Triple Injection Research Articles

TREATMENT OF INTRACORPOREAL INJECTION NONRESPONSE WITH SILDENAFIL ALONE OR IN COMBINATION WITH TRIPLE AGENT INTRACORPOREAL INJECTION THERAPY

We assess the efficacy of sildenafil as salvage therapy for intracorporeal injection therapy nonresponse. The study group comprised 93 patients with a mean age of 53.6 years (range 24 to 77) with chronic erectile dysfunction. In all cases a home trial of intracavernosal injection of high dose alprostadil and triple agent intracavernosal injection therapy had failed. Patients were treated with sildenafil citrate alone or in combination with intracavernosal injection therapy. The etiology of erectile dysfunction was arteriogenic in 29 cases, cavernosal venous leakage in 36, mixed vasculogenic in 24, psychogenic in 3 and post-priapism intracavernous fibrosis in 1. Of the 32 sildenafil responders (34% of the study group) 30 required 100 and 2 required 50 mg. The 29 sildenafil intracavernosal injection (combined therapy) responders (31% of the study group) required 100 mg. sildenafil. There were 32 nonresponders (34% of the study group). Mean International Index of Erectile Function questions 3 and 4 scores were 1.7 and 1.5 at baseline, 2.3 and 1.9 with intracavernosal injection, 4.6 and 42.2 with sildenafil, and 4.1 and 4.10 with combined therapy, respectively. Of the 93 patients 29 (31%) treated with intracavernosal injection reported adverse effects, including penile pain in 27, dizziness in 5 and headache in 2. Of the patients treated with sildenafil 34 (37%) reported side effects, including headache in 30, facial flushing in 25, dyspepsia in 12, nasal congestion in 9, dizziness in 5 and visual disturbances in 1. Of the 41 patients given combined therapy 20 (49%) reported adverse effects, including penile pain in 15, headache in 15, facial flushing in 12, dyspepsia in 7, nasal congestion in 3, dizziness in 12 and syncope in 1. Sildenafil alone or sildenafil plus intracavernosal injection is effective salvage therapy for intracavernosal injection nonresponse. Sildenafil in combination with intracavernosal injection is associated with a 33% incidence of adverse effects, including a 20% incidence of dizziness.

Differential effects of local application of BMP-2 or TGF-β1 on both articular cartilage composition and osteophyte formation

Objective: The related molecules bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-β1) have both been shown to stimulate chondrocyte proteoglycan (PG) synthesisin vitro. We investigated thein-vivoeffects of these factors on articular cartilage PG metabolism.Design: Several doses of BMP-2 or TGF-β1 were injected into the murine knee joint, once or repeatedly. Patellar cartilage PG synthesis was measured by [35S]-sulfate incorporation and reverse transcriptase polymerase chain reaction (RT-PCR). PG content was analyzed by measuring safranin O staining intensity on histologic sections.Results: A single injection of 200 ng BMP-2 induced a much earlier and more impressive stimulation of articular cartilage PG synthesis, than 200 ng TGF-β1. RT-PCR revealed that both factors upregulated mRNA of aggrecan more than that of biglycan and decorin. However, 21 days after a single injection of 200 ng TGF-β1 PG synthesis still was significantly increased, while stimulation by BMP-2 only lasted for 3 to 4 days. Stimulation by BMP-2 could be prolonged to at least 2 weeks by triple injections of 200 ng each, at alternate days. Remarkably, even after this intense exposure to BMP-2, stimulation of PG synthesis was not reflected in long-lasting enhancement of PG content of articular cartilage. In contrast, even a single injection with 200 ng of TGF-β1 induced prolonged enhancement of PG content. After repeated injections, both BMP-2 and TGF-β1 induced chondrogenesis at specific sites. ‘Chondrophytes’ induced by BMP-2 were found predominantly in the region where the growth plates meet the joint space, while those triggered by TGF-β1 originated from the periosteum also at sites remote from the growth plates.Conclusions: BMP-2 and TGF-β stimulate PG synthesis and PG content with different kinetics, and these factors have different chondro-inductive properties.

