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Biomedical subjects

S Sai

Publications and source records attributed to S Sai.

At least 19 recordsLinked to original sources

Liposome-mediated gene transfection of endothelial nitric oxide synthase reduces endothelial activation and leukocyte infiltration in transplanted hearts.

BACKGROUND: During cardiac ischemia-reperfusion injury, neutrophilic infiltration of the myocardium is mediated by adhesion molecule expression on activated coronary endothelium. Nitric oxide inhibits neutrophil adhesion to endothelium in vitro by blocking the nuclear factor (NF)-kappaB-dependent transcription of adhesion molecules. We investigated whether intraoperative gene delivery of endothelial nitric oxide synthase (eNOS) into donor hearts before transplantation would have a similar effect on an entire organ. METHODS AND RESULTS: In an allogeneic rabbit heart transplant model, liposomes complexed to the gene encoding eNOS were infused into the donor coronary circulation before transplantation. By 24 hours after transplantation, calcium-dependent nitrite production was significantly higher in eNOS-transfected donor hearts than in the 3 control groups: donor hearts transfected with empty plasmids alone, donor hearts treated with diluent only, and untransplanted native hearts. Intramyocardial neutrophil and T-lymphocyte populations were halved in eNOS-transfected hearts compared with control donor hearts (P<0.05). Moreover, the prevalence of NF-kappaB activation in microvascular endothelial cells and surrounding cardiac myocytes as well as endothelial vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression were all significantly reduced in eNOS-transfected hearts compared with control donor hearts (P<0.01). Without immunosuppression, eNOS-transfected hearts survived longer than controls. CONCLUSIONS: Intraoperative liposome-mediated gene delivery of eNOS to donor hearts can result in early gene expression sufficient to reduce ischemia-reperfusion injury by inhibiting NF-kappaB activation, adhesion molecule expression, and the early infiltration of leukocytes, all of which may improve graft survival.

Animals↗

Preoperative ampiroxicam reduces postoperative pain after hand surgery.

We performed a double blind randomised controlled study to assess whether the preoperative administration of ampiroxicam reduced the level of postoperative pain in 120 patients who underwent surgery to a hand under brachial plexus block. We found that preoperative (pre-emptive) administration of ampiroxicam significantly reduced the postoperative pain levels and the need for postoperative analgesia.

Adult↗

Vascular cell adhesion molecule-1 up-regulation and phenotypic modulation of vascular smooth muscle cells predate mononuclear infiltration in transplant arteriopathy.

OBJECTIVE: Expression of embryonic myosin heavy chain isoforms and vascular cell adhesion molecule-1 by neointimal vascular smooth muscle cells are independent indicators of atherosclerotic plaque development in both human beings and experimental animal models. We examined the chronologic change in smooth muscle cell myosin heavy chain isoforms, vascular cell adhesion molecule-1 expression, and mononuclear cell infiltration in a carotid arterial transplant model to ascertain whether similar phenotypic changes would occur in transplant arteriopathy. METHODS: Transplanted rabbit carotid arteries were examined at 7, 14, 21, and 35 days (n = 5, 7, 6, and 5, respectively). Lesion progression and the prevalence of smooth muscle cell myosin heavy chain isoforms, T-lymphocytes, macrophages, and vascular cell adhesion molecule-1 expression were evaluated immunohistochemically by computerized image analysis. RESULTS: In this carotid arterial transplant model, the intima/media area ratio increased significantly by 35 days (P =.01) as cell density decreased (P =.01), suggesting extracellular matrix elaboration. Intimal smooth muscle cells expressing embryonic phenotypes were seen as early as 7 days, a phenotypic change that predated mononuclear cell infiltration of the graft by at least 7 days. By 35 days, up to 70% of intimal smooth muscle cells expressed the embryonic phenotype, coinciding with the transition from inflammatory to chronic lesions. Although, in early lesions, vascular cell adhesion molecule-1 was identified on luminal endothelium overlying mononuclear infiltrates, in advanced lesions vascular cell adhesion molecule-1 was identified primarily on intimal vascular smooth muscle cells. CONCLUSIONS: Overall, these vascular smooth muscle cell changes mark important early events in transplant arteriopathy that may not be ameliorated by immunosuppressive regimens in routine use.

Animals↗

A display of hypomania in a depressed male in response to fluvoxamine.

The present report describes the behavioural and psychological changes in a 55-year-old depressed male who displayed hypomania after the use of fluvoxamine in addition to other antidepressant medications. The patient experienced his first major depressive episode after the bankruptcy of his company. When fluvoxamine was prescribed at a dose of 50 mg/day in addition to sulpiride at 150 mg/day and a 50 mg dose of trazodone before sleep seven months after admission, grinning and a violation of ward rules occurred repeatedly. The patient became verbally aggressive to the staff and addicted to gambling and alcohol. Six days after the cessation of fluvoxamine, his condition remitted. None of the neuromuscular abnormalities indicative of serotonin syndrome appeared during the episode. Upon review of previous reports on manic switches induced by SSRIs and other antidepressants, we speculate that the fluvoxamine accounted for his hypomania.

