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Biomedical subjects

V Shetty

Publications and source records attributed to V Shetty.

At least 19 recordsLinked to original sources
PubMed2006

Arterial stiffness and hand osteoarthritis: a novel relationship?

OBJECTIVE: Osteoarthritis (OA) and vascular stiffening may share elements of common pathogenesis, but their potential relatedness has been the focus of little prior inquiry. We tested the hypothesis that these two aging-associated conditions are related to each other. METHOD: We analyzed cross-sectional data from 256 participants of the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging. All underwent measurement of arterial pulse wave velocity (PWV), an index of vascular stiffness, as well as hand radiographs that were graded for evidence of OA. Twenty total joints across three joint groups (distal interphalangeal [DIP], proximal interphalangeal [PIP], carpal-metacarpal [CMC]) were each assigned a Kellgren-Lawrence grade (K-L) of 0 (normal) through 4 (severe), with K-L grades >or=2 considered evidence of definite OA. Radiographic hand OA was defined as definite OA changes in at least two of the three anatomic hand sites (DIP, PIP, CMC). OA burden was represented by the total number of affected OA joints, and a cumulative K-L grade was aggregated across all hand joint groups. The relationship of PWV with these three measures of hand OA was assessed by linear regression. RESULTS: Upon univariate analysis, the presence of radiographic hand OA (beta=218.1, P<0.01), the total number of OA joints (beta=32.9, P<0.01), and the cumulative K-L grade across all joint groups (beta=12.2, P<0.01) were each associated with increased PWV. These associations, however, were no longer significant in age-adjusted models. CONCLUSION: Although significant individual relationships between PWV and several measures of hand OA were observed, these associations were largely attributable to the confounding effect of age.

Aging↗
PubMed2006

Proximal loop jejunostomy is a useful adjunct in the management of multiple intestinal suture lines in the septic abdomen.

BACKGROUND: Bowel repair in the septic abdomen can be problematic. This study investigated the use of a proximal loop jejunostomy to protect injured or fistulated bowel that had been returned to the abdomen after repair and/or anastomosis. METHODS: Ten patients who underwent laparotomy for intra-abdominal sepsis and/or fistulation, followed by distal enteric repair and/or anastomosis and construction of a proximal defunctioning loop jejunostomy, were studied retrospectively. Seven patients had 21 intestinal suture lines returned to the peritoneal cavity in the presence of intra-abdominal sepsis (14 anastomoses, two enterotomy closures and five serotomy repairs). Two patients had a difficult relaparotomy for pelvic abscess (two distal anastomoses, one enterotomy closure and three serotomy repairs). The final patient had pelvic sepsis and radiation enteritis; the distal anastomosis was defunctioned by a loop jejunostomy. RESULTS: The median distance from the duodenojejunal flexure to the loop stoma was 80 (range 30-170) cm. All jejunostomies were closed via a local approach, a median of 11 (range 9-18) months after formation. There was no significant postoperative morbidity and no postoperative death. At a median follow-up of 7 (range 0.5-56) months eight patients had no requirement for nutritional support. CONCLUSION: Use of a loop jejunostomy to protect suture lines in the septic abdomen justifies consideration of this procedure in selected patients.

Abdomen↗
PubMed2006

Primitive neuroectodermal tumor (PNET) as second malignancy after treatment of Hodgkin's disease.

Hodgkin's disease survivors are at an increased risk of developing second malignant neoplasms including secondary bone tumors. Common secondary bone tumors are osteogenic sarcoma and fibrosarcoma. Secondary primitive neuroectodermal tumor is extremely rare in this group. We present below, a rare case of secondary PNET in an 8-year-old child with Hodgkin's disease which developed unusually early outside the radiation portal and discuss potential factors responsible for its causation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Presence of activation-related m-RNA for EBV and CMV in the bone marrow of patients with myelodysplastic syndromes.

