Safety and efficacy of hysteroscopic endomyometrial resection-ablation for menorrhagia.

OBJECTIVE: To assess the safety and efficacy of endomyometrial resection-ablation as a surgical means of treating patients with chronic, debilitating menorrhagia. STUDY DESIGN: A retrospective review was carried out of the records of 70 consecutive women of reproductive age who had severe uterine bleeding, who did not wish to retain their reproductive potential and who were managed uniformly at Wyckoff Heights Medical Center from July 1993 to March 1999 by operative hysteroscopy and endomyometrial resection-ablation under laparoscopic control. Demographic data were collected, and details of the clinical course were assessed for complications of the procedure. The patients were followed for an average of 24 months to evaluate how effective this technique was for correcting the bleeding problem. RESULTS: Immediate postoperative amenorrhea occurred in nearly all cases (97.1%). It lasted for only three months in most cases, but persisted for as long as eight months in a small number (5.7%). Some degree of hypomenorrhea was reported for as long as eight months in 88.6%. Overall, almost every women reported feeling better (94.3%). Uterine perforation occurred in 8.6%, one case of which was compounded by bladder and ureteral injury. One patient experienced fluid overload. Histopathologic examination of the endometrium obtained intraoperatively showed the range of benign conditions that were associated with the bleeding problems for which these women had sought care. CONCLUSION: Operative hysteroscopy and endomyometrial resection-ablation was safe and effective for surgical management of persistent, severe menorrhagia. Patients were largely satisfied with the results. Transient amenorrhea and hypomenorrhea occurred frequently. There was a satisfactory correlation between preoperative and postoperative histopathologic findings. No endometrial malignancy was missed. Fluid overload was almost entirely averted as a significant complication.

Transmembrane TNF (pro-TNF) is palmitoylated.

Human transmembrane tumor necrosis factor (pro-TNF) was examined for protein acylation. The cDNA encoding pro-TNF was expressed in both COS-1 cells and Sf9 cells and metabolic labeling with [(3)H]myristic or [(3)H]palmitic acid was attempted. The 17 kDa mature TNF secreted from the transfected cells was not labeled, whereas the 26 kDa pro-TNF was specifically labeled with [(3)H]palmitic acid. The [(3)H]palmitic acid labeling of pro-TNF was eliminated by treatment with hydroxylamine, indicating that the labeling was due to palmitoylation of a cysteine residue via a thioester bond. Site-directed mutagenesis of the two cysteine residues residing in the leader sequence of pro-TNF demonstrated that palmitoylation of pro-TNF occurs solely at Cys-47, located at the boundary between the transmembrane and cytoplasmic domains of pro-TNF. Thus, pro-TNF interacts with the plasma membrane via both its proteinaceous transmembrane domain and a lipid anchor.

A part of the transmembrane domain of pro-TNF can function as a cleavable signal sequence that generates a biologically active secretory form of TNF.

To determine the minimum requirement in the 76-residue leader sequence of pro-tumor necrosis factor (TNF) for membrane translocation across the endoplasmic reticulum (ER) and for the maturation of pro-TNF, we constructed pro-TNF mutants in which a part of the transmembrane domain of pro-TNF was directly linked to the N-terminus of the mature domain, and evaluated their translocational behavior across the ER-membrane and their secretion from the transfected cells. The in vitro translation/translocation assay involving a canine pancreatic microsomal membrane system including a mutant, Delta-75-47, -32-1, revealed that the N-terminal half of the transmembrane domain of pro-TNF consisting of 14 residues functioned as a cleavable signal sequence; it generated a cleaved form of TNF having a molecular mass similar to that of mature TNF. Analysis of the cleavage site by site-directed mutagenesis indicated that the site was inside the leader sequence of this mutant. When the mutant, Delta-75-47, -32-1, was expressed in COS-1 cells, efficient secretion of a biologically active soluble TNF was observed. Further deletion of the hydrophobic domain from this mutant inhibited the translocation, indicating that some extent of hydrophobicity is indispensable for the membrane translocation of the mature domain of TNF. Thus, the N-terminal half of the transmembrane domain of pro-TNF could function as a cleavable signal sequence when linked to the mature domain of TNF, and secretion of a biologically active secretory form of TNF could be achieved with this 14-residue hydrophobic segment. In intact pro-TNF, however, this 14-residue sequence could not function as a cleavable signal sequence during intracellular processing, indicating that the remainder of the 76-residue leader sequence of pro-TNF inhibits the signal peptide cleavage and thus enables the leader sequence to function as a type II signal-anchor sequence that generates a transmembrane form of TNF.