Bipolar Disorder↗

[A case of septic shock and disseminated intravascular coagulation following transrectal prostatic biopsy].

A 60-year-old man underwent transrectal six sextant ultrasound-guided prostatic biopsy because of gradual elevation of PSA. Despite postoperative use of amikacin, spiking fever developed the next day and after emergency admission (39 hours after the biopsy), his blood pressure decreased to 56/40 mmHg with WBC 800/mm3, platelets 6.9 x 10(4)/mm3 (decreased further to 0.4 x 10(4)/mm3 on the following day) and FDP 51 micrograms/dl. Intensive care including chemotherapy with broad-spectrum antibiotics and endotoxin removal therapy using a polymyxin B immobilized fiber column (PMX), was useful to recover the patient from septic shock and disseminated intravascular coagulation. As the number of systematic prostatic biopsy is increasing rapidly in Japan, more attention must be paid to potential hazards of this procedure.

Biopsy↗

Gene therapy of transplant arteriopathy by liposome-mediated transfection of endothelial nitric oxide synthase.

BACKGROUND: Transplant arteriopathy is the major factor limiting long-term survival after cardiac transplantation. We have previously demonstrated that liposome-mediated gene delivery of endothelial nitric oxide synthase (eNOS) to donor hearts reduces ischemia-reperfusion injury by blocking NFkappaB activation, adhesion molecule expression, and leukocyte infiltration. In this study, we used gene transfer of eNOS in a rabbit carotid transplant model to see whether these same effects would similarly ameliorate transplant arteriopathy. METHODS: Liposomes complexed to the gene encoding eNOS were injected into donor carotid arterial segments that were transplanted orthotopically into recipient carotid arteries (n = 10). Controls included transplanted carotids transfected with liposomes complexed to empty plasmids (no functional gene) (n = 4) and transplanted carotids treated with saline (n = 6). Transplanted arteries were harvested for processing at 21 days. Intima/media (I/M) area ratios were calculated by computerized image analysis. Infiltrating T-lymphocytes and macrophages, and expression of VCAM-1 and ICAM-1 were quantified on immunocytochemistry. RESULTS: The I/M ratio was significantly reduced in eNOS-transfected arteries compared with arteries transfected with empty plasmids and saline-treated controls. Compared to transplanted control arteries, eNOS-transfected arteries demonstrated significantly reduced T-cell infiltration into the intima and significantly reduced macrophage infiltration into the media. Cell surface expression of VCAM-1 and ICAM-1 were both reduced in eNOS-transfected arteries. CONCLUSIONS: ENOS gene delivery can suppress neointimal lesion formation and T-lymphocyte and macrophage infiltration in transplanted arteries, associated with a reduction in relevant adhesion molecule expression. Thus, gene therapy with eNOS may not only reduce ischemia-reperfusion injury but may also ameliorate transplant arteriopathy in transplanted hearts.

Animals↗

[A case of malignant lymphoma of the epididymis].

A 17-year-old man visited our hospital with the chief complaint of painless swelling of the left scrotal content. An elastic hard mass was palpable at the upper pole of the left testis. Left radical orchiectomy was performed. The tumor originated from the epididymis and did not involve the testis or the spermatic cord. Histologically, the tumor was diagnosed as a malignant lymphoma (non-Hodgkin's lymphoma, diffuse mixed cell type, B-cell type). No abnormalities were found in other organs. After establishment of the diagnosis of primary epididymal malignant lymphoma, 3 courses of chemotherapy (adriamycin, vincristine, cyclophosphamide, prednisolone) were performed. No evidence of recurrence or metastasis was found 26 months after surgery.

Adolescent↗

[A case of paravesical foreign body granuloma due to surgical sponge retained for 40 years].

A 67-year-old man complained of vague pain in the lower abdomen persisting over 10 years. A hard mass was palpable just under an operative scar (right Gibson incision for ureterolithotomy performed 40 years previously). In addition to the patient's history and physical examination, abdominal echography, computerized tomography and nuclear magnetic resonance imaging (MRI) were performed and resulted in a preoperative diagnosis of retroperitoneal gauzeoma. The paravesical mass, 7 x 6 x 6 cm in size, was surgically removed, which was an encapsulated granuloma surrounding a surgical sponge. The possibility of foreign body granulomas due to a retained surgical sponge (so-called gauzeomas) should be considered in patients who have a previous history of abdominal operations.