The bone marrow (BM) in myelodysplastic syndromes (MDS) undergoes pathobiological changes that mimic an inflammatory process, and hence, an infectious etiology was suspected in these disorders. In the present report, we examined the bone marrow mononuclear cells (BMMNC) of 19 MDS patients and seven normal donors for the expression of one latency-related (Latency membrane protein 1 (LMP-1) and immediate early protein (IEP)) and one activation-related (BZLF and DNA-Pol) m-RNA each for two herpes viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), respectively. Reverse transcriptase polymerase chain reaction was used for this purpose. The latency-related transcripts (EBV-LMP-1 and CMV-IEP) were present in all the MDS and normal specimens. Intriguingly, 10/19 MDS specimens ( approximately 53%) and 2/7 normal donors ( approximately 28%) were positive for active EBV-BZLF (P=0.0067), while 2/19 MDS specimens ( approximately 11%) with 1/7 normal ( approximately 14%) showed active CMV-DNA-Pol (P=0.1588). Later, from another set of MDS patients (n=7) and normal donors (n=4), BM stromal cultures were established, which, at a 75% confluency, were overlaid with cord blood mononuclear cells (CBMNC). IEP was detectable in the CBMNC before and after co-incubation with MDS, as well as normal stroma. So, it was also present both in MDS and normal stromal cells. The other three were absent both in MDS and normal stromal layers. In CBMNC though, active EBV-BZLF and CMV-DNA-Pol m-RNA were detectable in one of seven MDS co-cultures each, albeit from different patients. None of the normal co-cultures showed active virus, either in stroma or CBMNC. Thus, the present report demonstrates, for the first time, the presence of active herpes viruses in the BMMNC of MDS patients and reveals the ability of the MDS stroma to support the viral activation.

Bone Marrow↗
PubMed2001

Synthesis of some halogen-containing 1,2,4-triazolo-1,3,4-thiadiazines and their antibacterial and anticancer screening studies--part I.

A series of 7-arylidene-6-(2,4-dichloro-5-fluorophenyl)-3-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) were prepared by the condensation of 4-amino-5-mercapto-3-substituted-1,2,4-triazoles (1) and 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-2-propen-1-one (2). An alternative route for the synthesis of the title compound 3 has been described. The newly synthesised compounds were characterised on the basis of N-analyses, IR, 1H NMR and mass spectral data. Some of the newly synthesised compounds were tested for their antibacterial activities against Gram + ve and Gram - ve bacteria. Among the tested compounds 3n showed the highest degree of antibacterial activity against S. aureus and evaluation of the LD50 value of this compound was carried out. Some of the newly synthesised compounds were also screened for their anticancer activities. Among these, compounds 3b, 3g, 3n and 3p are found to be active against NCI-H460 (lung), MCF7 (breast), SF 268 (CNS) in the preliminary anticancer screening studies. Further, 60-cell-line anticancer studies of these compounds were carried out. The results of such studies are discussed in this paper.

Animals↗
PubMed2001

Successful establishment of long-term bone marrow cultures in 103 patients with myelodysplastic syndromes.

We used bone marrow biopsies instead of mononuclear cells to maintain long-term cultures from 103 patients belonging to all five sub-categories of myelodysplastic syndromes (MDS), as well as 12 normal controls. By week 4, 30-50% confluency was reached and could be maintained for up to 12 weeks with 100% confluency. The four prominent cells were fibroblasts, macrophages, endothelial cells and adipocytes. Immunohistochemical and electron microscopic studies provided lineage confirmation. Normal hematopoiesis was well supported by MDS stroma. Neither the FAB nor cytogenetics was co-related with the potency of growth. MDS stroma appears to be both morphologically and functionally normal.

Adipocytes↗
PubMed2001

The clinical and biological effects of thalidomide in patients with myelodysplastic syndromes.

Thirty patients with myelodysplastic syndromes (MDS) were treated with thalidomide at 100 mg/d p.o., increased as tolerated to 400 mg/d for 12 weeks. Levels of apoptosis, macrophage number, microvessel density (MVD), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined in the serum, bone marrow (BM) plasma and BM biopsies before and after therapy. Pretherapy biological characteristics of MDS patients were compared with similar studies performed in 11 normal volunteers. Ten patients demonstrated haematological improvement in the erythroid series, six becoming transfusion independent. Responders had a higher pretherapy platelet count (P < 0.048) and lower BM blasts (P < 0.013). Median time to response was 10 weeks, and four remain in remission beyond a year. Pretherapy MDS BMs showed higher MVD (P < 0.001) and TGF-beta (P < 0.03) and higher serum TNF-alpha (P < 0.008) compared with normal control subjects. After therapy, only BM TGF-beta decreased significantly (P < 0.002). Pretherapy haemoglobin was directly related to serum VEGF (P < 0.001) in responders and inversely related in non-responders (P < 0.05), suggesting the possibility that angiogenesis may be a primary pathology in the former and a consequence of anaemia-induced hypoxia in the latter. We conclude that thalidomide has important clinical and biological effects in at least a subset of MDS patients, but the precise mechanism of its action remains unknown and requires further study including a larger number of patients.

