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PubMed2001

Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens.

BACKGROUND AND PURPOSE: Tumor progression is often difficult to distinguish from nonneoplastic treatment response on the basis of MR images alone. This study correlates metabolite levels measured by preoperative MR spectroscopic (MRS) imaging with histologic findings of biopsies, obtained during image-guided resections of brain mass lesions, to clarify the potential role of MRS in making this distinction. METHODS: Twenty-nine patients with brain tumors underwent high-resolution (0.2-1 cc) 3D proton MRS imaging and MR imaging before undergoing surgery; 11 had a newly diagnosed neoplasm, and 18 had recurrent disease. Surgical biopsies were obtained from locations referenced on MR images by guidance with a surgical navigation system. MR spectral voxels were retrospectively centered on each of 79 biopsy locations, and metabolite levels were correlated with histologic examination of each specimen. RESULTS: All mass lesions studied, whether attributable to tumor or noncancerous effects of previous therapy, showed abnormal MR spectra compared with normal parenchyma. When the pattern of MRS metabolites consisted of abnormally increased choline and decreased N-acetyl aspartate (NAA) resonances, histologic findings of the biopsy specimen invariably was positive for tumor. When choline and NAA resonances were below the normal range, histologic findings were variable, ranging from radiation necrosis, astrogliosis, and macrophage infiltration to mixed tissues that contained some low-, intermediate-, and high-grade tumor. CONCLUSION: This study demonstrated that 3D MRS imaging can identify regions of viable cancer, which may be valuable for guiding surgical biopsies and focal therapy. Regions manifesting abnormal MR spectra had a mixture of histologic findings, including astrogliosis, necrosis, and neoplasm.

Adolescent↗
PubMed2004

[Geographical Information Systems and remote sensing technologies in parasitological epidemiology].

Parasites have natural habitats in the same way as a species: they are found in focal areas where the spatial distribution of the parasite, host, vector and required environmental conditions coincide. The spatial distribution of parasites is, therefore, a function of the interaction between abiotic and biotic environmental factors. The boundaries of distributions are not strictly fixed in space and time and may fluctuate with climate and other components of the environment or anthropical factors. Geographic Information Systems (GIS) and remote sensing (RS) technologies are being used increasingly to study the spatial and temporal patterns of disease. GIS can be used to complement conventional ecological monitoring and modelling techniques, and provide means to portray complex relationships in the ecology of disease. In addition, the use of GIS and RS to identify environmental features allows determination of risk factors and delimitation of areas at risk, permitting more rational allocation of resources for cost-effective control. Since 1996, GIS have been used in our territorial cross-sectional and longitudinal parasitological surveys in order to experiment new applications to plan sampling protocols and to display quickly, clearly, and analytically the spatial and/or temporal distribution of parasitological data. The use of GIS allowed us to draw the following types of descriptive parasitological maps: distribution maps, distribution maps with proportioned peaks, choroplethic maps with proportioned peaks, point distribution maps and point distribution maps with proportioned peaks. In a recent study, GIS and RS technologies have been used also to identify environmental features that influence the distribution of paramphistomosis in sheep from the southern Italian Apennines and to develop a preliminary risk assessment model. A GIS was constructed using RS and landscape feature data together with paramphistome positive survey records from 197 georeferenced ovine farms with animals pasturing in an area of the southern Italian Apennines. The GIS for the study area was constructed utilizing the following environmental variables: Normalized Difference Vegetation Index (NDVI), land cover, elevation, slope, aspect, and total length of rivers. In addition, data regarding the presence of watercourses smaller than rivers, namely, streams, springs and brooks were recorded in the field. All these variables were then calculated for "buffer zones" consisting of the areas included in a circle of 3 Km diameter centred on 197 farms. The environmental data obtained were analyzed by univariate and multivariate statistical analyses using the paramphistome farm coprological status (positive/negative) as the dependent variable. A multivariate stepwise discriminant analysis model was developed that included moors and heathland, sclerophyllus and coniferous forest vegetation, autumn-winter NDVI and presence of streams, springs and brooks on pasture. The variables entered in the model are consistent with the environmental requirements of paramphistomes and their snail intermediate host. In particular, the land cover types entered in the model in this area are indicators of marginal uncultivable and sloping zones where typically there is the presence of water (permanently or temporarily). In addition, since NDVI can be used as an indicator of regional thermal-moisture regime, the distribution of farms positive for paramphistomosis corresponding to relatively high values of winter NDVI indicated the presence of adequate moisture and temperatures favourable to the rumen fluke and the snails. In conclusion, GIS and RS are useful to define the habitats of parasites, especially for those with strong environmental determinants, and to produce forecasting maps requested for the planning and the monitoring of control strategies on small and large scale.