Aged↗

Anesthesia with sevoflurane, but not isoflurane, prolongs bleeding time in humans.

PURPOSE: Halothane has been shown to suppress platelet aggregation in vitro and ex vivo and to prolong bleeding time. In a previous in vitro study, we demonstrated that sevoflurane had a stronger suppressive effect on platelet aggregation than halothane. The present study investigated whether clinical use of sevoflurane affects bleeding time in vivo. METHODS: Thirty-four patients undergoing minor elective surgery were randomly assigned to sevoflurane or isoflurane. Anesthesia was induced with intravenous thiopental and maintained with sevoflurane or isoflurane with nitrous oxide. Bleeding time was measured by the Duke method. An initial (control) measurement was obtained in the operating room before the induction of anesthesia, and a second was obtained 5-10 min after endotracheal intubation but before starting the operation, when the end-expiratory concentration of sevoflurane or isoflurane had been stabilized at 1-1.5 times the minimum alveolar concentration (MAC), and the mean arterial pressures were between 80% and 120% of the preanesthetic values. RESULTS: Bleeding time was increased from the preanesthetic value of 2.07 +/- 0.82 min to 2.83 +/- 0.93 min (n = 15) in the sevoflurane group (P < 0.01) but was not significantly altered in the isoflurane group. CONCLUSION: Sevoflurane alters bleeding time in the clinical situation.

Clinical Trial↗

Severe Acanthamoeba sclerokeratitis in a non-contact lens wearer.

PURPOSE: To report a case of severe Acanthamoeba sclerokeratitis. METHODS: A 70-year-old male non-contact lens wearer was examined for severe pain in the left eye which began about 40 days after cataract surgery. In spite of a careful search, it required 6 weeks to detect Acanthamoeba. Systemic and topical fluconazol and miconazol did not help and the keratitis progressed into necrotic sclerokeratitis with protrusion of uveal tissue through the thin sclera. RESULTS: Those findings slowly got worse before the Acanthamoeba sclerokeratitis resolved 6 months later with scar formation. CONCLUSION: We describe the terminal and cicatricial stages of Acanthamoeba keratitis, and report that the healing process can follow the terminal stage and the eye does not need to be enucleated.

Acanthamoeba↗

Acute mitral valve regurgitation created in sheep using echocardiographic guidance.

BACKGROUND AND AIM OF STUDY: This study was designed to determine: (i) Whether acute mitral valve regurgitation (MVR) due to chordal rupture can be reproducibly created under echocardiographic guidance; (ii) what degree of MVR can be created; (iii) what degree of acute regurgitation is survivable; and (iv) whether acute MVR due to chordal rupture progresses over time. METHODS: In a pilot group of six juvenile farm-bred sheep, selected chordae tendineae were ruptured using either a biopsy needle or endoscopic scissors under echocardiographic guidance, without need for cardiopulmonary bypass. Sheep were sacrificed acutely (n = 2), and at six weeks (n = 2) or eight weeks (n = 2). When the technique was optimized, five sheep entered a study group in which chords were ruptured using endoscopic scissors; the sheep were sacrificed 16 weeks after surgery. RESULTS: In the pilot study, acute MVR (grade 2-4+) was produced in all sheep, normal ventricular wall motion was maintained, with minimal progression of regurgitation over time. In one pilot sheep which did not survive, grade 4+ MVR was created acutely. Use of endoscopic scissors was preferable to the biopsy needle. In the study group, acute MVR (grade 2-4+) was produced in all five sheep, and was still present at 16 weeks, with progression in only one animal. CONCLUSIONS: This pilot study demonstrated that controlled degrees of survivable acute MVR due to chordal rupture can be created under echocardiographic guidance, with minimal progression of MVR over time. This animal model can be applied to investigate the pathogenesis of clinical MVR, and to suggest appropriate medical or surgical intervention.

Acute Disease↗

[A case of metastatic tumor of spermatic cord with hydrocele from gastric cancer].

A 70-year-old man, who had undergone total gastrectomy for Borrmann III gastric cancer one year previously, was referred to us with a complaint of left scrotal swelling. Physical examination showed left scrotal hydrocele and a hard nodule in the ipsilateral inguinal area. Excretory pyelography and abdominal computed tomography showed mild left hydronephrosis and no stone. A left orchiectomy was performed. The mass in the spermatic cord was 2.5 x 1.0 x 1.0 cm in size, and the pathological diagnosis was tubular adenocarcinoma, identical to that of the previous gastric cancer. Five months after orchiectomy, the patient underwent percutaneous nephrostomy to manage postrenal renal failure caused by massive metastasis of retroperitoneal lymph nodes. He died one month later. We found a total of 84 cases of metastatic tumors of the spermatic cord reported in Japan, approximately half of which were metastases from gastric cancer. In 10 cases, including ours, the tumor was accompanied by hydrocele of the scrotum or spermatic cord. Although this association is rare, cancerous lesions should be considered in the management of hydrocele.

