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J Gallo

Publications and source records attributed to J Gallo.

At least 19 recordsLinked to original sources

Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours.

To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg(-1), mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg(-1), clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg(-1) when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (> or =280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy.

Adult↗

The immature reticulocyte fraction: a negative predictor of the harvesting of CD34 cells for autologous peripheral blood stem cell transplantation.

The optimal time for the harvesting of peripheral blood stem cells following chemotherapy and growth factors for autologous transplantation is based on the CD34 cell count. In this study, 51 patients having 59 stem cell mobilizations were assessed for the timing of the harvest by a CD34 cell count and an immature reticulocyte fraction (IRF). Results from 272 preharvest tests showed that when the CD34 cells were not harvestable, defined as a CD34 cell count of < 15 cells/microl, the IRF was always < or = 0.2. A low IRF resulted in a negative predictive value of 1 for the harvesting of stem cells. The IRF is therefore a valuable negative predictor of the timing of autologous stem cell harvesting.

Antigens, CD34↗

[Measurement of acetabular polyethylene wear of total hip replacement, using a universal measuring microscope. Characteristics of measurements].

PURPOSE OF THE STUDY: The aim of the study was to present our own method of measuring acetabular polyethylene wear in total hip arthroplasty, including assessment of basic measurement characteristics. It is a well known fact that, in total hip replacement, polyethylene liners wear out with use. The rate of acetabular polyethylene wear can then be related to clinical or demographic data. MATERIAL AND METHODS: Our method, using a universal measuring microscope, is based on the ability of exact identification of central positions of the head of total hip replacement before implantation and after prosthesis removal. The difference between the original and final positions allows us to calculate both linear and volumetric wear of polyethylene. During one month, the same components were repeatedly measured by two independent investigators and a total of 10 ABG 1 acetabular components were checked. The results of measurements were evaluated by a series of statistical tests, including correlation and regression analyses and analysis of variance. RESULTS: High correlations were found among individual measurements made by each observer (r = 0.998; r = 0.973) as well as between the mean values obtained from the two observers (r = 0.996). The reliability of measurements was proved by a high correlation of the regression curve of each measurement with the "ideal" line. With two exceptions, the differences between paired measurements were not significant. CONCLUSIONS: Our method facilitates an in vitro measurement of polyethylene wear with considerable accuracy and high reliability.

Acetabulum↗

[Molecular diagnostics for the detection of prosthetic joint infection].

PURPOSE OF THE STUDY: Ten years after inauguration of the molecular methods into the orthopaedic practice for diagnosing Prosthetic Joint Infection (PJI), this approach is still in the limelight of research and discussion. The aim of the current study was to determine the diagnostic power of our Polymerase Chain Reaction (PCR) protocol for preoperative detection of bacterial nucleic acid in the synovial joint fluid. MATERIAL AND METHODS: Synovial fluids obtained from thirty-five septic hip or knee arthroplasties and sixty-six aseptic controls were investigated by the conventional PCR technique. Two subgroups were established with regard to antibiotic administration before sample collection; with (n=13) and without (n=22) previous antibiotic exposition, respectively. All the surgeries were performed under the identical conditions with strictly established and fulfilled inclusion criteria. The study design applied was a prospective cohort trial. Primers targeting phylogenetically conserved regions of the bacterial gene were used to detect the bacterial 16SrRNA gene in the retrieved samples. If this was positive, a restriction endonuclease treatment of the amplified DNA was performed to reveal the PJI pathogen. Current guidelines were used to evaluate the test performance, including the confidence intervals. The concordance between the culture and PCR identification of PJI pathogens was estimated providing both of the relevant data were available. RESULTS: A qualitative analysis showed the following figures in the subgroup without previous antibiotic exposition: sensitivity (0.64), specificity (0.97), accuracy (0.89), positive predictive value (0.88), negative predictive value (0.89), likelihood ratio for positive result (21.0), and likelihood ratio for negative result (0.38). In the second subgroup the corresponding figures were as follows: 0.85, 0.97, 0.95, 0.85, 0.97, 27.9, and 0.16. The rate of concordance between the microbial and PCR findings was almost identical in both of the subgroups. DISCUSSION: There were large discrepancies in sensitivity and positive predictive values found in the published results. The earlier studies have had various methodological weaknesses, including a lack of strictly formulated inclusion criteria and control groups. In addition, there are differences among research centers in PCR laboratory procedures and specimen retrieval tactics which may potentially have an impact on PCR results. Low sensitivity and high specificity of our PCR technique may be explained by both the intrinsic (DNA extraction protocol, configuration of inner controls, choice of detection threshold, etc.) and extrinsic factors (in particular intra-operative retrieval of specimens). A hypothesis on the inadequacy of PCR techniques for PJI detection still remains to be excluded. CONCLUSION: Based on the current study, the positive results of our PCR technique may be perceived as a mild criterion from the point of power for PJI diagnosis support. However, its clinical utility should be significantly increased in cases with higher pretest probability of PJI, but negative cultures.