Animals↗
PubMedDate not supplied

[Fractal properies of gating in potential-dependent K+-channels in Lymnaea stagnalis neurons].

Sets of the channel open times, [tau(o)], and closed times, [tau(c)], and the full set of the channel open and closed times, [tau(o), tau(c)], in the activity of single voltage-dependent K+-channels in mollusc L. stagnalis neurons were analyzed using the rescaled range analysis (Hurst method), fast Fourier and wavelet transforms. It was found that the Hurst dependence for each time series could be approximated by a polygonal line with at least two slopes: H1 and H2 (Hurst exponents). The averaged values of H1 and H2 for the sets [tau(o), tau(c)] were equal to 0.61 +/- 0.03 and 0.83 +/- 0.11, respectively; for the [tau(o)] sets H1 = 0.66 +/- 0.03 and H2 = 0.95 +/- 0.10; for the [tau(c)] sets, H1 = 0.62 +/- 0.05 and H2 = 0.85 +/- 0.10. In some cases, a third slope appeared on the Hurst dependences. It was very variable and ranged between 0.5 and 1. The Hurst exponents H1, H2, and H3 characterized short, intermediate, and long time ranges, respectively. The ranges greatly varied from experiment to experiment. The data obtained show that the channel openings and closings (gating process) represent a persistent process correlated in time. The randomization of the time sets resulted in a single slope, H, of 0.52 +/- 0.02 characteristic of random processes. The results were confirmed by the fast Fourier and wavelet transforms. In addition, possible voltage dependences of Hurst exponents and their correlation with tau(o) and tau(c) were investigated. As a whole, single channel activity may be characterized as a multifractal process with a slight voltage dependence of the Hurst exponents.

Animals↗
PubMed2005

Update of fasciolosis-transmitting snails in Egypt (review and comment).

Several snail species may contribute in transmission of fasciolosis in Egypt. These molluscs show a variable sensibility to natural infections with Fasciola species. Radix natalensis is considered to be the essential intermediate host for F. gigantica based on field and experimental studies. Cercarial production from R. natalensis experimentally infected with F. gigantica is affected by the species of definitive host from which the eggs are obtained, as well as the different laboratory conditions. Another lymnaeid, Galba truncatula, may play a role in transmitting this parasite in Egypt, as it was found naturally infected with F. gigantica. Latter snail species, originated from France, was susceptible to experimental infections with Egyptian miracidia of F. gigantica and it had a cercarial production close to that of local R. natalensis. Two other snails, Pseudosuccinea columella and Biomphalaria alexandrina, were naturally found harboring larvae of Fasciola sp. At the level of intermediate hosts of F. gigantica, the conditions are thus favorable in Egypt to transmit fasciolosis which could also be caused by another fasciolid, F. hepatica, as the existance of this fluke was confirmed in Egypt.

Animals↗
PubMedDate not supplied

Prevalence and determinants of water pipe or narghile use among students in Beirut's southern suburbs.

OBJECTIVES: Measuring the prevalence and determinants of narghile smoking among teenagers in schools in the southern suburbs (Dahia) of Beirut, Lebanon. METHODS: A simplified questionnaire was self-completed by intermediate and secondary students selected from private and public schools in Dahia the year 2001-2002. Variables obtained included details on narghile and cigarette smoking, socio-demographic characteristics of the student and his/her family, friendship networks, and beliefs regarding health. RESULTS: A total of 1461 students completed the questionnaire, of which 24% admitted regularly (> once/week) smoking the narghile and 14.4% occasionally, with a male predominance. The initiation was at about 13.6 yrs of age, but it varied from as low as 5 to 18 yrs. At least 28% of first narghile trial took place with a member of the immediate family, even though 58.2% initiated with a user friend. The monthly cost of using narghile did not exceed 7 USD for about half of narghile users in that area. CONCLUSIONS: Narghile use is a behavior gaining in importance in Lebanon in general, and in the Dahia area in particular. Its initiation among adolescents means that the probability of addiction is higher and the adverse health consequences are potentially more severe. It requires immediate interventional procedures including the launching of a campaign of national awareness for which hard data, such as those provided by this study, will be needed.