Aged↗
PubMed2001

Clinician variability in characterizing mandible fractures.

PURPOSE: This study evaluated variability in the clinical parameters commonly used to characterize mandible fractures. PATIENTS AND METHODS: Inter-rater reliability of 18 oral and maxillofacial surgeons was assessed using radiographs of 22 cases of mandible fractures. Raters were asked to evaluate each case based on several parameters including number, location, and displacement of the individual fractures and severity of the composite injury. To evaluate intra-rater reliability, selected cases were reviewed at a second session by a subgroup of these surgeons. Tests of concordance used to quantify measurement reliability included the interclass correlation coefficient and multiple-rater kappa statistics. RESULTS: Inter-rater agreement on the number of constituent fractures ranged from excellent for simpler fractures to poor for complex gunshot injuries. Even within raters, the range of interclass correlation for complex injuries was only 0.33 to 0.42 between the 2 assessments. Clinicians appeared to be better at delineating coronoid, condyle, ramus, and angle fractures; symphyseal and canine region fractures had lower inter- and intrarater agreement. Tests of concordance showed moderate to excellent reliability when fracture displacements were expressed in millimeters, but only fair reliability when displacements were expressed as categories. Even when the clinicians concurred on displacement measurements, a large overlap was observed in their categorization of these displacements. Despite the differences in the assessment of individual parameters, the high intrarater reliability coefficient (0.78) indicated that the individual clinicians had a high internal consistency in their assignment of summary severity scores. Multiple regression analysis revealed the number of constituent fractures, the type of fracture, and amount of fracture displacement (millimeters) to be significant predictors of clinician ratings of injury severity. CONCLUSIONS: The clinician variability underscores the difficulties involved in trauma description and scoring. The study identifies some sources of clinician variability and emphasizes the need to standardize the characterization of mandible fractures by using explicit guidelines.

Adult↗
PubMed2001

A comparative evaluation of three fluoride varnishes: an in-vitro study.

This study was conducted to compare the caries preventive efficacy of Fluoritop - SR; the first fluoride varnish manufactured in India with Fluor Protector and Bifluorid 12, the two commercially available fluoride varnishes which have to be imported from other countries and are cost prohibitive. The demineralization inhibitory effects and the antibacterial effects on Streptococcus mutans were studied (in vitro). Calcium and Phosphorus dissolutions were estimated as a measure of the demineralization inhibitory effect. Antibiotic sensitivity tests using the serial tube dilution method and disk diffusion method were used to evaluate the antibacterial effects of the fluoride varnishes. Of the three varnishes, Fluor Protector was seen to exhibit the highest demineralization inhibitory effect, while Fluoritop-SR was found to be comparable to Bifluorid 12 in its caries protective effects.

Analysis of Variance↗
PubMed2000

Intramedullary apoptosis of hematopoietic cells in myelodysplastic syndrome patients can be massive: apoptotic cells recovered from high-density fraction of bone marrow aspirates.