Adult↗

[Reconstruction of severe acetabular bone defects using Burch-Schneider cage].

PURPOSE OF THE STUDY: The Burch-Schneider cages (BSC) are designed to manage severe acetabular defects by bridging large bone gaps and preventing medial and superior migration of the prosthetic cup. The purpose of the study was to evaluate the results of such revisions after prolonged follow-ups. MATERIAL AND METHODS: From 1985 to 2000 sixty-nine acetabular revisions with BSC were performed in 68 patients with an acetabular defect classified as type Paprosky 3A (32) and 3B (37) at our institutions. After meticulous debridement of the entire acetabulum cancellous chips were pressurized into the bone defects to restore the hemispherical shape. The cage flange for the ischium was then placed after slight contouring into the foramen obturatum or inside the ischium. Finally, the cage was fixed against the ilium with at least three screws. The average age at the time of surgery was 67.9 years (range, 51-78), the mean follow-up equalled 8.3 years (range, 5-20), and the mean Harris hip score was 48 points (range, 29-76). A clinical follow-up study was performed with using conventional measures such as Harris hip score, x-ray analysis, strength of the abductor muscles, and ability to walk without support. RESULTS: A total of 55 patients (80.9 %) remained without any revision until the latest follow-up. Six components were removed due to aseptic loosening (8.7 %); five for septic loosening (7.2 %), and two revisions had to be performed for recurrent instability (2.9 %). Moreover, there were another six hips definitely or probably loose according to x-ray analysis resulting in a 17.4 % (12/69) rate of aseptic failure. Successful cage re-replacement was achieved only in two cases while the remaining nine hips ended as resection arthroplasties. At the time of follow-up examinations the average Harris hip score was 74 points (range, 51-91), only twelve patients were able to walk without support (12/68, 17.6 %), and insufficiency of the abductor muscles was found in fifteen hips (15/69, 21.7 %). Consolidation of the bone graft was observed in 79.7 % (55/69) of our hips. DISCUSSION: The severe acetabular bone defect reconstructions have been deteriorating with time as reported by most of the published studies. The results of the current study are no exception. On the other hand, the rate of complications observed in our study was comparable or even lower than in similar studies. CONCLUSIONS: Despite relatively worse results with prolonged follow-ups, the BSC remains a considerable part of the current orthopaedic armamentarium especially when extensive acetabular bone loss is countered. Loosening belongs to the most common complications of the BSC.

Acetabulum↗

[Current strategies for prevention of prosthetic joint infection].