Lack of topography in the ventral nucleus of the lateral lemniscus.

In contrast to the ease of finding tonotopicity in other nuclei, both anatomical and electrophysiological methods have failed to demonstrate a clear and simple tonotopic map within the ventral nucleus of the lateral lemniscus (VLL). The present study was undertaken in cat with the hope that methods not used previously in studies of VLL might succeed in demonstrating an orderliness in its exiting fibers (i.e., efferents) or its incoming fibers (i.e., afferents). Since the same organization of ascending frequencies present in the cochlea is maintained in these fibers as well as in all main auditory nuclei, demonstration of a similar organization of frequencies in VLL would be evidence of the cochleo- or tono-topicity of this nucleus. Using triple injection of 3 different fluorescent dyes in inferior colliculus to study efferents, orderly and tonotopic cell-labeling is found in each of the brainstem auditory nuclei, with the notable exception of VLL. Instead, labeling of cell clusters, each cluster containing a small number of cells, is found randomly distributed throughout VLL in all 3 of its spatial dimensions. Using the 2-deoxyglucose (2-DG) method, during stimulation at 6 different frequencies, afferent orderliness, indeed, tonotopicity is found in all major brainstem auditory nuclei, again with the notable exception of VLL. Rather, each frequency evokes 2-DG label throughout VLL. In agreement with the results based on electrophysiological methods, therefore, the anatomical methods used here also yield no evidence of tonotopicity in VLL. Thus, if there is orderliness in VLL's efferents or afferents, it is based on an auditory dimension incommensurate with frequency.

2-31-15 A multicentre longitudinal study comparing the sensitivity of monthly enhanced MRI after single and triple dose Gd-DTPA injection for monitoring disease activity in multiple sclerosis

2-31-15 A multicentre longitudinal study comparing the sensitivity of monthly enhanced MRI after single and triple dose Gd-DTPA injection for monitoring disease activity in multiple sclerosis

Kuparuk Large-Scale Enhanced Oil Recovery Project

Summary The Kuparuk River oil field has had a "miscible" water-alternating-gas (MWAG) enhanced-oil-recovery (EOR) pilot in place since 1988. This original pilot was implemented on two drillsites previously on waterflood. The pilot was expanded to a third drillsite in 1993 to test the MWAG process in an area previously flooded by an "immiscible" water-alternating-gas (IWAG) recovery technique. Large-scale application of MWAG at Kuparuk is in progress, with a project that will more than triple current MWAG injection. Full implementation is slated for mid-1996. When completed, the Kuparuk large-scale EOR (LSEOR) project will be among the largest of its kind in the world. This paper covers the basic aspects of moving the EOR process at Kuparuk from pilot to large-scale application. A number of hurdles had to be overcome, including scaleup of field and simulation results in a consistent manner and the need to use existing infrastructure to ensure economic viability

Induced spawning in bream, Abramis brama (L.), using carp and bream pituitary extract and hCG

Induced spawning in bream, Abramis brama (L), was studied using acetone-dried common carp pituitary (CP) and bream pituitary (BP) with or without the addition of human chorionic gonadotrophin (hCG). The total dose administered to fish was of 5.0 mg kg−1 BP or 4.0 mg kg−1 CP with or without 2000-2200 IU hCG kg−1 for females and 2.5 mg kg−1 BP or 2.0 mg kg−1 CP with or without 1000–1100 IU HCG kg−1 for males. In all male treated groups 100% of spermiation was observed: in females the most effective method was a triple injection with hCG and carp pituitary, resulting in 79% of females ovulated (over 68% of eyed eggs). Biological quality of eggs, expressed as a percentage of eyed eggs, was negatively correlated with time elapsing between resolving (final) injection and ovulation. Spawning success, expressed as a value of Se (spawning effectiveness coefficient), was higher in fish treated with triple injection.