Adolescent↗
PubMed1989

Kochia (Kochia scoparia) toxicosis in cattle: results of four experimental grazing trials.

Four kochia grazing trials were completed over a period of 3 years. Yearling steers were allowed to graze pure stands of irrigated and fertilized kochia (Kochia scoparia) for periods of 14 to 105 days. A total of 116 steers were given kochia as their sole forage. Twenty control steers were allowed to graze native grass pasture, and 20 steers were allowed to graze both native grass and kochia pastures. Steers grazing only kochia lost weight or gained poorly compared with control steers grazing native grass. Steers that grazed both kochia and native grass had intermediate rates of gain. Signs of toxicosis were observed only in steers grazing kochia alone. Considerable variability in the degree of toxicosis was observed from one year to another. Morbidity in the steers grazing only kochia varied from 0% (Trial 4) to 28% (Trial 1), and mortality varied from 0% (Trials 3 and 4) to 10% (Trial 2). The most common signs observed in clinically affected steers were depression, dehydration, weight loss, muscular weakness, photosensitization, ocular discharge, and crusty muzzle. In all 4 trials, significant elevations in serum glutamic oxaloacetic transaminase (GOT) and serum gamma glutamyl transpeptidase (GGT) were observed in steers grazing kochia. In 3 of the 4 trials, significant elevations in serum bilirubin, serum calcium, and serum protein were also observed in kochia-fed steers. Necropsies were performed on 6 of 9 steers that died or were euthanized. The primary pathologic findings were severe chronic nephrosis (5 steers) and degenerative hepatopathy (5 steers).(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1984

Somatic findings at age 9 years on three ethnic groups of Nigerian urban and rural boys.

Somatic data were collected in 1983 on 577 Nigerian boys age 9 years drawn from Ibo, Yoruba, and Hausa ethnic groups living in urban and rural locations. On each subgroup, measures of body size, body form, and body composition were analysed for central tendency and variability. From urban samples, means for standing height and body weight were highest on Ibo boys, intermediate on Yoruba boys, and lowest on Hausa boys. Ibo urban boys, on average, were larger than their rural peers by 5.9 cm in standing height, 3.3 kg in body weight, and near 1.5 cm in shoulder width, arm girth, and calf girth. From pooled urban and rural subgroups, calf girth relative to lower limb height was near 40% on Ibo boys, 39% on Yoruba boys, and 38% on Hausa boys. From the three ethnic groups combined, means for thickness of skin and subcutaneous tissue on the arm and abdomen were higher on urban than rural boys. Composite means for 494 Nigerian Ibo and Yoruba urban and rural boys were lower than means for 208 United States Black boys measured during 1974-1977 in Richland County, South Carolina, by 1.7 cm in standing height, 3.0 kg in body weight, and near 1.5 cm in arm girth and calf girth.

Body Composition↗
PubMed1977

Effects of methylprednisolone on the physical properties of the human red cell.

Prompted by evidence suggesting preserved red cell deformability in cardiac surgical patients pretreated with pharmacologic dosages of methylprednisolone, we performed in vitro experiments to examine the ability of similar levels of methylprednisolone and hydrocortisone to modify erythrocyte membrane changes produced by metabolic depletion or membrane-active compounds. Variables measured included cell morphology, blood biscosity, membrane deformability, osmotic fragility, red cell cholesterol, and glycolytic intermediates. In incubated samples, methylprednisolone partially prevented the transition of discs to echinocytes, the rise in whole blood viscosity, the decrease in membrane deformability, and the loss of red cell cholesterol which accompany ATP depletion, but it had no apparent effect on red cell glycolysis. The drug also inhibited esterification of cholesterol in cell-free serum. In unimcubated samples to which lysolecithin was added, methylprednisolone partially prevented and reversed morphologic and rheologic responses without affecting membrane cholesterol. Hydrocortisone demonstrated similar properties. Possible mechanisms for these actions are discussed. The concept is advanced that preserved blood fluidity may contribute to the beneficial responses to these drugs in certain clinical conditions.