Deep sepsis still remains the second most common cause of prosthetic joint failure despite its overall incidence is decreasing. It can be defined as a bacterial growth and replication on the prosthetic joint surface resulting in periprosthetic tissue damage and prosthesis loosening. The implants are colonized by airborne-, skin-, tool-, and/ or surgeon-related bacteria during surgery even though majority of procedures are performed under strictly respected conditions nowadays. After the insertion of the prosthesis into the human body the race between bacteria and host cells begins on what will colonize the prosthetic surface first. If the bacteria are more successful then they develop on formation of biofilm which is the biological correlative for the prosthetic joint infection (PJI) resisting effectively against host immune response and antibiotics. That is why preventative measures are strongly worth to do it, and removal of the prosthesis is the single optimal treatment. Each step in the pathogenesis of prosthetic joint infection may represent relevant targets against which prevention strategies may be directed. Of them the most useful seems to be identification of individual factors predisposing for PJI development, antibiotic prophylaxis given before the surgery, and operating room/ surgical quality parameters. Key words: prevention, prosthetic joint infection, deep sepsis, biofilm, total joint replacement.

Antibiotic Prophylaxis↗

Prevention and management of bicalutamide-induced gynecomastia and breast pain: randomized endocrinologic and clinical studies with tamoxifen and anastrozole.

A randomized, double-blind, placebo-controlled multicenter trial involving 107 men receiving bicalutamide ('Casodex') 150 mg/day therapy following radical therapy for prostate cancer assessed tamoxifen ('Nolvadex') 20 mg/day and anastrozole ('Arimidex') 1 mg/day for the prophylaxis and treatment of gynecomastia/breast pain. Tamoxifen, but not anastrozole, significantly reduced the incidence of gynecomastia/breast pain when used prophylactically and therapeutically. Serum testosterone levels increased with tamoxifen relative to placebo but prostate-specific antigen levels declined in all treatment groups. Further studies are needed to define the optimum tamoxifen dose and to assess any impact on cancer control. The use of tamoxifen in this setting remains to be investigated.

Aged↗

[Surgical therapy of osteolysis around stable cementless hip arthroplasty].

PURPOSE OF THE STUDY: The article presents results of surgical treatment of osteolysis around stable cementless THA. MATERIAL AND METHODS: The authors evaluated 18 operated on cases of osteolysis around stable THA of ABG 1 type with a minimal follow-up of 4 years (49-70 months). The group included 6 men and 12 women who were at the time of revision 47 years old (36-56, SD 6.52). The average period between the primary and revision surgery was 45 months (23-66, SD 13.84), the average size of the original cup was 49.6 mm (44-54, SD 3.03), the median thickness of polyethylene was 7.5 mm (4.9-8.9). The average HHS prior to reoperation was 68.5 points (10-98, SD 18.3) and only three hips were completely asymptomatic (3/18, 17%). Polyethylene inlay was replaced twice, both acetabular components in twelve cases, the acetabular and femoral components in four cases. In 16 cases radical debridement and treatment of defects by bone grafting was an important part of surgery. OUTCOMES: By the time of the latest check, in total three revision surgeries were performed (3/18, 17%). Neither of them was necessitated by loosening of the revision cup or use of bone grafts. Revised were both hips after the replacement of polyethylene cup inlay. Stable bone fixation and healing of bone defect was achieved in 15 hips in which the implant replacement was combined with bone grafting (15/16, 94%). The revision cup was on average by 3.16 mm bigger than the original cup (p = 0.001). The average HHS during the latest check was 79 points (p = 0.056). DISCUSSION: In osteolysis around a stable implant, many North-American authors prefer the replacement of polyethylene cup inlay in case of an undamaged well-oriented metal cup with a functional lock. By contrast, the authors of this study in such indication replace the whole acetabular component. This discrepancy may be explained by the ABG 1 THA which often triggers an extensive osteolysis and fails relatively soon. CONCLUSION: Despite a small number of cases the study has proved that the bone bed damaged by osteolysis is able to accommodate a new cementless implant. A necessary part of the surgery is radical debridement and in more extensive defects also bone grafting.

