Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats.

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.

National hospital readiness for COVID-19 in Lesotho: evidence for oxygen ecosystem strengthening.

SETTING: Sub-Saharan African country, Lesotho, during the SARS-CoV-2 COVID-19 pandemic. OBJECTIVE: To evaluate COVID-19 hospital capacity in Lesotho. DESIGN: We conducted a pragmatic assessment of all public hospitals in Lesotho using a WHO COVID-19 hospital assessment tool during July 2020 (baseline), with targeted follow-up in December 2020. We adapted the WHO tool into a questionnaire with a focus on hospital services and included oxygen ecosystem elements (pulse oximeters, oxygen, and advanced respiratory care). We converted qualitative questionnaire answers into quantitative ordinal variables and used standard statistics for analysis. RESULTS: At baseline, we found all 12 questionnaire domains demonstrate both hospital preparedness and weakness in infection prevention and control. Key baseline gaps were lack of a dedicated team, and insufficient personal protective equipment and space for donning and doffing. Substantial limitations were noted in hypoxemia diagnosis and treatment; information management and care coordination pathways were also suboptimal. Targeted follow-up after 5 months revealed improvement in the availability of pulse oximetry, oxygen capacity, and heated high-flow nasal cannula devices. CONCLUSION: Our baseline findings may reflect uneven early pandemic care quality; targeted follow-up suggests strengthening of the oxygen ecosystem.

LIEU: Pays d'Afrique subsaharienne, Lesotho, pendant la pandémie de COVID-19 due au SARS-CoV-2. OBJECTIF: Évaluer les capacités hospitalières relatives à la COVID-19 au Lesotho. MÉTHODE: Nous avons réalisé une évaluation pragmatique de tous les hôpitaux publics du Lesotho en utilisant un outil d'évaluation hospitalière de l'OMS pour la COVID-19 pendant le mois de juillet 2020 (point de référence), avec un suivi ciblé en décembre 2020. Nous avons adapté l'outil de l'OMS en un questionnaire se concentrant sur les services hospitaliers. Nous y avons inclus les éléments relatifs à l'écosystème de l'oxygène (oxymètres de pouls, oxygène et soins respiratoires avancés). Nous avons converti les réponses au questionnaire qualitatif en variables ordinales quantitatives et avons utilisé des méthodes statistiques standards pour l'analyse. RÉSULTATS: Au point de référence, nous avons observé que l'ensemble des 12 thèmes abordés par le questionnaire a indiqué une certaine capacité de réaction et des faiblesses en matière de prévention et de contrôle des infections des hôpitaux. Les lacunes clés initiales étaient l'absence d'une équipe dédiée, un équipement de protection individuelle insuffisant et un manque d'espace dédié pour enfiler et enlever cet équipement. Des limites conséquentes ont été observées pour le diagnostic et le traitement de l'hypoxémie. La gestion de l'information et la coordination des soins étaient également sous-optimales. Le suivi ciblé après 5 mois a révélé une amélioration en matière de disponibilité des oxymètres de pouls, des capacités en oxygène et des canules nasales chauffées à haut débit. CONCLUSION: Nos résultats au point de référence peuvent refléter une qualité des soins inégale au début de la pandémie. Le suivi ciblé suggère qu'il conviendrait de renforcer l'écosystème de l'oxygène.

Cure of mice infected with Trypanosoma rhodesiense by cis-diamminedichloroplatinum (II) and disulfiram rescue.

Mice infected with Trypanosoma rhodesiense were treatment concurrently with cis-diamminedichloroplatinum (II) (DDP), disulfiram, and hydration. Most of the mice (92.5 percent) were cured; inoculation of blood or suspensions of brain or heart from these animals did not produce disease in recipient mice. The dose of DDP needed to eliminate the trypanosomes, 3 milligrams per kilogram of body weight per day for 7 days, was lethally toxic unless the animals received disulfiram orally and subcutaneous injections of physiologic saline, which reduced the acute renal necrosis caused by DDP alone. Some mild to moderate reversible renal damage was noted upon pathologic examination of the treated mice.

Growth and development after hematopoietic cell transplant in children.

