The effect of the radial function on I-125 seeds used for permanent prostate implantation.

The purpose of this study was to evaluate the integrity of eight commercially-available low-activity Iodine-125 (125I) seeds for their radial function g(r) and its effect on the dose delivered to the adjacent critical structures when used in permanent prostate implants (PPI). Ten previously treated patients were retrospectively used in this comparison. The Amersham Health Oncura seed was used to peripherally design an isodose distribution with urethral and anterior rectal wall sparing. Plan criteria included minimum coverage of 144 Gy to the planning target volume (PTV), < or = 70% dose to 150% of the PTV volume (V150-PTV), and the quantity of needles < or = 70% of the size of the PTV, in cc. Upon completion of the Oncura plan, the seed type was changed and the activity was adjusted until the V100-PTV for each of the other 7 seed types matched the V100-PTV defined by the Oncura seed. Computed tomography (CT)-based postimplant dosimetry was used to determine the dose to 40% (D40) of the bulb of the penis (in Gy). Dose-volume histograms (DVH) were used to evaluate the differences to V100 (in %) and D40 (in Gy) of the anterior rectal wall and bulb of the penis, and V100 (in %) of the urethra. The data was tabulated. Radioactive 125I sources included in this study were 125I Source 2301 (Best); I-Plant (MedTech), IoGold (Mentor), Oncura (Amersham Health), ProstaSeed (UroCor), SelectSeed (Nucletron), SourceTech (Bard), and Symmetra (UroMed). The sizes of the PTV for the 10 patients ranged from 18.82 cc to 48.99 cc. The Oncura seed was used as the reference seed and all other seed types were normalized to it for data comparison. It was determined that the dose rate constant (Delta) and anisotropy factor (phi) contribute to the activity needed to achieve comparable V100-PTV doses, but a strong dependence on the radial function g(r) was found to effect the doses to the critical structures studied. Values of g(r) at 4 cm were calculated and the IoGold and SourceTech seeds were determined to have the highest g(r) values, with ProstaSeed and SelectSeed having the lowest values. 125I Source 2301 and IoGold required less activity per seed to achieve the same dose to the V100-PTV due to the higher dose rate and anisotrophy constants (Delta.phi). The seed types with silver were less penetrating and resulted in the production of characteristic x-rays that modified the energy spectrum and influenced the radial function. The seeds requiring the lowest activity showed the highest dose to the anterior rectal wall, a posterior adjacent structure; the urethra, an interior structure; and the bulb, an inferior structure. This study was designed to investigate the integrity of eight different commercially-available seed types, and their dependence on the g(r) in seed choice. It was determined that the dose rate constant and anisotropy factor determine the activity needed for implantation but a strong dependence on the radial function was found to effect the doses to the adjacent structures.     

Increases in adipose and total body weight,but not in lean body mass,associated with subcutaneous administration of Sonic hedgehog‐Ig fusion protein to mice

Sonic hedgehog (Shh) is a member of a family of proteins that are involved in embryonic development. The receptor signaling pathways for Shh persist in adults and stimulation of this pathway has shown therapeutic efficacy in animal models of neurodegeneration/regeneration. This study was conducted to evaluate the safety of repeat dose administration of an IgG fusion protein of Shh (Shh‐Ig) in adult mice. Routine toxicology evaluations were performed. In addition, body composition analysis was conducted by densitometry. Shh‐Ig treatment caused a significant increase in body weight gain relative to controls and a slight increase in liver and spleen weights. The increase in body weight could be largely accounted for by an increase in body fat. The treatment‐related increases in body weight were reversible upon cessation of treatment. Shh‐Ig treatment produced no significant changes in clinical chemistry or hematology. There were no gross or histomorphologic findings in any tissue except for skin and spleen. Microscopic findings in the skin were limited to minimal to slight local epidermal hyperplasia at the sc injection site and increased thickness of the fat layer. In the spleen a slight increase in extramedullary hematopoiesis was seen. This finding is possibly a secondary response following inflammation at the injection site in some animals due to the administration of a foreign protein. This study showed that Shh‐Ig administration was well tolerated. The most significant finding was a reversible increase in body weight. Drug Dev. Res. 57:107–114, 2002. © 2002 Wiley‐Liss, Inc.     

Management of Rh-isoimmunised Pregnancies : Our Experience

Background

The aim of this study was to assess the role of middle cerebral artery peak systolic velocity (MCA-PSV), as measured by doppler ultrasound, in detecting foetal anaemia in Rh- isoimmunised pregnancies. Intra-uterine foetal blood transfusion was performed in such anaemic foetuses to tide over the crisis of foetal immaturity till considered fit for extra-uterine survival.

Methods

Rh-isoimmunised pregnancies reporting to a tertiary institute from 2003 to 2005, were screened by doppler ultrasound to estimate MCA-PSV to detect foetal anaemia. If the foetus developed MCA-PSV of more than 1.5 multiple of median (MoM) for the gestational age, foetal blood sampling through cordocentesis was performed to confirm foetal anaemia, followed by intrauterine foetal blood transfusion to all anaemic foetuses at the same sitting. Neonatal outcome was evaluated by recording gestational age at the time of delivery, duration of gestational time gained and need for blood transfusion in the neonatal period.