Adult↗

[Is osteolysis associated with a stable total hip replacement asymptomatic?].

PURPOSE OF THE STUDY: It has been reported that periprosthetic osteolysis in a stable cementless total hip prosthesis is often free from symptoms. The aim of this study is to check this assumption and provide details on the clinical presentation of this troublesome and worrying complication of hip arthroplasty. MATERIAL: Between March 1999 and June 2002, 76 hips in 72 patients underwent revision arthroplasty for periprosthetic osteolysis associated with stable ABG I prostheses. This patient group included 53 females and 19 males. The average age at the time of revision was 49 years (range, 32 to 63). The average time between the primary and revision surgery was 54.6 months (range, 23 to 85). The average cup size was 49.7 mm (range, 44 to 60), the modular 28-mm CoCr head was used in 69 hips, 28-mm ceramic head in six hips, and 22-mm CoCr head in one patient. METHODS: The following characteristics were recorded: gender, age, type of patient, height, weight, symptoms, diagnosis, ERS, CRP, Harris hip score, cup size, abduction angle and extent of bony defects. The data of symptomatic and asymptomatic patients were compared by parametric or non-parametric tests. RESULTS: Before revision, 61 hips (80%) were symptomatic. The patients complained of pain or signs of instability or both, and these complaints were taken as indications for revision surgery. The remaining 15 hips (20%) were asymptomatic. The average period from the primary surgery to the appearance of the first symptoms was 43 months (range, 5 to 80). The average Harris hip score before revision was 68 points (range, 37 to 90) and 82 points (range, 10 to 98) in the symptomatic and asymptomatic patients, respectively (p = 0.002). There were no other significant differences between these patients. DISCUSSION: The results of our study are in agreement with the findings of Hozack et al., but not with those of Maloney et al. and others who have reported that the progression of osteolysis developing in association with hip arthroplasty can be without symptoms. CONCLUSIONS: Osteolysis developing around a stable cementless hip prosthesis is generally symptomatic, with pain being the most frequent symptom. Even without a periprosthetic fracture, osteolysis may seriously impair the function of a joint and comfort of the patient. Since symptomatic patients are likely to see their attending physicians, it is emphasized that attention should also be paid to asymptomatic patients who have prostheses with unsuitable designs or pairings.

Adult↗

[Validity of bone scintigraphy for the diagnosis of periprosthetic complications in hydroxyapatite-coated total hip arthroplasty].

PURPOSE OF THE STUDY: To evaluate the efficacy and usefulness of 99Tc-MDP bone scans for the diagnosis of complications associated with hydroxyapatite- coated total hip prostheses. MATERIAL AND METHODS: 99Tc-MDP bone scans of 42 hips were taken before revision surgery in 41 patients with ABG 1 prostheses. Of these, 26 patients (27 hips) were included in our study on the basis of the following criteria: at least 23 months between the index surgery and scintigraphic examination and the availability of good quality bone scans. The average patients' age at the time of index and revision operations was 45.3 years (range, 32-57; SD, 6.02) and 50.2 years (36-61; SD, 6.01), respectively. The average time between the index surgery and bone scintigraphy was 50.3 months (23-84; SD, 15.9). Two experienced specialists in nuclear medicine, who were unaware of any clinical conclusions, participated in the study. RESULTS: Pre- and intra-operative findings showed aseptic loosening in three cups (3/27, 11 %) and one stem (1/27, 4 %). Four hips were suspected to have an infection on the basis of the positive results of intra-operative culture. In the diagnosis of aseptic loosening, sensitivity, specificity, accuracy, and positive and negative predictive values of bone scintigraphy were 100 %, 57 %, 62 %, 23 %, and 100 %, respectively, for the ABG I cup and 100 %, 52 %, 54 %, 8 %, and 100 %, respectively, for the ABG I stem. These characteristics were 67 %, 96 %, 93 %, 67 %, and 96 %, respectively, for the ABG I cup, when plain X-ray was used for evaluation of aseptic loosening. Specificity, accuracy and negative predictive value of plain X-ray for ABG I stem aseptic loosening were 100 %, 96 %, and 96 %. Bone scintigraphy gave one false positive result of sepsis; on the other hand, none of the four hips with positive intraoperative culture was diagnosed as septic. DISCUSSION: The fact that 99Tc-MDP bone scintigraphy as a method of diagnosing periprosthetic complications has a high sensitivity and a relatively low specificity has often been discussed in the literature. Currently, there are only a few studies on bone scintigraphy investigations of hydroxyapatite-coated prostheses. Some authors report that a slight increase in peri-prosthetic radionuclide activity may persist for up to 8 years which can explain the problematic accuracy of the technique. CONCLUSIONS: 99Tc-MDP bone scintigraphy is an intermediate useful tool for detecting complications of total hip arthroplasty with hydroxyapatite- coating. A negative bone scan almost always suggested the absence of aseptic loosening. However, the value of a positive result was regarded as controversial for the diagnosis of both aseptic and septic complications.

