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Biomedical subjects

J Manabe

Publications and source records attributed to J Manabe.

At least 19 recordsLinked to original sources

Unusual huge intramuscular granuloma with calcium phosphate crystal deposition in the buttock.

An unusual case of a huge granuloma featuring marked calcium phosphate crystal deposition in muscle is presented. A 58-year-old male demonstrated a well-circumscribed, large, elastic firm mass which had slowly grown over 8 years in the left buttock. Clinical examinations including X-ray, ultrasonography and computed tomography all suggested a neoplastic growth. Surgical excision revealed three inter-connected irregular-shaped masses, measuring up to 11 x 10 x 6 cm in size. The histological appearance was of granulomas composed of numerous small crystals surrounded by reactive mononuclear cells embedded in fibrous tissue containing many foreign body type giant cells. Chemical analysis demonstrated the crystals to be made up of calcium phosphate.

Buttocks

[Surgical and preoperative treatment of soft tissue sarcoma].

Preoperative therapy effects, resected margin and local radicality were investigated in 40 cases of soft tissue sarcoma in which preoperative therapy (mainly radiation therapy) had been given. The results indicated that there was no effect upon prognosis due to postponement of surgery in order to perform preoperative treatment. In cases in which radiation therapy was used for preoperative treatment, even when a surgical margin resulted with in a tumor, no recurrence was found. However, histologically there was concern that some portion of the living tumor cell in marginal area of the tumor might have remained. Thus, at the present stage in cases having undergone initial treatment, radiation limited to the specific area of the resected margin causing non-curative margin should be given. If combined with preoperative radiation therapy, surgical intervention involving "wide margin" can be considered radical. On the other hand, cases having undergone surgery before and receiving preoperative therapy that show good response nevertheless show numerous recurrences. These recurrences, however, invariably occur outside of the irradiated area, and may be attributed to the fact that tumor cell dissemination from the earlier surgery was not within the radiation field. Hence, it was considered that the area for radiation in the case of a recurrence should extend well beyond the scar area.

Combined Modality Therapy

Differential effects of cefmetazole sodium on the reproductive system of infant and pubertal male rats.

The effects of cefmetazole (CMZ), a cephem antibiotic which contains the N-methyltetrazolethiol (NMTT) side-chain moiety, were compared in infant (6-42 days of age) and pubertal (6-10 weeks of age) male Sprague-Dawley rats. High doses of either CMZ or free NMTT caused reductions in testicular weight and delayed maturation of spermatogenic germ cells in the testes of infant rats, implicating NMTT as the active component in causing these effects. Pubertal rats expressed neither of these effects, even when treated with doses of CMZ far in excess of those used in infant rats. The effects of CMZ and NMTT on testicular weights and histologic features of testes of rats treated as infants were mainly reversed when these animals were examined 35 and 70 days after cessation of treatment. All reproductive functional parameters were normal in mating studies using male rats which had been treated with CMZ or NMTT as infants and allowed to recover. Because of the species differences in rates of sexual maturation and the greater rate at which rats metabolize CMZ to NMTT, the relevance to humans of the testicular effects of CMZ in infant rats is unknown.

Animals

Preclinical safety studies of cefmetazole.

In order to assess the safety of cefmetazole, preclinical multiple-dose parenteral studies, varying from one to three months in length, were conducted in Sprague-Dawley rats and beagle dogs. Although the largest doses used were in multiples of several times the weight-adjusted doses intended for humans, cefmetazole was generally well tolerated. The principal adverse effect noted in the adult rats receiving the largest doses (2000 and 2500 mg/kg/day) of cefmetazole was slight elevation of serum alanine aminotransferase. Infant rats injected subcutaneously with 300 mg/kg/day or more of cefmetazole for 35 consecutive days had reversible reductions in testicular weight and maturation of spermatogenesis, but not lasting discernible effect on reproductive function. The most consistent effects of longterm multiple dosing with cefmetazole in dogs consisted of vomiting and retching during dosing and reversible haematological changes (mild regenerative anaemia, positive Coombs' test, clinically-silent thrombocytopenia) in a number of the dogs. These findings supported the interpretation that cefmetazole was acceptably safe for clinical studies in humans.

Animals

[Hyoid bone position and airway accompanied with influence of head posture].

The position of hyoid bone has been analyzed using roentgenogram. But, due to the great variability with the change of head posture, the position could not be determined correctly. In the present study, we investigated the influence of head posture to the position of hyoid bone. Subjects consisted of 32 Japanese males, those mean age was 25.8 years. Lateral cephalograms had been taken for each subjects at 5 different head posture. The findings were as follows. 1. Superimposed on SN plane, hyoid bone moved along the line of menton to 4th cervical vertebrae (C4) with the change of head posture. The hyoid bone moved in parallel with the line of 3rd cervical vertebrae (C3) to C4 (cervical plane). In spite of these movements, RH kept an uniform ratio. 2. The distances between sella turcica and hyoid bone and between C3 and hyoid bone, and the angle between menton, porion and hyoid bone, were at constant value. 3. Some measurements included the distance between hyoid bone and menton and the angle between nasion, sella turcica, hyoid bone showed very high correlation with the change of head posture. 4. EpPW1 (the width of airway) and the distance from C4 to hyoid bone showed almost the same change. It means the position of hyoid bone has a great influence on airway.