Adenocarcinoma↗

Intracellular calcium changes and chemosensitivities of human epidermoid carcinoma cell lines after exposure to cisplatin.

In order to elucidate the mechanisms of cisplatin (cis-diamminedichloroplatinum; CDDP)-resistant tumor cells, we previously established a CDDP-resistant KB cell line (KBrc cells) from a parental KB cell line derived from epidermoid carcinoma (KB cells). The KBrc cells were resistant to 5 kinds of platinum (Pt) drugs. Intracellular Pt concentrations in KBrc cells were lower than in KB cells. Decrease of intracellular Pt concentrations was one of the CDDP-resistant mechanisms. When we measured changes of intracellular calcium ion concentration ([Ca2+]i) during exposure to high-dose CDDP, a sustained elevation of the [Ca2+]i level was observed in the KB cells. These results suggest that the mechanisms underlying CDDP resistance involve changes in calcium channels and an alteration of calcium homeostasis in the tumor cell line.

Antineoplastic Agents↗

[Migration of surgical sponge retained at transvaginal hysterectomy into the bladder: a case report].

Urge incontinence and frequency, persisting despite oral anticholinergics and antibiotics for four months, brought a 72-year-old woman to our hospital. Plain abdominal X-ray followed by cystoscopy demonstrated a large stone (43 x 37 mm) in the bladder, and the patient underwent suprapubic cystotomy to remove the stone. The stone contained a surgical sponge, which was apparently left in situ at transvaginal hysterectomy two years previously. The sponge had most likely eroded the bladder wall and migrated into the cavity. We found a total of 17 cases reported in Japan of a surgical sponge migrating into the bladder. In particular, our case was associated with transvaginal surgery, while the other 16 cases involved transabdominal surgery.

Aged↗

Prolonged allogeneic and xenogeneic microchimerism in unmatched primates without immunosuppression by intrathymic implantation of CD34+ donor marrow cells.

Engraftment of stem cell-enriched donor marrow implanted in the thymus of a foreign host might facilitate acceptance of donor-specific organ or tissue grafts. To test this hypothesis, allogeneic and xenogeneic CD34+ marrow cells from unrelated adult male baboons and humans were injected intrathymically in eight infant female baboons, both with and without standard cyclosporine-based immunosuppression. In allogeneic experiments, male (donor) cells, of both T- and B-cell lineages, were detected by PCR in the peripheral blood of all six recipients and persisted for at least 15 months in 2/4 recipients studied longtutudinally. Donor-derived skin grafts survived twice as long as third party grafts in unimmunosuppressed recipients. In xenogeneic protocols, human male (donor) cells were demonstrable for 7 and 15 months, respectively, in two baboon recipients with evidence that implanted human CD34+ cells had produced lymphoid progeny. Survival of donor-specific skin xenografts was prolonged in one of two recipients. These experiments demonstrate that the intrathymic injection of CD34+ marrow cells can result in long-lasting lymphohematopoietic microchimerism in unrelated primates even without immunosuppression and can alter donor-specific skin graft survival.

Animals↗

Platelet aggregation is impaired during anaesthesia with sevoflurane but not with isoflurane.

PURPOSE: Halothane suppresses platelet aggregation in vitro and ex vivo, and prolongs bleeding time. In a previous in vitro study we demonstrated that sevoflurane had a more suppressive effect on platelet aggregation than did halothane. The present study investigated whether the clinical use of sevoflurane affected platelet aggregation ex vivo. METHODS: Thirty-eight patients undergoing minor elective surgery were divided randomly into sevoflurane and isoflurane groups. Anaesthesia was induced with thiopentone i.v., and was maintained with sevoflurane or isoflurane with nitrous oxide. Blood was collected to measure platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine. The first (control) blood collection was performed in the operating room before induction of anaesthesia, and the second 5-10 min after tracheal intubation but before the start of surgery, when the end-expiratory sevoflurane or isoflurane concentrations had stabilised at 1-1.5 times the minimum alveolar concentration (MAC) and mean arterial pressures were between 80-120% of preanaesthetic values. RESULTS: In all samples obtained during sevoflurane anaesthesia (n = 15), ADP and epinephrine could not induce secondary aggregation, although they did induce primary aggregation. In contrast, in the isoflurane group, both primary and secondary aggregation were observed in 14 out of 15 patients, and secondary aggregation was abolished in only one of the samples obtained during anaesthesia. CONCLUSIONS: Sevoflurane, but not isoflurane, alters platelet aggregation in the clinical situation, possibly by suppression of thromboxane A2 formation.

Adult↗