Induced spawning in perch, Perca fluviatilis L. using carp pituitary extract and HCG

Induced spawning in Eurasian perch, Perca fluviatilis L., was studied using human chorionic gonadotrophs (hCG) or acetone-dried common carp pituitary with or without hCG. The dose administered to fish was 5700 IU hCG kg-1 or 4.0 mg kg-1 carp pituitary with or without 500-700 IU hCG kg-1 for females and 2850 IU hCG kg-1 or 2.0 mg kg-1 carp pituitary with or without 250-350 IU hCG kg-1 for males. There were no statistically significant differences in quantity of milt in treated and control groups, although the best result was observed when males were treated with a triple injection of hCG and carp pituitary extract. Male spermiating success, expressed as a quantity of milt, was negatively correlated with fish weight. All females treated in this experiment had oocytes at the same division, so time of ovulation was highly synchronous. Spawning success, expressed as a spawning effectivity coefficient (Sc), was highest in fish treated with the triple injection. Spawning methods described in this paper were successful, even though hormones from another order of fish were used.

Wrist arthrography versus arthroscopy: A comparative study of 150 cases

One hundred fifty patients with suspected wrist ligamentous injuries were studied with both triple injection wrist arthrography and arthroscopy. The diagnoses obtained by these two techniques were compared to determine the differences between these two modalities. All the patients in this study had both the clinical diagnosis of ligamentous injuries of the wrist and normal findings on x-ray films. Intercarpal abnormalities were found in 106 patients (71%) at wrist arthrography and in 136 patients (91%) at arthroscopy. There was only 42% agreement (63 patients) between the arthrographic and arthroscopic diagnoses. Eighty-seven patients (58%) had alterations of their arthrographic diagnoses following arthroscopy. For patients with normal arthrographic findings (44 patients), 88% underwent arthroscopy because there was insufficient correlation between the physical examination findings and the arthroscopic findings. Out of the 44 patients with normal arthrographic findings, 35 patients (80% of the subgroup) had injuries found at arthroscopy. Over half of the patients had alterations in their arthrographic diagnoses following arthroscopy. In a patient with suspected ligamentous injury of the wrist, wrist arthroscopy may be the most efficient method in arriving at a definitive diagnosis.

In vivo depletion of NKR-P1 positive cells in the recipient prior to small bowel transplantation enhances graft-versus-host disease (GvHD) in the rat.

Recent evidence for major histocompatibility complex (MHC) class I antigen-directed recognition mechanisms of natural killer cells (NKs) have revived interests in investigating non-adaptive immune responses in the framework of solid organ transplantation. A semi-allogeneic rat model of heterotopic small bowel transplantation (HSBTx) from male DA parental to male F1 hybrid rats (DA x LEW) was established to investigate the role of host NKs to attenuate graft-versus-host (GvH)-mediated immunosuppression and tissue injury. By use of anti-NKR-P1 monoclonal antibody (mAb) 3.2.3, host NKs were depleted effectively in vivo after triple intraperitoneal injection prior to HSBTx. In contrast to non-depleted animals, an initial lack of NK activity in F1 hosts significantly decreased the mean survival (P < 0.01) and substantially enhanced graft-versus-host disease (GvHD)-related damage to lymphoid and non-lymphoid target organs. These findings emphasize the important immunoregulatory role of host NKs during the early onset of GvHD.

Root surface defects in rat molar induced by 1-hydroxyethylidene-1,1-bisphosphonate.

Cementum surface alterations induced by 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) in the maxillary first molars in rats were studied by means of scanning electron microscopy. Single or triple injections of HEBP inhibit the formation of acellular extrinsic fiber cementum and delay the formation of cellular mixed-fiber cementum. The results indicate the importance of acellular extrinsic fiber cementum as a protection barrier against root resorption and the different mechanisms underlying the formation of the two cementum varieties.

Merrill C. Sosman Lecture. MR imaging of the wrist.