Adult

[Preoperative radiotherapy of bone and soft tissue sarcomas].

UNLABELLED: The role of preoperative radiotherapy was evaluated in 16 cases with soft tissue sarcoma and 13 cases with osteosarcoma. Nine osteosarcoma cases underwent radiotherapy of whole lesion, and 4 cases had radiotherapy only of the surgically incurable portion. There were no local recurrences in M0 cases, but skin necrosis occurred in the whole radiation group. As for the soft tissue sarcomas, local recurrence was not seen in virgin cases, but two cases which had received previous treatment showed local recurrence. There were no cases with severe side effects. CONCLUSION: 1. Partial radiotherapy was effective as preoperative treatment for osteosarcoma. 2. preoperative radiotherapy is better than postoperative radiotherapy from many standpoints.

Adolescent

[Evaluation method of surgical margin in musculoskeletal sarcoma].

The evaluation of surgical margin is useful in determining the curability of surgical treatment of musculoskeletal sarcoma and the degree of possibility to reduce later surgery as part of preoperative therapy. However, at present there has been no worthwhile evaluation method developed for these purposes. In this paper we propose a new evaluation system for surgical margin as drafted by the Bone and Soft Tissue Tumor Committee of JOA. This system was applied in 197 cases at the Cancer Institute Hospital to determine the clinical significance in the treatment of musculoskeletal sarcoma. In this method, surgical margin was classified into four types according to the distance between the surgical margin and the reactive zone of the tumor. The types of surgical margins (in order of surgical extent) are curative margin, wide margin, marginal margin, and intralesional margin. Surgical margin is said to be curative if the margin is more than 5cm outside the reactive zone. It is referred to as wide if the margin is less than 5cm and marginal if the margin is at the reactive zone. In our evaluation, a thin barrier is estimated as a 2cm thickness of normal tissue, a thick barrier as a 3cm thickness of normal tissue, and joint cartilage as 5cm thickness. Moreover, in all cases the surgical margin is considered to be curative if the margin is outside a barrier and there is normal tissue between the barrier and the reactive zone of the tumor. The results of the study were as follows.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Neoplasms

[Bolus and maintenance infusion of high-dose methotrexate].

For 17 patients with bone and soft tissue sarcoma, 32 bolus and maintenance infusions of high-dose methotrexate (MTX) were performed to induce rapid elevation of plasma MTX concentration and to maintain it. At the doses of 200-300 mg/kg, plasma MTX concentrations were measured by enzyme assay. It needed four hours to reach the steady state by five hours' constant rate infusion, with the plasma plateau concentration at about 1 X 10(-3) M/L. On the other hand, bolus infusion of MTX needed only one hour to reach over 5 X 10(-4) M/L, and the plateau concentration lasted during the maintenance infusion period. By the constant rate infusion as well as bolus infusion, it was possible to maintain the plasma concentration over 1 X 10(-4) M/L for 12 hours, but both infusions can not maintain 1 X 10(-3) M/L for a long time. From these results, clinical effects of high dose MTX against sarcomas seemed to be evaluated by the plasma MTX plateau concentration and the maintenance time.

Bone Neoplasms

[Urinary beta 2-microglobulin as an indicator for impaired excretion of methotrexate].

Twenty cases treated with high-dose methotrexate (MTX) infusions were studied to determine whether urinary beta 2-Microglobulin (beta 2-M) is a reliable indicator to predict impaired excretion of methotrexate. Before and after MTX infusions, the levels of urinary beta 2-M were measured along with serum creatinine, uric nitrogen, and creatinine clearance. MTX clearance was found to be impaired in four of the 20 infusions, although concentrations of serum creatinine and uric nitrogen, and creatinine clearance were normal prior to the infusions. In the four cases that resulted in impaired excretion, a significant increase of beta 2-M levels was noted before and after the high-dose MTX infusion (p less than 0.01). Although one of the four cases showed a normal level of beta 2-M before the infusion, the post-infusion level of beta 2-M extremely high. This raised level of beta 2-M was thought to be caused by impaired excretion due to decreased amounts of urine. We conclude that urinary beta 2-M is a sensitive indicator of impaired excretion of high-dose MTX infusion, and especially when levels of more than 250 ng/ml of urinary beta 2-M are found to exist, it seems to difficult to clear the drug following high-dose MTX treatment.

Blood Urea Nitrogen

[Procedures and results of limb salvage surgery of musculoskeletal sarcoma].