A higher percentage of apoptotic cells (apoptotic index or AI) is consistently found in bone marrow (BM) biopsies compared to BM aspirates of patients with myelodysplastic syndrome (MDS). Most studies have only investigated the low-density fraction (LDF) mononuclear cells from BM aspirates following density separation for AI determination. In the present study, both LDF and high-density fraction (HDF) cells for AI were examined by electron microscopy (EM) in 10 MDS patients and 4 healthy donors. Matched BM biopsies were subjected to AI detection by in situ end labeling (ISEL) of fragmented DNA. The results indicate that in LDF and HDF cells, AI is consistently higher in MDS patients (8.5% vs 1.5%, respectively; P =.039) compared to healthy donors (27% vs 4%, respectively; P =. 004). The BM biopsy AI was also higher in MDS patients than in healthy donors (3+ vs 0+, respectively; P =.036). In addition, in MDS patients, more apoptotic cells were found in HDF cells than in LDF cells (27% vs 8.5%, respectively;P =.0001). All stages of maturation, ranging from blasts to terminally mature cells belonging to all 3 lineages, were represented in the dying cells in both compartments. Using EM, typical Pelger-Huett-type cells appeared to be apoptotic granulocytes. Both LDF and HDF cells should be examined for an accurate estimation of apoptotic cells because AI would be underestimated if only the LDF cells were studied. Ultrastructural studies consistently show a higher AI in BM biopsies compared to BM aspirates despite the correction factor of HDF cells provided by AI. This may represent the actual extant state, which could conceivably be due to a higher concentration of proapoptotic signals in the biopsies. (Blood. 2000;96:1388-1392)

Apoptosis↗
PubMed2000

Signal antonymy unique to myelodysplastic marrows correlates with altered expression of E2F1.

Myelodysplastic syndromes (MDS) have previously been reported to show competitively high rates of apoptosis and proliferation in the bone marrow (BM). Using a double-labelling technique in the present study, we demonstrated that a significantly high number of S-phase cells were simultaneously apoptotic (signal antonymy; SA) in MDS (mean +/- s.e.m. 53.5 +/- 6.7%, n = 24, P < 0.001). In contrast, SA was negligible in all other specimens studied, including normal control BM (n = 13) from non-Hodgkin's lymphoma (NHL) patients, BM from patients with de novo acute myelogenous leukaemia (1'AML; n = 5), or secondary AML that had transformed from MDS (2'AML; n = 10), or the solid tumours from patients with NHL (n = 9) or head and neck squamous cell carcinoma (HNSCC; n = 10). Subsequently, the expression of a transcription factor, E2F1, was studied in density-separated BM aspirate mononuclear cells from MDS patients (n = 9) and a normal control. Two separate sets of primers were used that recognized the regulatory retinoblastoma (Rb) protein-binding region and the functional DNA-binding region of E2F1. Interestingly, although the latter manifested the expected band (280 bp) in all samples, the Rb-specific primers showed the expected band (380 bp) in the normal and in 4/9 MDS specimens. Two other MDS specimens also showed a smaller band ( approximately 325 bp), whereas 3/9 MDS patients showed exclusively the smaller band. The levels of SA were significantly higher in those MDS cases that showed the smaller Rb-specific band either alone or in addition to the expected band (median 19.5%, n = 4, P = 0.037) than in those showing exclusively the expected band (median 0.4%, n = 3). Our present studies show SA as a characteristic feature of MDS and, importantly, demonstrate its link with an altered expression of E2F1 in some MDS patients.

Apoptosis↗
PubMed2000

The clinical and biologic significance of abnormal lipid profiles in patients with myelodysplastic syndromes.

Serum lipid profiles were obtained in 108 patients with myelodysplastic syndrome (MDS) and compared to 28 healthy volunteers. Serum cholesterol and low-density and high-density lipoproteins (LDL and HDL) were found to be significantly lower in MDS patients than in normals (p = 0.0001, 0.0038 and 0.037, respectively). This difference was significant for all MDS categories. Serum cholesterol and HDL were negatively related to biopsy cellularity (p = 0.001 and 0.0001, respectively), and serum triglycerides were negatively related to labeling index (p = 0.0003). No differences were noted in the lipid profiles of MDS patients with normal versus abnormal karyotypes. However, low-risk MDS patients with abnormal karyotypes had significantly lower triglyceride levels compared with the high-risk patients (p = 0.027), as did low-risk patients with normal cytogenetics (p = 0.015). Serum HDL levels were significantly higher for the low-risk group with normal cytogenetics as well (p = 0.003). We conclude that serum cholesterol, LDL, and HDL are significantly reduced in MDS patients, probably indicating excessive intracellular lipid biosynthesis in the expanding clone. These relatively simple measurements could serve as important prognostic markers and reliable indicators of disease activity in individual patients. Prospective studies to determine their utility as independent variables that guide the need for active therapeutic intervention are warranted.