Blood Viscosity↗
PubMed1996

Is there a role for parenteral feeding in clinical medicine?

Protein-calorie malnutrition as evidenced by loss of weight or of lean body mass is a commonly seen disorder. Although its cause is clearly multifactorial, objective measures of protein-calorie malnutrition have been repeatedly correlated with poor patient outcomes. Total parenteral nutrition was developed to halt or reverse this disorder, but its ability to improve the short- to intermediate-term outcome in patients with impaired nutrient intake has been highly inconsistent. Factors influencing this variable outcome include the degree of functional impairment in the treatment group, the underlying disease causing the impaired intake, and possibly the amount and composition of nonprotein calories delivered. In particular, considerable evidence points to intravenous soybean oil emulsion as a negative factor in the nutritional support of stressed patients. Taken in combination, current information suggests reserving the use of parenteral feeding for patients meeting objective criteria for protein-calorie malnutrition and making parsimonious use of lipid emulsion, especially in stressed patients.

Humans↗
PubMed1996

The superficial peroneal nerve at the foot. Organisation, surgical applications.

The authors report the results of the dissection of the superficial peroneal nerves of 30 adult cadavers, from its emergence through the deep sural fascia up to its terminal branches. Its emergence was located, on average, 11 cm from the lower end of the lateral malleolus (min: 9 cm, max: 11.5 cm). The division of the nerve into the medial dorsal cutaneous n. and the intermediate dorsal cutaneous n. was found in 29 cases after its emergence from the sural fascia and before its passage on the proximal edge of the extensor retinaculum. The distance between the medial dorsal cutaneous n. and the medial malleolus was more than 2 cm. This nerve divided into three branches at a level varying from 5 to 20 cm in relation to the first interdigital space (average 9 cm). The intermediate dorsal cutaneous n. was found in 27 cases. It divided into two branches at a variable distance from the fourth interdigital space (4 to 6 cm). According to Kosinski's classification, we found 24 cases of type I (80%), three cases of type II (10%) and three cases of type IV (10%). The authors stress the numerous topographic variations and the multiple anatomical types.

Aged↗
PubMed1998

L-selectin(-/lo) and diabetogenic T cells are similarly distributed in prediabetic and diabetic nonobese diabetic mice.

We have previously shown that in the nonobese diabetic (NOD) mouse, an experimental model for autoimmune insulin-dependent diabetes, spleen diabetogenic T cells are contained within the T-cell subpopulation that express no or low levels of L-selectin. This phenotype characterizes activated/memory T cells. In the present study, we have compared the distribution of autoreactive T cells to that of L-selectin -/lo T cells in prediabetic and diabetic mice. Activated/memory T cells were found in decreasing concentrations in the bone marrow (BM), spleen, peritoneum, lymph nodes, and blood. This distribution correlated perfectly with that of T cells capable of transferring diabetes into syngeneic nondiabetic recipients. In diabetic mice, the highest levels of diabetogenic cells were observed in the spleen and BM. The peritoneum and lymph nodes contained intermediate frequencies of autoreactive cells. In the peripheral blood, the number of autoreactive T cells was variable, usually low; in some cases, they were undetectable. These cells were rare in the thymus. Diabetes-transferring cells were present in the spleen and BM of prediabetic mice. In these animals, diabetogenic cells were present in the blood circulation with frequencies higher than in diabetic mice, suggesting that after disease onset, when almost all target beta cells have disappeared, the recirculation of autoreactive cells is greatly decreased and finally stops. These observations: (a) suggest that T cells from BM of prediabetic and diabetic patients may be a better source of diabetogenic cells than the blood for analyzing diabetes-associated responses or for generating diabetogenic T-cell clones, and (b) point up the risk of using healthy autoimmune-prone donors for BM transplantation.

Animals↗
PubMed1986

Variation and frequency of cytokeratin polypeptide patterns in human squamous non-keratinizing epithelium.