During the 8-year period beginning 1979, 116 cases of musculoskeletal sarcoma were treated by limb salvage operation. Of these, the local recurrence rate was 9% and the postoperative metastatic rate was 28%. The limb salvage rate was about 80%. Limb salvage procedures were generally performed using curative surgical procedures without preoperative adjunctive therapy. However, reduction of the surgical margin to achieve local cure was made possible by combined therapy with preoperative adjunctive chemotherapy or radiotherapy. The wide procedures combined with preoperative adjunctive therapy achieved a local curability rate equal to curative procedures. Marginal procedures following preoperative radiotherapy were also undertaken in those cases in which the tumor was located in an area for which curative or wide procedures were not feasible. Also, similar procedures were performed for patients of advanced age, patients with lung metastasis, patients who refused ablative surgery, and for extirpation of lymph node metastases. Accordingly, we were able to determine which procedures best ensure local curability. Also, the most significant prognostic factor was found to be local recurrence caused by inadequate surgical margin. This was especially true in the treatment of high malignant sarcoma. Moreover, from analysis of recurrent cases, the suggested factors contributing to local recurrence were: the invasive character of the tumor, lymph node metastasis, skip metastasis, tumor dissemination due to pathological fracture, previously performed inadequate surgery, venous invasion, and multicentrical occurrence of certain tumors.

Adult

[Surgical treatment for bone and soft tissue sarcomas of the shoulder part].

Since 1977 we have treated 18 bone sarcomas and 16 soft tissue sarcomas of the shoulder part. For 10 bone sarcomas of the proximal humerus, four fore-quarter amputations, two curative wide resections, and four wide excisions were performed as radical operations. The reconstructive procedures after the six resections were two spacer insertions, one total shoulder replacement, and three arthrodeses with autografts. Considering the functional result, the arthrodesis is the most-recommended method. For eight bone sarcomas of the scapula, three total resections and four partial resections of the scapula, and one debulking operation were performed. For 16 soft tissue sarcomas, we performed two ablative operations, three curative wide resections, five wide excisions, and six conservative operations after adjunctive chemo-and/or radiotherapy. Among all 34 bone and soft tissue sarcomas, the success rate for limb salvage was 74%, while the recurrence rate was 18%. The functional result of the limb salvage operations was far better than that of ablative operations of the shoulder part. In fact the rate of satisfactory ADL (excellent and good) was 81% among the limb salvage cases, while for ablative operations, the ADL ratings were all poor.

Bone Neoplasms

Lung fibrosis induced by diquat after intratracheal administration.

Diquat toxicity to lung was evaluated at various intervals after intratracheal administration to rats. Twelve hours after the injection, both type I and type II pneumocytes developed degenerative changes which were similar in nature to those induced by paraquat. A much larger dose of diquat, however, was needed for the changes compared to paraquat, which is known to be actively taken up by the lung. This morphological evidence suggests that diquat may cause alveolar damage by the same mechanism as paraquat, although it is not actively taken up by the lung. Moreover, initial alveolar damage induced by diquat was followed by lung fibrosis, as with paraquat. Since paraquat is a well known fibrogenic agent, the common property of these two agents in alveolar damage may be a key to interpreting the development of lung fibrosis.

Animals

[Intra-arterial infusion of cisplatinum in bone and soft tissue tumors].

Cisplatin was administered by intravenous injection, intra-arterial injection, and balloon-occluded arterial infusion. The total Pt, ultrafiltrated Pt, and free Pt levels were measured. Intra-arterial injection, in which ultra-filtrated Pt level on the normal side is the same as in intravenous injection, acts to increase the ultrafiltrated Pt level on the affected side. Thus, intra-arterial injection is as effective as preoperative chemotherapy. In two-route chemotherapy, free Pt level on the affected side is extremely high, so for only local control of tumors, two-route chemotherapy is very effective.

Animals

[The value of limb-saving surgery in the treatment of osteosarcoma].

Since 1981, 38 limb-saving operations for malignant bone tumors have been performed. Of these, 22 cases were osteosarcomas. The principle of limb-saving surgery for osteosarcoma is the same as for curative wide resection in cases of soft tissue sarcoma. Among the osteosarcoma cases for which limb-saving procedures were carried out, five complicated cases (two skip metastases and two infections) were noted. However, in the other cases, patients had better functional benefits and psychological acceptance compared with those subjected to radical ablative procedures. Indication for limb-saving surgery is usually decided by patient age, existence of skip metastasis and venous infiltration, effect of preoperative adjunctive therapy and the relationship of the tumor with the major artery necessary for preserving the affected limb. If the adjunctive therapy is effective, local control can be achieved by establishing a wide margin.

Adolescent

[Surgical treatment of malignant soft tissue tumors].

The ultimate survival of patients with soft tissue sarcoma is determined by a number of factors. Radical removal by adequate surgery is one of the most important factors together with early treatment and chemotherapy. We usually select curative wide resection, amputation, or resection after radiotherapy as forms of radical surgery for soft tissue sarcomas according to each clinical stage. The method of curative wide resection is based on biological barrier effects. In this report we discuss the operative results obtained in 148 cases of soft tissue sarcoma which we have treated over the past ten years, and also discuss the causes of recurrence after radical operation. Among 55 primary NoMo which were treated by the curative wide resection cases, the recurrence rate was 5.5%, the metastatic rate was 21.8%, and 5-year survival was 79.3%. These results were better than those for 30 recurrent and additional NoMo cases. Of cases involving the extremities, 81% were controlled by limb-saving operations.

Adult