Results

A total of thirteen isoimmunised pregnancies were evaluated. Three pregnancies did not require in-utero foetal blood transfusion. Twenty-one intrauterine foetal blood transfusions were performed in the remaining ten patients. Five received blood transfusion in the neonatal period. Intra uterine foetal death occurred in one grossly hydropic foetus and favourable neonatal outcome was recorded in the rest.

Conclusion

The clinical outcome of these pregnancies justifies the use of doppler studies of MCA-PSV in detecting foetal anaemia and intra uterine foetal blood transfusion is the only hope of prolonging pregnancy and salvaging such foetuses.Key Words: Rh-isoimmunisation, Middle cerebral artery peak systolic velocity, Foetal anaemia, Foetal blood transfusion     

Effectiveness of a nursing support program for patients with recurrent ovarian cancer receiving pegylated liposomal doxorubicin (Caelyx/Doxil).

Pegylated liposomal doxorubicin (PLD) has become the preferred alternative for ovarian cancer patients who have failed platinum-based therapy, but side effects, such as palmar-plantar erythrodysesthesia (PPE), may lead to sub-optimal drug exposure and treatment discontinuation. A prospective Canadian multicentre open-label study evaluated the effects of a nurse-administered education and support program on treatment adherence and tolerability in 112 women with recurrent ovarian cancer. Subjects received an average of four four-week PLD cycles, the recommended number of courses required to evaluate the efficacy from PLD. Side effects were common, but 75% of patients were able to complete > 3 cycles and 59% completed > 4 cycles of PLD chemotherapy. With proactive nursing intervention, the incidence of PLD-associated grade three-four toxicities such as PPE and mucositis was substantially decreased. Nursing intervention may allow more patients to receive chemotherapy on schedule, thus reproducing the conditions of the clinical study in which the efficacy of the drug has been established.     

The immunohistology of follicle lysis in lymph node biopsies from homosexual men

Follicle lysis is a characteristic alteration of B cell follicles described recently in lymph node biopsies from homosexual men. It consists of disruption of germinal centers by aggregates of small mature lymphocytes variably associated with erythrocyte extravasation. We studied the immunohistology of follicle lysis identified in lymph node biopsies from 11 homosexual men. The results indicate that follicle lysis has two principal immunohistologic features: (1) intrafollicular aggregates of small lymphocytes predominantly of polytypic mantle B cell phenotype (T015+/Leu-8+/mu+/delta+/k+ or lambda+), and (2) disruption of the normal, unified follicular meshwork of R4/23+ dendritic reticulum cells by these B cell aggregates. These structural alterations may affect the functional integrity of the germinal center as it pertains to the abnormal B cell effector function and the increased prevalence of B cell lymphoma recently documented in the acquired immunodeficiency syndrome and related disorders. Because dendritic reticulum cells weakly express the Leu-3 (T4) antigen, which is known to be an essential component of the receptor for human T- lymphotropic virus type III/lymphadenopathy-associated virus (HTLV- III/LAV) retrovirus infection, it is possible that retroviral infection of dendritic reticulum cells may play a role in the pathogenesis of follicle lysis.     

The effect of local anesthetic and corticosteroid combinations on chondrocyte viability

Purpose

Local anesthetic and corticosteroid combination injections are often used in clinical practice, however research investigating the chondrotoxic properties of these combinations is minimal. The goal of this study was to evaluate the effect of single injection doses of 1% lidocaine or 0.25% bupivacaine in combination with single injection doses of dexamethasone sodium phosphate (Decadron^?), methylprednisolone acetate (Depo-Medrol^?), betamethasone sodium phosphate and betamethasone acetate (Celestone^? Soluspan^?), or triamcinolone acetonide (Kenalog^?) on human chondrocyte viability.

Methods

All treatment conditions were delivered to human chondrocytes in vitro for the medication’s respective average duration of action using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A two-color fluorescence assay was used to evaluate cell viability. A mixed-effects regression model was used to evaluate the mean differences in cell viability between treatment groups.

Results

At 14?days, a single injection dose of 1% lidocaine or 0.25% bupivacaine in combination with betamethasone sodium phosphate and betamethasone acetate solution illustrated significant chondrotoxicity when compared with the local anesthetics alone (P?P?=?0.013; P?=?0.016, respectively) when used in combination with 1% lidocaine compared with lidocaine alone, but showed no significant chondrotoxicity in combination with 0.25% bupivacaine (P’s?=?n.s.).

Conclusions

Clinicians should use caution when injecting 1% lidocaine or 0.25% bupivacaine in conjunction with betamethasone sodium phosphate and betamethasone acetate solution due to its pronounced chondrotoxic effect in this study. 1% lidocaine used in combination with methylprednisolone acetate or triamcinolone acetonide also led to significant chondrotoxicity.