Adult↗

[Early failure of the polyethylene liner in the ABG I total hip prosthesis].

PURPOSE OF THE STUDY: The polyethylene liner has appeared to be a weak point in total hip arthroplasty. An early wear-through or a fracture of the polyethylene liner have been referred to as a catastrophic failure. The aim of the present study is to report our experience with this rare complication in ABG I hip prostheses. MATERIAL: Between September 1994 and January 2000 a total of 506 ABG I prostheses were implanted at our clinic. Due to wear-related complications, revision arthroplasty had to be performed in 90 hips in 23 male and 63 female patients by January 2002. Extensive titanium metallosis associated with polyethylene failure was found in 11 hips of 11 female patients. The remaining 56 hips of 52 female patients served as a control group. METHODS: The characteristics recorded in every patient's included age, type of patient, sex, height, weight, ESR, CRP, diagnosis, Harris hip score before revision, cup size, abduction angle of the cup, time between the primary and revision surgery and implant stability. Student's t-test, the Mann-Whitney U-test and Pearson's chi 2 test were used to evaluate the results. RESULTS: The complete failure of ABG I prostheses occurred in 2.17% of the replaced hips (11/506). A fracture or complete wear-through were the causes of failure in three (3/11, 27%) and eight (8/11, 73%) hips, respectively. The average cup size in hips without metallosis was 48.9 mm (range, 44-58; SD, 3.1) and that in hips with metallosis was 46.5 mm (range, 46-48; SD, 0.9). This difference was highly significant (t-test, p = 0.00002; U-test, p = 0.014). In the hips with metallosis, the average thickness of the polyethylene liner was 5.17 mm (range, 4.9-5.9; SD, 0.45) and the Harris hip scores before revision were significantly lower than in the hips without metallosis (59 versus 70.3 points; t-test, p = 0.023; U-test, p = 0.044). There were no other significant differences between the hips with early catastrophic failure of the polyethylene liner and those without it. DISCUSSION: Several studies have shown an indirect relationship between polyethylene thickness and its wear. Berry et al. reported catastrophic failure in hip prostheses with a polyethylene thickness of less than 5 mm; in our study, the three failed polyethylene liners were 5.9 mm in thickness. CONCLUSIONS: This is the first report on a wear-through of the polyethylene liner in ABG I cups. It is suggested that a thin polyethylene liner, design characteristics and probably also poor polyethylene quality are crucial factors responsible for rapid wear in ABG I cup. The highest risk is associated with the combination of a 46 mm cup and a 28 mm head. Patients who have prostheses of this size should be checked up more frequently.

Adult↗

Effects of FTDP-17 mutations on the in vitro phosphorylation of tau by glycogen synthase kinase 3beta identified by mass spectrometry demonstrate certain mutations exert long-range conformational changes.