Endometriosis is not detrimental to embryo implantation in oocyte recipients.

PURPOSE: Our purpose was to determine the effects of endometriosis on implantation and pregnancy rates in ovum recipients. METHODS: The medical records of 239 consecutive oocyte recipient patients who were treated between January 1, 1991, and June 30, 1995, were analyzed retrospectively. Recipients with endometriosis (group 1; n = 55) were compared to recipients without endometriosis (group II; n = 184). Patients in group I had active endometriotic disease confirmed by laparoscopy and were subdivided into mild (Stages I and II; n = 18) and moderate to severe (Stages III and IV; n = 37) endometriosis. RESULTS: No difference was found in recipient age, endometrial thickness, donor age, and embryos transferred. The pregnancy rates (28 versus 29%) and implantation rates (12 and 13%) were also comparable between group I and group II, as well as between patients with mild and patients with moderate to severe endometriosis. CONCLUSIONS: The presence of endometriosis in oocyte recipients does not lower implantation or pregnancy rates. We conclude that the adverse effect of endometriosis on reproductive outcome is not related to implantation but, in fact, is most likely an effect on oocyte or embryo quality.

A simple method for the determination of YM060 in plasma and urine by high performance liquid chromatography.

We developed a simple method for the determination of YM060, a new 5-HT3 receptor antagonist, in plasma and urine. The method has good accuracy and precision, and sufficient sensitivity to allow use in pharmacokinetic studies of YM060 in humans and laboratory animals.

Paroxysmal nocturnal hemoglobinuria with myelofibrosis: progression to acute myeloblastic leukemia.

A 58-year-old male was diagnosed as having paroxysmal nocturnal hemoglobinuria (PNH) with myelofibrosis in 1984. The administration of hydroxyurea and low dose splenic irradiation were initiated for abdominal distention due to splenomegaly in 1987. In May 1990 the patient developed smouldering acute myeloblastic leukemia (AML); and the blasts proliferated in response to G-CSF administered for refractory pneumonia. The patient died of pneumonia and pleural involvement of leukemia in September 1990. FACS analysis of the blasts using anti-decay accelerating factor (DAF) (CD55) and CD59 (membrane attack complex inhibition factor: MACIF) monoclonal antibodies demonstrated that 25.5% and/or 87.3% of the blasts were negative for DAF or CD59 respectively. There is the earlier evidence that about 90% leukemic myeloblasts from non-PNH AML patients are positive for DAF, and nearly 100% of non-PNH neutrophils have been shown to be positive for both DAF and CD59. Our data suggest that the leukemic blasts from this patient may have derived from the PNH clone.

[Reevaluation of the unilateral pulmonary artery occlusion test--hemodynamics after lobectomy and pneumonectomy for lung cancer].