Hematopoietic cell transplantation (HCT) following high-dose chemotherapy or chemoradiotherapy for children with malignant or nonmalignant hematologic disorders has resulted in an increasing number of long-term disease-free survivors. The preparative regimens include high doses of alkylating agents, such as CY with or without BU, and may include TBI. These agents impact the neuroendocrine system in growing children and their subsequent growth and development. Children receiving high-dose CY or BUCY have normal thyroid function, but those who receive TBI-containing regimens may develop thyroid function abnormalities. Growth is not impacted by chemotherapy-only preparative regimens, but TBI is likely to result in growth hormone deficiency and decreased growth rates that need to be treated with synthetic growth hormone therapy. Children who receive high-dose CY-only have normal development through puberty, whereas those who receive BUCY have a high incidence of delayed pubertal development. Following fractionated TBI preparative regimens, approximately half of the patients have normal pubertal development. These data demonstrate that the growth and development problems after HCT are dependent upon the preparative regimen received. All children should be followed for years after HCT for detection of growth and development abnormalities that are treatable with appropriate hormone therapy.

A unique device for controlled electrospinning.

The purpose of this research was to develop a system for controlled electrospinning of fibro-porous scaffolds for tissue engineering applications and to use this system to assess mesh architecture sensitivity to manufacturing parameters. The intent was to achieve scaffolds with well-controlled fiber diameters and inter-fiber spacing. To accomplish these objectives, a custom, closed-loop controlled, electrospinning system was built. The system was unique in that it had a collection surface that was independent of the electrodes. The system allowed independent manipulation and analysis of a number of manufacturing parameters: distance between the electrodes, distance from the nozzle to the collection surface, applied voltage, temperature of the melt, collection surface dielectric strength, and collection surface area. Morphological analysis of fabricated meshes showed that all test parameters significantly affected fiber diameter and inter-fiber spacing. Further, contrary to what is generally accepted in the electrospinning literature, voltage and temperature (inversely related to viscosity) were not the most significant parameters. Features of the collection surface, including dielectric strength and surface area, were more significant. This dominance is, in part, a reflection of the unique electrospinning system used. The collection surface, which was not connected to either of the electrodes, substantially altered the electric field between the electrodes. Using the developed controlled electrospinning system, thermoplastic polyurethane meshes with fiber diameters ranging from 5 to 18 microm with variability less than 1.8% were made; inter-fiber spacing ranged from 4 to 90 microm with variability less than 20.2%. The system has potential use in biomedical applications where meshes with controlled fiber diameter and inter-fiber spacing are of interest.

Effects of fluid insert volume changes on socket pressures and shear stresses: case studies from two trans-tibial amputee subjects.

Fluid inserts potentially help to overcome prosthetic fit problems resulting from stump volume change. The purpose of this investigation was to add fluid to fluid inserts positioned on the inner socket walls of trans-tibial prostheses and to assess their influence on socket stresses. Pressures and shear stresses were measured at 13 sites on the sockets of two trans-tibial amputee subjects while they ambulated at their self-selected walking speeds. Stresses at the transducer sites generally increased with greater fluid addition and, interestingly, both subjects found relatively high fluid insert volumes most comfortable. The magnitudes of stress change were larger than those resulting from alignment, cadence, and componentry changes as reported in the literature. Possible explanations for why subjects found settings that induced higher measured socket stresses more comfortable than those that induced lower measured stresses include: A reduced shear: pressure ratio; the short duration of the study; and reduced stresses at sites not monitored with transducers.

Bone marrow transplantation for childhood Ki-1 lymphoma.

Two children with Ki-1 antigen-positive, non-Hodgkin's lymphoma received high-dose chemotherapy, fractionated total body irradiation (TBI), and allogeneic bone marrow transplantation. Both patients had relapsed multiple times on conventional chemotherapy and radiation therapy. Following transplantation, there was successful engraftment with disappearance of clinical signs and symptoms of their disease. As of June 1, 1989 they are in continuous unmaintained complete remission, 56 and 40 months, respectively, after bone marrow transplantation.

Autologous marrow transplantation for patients with acute myeloid leukemia in untreated first relapse or in second complete remission.