The squamous non-keratinizing epithelium of the human upper digestive tract was analyzed for keratin-like cytoskeletal proteins (cytokeratins) by both high resolution one- and two-dimensional gel electrophoresis. The Triton/high salt-insoluble portion of pure epithelial homogenates contains a number of SDS- and urea-extractable polypeptides, whose two-dimensional gel pattern (NEpHG/SDS) typically represents a defined subset of human cytokeratins. The cytoskeletal preparations of epithelial tissue samples obtained from different individuals were found to be uniform with respect to their content of cytokeratin polypeptides 55.0 kD/basic, 52.0 kD/acidic, and 49.0 kD/acidic. However, we have observed that four basic members of apparent molecular weight 60.0, 59.0, 56.5, and 56.0 kD occur at an inconstant rate. Consequently, the cytokeratin polypeptide patterns appeared highly variable as a result of the presence of constant plus compositionally different subsets of inconstant members. From the analysis of cytoskeletal portions of more than 300 individual tissue samples we demonstrate eight different keratin-like polypeptide patterns including their frequencies and propose the existence of no more than nine. These, most probably, encompass all the possible inter-individual variations to which the cytokeratins of this type of epithelium will combine for forming intermediate-sized filaments in vivo. We furthermore hypothesize that the observed variation of cytokeratin patterns may reflect a polymorphism of genes coding for the variable keratin-like polypeptide members.

Digestive System↗
PubMedDate not supplied

Filamentous inclusions in nonneoplastic and neoplastic pancreas: an ultrastructural and immunogold labeling study.

Filamentous inclusions (FI) are unusual, irregularly shaped cytoplasmic inclusions, which are mostly found in acinar cell carcinomas of the pancreas and are consequently thought to be an abnormal zymogen granule type. This study describes identical inclusions in acinar, centroacinar, and small duct epithelial cells from nonneoplastic pancreas, as well as those found in tumor cells from a mixed acinar-endocrine pancreatic carcinoma. An ultrastructural and immunogold labeling demonstration indicates that these inclusions are aggregates of intermediate filaments immunoreacting with the anti-cytokeratin AE1/AE3 mixture and with V9 clone anti-vimentin monoclonal antibodies. Their pleomorphic appearance, variable immunoreactivity, and frequent association with lipid droplets and secondary lysosomes, mostly of the angulate type, led to the hypothesis that the FI undergo a degenerative remodeling pathway similar to that proposed for hepatic Mallory bodies. A survey of the literature on FI and human tumors suggests that they are a variably expressed ultrastructural feature of tumor cells originating from exocrine cell-containing tissues, namely the pancreas and gastrointestinal tract.

Carcinoma, Acinar Cell↗
PubMed2004

Incidence and management of penetrating renal trauma in patients with multiorgan injury: extended experience at an inner city trauma center.

PURPOSE: Patients with penetrating trauma often have multiorgan involvement that may complicate the management of any single organ system. Here we review the incidence of associated injuries in patients with penetrating renal trauma and our extended experience treating these patients at a busy inner city trauma center. MATERIALS AND METHODS: All trauma cases presenting to Temple University Trauma Center during a 6-year period were identified through our institutional databases and were reviewed (5,276). Penetrating trauma represented 41% of all cases (2,163). Of these we identified 123 patients with penetrating renal trauma (5.7%). A total of 93 cases were available for review. Multiorgan injury was staged in the operating room if patients were hemodynamically unstable or radiographically if they were stable. Renal injuries were staged by high dose, single shot excretory urogram in patients taken immediately to surgery or by computerized tomography if stable. Renal injuries were classified using the American Association for Surgery of Trauma (AAST) grading system. AAST classifications were subcategorized for purposes of streamlining. Grade 1 and 2 injuries were grouped as low grade, grades 3 and 4 nonvascular injuries were grouped as intermediate grade, and AAST grade 4 vascular and grade 5 injuries were grouped as high grade. Demographic, clinical and intraoperative variables, as well as number and severity of associated injuries, were then assessed to determine the relationship with various renal surgical outcomes including the requirement of surgical intervention, type of surgical intervention, need for nephrectomy and associated adverse outcomes. RESULTS: The median age of injured patients was 28 years (range 14 to 80). The majority of victims were male (93%). The mechanism of injury was predominantly gunshot wound (GSW, 86%) while 14% were due to stab wounds. Renal injuries were low grade (19%), intermediate grade (44%) and high grade (37%). Nearly all patients with penetrating renal injury had associated multiorgan injury (94.6%). Associated injuries for penetrating renal trauma on the right side predominately involved the liver, small bowel and vertebra while injury to the left kidney was most often associated with trauma to the stomach, colon and spleen. Patients suffered extensive renal injury as evidenced by the high rate of intraoperative urinomas (30.1%) and hematomas (97.5%) identified. In the absence of an expanding hematoma and/or hemodynamic instability, associated injuries by themselves did not increase the risk of nephrectomy. Despite multiorgan penetrating injury 54% of kidneys were salvageable. CONCLUSIONS: Isolated penetrating trauma to the kidney is rare. The majority of patients with penetrating renal trauma have associated adjacent organ injuries that may complicate treatment. In the absence of an expanding hematoma with hemodynamic instability, associated multiorgan injuries did not increase the risk of nephrectomy. With appropriate radiographic and/or surgical staging, it is possible to repair and salvage many of these kidneys despite extensive associated intraabdominal trauma.