Adult↗
PubMed2000

Radiographic assessment of the cement mantle thickness of the femoral stem in total hip replacement: a case study of 112 consecutive implants.

The results are reported of a radiographic study of cement mantle thickness in 112 consecutive primary hip replacements. Measurements were made by three observers of the apparent cement thickness medially and laterally using standard anterior-posterior radiographs. The average cement thickness was 3.2 mm, which is 1.2 mm greater than the size difference between the broach and the prosthesis, and was in the range 2-5 mm in 67 per cent of all measurement points. This has significance for the design of instrumentation to prepare the femoral cavity to give a defined cement mantle thickness. There was a greater cement mantle thickness proximally than distally. In 95 cases it was possible to determine the orientation of the stem within the cement mantle, which showed an even distribution between varus and valgus orientation; 49 per cent were within 1 degree of neutral and only one case was more than 5 degrees from neutral.

Biomechanical Phenomena↗
PubMed1999

Correlation of tumor necrosis factor alpha (TNF alpha) with high Caspase 3-like activity in myelodysplastic syndromes.

Increased intramedullary apoptotic death of hematopoietic cells is thought to contribute to the ineffective hematopoiesis in myelodysplastic syndromes (MDS). Furthermore, high amounts of tumor necrosis factor alpha (TNF alpha) have previously been correlated with apoptosis in MDS marrows. The present studies were undertaken to examine the status of two key downstream effectors of TNF alpha signaling, i.e. Caspase 1 and Caspase 3 enzymes, using a fluorometric assay in the bone marrow aspirate mononuclear cells (BMMNC) in relation to apoptotic DNA fragmentation detected by in situ end-labeling (ISEL) of DNA and with localization of TNF alpha in the corresponding biopsies from 14 MDS patients. Both Caspase 1 and 3 were detectable in freshly harvested BMMNC, albeit median Caspase 3 levels (47.5 units/mg protein) being almost 10 times higher than Caspase 1 (4.0 units/mg protein). Upon short-term culture for 4 h in a serum-supplemented medium in vitro a significant increase was seen in Caspase 3 activity (58.8 +/- 13.9 at 0 h vs. 177.8 +/- 55.2 units/mg protein at 4 h, n = 14, P = 0.017) and in percent cells labeled by ISEL (apoptotic index or AI%: 0.76% +/- 0.25% vs. 3.99% +/- 1.1%, n = 14, P = 0.004, respectively). Caspase 1 activity increased after 15 min in culture. Interestingly, TNF alpha levels measured by immunohistochemistry correlated with the net increase in Caspase 3 activity after 4 h (p = 0.517, n = 13, P = 0.07) and the starting levels of Caspase 1 at 0 h correlated with the Caspase 3 levels attained at 4 h (p = 0.593, n = 13, P = 0.033). Additionally when TNF alpha-positive bone marrows (8/14) were compared with the negative marrows (6/14) the Caspase 3 levels were significantly higher in the TNF alpha-positive marrows (189.6 +/- 66.2 vs. 25.0 +/- 14.6 units/mg protein, respectively, P = 0.043). The increase in AI%, though not statistically significant, was also higher in the TNF alpha-positive marrows. Finally in HL60 cells the effects of different Caspase inhibitors and pentoxifylline (PTX) (interferes with lipid signaling of cytokines) on TNF alpha-induced apoptosis were evaluated. TNF alpha treatment significantly increased AI% (P < 0.003) as compared to the untreated controls. A co-treatment with three Caspase inhibitors, zVAD.FMK (inhibitor of Caspases 1 and 3, 10 microM/l), Ac.YVAD.FMK (Caspase 1 inhibitor, 1 microM/l), Ac.DEVD.FMK (Caspase 3 inhibitor, 10 microM/l) as well as PTX (250 microM/l) significantly curtailed the AI% induced by TNF alpha. The present studies thus identify the downstream effectors of TNF alpha-inducible apoptosis in MDS and so also the suppressors of TNF alpha apoptotic signaling. These results may have significant clinical implications in the therapy of MDS in the future.

Apoptosis↗
PubMed1999

Biologic characteristics of patients with hypocellular myelodysplastic syndromes.