PURPOSE: This study compares outcomes of autologous bone marrow transplantation (ABMT) in patients with acute myeloid leukemia (AML) in untreated first relapse (REL1) or in second complete remission (REM2). PATIENTS AND METHODS: Forty-seven patients with AML in REL1 (n = 21) or in REM2 (n = 26) were treated with busulfan (BU) and cyclophosphamide (CY) with or without total-body irradiation (TBI) followed by ABMT. All REL1 patients and four REM2 patients had marrow stored during first remission (REM1). Twenty-seven had marrow stored with and 20 without treatment in vitro with 4-hydroperoxycyclophosphamide (4-HC). Eighteen patients received BU and CY and 29 received BU, CY, and TBI. REL1 patients relapsed within a median of 9 months (range, 2 to 26) after marrow harvest and were transplanted a median of 30 days (range, 9 to 87) from detection of relapse. RESULTS: With a median follow-up of 2.1 years (range, 0.4 to 5.3), 19 patients survive in remission (10 of 21 in REL1; nine of 26 in REM2). The actuarial probabilities of relapse-free survival at 2 years for patients transplanted in REL1 and REM2 were 45% +/- 22% and 32% +/- 18%, respectively (P = .33). The corresponding probabilities of relapse were 30% +/- 26% and 44% +/- 23%, respectively (P = .45). No conclusions could be drawn about the benefits of adding TBI to BU plus CY. There were no significant differences in neutrophil or platelet recovery or in posttransplant probabilities of relapse and nonrelapse mortality between patients who received marrow treated or not treated with 4-HC. CONCLUSION: These results suggest that ABMT may produce long-term leukemia-free survival in approximately one third of patients with AML in REL1 or in REM2. There is no apparent clinical advantage in attempting to obtain second remissions in relapsed patients before ABMT if marrow has been cryopreserved during REM1. Although a strategy of transplantation in REL1 has advantages for the patient, such an approach involves the storage of marrow, which may not be used, and is impractical without the coordinated support of the treating physician, the patient, and the marrow transplant center.

Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens.

PURPOSE: The impact of a second marrow transplant on long-term disease-free survival (DFS) was evaluated for 77 consecutive patients aged 2 to 51 years who relapsed subsequent to allogeneic marrow transplantation after high-dose chemotherapy and total-body irradiation (TBI). PATIENTS AND METHODS: Patients received a second transplant for recurrent chronic myelogenous leukemia (CML) (n = 28), acute myelogenous leukemia (AML) (n = 32), and acute lymphoblastic leukemia (ALL) (n = 15) or lymphoma (n = 2) that used the same marrow donor as the initial transplant. High-dose chemotherapy of busulfan (BU) and cyclophosphamide (CY), or CY, carmustine (BCNU), and etoposide (VP-16), was used as a preparative regimen for the second transplant. Graft-versus-host disease (GVHD) prophylaxis consisted of the following: no prophylaxis (n = 8), T-cell depletion (n = 36), methotrexate (MTX) only (n = 21), cyclosporine (CSP) only (n = 1), MTX and CSP (n = 9), or anti-thymocyte globulin (ATG) and prednisone (n = 2). RESULTS: Engraftment occurred in the 74 assessable patients. Severe veno-occlusive disease (VOD) was the most frequent cause of grades 3 and 4 regimen-related toxicity (RRT); it occurred in 20 patients. The probability of death before day 100 from nonleukemic causes was 36%. The probability of relapse after second transplant was 70%, and the DFS rate was 14% (median DFS, 36 months; range, 22 to 87). The DFS rates for ALL, AML, and CML were 8%, 10%, and 25%, respectively. Multivariate analysis showed that the risk of relapse was inversely associated with acute GVHD (relative risk [RR] of relapse = 0.2; P = .0009). No other factor was associated with relapse. DFS was associated with the presence of acute GVHD (RR of treatment failure = 0.5; P = .0085), and a reduction of DFS was associated with severe VOD (RR = 10.6; P = .0001) and those patients older than 10 years (RR = 2.5; P = .0337). CONCLUSION: These data show that some patients may benefit from a second marrow transplant for recurrent leukemia after an initial marrow transplant. Younger patients and patients with CML especially should be considered as potential candidates for a second transplant.

Ovarian function following marrow transplantation for aplastic anemia or leukemia.

One hundred eighty-seven women between 13 and 49 years of age had ovarian function evaluated from 1 to 15 years (median, 4) after marrow transplant for aplastic anemia or leukemia. Among 43 women transplanted for aplastic anemia following 200 mg/kg cyclophosphamide (CY), all 27 less than 26 years of age, but only five of 16 greater than 26 years of age recovered normal ovarian function. Nine of the 43 have had 12 pregnancies, resulting in eight live births, and two elective and two spontaneous abortions. All eight children are normal. Nine of 144 women transplanted for leukemia following 120 mg/kg CY and 9.20 to 15.75 Gy total body irradiation (TBI) recovered ovarian function. Two of these nine have had three pregnancies, resulting in two spontaneous and one elective abortion. The probability of having ovarian failure was 0.35 by 7 years for patients receiving CY alone and was 1.00 at 1 year for patients receiving CY plus TBI (P less than .0001). By 7 years after transplant the probabilities of having normal ovarian function were 0.92 after CY alone and 0.24 after CY plus TBI (P less than .0001). Multivariate analysis showed that TBI was the only factor significantly influencing ovarian failure and that both TBI and greater patient age at transplant were significantly associated with a decreased probability of recovering normal ovarian function. These data demonstrate that after high-dose CY, recovery of ovarian function occurs in younger women and in a minority of older women, but after CY and TBI, recovery occurs in only a few younger women and none of the older women.

