduced binding ability to LDL-receptor and heparin, may induce an accumulation of apoE-rich lipoproteins. These observations suggest that the difference in distribution of apoE3 variant in plasma lipoproteins between the proband and her brother (combined with its reduced affinity for the LDL receptor) may provide key insights into the pathogenesis of hypertriglyceridemia.

Genetic alterations and growth pattern in biliary duct carcinomas: loss of heterozygosity at chromosome 5q bears a close relation with polypoid growth.

Biliary duct carcinomas (BDCs) are relatively rare and the carcinogenic mechanisms underlying their induction are poorly understood. There are two growth patterns, polypoid and non-polypoid infiltrative type, but little information is available concerning the relation between growth pattern and genetic alterations. A comparative study was therefore conducted to clarify if differences in genetic changes, including loss of heterozygosity (LOH) at 5q, 9p, 17p, and 18q, and K-ras mutations exist between polypoid and non-polypoid infiltrative type BDCs. LOH analysis was performed using microsatellite markers and K-ras point mutations were analysed by dot blot hybridisation. The incidences of changes for polypoid and non-polypoid infiltrative types were 73% and 26% on 5q, 63% and 59% on 9p, 55% and 50% on 17p, and 20% and 18% on 18q, and 25% and 27% for K-ras mutations. Most importantly, we found the frequency of 5qLOH to be significantly higher with polypoid growth than in the non-polypoid infiltrative type (p<0.05), especially in extrahepatic duct carcinomas (p<0.05). The incidences of other genetic alterations (LOH at 9p, 17p, and 18q, and K-ras mutations) showed similar rates with both tumour types. The present data suggest that 5qLOH may have a close relation with polypoid growth in BDCs.

Immunohistochemical demonstration of alpha1,4-N-acetylglucosaminyltransferase that forms GlcNAcalpha1,4Galbeta residues in human gastrointestinal mucosa.

alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase that mediates transfer of GlcNAc to betaGal residues with alpha1,4-linkage, forming GlcNAcalpha1--> 4Galbeta-->R structures. In normal human tissues, glycoproteins having GlcNAcalpha1-->4Galbeta-->R structures at non-reducing terminals are exclusively limited to the mucins secreted from glandular mucous cells of gastric mucosa, Brunner's gland of duodenum, and accessory gland of pancreaticobiliary tract. Recently, we have isolated a cDNA encoding human alpha4GnT by expression cloning. Although alpha4GnT plays a key role in producing this unique glycan in vitro, the actual localization of alpha4GnT was not determined. In this study we examined the localization of alpha4GnT in various human tissues, including gastrointestinal mucosa, using a newly developed antibody against human alpha4GnT. The specificity of the antibody was confirmed by analyses of human gastric adenocarcinoma AGS cells transfected by alpha4GnT cDNA. Expression of alpha4GnT was largely associated with the Golgi region of mucous cells that produce the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R, such as the glandular mucous cells of stomach and Brunner's gland. An immunoprecipitation experiment disclosed that two distinct mucin proteins, MUC5AC and MUC6 present in gastric mucin, carried the GlcNAcalpha1-->4Galbeta-->R structures. These results indicate that alpha4GnT is critical to form the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R on MUC6 and MUC5AC in vivo.(J Histochem Cytochem 49:587-596, 2001)

Induction of primary root curvature in radish seedlings in a static magnetic field.

Primary roots of radish (Raphanus sativus L.) seedlings were exposed to an inhomogeneous static magnetic field generated by a permanent magnet, during continuous rotation on a 0.06 rpm clinostat, thereby reducing the unilateral influence of gravity. The roots responded tropically to the static magnetic field with the tropism appearing to be negative. These roots responded significantly (P < 0.05) to the south pole of the magnet. The significant tropic response was found for a magnetic flux density of 13-68 mT, for a field gradient of 1.8-14.7 T/m, and for the product of magnetic field and field gradient of 0.023-1.0 T(2)/m. A small, but insignificant, response of the roots to the north pole has also been found.

Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene.

We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c-kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val-->Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c-kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease.

Origin of giant cells in osteoclast-like giant cell tumors of the pancreas.

To clarify the origin of giant cells in osteoclast-like giant cell tumors (OGCTs) of the pancreas, we performed microscopical, immunohistochemical, and K-ras gene mutation analyses with a microdissection approach in 3 cases, featuring 4 cellular components (osteoclast-like giant cells [OGCs], pleomorphic large cells [PLCs], mononuclear cells, and ductal carcinoma cells). Two cases had abundant OGCs, and 1 case contained large number of both OGCs and PLCs. In each, none of the microdissected OGCs contained any K-ras gene mutation while they were positive for a histiocytic marker (CD-68). In contrast, PLCs, when present, frequently harbored K-ras gene mutations and were negative for CD-68. In all cases, mononuclear cells, a mixture of histiocyte-like and atypical, from microscopic and immunohistochemical viewpoints, also frequently showed K-ras alteration. Histiocyte-like mononuclear cell was equipped with a regular and oval nucleus similar to those in OGCs and was positive for CD-68. Atypical mononuclear cell showed an irregular, pleomorphic, or sometimes bizarre nucleus similar to those in PLCs and was negative for CD-68. All of the K-ras gene mutations found in PLCs and mononuclear cells were the same as in the ductal carcinoma cells within the same tumor. Thus, OGCs differ in origin from ductal cells and are strongly suggested to be nonneoplastic and of mesenchymal origin, whereas PLCs, which harbor K-ras gene mutations, are neoplastic and presumably derived from ductal carcinoma cells. Moreover, mononuclear cells may be classified into 2 types, histiocyte-like and atypical.

Japanese family with an autosomal dominant chromosome instability syndrome: a new neurodegenerative disease?

We report on a Japanese family having an autosomal dominant neurodegenerative disease with chromosomal instability and radiosensitivity. Clinical manifestations of affected members included short stature, osteoporosis, severe dental caries, and various neurological abnormalities, such as mental retardation, depression, dysarthria, hyperreflexia, and ataxic gait. MRI demonstrated a markedly atrophic spinal cord and degeneration of the white matter. Cytogenetic examination showed spontaneous chromosome rearrangements at 14q11.2 and hypersensitivity to radiation and bleomycin. The degree of these cytogenetic abnormalities was significantly higher in the patients than in normal controls but lower than in patients with ataxia telangiectasia or Nijmegen breakage syndrome. Moreover, genetic anticipation was observed in this family: the age of disease onset became earlier, MRI abnormalities more extensive, and the chromosome hypersensitivity to radiation increased in successive generations. We speculate that a basic defect in this family is a mutation in the gene that is responsible for DNA double-strand breakage repair.