Imaging of the wrist should always begin with a plain film examination. Sonography and tenography are sometimes used to evaluate tendon abnormalities. Sonography is operator dependent; tenography, because of its invasive nature, is rarely used today. Arthrography, with single or triple injection techniques, with [1] or without [2] digital subtraction, has been the procedure of choice for detecting abnormalities of the interosseous ligaments and the triangular fibrocartilage (TFC). MR imaging is the only imaging technique that can directly depict the interosseous ligaments and the TFC. It is the imaging technique of choice for the early diagnosis of aseptic necrosis, for tumor staging, and for evaluating soft-tissue masses. MR imaging enables noninvasive global examination of the wrist that is extremely sensitive in detecting osseous and soft-tissue disease. Because technical advances will allow more rapid data acquisition, thinner slices, and higher resolution, I predict MR imaging will replace arthrography in the near future.

Nuclei within the rostral ventromedial medulla mediating morphine antinociception from the periaqueductal gray

The relative contributions of nuclei within the rostral ventromedial medulla (RVM) involved in mediating morphine induced antinociception from the periaqueductal gray (PAG) were examined. Lidocaine injections (4%) at the time of morphine's maximal response were used to provide a localized neural block and were administered in the nucleus raphe magnus/reticularis gigantocellularis pars alpha (RMg/GiA; commonly referred to as RMg), reticularis gigantocellularis (Gi) and reticularis paragigantocellularis lateralis (LPGi). Microinjection of morphine (6 nmol; 0.5 μl) into the PAG of awake rats produced an inhibition of the tail-flick reflex that was maximal after 30 min. This response was unaffected by a single medial lidocaine injection (0.5 μl) into the RMg/GiA or Gi, bilateral injections into the Gi or LPGi or triple injections that included both the RMg/GiA and LPGi. A partial, non-significant block of morphine's response was observed either by bilateral injections (0.5 μl) into both the Gi and LPGi (%inhibition= 16.4±24.8) or by bilateral injections in the LPGi and a single medial injections into the Gi (%inhibition= 41.5±29.8). However, injection of a greater volume of lidocaine (1 μl) into the RMg/GiA or bilaterally into the LPGi affected adjacent medial and lateral tissue, and completely inhibited morphine's response. Furthermore, triple injections of lidocaine (0.5 μl) into the Gi or bilateral injections (0.5 μl) into the Gi and a single medial injection into the RMg/GiA completely blocked morphine's antinociceptive response. These results indicate that morphine antinociception from the PAG is mediated by a large volume of tissue in the RVM containing nuclei located both medially and laterally. Additionally, the principal nuclei involved in this response appear to be the Gi and RMg/GiA.

Comparison of the Safety of Standard and Triple Dose Gadodiamide Injection in MR Imaging of the Central Nervous System

Gadodiamide injection was administered intravenously to 49 patients with known or suspected CNS lesions undergoing MR imaging. Two parallel groups were used to evaluate the efficacy and safety of single doses of 0.1 (25 patients) and 0.3 (24 patients) mmol/kg b.w. The principal measures of efficacy were diagnostic yield of MR and the overall contrast enhancement. Adverse events and serum bilirubin were the main safety parameters. Contrast enhancement of the lesion was observed for 16 patients in each dose group. Thirteen patients in the 0.1 and 17 in the 0.3 mmol/kg group had their diagnosis amended following the postcontrast image, but only one patient in each dose group had their management affected by new information from the postcontrast image. The overall diagnostic utility of gadodiamide injection was good, but there were no differences between the 2 doses studied in this respect. No injection-associated discomfort or other adverse events were reported. No clinically important changes in serum bilir...