After lobectomy, it is recognized that functional as well as absolute reduction occurs in residual lobes of the operated side. So whether lobectomy is indicated or not is determined by the same criteria as those for pneumonectomy, namely, by the unilateral pulmonary artery occlusion (UPAO) test. However, is it really appropriate to use the same criteria for both lobectomy and pneumonectomy? To answer to this question, in patients with lung cancer we compared the hemodynamics after lobectomy (13 cases) and pneumonectomy (14 cases) with that at the UPAO test. After pneumonectomy, the mean pulmonary arterial wedge pressure (mPWP) was significantly lower than that on the preoperative day and at the test. It seemed that hypovolemic change occurred in the hemodynamics after pneumonectomy. After pneumonectomy, the pulmonary arteriolar resistance index (PARI) was significantly higher than the preoperative value. It was the same as that as at the time of the UPAO test. The total pulmonary vascular resistance index (TPVRI) at the time of the test was significantly higher than the preoperative value, but the TPVRI after pneumonectomy was not significantly higher. The TPVRI tended to decrease after pneumonectomy, compared to the value predicated by the test. These results indicated that some of the cases judged inoperable on the basis of the UPAO test might be operable. On the day of lobectomy, the PARI was significantly higher than the preoperative value, but significantly lower than that at the time of the test. The cardiac index (CI) was significantly higher and the mPWP was significantly lower than each preoperative value.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary Thrombocythemia in Japan: A Survey of 225 Patients.

Data on 225 Japanese patients with primary or essential thrombocythemia (ET) were analyzed in an attempt to characterize the clinical and laboratory features in subgroups with thrombosis (T), hemorrhages (H), thrombohemorrhagic events (TH) or a non-thrombohemorrhagic (O) group, and in order to examine survival and the incidence of blastic transformation in the entire group and in the different subgroups. Higher platelet and leukocyte counts were related to hemorrhage (H and TH), prolonged activated partial thromboplastin times and high LDH levels to H while elevated FDP levels were more frequently linked to T. Increased spontaneous platelet aggregation (SPA) was noted in 80.3% of the entire group, independent of whether there was a tendency for thrombohemorrhagic events or not. Bleeding time, as measured by the Duke method, and hemoglobin levels were not different in the various subgroups. Transformation occurred in 11 patients (1.9% per year); seven developed acute leukemia (myeloblastic 4, lymphoblastic 2, megakaryoblastic 1) at a rate of 1.2% per year; and 4 developed other types of chronic myeloproliferative disorders. Nineteen patients died (3.3% per year), six from leukemia (32%), 4 from bleeding (21%) and 9 from unrelated diseases (47%). Survival was estimated to be 65% at ten years, and was significantly longer in females, younger individuals, and the groups with lower leukocyte counts, but did not differ between the subgroups when platelet count and hemoglobin level were considered. Survival was similar in patients with platelet counts between 700-1000 × 10(9)/L and in those with an even higher platelet count. These findings suggest that (1) young female patients with low leukocyte counts may survive longer, (2) SPA is not indicative of either a thrombotic or an hemorrhagic tendency and (3) the limit of the platelet count for establishing the diagnosis of this disorder could perhaps be lowered to 700 × 10(9)/L.

A defect of platelet release reaction in a patient with SLE: impaired platelet aggregation induced by phorbol ester with a normal phosphorylation of 40K protein.

A 37-year-old female who suffered from SLE had a bleeding disorder. At the time of initial evaluation, the main disease demonstrated was a delta-storage pool deficiency. After this improved, a marked decrease of aggregation still remained, when induced by either ADP, epinephrine, collagen, A23187, thrombin, or PAF-acether. Although arachidonate-induced aggregation was slightly decreased, thromboxane B2 was produced normally in response to exogenous arachidonate. The patient's endoperoxides and/or thromboxane A2 aggregated aspirin-treated platelets, though her platelets were themselves unresponsive. Impaired aggregability induced by TPA (12-0-tetradecanoylphorbol-13-acetate) or OAG (1-oleoyl-2-acetyl-glycerol) was also found. However, the phosphorylation of P43 and P20 induced by several stimulators including CA++ ionophore was normal, using 32P-labelled platelets. It is suggested that TPA or OAG-induced platelet aggregation requires not only the phosphorylation of those proteins, but also another unknown mechanism after the phosphorylation, and that the platelet dysfunction of this patient was due to a defect of some mechanism involving Ca++ uptake or mobilization of cytoplasmic Ca++ from intracellular storage sites.