In vitro phosphorylation of recombinant wild-type 2N4R tau and FTDP-17 exonic mutant forms P301L, V337M and R406W by glycogen synthase kinase 3beta (GSK3beta) was examined by two dimensional phosphopeptide mapping analysis on thin layer cellulose plates. Comparison of these peptide maps with those generated from wild-type 1N4R tau isoform from which the phosphopeptide constituents and sites of phosphorylation had been determined previously, enabled us to monitor directly changes in phosphorylation of the individual tau proteins. No differences were found in the phosphorylation of wild-type, P301L or V337M tau by GSK3beta but the R406W mutant showed at least two clear differences from the other three tau proteins. The peptides, identified by mass spectrometry corresponding to phosphorylation at both threonine 231 and serine 235 (spot 3), serines 396, 400 and 404 (spot 6a) and serines 195 and 199 (spot 6b) were absent from the R406W peptide map. The findings imply that the R406W mutation in tau exerts long-range conformational effects on the structure of tau.

Calcium-Calmodulin-Dependent Protein Kinases↗

Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.

AIM: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. METHODS: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. RESULTS: With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. CONCLUSION: danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.

Aged↗

Psychopathology and attrition in the Baltimore ECA 15-year follow-up 1981-1996.

Predictors of non-response were investigated in a 15-year follow-up (1981-1996) of 3,481 individuals in a probability sample from the household population of East Baltimore. Demographics (age, sex, race, education, marital status, and unemployment), household factors (living arrangements, household income, household size, and number of children), cultural variables (ancestral ethnicity and foreign language), social variables (social support and networks, committing felony, carrying a weapon, using an alias, and wandering), health factors (physical illness, health insurance, medical assistance, Medicare, receiving disability benefits, social security, and welfare), interviewer's observation, and psychopathologic variables (mental disorders, suicide behavior, comorbidity, and drug use) were collected at baseline in 1981 and in 1982, then linked to follow-up data between 1993 and 1996. A tracing process involving mail, phone, criss-cross directories, motor vehicle administration records, a commercial credit bureau, the state criminal justice system, hospital records, the US National Death Index, and field tracing were used to locate the original sample. A total of 3,066 respondents of the original sample (88.1%) were traced. Non-response was categorized into Sample Mortality (that part of the original sample that died during follow-up), Sample Loss (that part of the original sample that survived but could not be found) and Refusal (that part of the original sample that survived and was found but refused to participate). Stratified analysis and adjusted multiple logistic regression modeling found sample mortality and sample loss were strongly influenced by individual and household variables and by psychopathology. Sample mortality was influenced by specific mental disorders or conditions as mania, drug abuse/dependency, antisocial personality, cognitive impairment, alcohol abuse/dependency, phobia, drug use (except PCP), and comorbidity. Household factors protective against mortality include higher household income, not living as extended members in a married couple family, and living with children in the household. Persons who were unemployed, widowed or single, without high school education, male, and 65 years of age or older were more likely to die. Sample loss was influenced by cognitive impairment, antisocial personality, and cocaine use. Household factors linked to sample loss include living in female-headed families, or non-family households, and living alone. Young nonwhite, divorced/separated, without high school education, and unemployed were also harder to find. Refusal was associated with being white, with incomplete elementary education, living as a spouse in traditional married couple families, or as a child in female-headed families. Psychopathology did not influence refusal.

Adolescent↗

Novel chromosome 16 abnormality--der(16)del(16) (q13)t(16;21)(p11.2;q22)--associated with acute myeloid leukemia.