Comparison of the Safety of Standard and Triple Dose Gadodiamide Injection in MR Imaging of the Central Nervous System

Gadodiamide injection was administered intravenously to 49 patients with known or suspected CNS lesions undergoing MR imaging. Two parallel groups were used to evaluate the efficacy and safety of single doses of 0.1 (25 patients) and 0.3 (24 patients) mmol/kg b.w. The principal measures of efficacy were diagnostic yield of MR and the overall contrast enhancement. Adverse events and serum bilirubin were the main safety parameters. Contrast enhancement of the lesion was observed for 16 patients in each dose group. Thirteen patients in the 0.1 and 17 in the 0.3 mmol/kg group had their diagnosis amended following the postcontrast image, but only one patient in each dose group had their management affected by new information from the postcontrast image. The overall diagnostic utility of gadodiamide injection was good, but there were no differences between the 2 doses studied in this respect. No injection-associated discomfort or other adverse events were reported. No clinically important changes in serum bilirubin, or other parameters of blood chemistry, or hematology were observed. Overall, the safety profile of gadodiamide injection 0.3 mmol/kg b.w. in this study was similar to that of 0.1 mmol/kg b.w.

7 Therapy of Burkitt and other B-cell acute lymphoblastic leukaemia and lymphoma: Experience with the LMB protocols of the SFOP (French Paediatric Oncology Society) in children and adults

Burkitt's lymphoma and L3-ALL are different forms of the same disease: B-cell disease. Therapeutic improvement has been considerable over the past 10 years. In France, four consecutive multicentre LMB studies of the SFOP greatly contributed to this improvement. An overall cure rate of 90% can now be achieved in children with a short intensive risk adapted polychemotherapy regimen based on high-dose fractionated CPM, HD MTX (3 g/m2), Ara-C in continuous infusion. For patients with ALL or with CNS involvement, the addition of CNS-directed therapy with a higher dose of MTX (8 g/m2), HD Ara-C (3 g/m2 x 4), VP 16, triple intrathecal injections and cranial irradiation greatly improved survival: 87% for ALL and 73% for patients with CNS involvement. In adults, the application of the paediatric protocol is possible with acceptable toxicity and a retrospective study of 41 cases treated according to a LMB protocol showed a cure rate of 71%. Such a regimen should now be proposed to adults and studied prospectively.

Comparison of the Safety of Standard and Triple Dose Gadodiamide Injection in MR Imaging of the Central Nervous System

Comparison of the Safety of Standard and Triple Dose Gadodiamide Injection in MR Imaging of the Central Nervous System

FGF-2 modulates dopamine and dopamine-related striatal transmitter systems in the intact and MPTP-lesioned mouse.

Following a previous study in which we showed ameliorative effects of basic fibroblast growth factor (FGF-2) locally applied to the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice, we investigated FGF-2 actions at different time intervals after the lesion and effects on non-dopaminergic striatal transmitter systems. A triple intraperitoneal injection of 30 mg/kg MPTP at 24 h intervals caused a reduction of striatal dopamine to 23% of control levels that lasted for at least 4 weeks. Four micrograms FGF-2 soaked into gel foam and placed onto the right striatum partially and bilaterally restored dopamine levels and tyrosine hydroxylase activity after 2 weeks, when the treatment started simultaneously or 1 day after the toxin lesion. FGF-2 was ineffective, if administration commenced with a delay of 7 days. Striatal neurotransmitters that are known to be linked to the dopaminergic system were also altered by the MPTP treatment. GABA was significantly increased, while somatostatin levels were reduced. Upon FGF-2 administration both GABA and somatostatin levels were partially normalized. Our data are consistent with the notion that FGF-2 protects and rescues acutely and subacutely MPTP-lesioned nigrostriatal neurons and that its effects must be mainly indirect. Likewise, positive effects of FGF-2 on non-dopaminergic neurons may be due to the partial restoration of striatal dopamine.

Retinotopy of cortical connections between the striate cortex and extrastriate visual areas in the rat.