Treatment of malignant lymphoma in 100 patients with chemotherapy, total body irradiation, and marrow transplantation.

Between July 1970 and January 1985, 100 patients with malignant lymphoma were treated with high-dose chemoradiotherapy and bone marrow transplantation. Twenty-eight of the 100 are alive and the actuarial probability of disease-free survival 5 years from transplantation is 22%. The most common reason for treatment failure was disease recurrence, with an actuarial probability of 60%. A proportional hazards regression analysis showed that the likelihood of disease-free survival was less in those patients transplanted in resistant relapse and in those previously treated with chest radiotherapy. Neither disease histology (Hodgkin's disease, high-grade lymphoma or intermediate-grade lymphoma), nor source of marrow (syngeneic, allogeneic, or autologous) significantly influenced either disease-free survival or probability of relapse. The use of high-dose chemoradiotherapy and marrow transplantation appears to offer a better chance for long-term survival than any other form of therapy for young patients with disseminated malignant lymphoma whose disease has progressed after initial combination chemotherapy. The best results with marrow transplantation were obtained in patients transplanted in early relapse or second remission who had not received prior chest radiotherapy.

Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy.

Of 455 acute nonlymphocytic leukemia (ANL) patients who underwent marrow transplantation, 95 (21%) relapsed a median of 6.5 months posttransplantation and 62 received further treatment. Twenty achieved remission. Success of therapy was related to the length of time from marrow transplant to relapse and to the use of cytarabine (Ara-C) and daunomycin. Aggressive chemotherapy for patients relapsing within 100 days of marrow transplant was associated with a high incidence of early death (six of 14 patients) and a low probability of remission (one of 14). Of 23 patients who relapsed in excess of 1 year from marrow transplant, 15 achieved a complete remission. The median disease-free survival is 6 months (range, 0.4 to 53+ months). Acute lymphocytic leukemia (ALL) recurred in 130 of 366 patients (36%), and 94 received further therapy. Fifty-two achieved a remission. Remissions were more common in late relapse patients (greater than 1 year from transplantation): 65% v 7% for those relapsing within 100 days from transplant (P less than .05). Testicular relapse occurred in 11 patients and was the sole site of relapse in seven. Three are alive and free of disease 58 to 109+ months after relapse. The median survival for the treated patients is 10.5 months (range, 5 to 109+ months). We propose that reinduction be attempted in all patients relapsing greater than 1 year from marrow transplantation. Ara-C and daunomycin should be employed in the treatment of ANL. The decision for treatment of patients relapsing earlier than 1 year should be made on an individual basis.

Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation.

PURPOSE: To describe the prevalence of sexual difficulties in men and women after marrow transplantation (MT), and to define medical, demographic, sexual, and psychologic predictors of sexual dysfunction 3 years after MT. PATIENTS AND METHODS: Four hundred seven adult MT patients were assessed pretransplantation. Survivors repeated measures of psychologic and sexual functioning at 1 and 3 years posttransplantation. RESULTS: Data were analyzed from 102 event-free 3-year survivors who defined themselves as sexually active. Men and women did not differ in sexual satisfaction pretransplantation. At 1 and 3 years posttransplantation, women reported significantly more sexual dysfunction than men. Eighty percent of women and 29% of men reported at least one sexual problem by 3 years after MT. No pretransplantation variables were significant predictors of 3-year sexual satisfaction for women. For men, pretransplantation variables of older age, poorer psychologic function, not being married, and lower sexual satisfaction predicted sexual dissatisfaction at 3 years (R2=.28; P < .001). Women who were more dissatisfied 3 years after MT did not receive hormone replacement therapy (HRT) at 1 -year posttransplantation and were less satisfied at 1 year, but not pretransplantation (R2=.35; P < .001). CONCLUSION: Sexual problems are significant in the lives of MT survivors, particularly for women. Although HRT before 1 year posttransplantation improves sexual function, it does not ensure sexual quality of life. Intervention for women is needed to apply hormonal, mechanical, and behavioral methods to prevent sexual difficulties as early after transplantation as possible.

Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.

PURPOSE: To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS: Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS: The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION: Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow.

Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease.

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.

Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle.