Inversion of chromosome 16 is a common feature of acute myeloid leukemia (AML) M4, while t(16;21), although also associated with AML, appears to be a separate entity. We present a patient with myelodysplastic syndrome (MDS) who transformed to AML-M1. The karyotype was normal at diagnosis; at 15 months, hematological evidence of transformation was present, and repeat cytogenetics showed a novel rearrangement of one chromosome 16. Two breaks had occurred; one in the short arm at 16p11, with translocation of the segment distal to this onto chromosome 21q, and the other in the long arm at 16q22 with subsequent deletion of the segment from 16q22-->qter. Fluorescence in situ hybridization (FISH) confirmed the abnormalities detected by cytogenetics and excluded involvement of the AML1 gene on 21q22. While the 16q22 breakpoint was at the usual site for the inv(16), the 16p11 was not. The patient is more characteristic of t(16;21) than inv(16), and adds to the spectrum of chromosome 16 abnormalities in AML.

Aged↗

Phase I trial of multiple cycles of high-dose chemotherapy supported by autologous peripheral-blood stem cells.

PURPOSE: To determine the safety and feasibility of delivering multiple cycles of front-line high-dose carboplatin and paclitaxel with hematopoietic peripheral-blood stem cell (PBSC) support. PATIENTS AND METHODS: Patients were required to have a malignant solid tumor for which they had received no prior chemotherapy. Mobilization of PBSC was achieved with cyclophosphamide, etoposide, and granulocyte-macrophage colony-stimulating factor (GM-CSF). After one cycle of conventional-dose carboplatin and cyclophosphamide with GM-CSF, patients received multiple cycles of high-dose carboplatin (area under the concentration-time curve [AUC], 12 to 20) and paclitaxel (250 mg/m(2)) with PBSC and GM-CSF repeated every 28 days. RESULTS: Twenty-four of 28 patients were assessable for toxicity and clinical outcome. Dose-limiting toxicities were dehydration, diarrhea, and electrolyte imbalances. The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m(2)). The relationship of target AUC to measured AUC was linear (r(2) =. 29; P =.0011). The overall response rate was 96%, with a complete clinical response rate of 67%. The median time to progression from the first PBSC reinfusion was 49.5 weeks (range, 8 to 156+ weeks). CONCLUSION: Multiple cycles of high-dose carboplatin (AUC 16) and paclitaxel (250 mg/m(2)) can be safely administered with GM-CSF and PBSC support. Although this regimen is safe, feasible, and active, the use of multiple cycles of high-dose chemotherapy as front-line treatment remains experimental and should only be used in the context of a clinical trial.

Adult↗

Psychopathology as a predictor of disability: a population-based follow-up study in Baltimore, Maryland.

To determine whether psychopathology is associated with disability as a result of underlying physical illness or whether such psychopathology antedates disability and is an independent determinant of disability, the authors conducted a nested case-control study within the Epidemiologic Catchment Area Follow-up Study in Baltimore, Maryland. From a 1981 random sample of 3,481 persons from Baltimore interviewed for psychopathology, disability, and other comorbidity, 1,920 who were alive in 1993 were traced and were reinterviewed with a similar instrument. Within the study population, 168 new cases of disability were identified as occurring between 1981 and 1993, as measured by the inability to perform activities of daily living. These cases were compared with 1,715 controls who reported no disability. The sociodemographic factors that were significantly related to incident disability in this analysis were age, female gender, and less than a high school education. These comparisons revealed associations of incident disability in activities of daily living with almost all antecedent chronic physical illnesses. Significant age- and gender-adjusted associations were observed between incident disability in activities of daily living and antecedent (in 1981) alcohol abuse and dependence (odds ratio (OR)=2.5, 95% confidence interval (CI) 1.5-4.2), major depressive disorder (OR=4.2, 95% CI 2.2-8.3), and phobia (OR=1.9, 95% CI 1.3-2.8). The adjusted odds ratio for the joint effect of antecedent depression and chronic physical illness on incident disability in activities of daily living was 17.0 (95% CI 6.9-41.7). There was a significant independent effect of antecedent major depression on activities of daily living disability. The effect of psychopathology on incident disability is nonspecific as to type of baseline chronic physical illness. Such a finding has important implications for defining strategies to prevent disability.

Adolescent↗