Previous studies have determined that the striate cortex of the rat is reciprocally connected with multiple extrastriate cortical areas that are retinotopically organized. The objective of this study was to investigate the retinotopy of the striate-extrastriate connections in the rat, by placing triple or double injections of fluorescent tracers (fluorogold, fast blue, rhodamine dextran, or rhodamine-labeled microspheres) in different regions of the striate cortex (Oc1) and mapping the distribution of cells and fibers labeled with the different tracers in the lateral (Oc2L) and medial (Oc2M) extrastriate cortex. The tracer injection sites were visualized in tangential sections of the flattened cortex and correlated with the myelin layout of the striate cortex and with an electrophysiological map from previous studies. The results showed retinotopically organized Oc1 connections with ten different extrastriate cortical areas. The location of these extrastriate areas and the retinotopy of their striate connections remained mostly invariant despite changes of the injection sites in Oc1. Thus, the quadrantic retinotopy was obtained for striate connections to areas posterior, posterolateral, lateromedial, laterointermediate, laterolateral, anterolateral and rostrolateral in Oc2L; and to areas posteromedial, anteromedial, and anterior in Oc2M. The present anatomical map correlates well with electrophysiological maps of the rat extrastriate cortex from previous studies. Furthermore, they provide a definition of the retinotopy of some areas that have not been completely mapped before. These results reaffirm the existence of multiple extrastriate visual areas in the rat.

猫3種混合不活化ワクチンの開発

A feline tri-valent inactivated vaccine adjuvanted with oil emulsion (F3V·OE) has been developed against feline panleukopenia virus (FPLV), feline viral rhinotracheitis virus (FVRV), and feline calicivirus (FCV) infections. This vaccine contains lyophilized antigens consisting of formalin-inactivated and concentrated FCV and FPLV from cell cultures, and detergent-solubilized cells infected with FVRV. When kittens were immunized with the F3V·OE, high antibody titers were elicited.Three-to 5-month-old kittens were injected twice with the F3V·OE in a single or triple dose at an interval of 3weeks, and were examined for pathological changes of injection sites every 3weeks from 1 to 15 weeks after injection. No adverse clinical signs were recognized durig the observation period. Macroscopically, at 1week after injection, slight swelling at the injection sites was observed only in the triple dose injection group, but the change disappeared after 3weeks. In the single dose injection group, no gross chages such as swelling or hemorrhage or microscopic changes such as muscle degeneration or necrosis were obseved.However, formation of adjuvant granuloma, infiltration and accumulation of lymphoid cells in the connective and muscle tissue were observed until 9weeks, diminishing after 12 weeks.Three-to 5-month old kittens were vaccinated with F3V·OE twice at a 3-week interval. Following challenge with virulent FPLV, FVRV and FCV at 6months post-vaccination, none of the vaccinates showed significant clinical signs of infection.It was demonstrated that the F3V·OE is effective in preventing FPLV, FVRV, and FCV infections, and that the vaccine is safe in kittens.

Treatment of Acute Lymphoblastic Leukemia in the Tokyo Children's Cancer Study Group—Preliminary Results of L84-11 Protocol

The Tokyo Children's Cancer Study Group (TCCSG) has performed prospective randomized controlled studies since 1984 for childhood acute lymphoblastic leukemia (ALL). Four hundred and ninety-eight newly diagnosed patients were treated with 5 different regimens designated as S1, S2 for a standard risk group (SRG), H1 and H2 for a high risk group (HRG) and HEX for an extremely high risk group of patients. We added intermediate-dose methotrexate as early intensification therapy in the S2 and H2 groups to reduce extramedullary and medullary relapses. Event-free survival of all patients at 4 years 6 months from the start of this regimen (median follow-up period 32 months) was 67.5%. The CNS relapse rate was significantly decreased to 2.2% compared to previously reported studies and our own experience. There were some unexpected complications of the CNS such as myelopathy and/or leukoencephalopathy. For the SRG early ID-MTX seemed to be useful to improve the prognosis, but triple intrathecal injections (TIT) should be limited in number. The 24Gy cranial irradiation (CRX) was effective but possibly excessive for the HRG. As evidenced by the success of the HEX group regimen, more intensive multi-drug consolidation in the early post-remission phase might be necessary to improve further the prognosis and to make it possible to shorten the treatment periods.