Between October 1979 and January 1988, 101 patients with malignant lymphoma who failed initial induction treatment or relapsed received high-dose combination chemotherapy or chemoradiotherapy followed by infusion of autologous bone marrow. Twenty-eight of the 101 patients survive, 18 of whom are disease-free for a median of 26 (range, 12 to 66) months. The 5-year actuarial probabilities of survival, event-free survival (EFS), and relapse from transplantation were 20%, 11%, and 84%, respectively. Multivariate analysis showed that the likelihood of EFS was decreased among patients transplanted with a Karnofsky score of less than 80%. Recurrent lymphoma after transplant was the most important cause of treatment failure with 36 of 62 relapses occurring within 100 days from marrow infusion. Early, but not late relapse, was more frequent in patients transplanted for advanced lymphoma, and both early and late relapses were increased among patients with impaired pretransplant clinical performance or high-grade histology of lymphoma. Ten patients who relapsed post-transplant are alive, seven in remission. Further improvement of these results will require earlier transplantation, improved preparative regimens, or early posttransplant therapy.

Small fiber diameter fibro-porous meshes: tissue response sensitivity to fiber spacing.

The purpose of this research was to determine if fiber spacing for small fiber diameter fibro-porous meshes affected tissue response in vivo. Disk-shaped polyurethane meshes, with mean fiber diameters of 7.6 microm and fiber spacing between 6 and 68 microm, were implanted in rat subcutaneous dorsum for 5-week intervals and then prepared for light microscopy and morphological analysis. Results showed that implants with 12- to 68-microm spacing had no histologically apparent fibrous capsule around the perimeter, a result different from that for 6-microm spacing samples that had a capsule around a mean of 34.2% of the perimeter. For the 12- to 68-microm spacing range, a mean of 21.0% of individual fibers within the meshes were encapsulated. Qualitatively, it appeared that larger fibers were encapsulated more frequently than smaller ones. When nodeless or baggy meshes were implanted, cells tended to cluster three or more fibers into groups and then encapsulate each group. Over the 6- to 68-microm spacing range, cell nuclei volume fraction within the meshes increased from the 6- to the 29-microm spacing (p = 0.000) and then decreased from the 29- to the 68-microm spacing (p = 0.015). There was a trend of an increase in local vessel volume fraction with spacing over the 6- to 68-microm range, though the relationship was weak. The results indicate that the reason for the lack of encapsulation of small-fiber fibro-porous meshes is not exclusively a pore boundary explanation, as is proposed for small-pore porous meshes.

Changes in interface pressures and shear stresses over time on trans-tibial amputee subjects ambulating with prosthetic limbs: comparison of diurnal and six-month differences.

For trans-tibial amputees maintenance over time of a quality fit of the prosthesis to the residual limb is an important clinical challenge. The purpose of this research was to compare diurnal and long-term (5 weeks to 6 months) interface stress changes as well as variance in the change in cross-sectional area down the length of the residual limb. If long-term changes were simply accentuated diurnal fluctuations then this result would suggest similar treatment methods should be used for both conditions. Interface pressures and shear stresses at 13 sites and residual limb shape were measured on eight trans-tibial amputee subjects using patellar-tendon-bearing prostheses. Data were collected at diurnal intervals (within the same day at least 5 h apart) as well as at long-term intervals (5, 10, 15, 20, and 25 weeks apart). Absolute diurnal interface stress changes were not significantly different from those at 5-weeks intervals but were significantly smaller than those at 15, 20, and 25-weeks intervals. Mean interface stress changes increased significantly (p<0.05) for increased session-to-session intervals. Variance of the change in cross-sectional area down the length of the residual limb was significantly smaller for diurnal intervals than for 6-months intervals, indicating that long-term changes were more localized than diurnal changes. These results indicate that long-term changes are not simply accentuated diurnal fluctuations, suggesting that different treatment methods should be used to treat each condition.

Allogeneic marrow grafting for acute leukemia: a follow-up of long-term survivors.

We have reported 100 consecutive patients with refractory acute leukemia treated with chemotherapy, total body irradiation (TBI) and marrow from an HLA identical sibling. At the time of the report 17 patients were alive after 11-53 months. All patients have now been followed more than 3 years. At the time of the last report 4 of the 17 patients had relapsed: two in the marrow, one in the central nervous system and one in the testicle. Three of these four patients have died of their disease 27, 34 and 50 months following transplant. The patient with a solitary testicular relapse remains in complete remission 49 months after local irradiation without concomitant systemic therapy. One other patient died 26 months following transplantation from cardiopulmonary complications following multiple respiratory infections. Of the 13 surviving patients, three suffer from chronic graft-versus-host disease. Summaries of the problems encountered in these patients after the first 100 days are presented. Ten of the original 100 patients are living productive lives 36-80 months after transplantation. The data clearly demonstrate that long-term unmaintained remissions are possible in a small fraction of patients with terminal leukemia treated with various chemotherapy regimens and TBI followed by marrow transplantation.