Rates of proliferation and apoptosis as well as expression of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and the number of macrophages were measured in bone marrow (BM) biopsies of 33 patients who presented with hypocellular (cellularity < 30%) myelodysplastic syndromes (MDS). Results showed that 2/3 of the patients had high apoptosis, high cytokine levels and large number of macrophages in their biopsies while 1/3 did not. Apoptosis and TNF-alpha levels were directly related (r = 0.583, P = 0.003, n = 24) as was apoptosis and the degree of anemia (P = 0.033, n = 18). A subgroup of patients with abnormalities of chromosomes 5 or 7 had higher platelets (P = 0.026) and higher apoptosis (P = 0.038) when compared with the rest of the group. Eight patients had no evidence of apoptosis and almost no detectable TNF-alpha in their biopsies. We conclude that within the hypocellular variant of MDS, there may be two distinct sub-groups of patients, one who present with high cytokine-mediated intramedullary apoptosis and the other who may be better characterized as having a stem-cell failure defect since they showed no evidence of apoptosis.

Adolescent↗
PubMed1999

Correlates of missed appointments in orofacial injury patients.

OBJECTIVE: The purposes of this study were to compare the sociodemographic and health-related characteristics of orofacial injury patients who miss appointments with those of patients who do not and to determine which patient characteristics best predict missed-appointment behaviors (e.g., the number of missed clinic visits). STUDY DESIGN: A total of 190 patients (134 African American and 56 Hispanic) treated for mandible fractures at the King/Drew Medical Center, Los Angeles, participated in a prospective study involving structured interviews at 4 points (denoted recalls 1-4) over a 6-month period. To be included in the study, patients were required to have attended recall 1. Most patients in the study sample were male, more than 32 years of age, unmarried, and unemployed; most had completed high school; and most had sustained their injuries as a result of assault. RESULTS: Only 22% of the patients attended all 4 recall clinic appointments. However, 42% completed 3 recall visits, and 69% completed 2 recall visits. Patients who missed appointments were more likely to be African American than Hispanic and more likely to be unemployed than employed. There was a significant negative association between perceived social support and missed appointments (r = -0.18, P = .01). Patients who missed more appointments perceived themselves to have less social support than those who missed fewer or no appointments. The data revealed no associations between missed appointment behavior and age, gender, marital status, or education. None of the health-related variables investigated were associated with missed appointments. Multiple regression analysis confirmed that race, unemployment, and perceived social support were the best predictors of missed appointments. CONCLUSIONS: Social variables have a greater impact than health variables in predicting missed-appointment behavior. Unemployed African American patients are at the greatest risk for missing recall clinic appointments; however, this finding is independent of health insurance. Accessing and enlisting patients' social networks to support follow-up medical care has potential for improving appointment-keeping behavior and should be further examined.

Adult↗
PubMed1999

Sequential activation of caspase-1 and caspase-3-like proteases during apoptosis in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders characterized by the concomitant presence of peripheral cytopenias and normocellular to hypercellular BM. This paradox has been proposed to be due to the presence of excessive proliferation matched by excessive intramedullary apoptosis of hematopoietic cells. When cultured in vitro MDS BM mononuclear cells (BMMC) undergo apoptosis within 4 h. We measured caspase-1-like and caspase-3-like activity in 22 MDS and 4 normal BM immediately following cell separation or after 4 h culture. When cultured in vitro, MDS BMMC demonstrated an increased apoptotic index within 4 h as measured by in situ end-labeling of fragmented DNA that was matched by a concurrent increase in caspase-3-like specific activity, and the two were significantly correlated. During the 4 h culture, a sequential activation of caspase-1-like and caspase-3-like activities was detected. Caspase-1-like specific activity was detected early and transiently at approximately 15 min, followed by a gradual increase in caspase-3-like-specific activity peaking at 2 h. When the broad-spectrum caspase inhibitor, Z-VAD.FMK, was included in the MDS BM aspirate 4 h culture, apoptosis was attenuated. We conclude that sequential activation of caspase-1-like and caspase-3-like activities may form the central biochemical pathway of apoptosis in BMMC from some MDS patients, and prevention of this process by caspase inhibitors may be of significant therapeutic value for these patients, in whom supportive care continues to be the mainstay of therapy.

Amino Acid Chloromethyl Ketones↗