Abdominal Injuries↗
PubMed1982

[The system of intermediate filaments in the cells of the epitheloid line RL 19. An electron microscopy study].

The occurrence and distribution of intermediate-sized filaments (100 A filaments) in an established epitheloid cell line RL 19 originally derived from rat liver was described by use of ultrathin sections tangentially and crossly to the cell substrate. The epithel-like cells showed in the cytoplasm a highly developed system of intermediate-sized filaments. The intermediate-sized filaments are either individually traversing in different directions or are grouped to loosely arranged bundles randomly running wavy-like through the whole cytoplasm. The bundles of highly variable thickness (20 to 40 filaments) are branched or are uniting and assembled to a three-dimensional network. The nucleus and Golgi-system are surrounding by a large ring of densely packed intermediate-sized filaments. Occasionally parallel running single filaments are associated to electron dense aggregates.

Animals↗
PubMed1984

Protein-energy malnutrition and associated variables among Indian pre-school children in a selected area of Natal.

The nutritional status patterns of a sample of 62 male and 64 female Indian pre-school children in an urban area are reported. High figures for malnutrition were obtained on weight-for-age measures, and low figures on height-for-age measures. Intermediate figures for malnutrition were reported on weight-for-height measures. Birth order, family size, sex differences, maternal educational levels and family income were not significant variables. The importance of classification criteria is stressed and proposals of other relevant variables in community malnutrition are presented.

Anthropometry↗
PubMed2004

Quinolone resistance-determining region mutations and por type of Neisseria gonorrhoeae isolates: resistance surveillance and typing by molecular methodologies.

Quinolone resistance is increasing rapidly in Neisseria gonorrhoeae and is a significant public health problem that requires ongoing surveillance. To examine the feasibility of molecular surveillance of quinolone resistance, and to further characterize an outbreak of resistant N. gonorrhoeae in Israel, the quinolone resistance-determining region (QRDR) sequences and the por types of 80 N. gonorrhoeae isolates were determined using molecular techniques. QRDRs of gyrA and parC were amplified by polymerase chain reaction and were sequenced directly. The por type was determined by checkerboard hybridizations performed using oligonucleotide probes to regions encoding 5 variable loops of the porin protein. All 42 ciprofloxacin-resistant (CipR) isolates had mutations in QRDRs of both gyrA and parC, and identical mutations were found in 93% of these isolates. One intermediately resistant isolate had 1 mutation in gyrA, and susceptible isolates showed no mutations. Forty isolates had 1 of 2 por types that differed only by an in-frame deletion in variable region 5; all but 1 of these isolates were CipR. QRDR sequencing and por type determination showed that the outbreak of CipR N. gonorrhoeae in Israel was clonal. QRDR mutations were consistent with those previously characterized; this indicates that DNA probes can be developed for rapid detection and surveillance of quinolone-resistant N. gonorrhoeae in settings in which nonculture diagnostic methods are used.

Anti-Infective Agents↗
PubMed1994

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Adolescent↗