Superior sagittal sinus thrombosis after spinal anesthesia

Superior sagittal sinus thrombosis is an uncommon phenomenon that could occur in patients with a risk for thrombosis. It has been reported after spinal anesthesia with persistent cerebrospinal fluid leak. The current case is a young 29-year-old man who was complaining of persistent headache after spinal anesthesia for varicocelectomy and a new onset of blurred vision with a sign of papilledema. The diagnosis was confirmed with magnetic resonance imaging and proved to be superior sagittal sinus thrombosis. He was started on anticoagulant therapy and showed gradual improvement. No previous case has been reported in the literature in a patient without prothrombotic status risk. Received 8th January 2020. Accepted 26th March 2020.

Cerebral venous sinus thrombosis (CVT) is an uncommon alarming pathological process. Moreover, women affected more commonly than men and the incidence in annual basis is about 0.9 per 100,000.1,2 It commonly occurs secondarily to a genetic or acquired hypercoagulable state such as pregnancy, malignancy, infection, trauma, mechanical heart valve, and oral contraceptive use.3 Cerebral venous sinus thrombosis has variable clinical presentations. The most common presenting symptom is headache that can be accompanied with vomiting, papilledema, visual disturbance, and/or focal neurological syndrome such as focal neurological deficit with or without seizures. It can also associate with mental status changes such as stupor or with coma in some occasions.2,3The positional headache considered as the common presenting neurological symptoms after spinal anesthesia, and it occurs in 10 to 30% of patients. The mechanism behind it, is secondary to persistent cerebrospinal fluid leakage after epidural anesthesia. The course of the headache is usually benign in nature with almost complete recovery a few weeks. A rare complication can occur, which is secondary to brain stem compression such as subdural hygroma and neurological deficits.4 It has been reported that CVT rarely occurs in post-partum women after epidural anesthesia who have a tendency for thrombosis secondary to hypercoagulable state.4 Herein, we report a rare occurrence of superior sagittal sinus thrombosis in a healthy young man without prothrombotic status who underwent a day surgery procedure with microscopic varicocele ligation, which was performed under spinal anesthesia.     

Antitumor activity of a new orally active organotin compound: a preliminary study in murine tumor models

The toxicity and antitumor activity of the novel organotin compound triethyltin(IV)lupinylsulfide hydrochloride (IST-FS 29), administered by the oral route, have been evaluated against three transplantable murine tumor models: P388 lymphocytic leukemia, B16F10 melanoma and 3LL Lewis lung carcinoma. Mild and reversible signs of acute toxicity such as behavioral symptoms, weight loss and histological alterations were mainly reported at the highest single dose of 28 mg/kg. Conversely, lower concentrations of compound ranging from 7 to 21 mg/kg did not result in major toxic effects, even after repeated dosing. The antitumor activity studies showed that fractionation dosing, rather than single bolus administration, over 1 week, might prove more active and better tolerated by allowing the achievement of the highest therapeutic total dose of IST-FS 29 (42 mg/kg). Indeed, repeated administrations of IST-FS 29 resulted in marked significant improvement of antitumor activity against B16F10 (50% of tumor volume inhibition, p = 0.0003) and, to a greater extent, 3LL (90% of tumor volume inhibition, p = 0.0001) tumors. These results indicate that IST-FS 29 might be a suitable candidate as an orally administrable anticancer drug and support its further development in human tumor xenografts.     

Pulling strings below the surface: hormone receptor signaling through inhibition of protein tyrosine phosphatases

Hormones, cytokines, and related proteins (such as soluble hormone receptors) play an important role as therapeutic agents. Most hormone receptors signal through a mechanism that involves phosphorylation of the receptor's tyrosine residues. At any given moment, the receptor's phosphorylation state depends on the balance of kinase and phosphatase activities. Recent findings point to the exciting possibility that receptor signaling can be regulated by inhibition of protein tyrosine phosphatases (PTPs) that specifically hydrolyze receptor tyrosine-phosphates, or their immediate downstream effectors. This strategy has now been firmly validated for the insulin receptor and PTP1B; inhibiting PTP1B activity results in stimulation of the insulin receptor and signaling, even in the absence of insulin. This and similar findings suggest that PTP inhibitors have potential as hormone mimetics. In the present review, we outline this new paradigm for therapeutic regulation of the insulin receptor and discuss evidence that hints at other specific receptor-PTP pairs.     

Unsymmetrical methylene derivatives of indoles as antiproliferative agents

Indole-3-carbinol is a natural product which has been shown to reduce the incidence of spontaneous and carcinogen-induced mammary tumours in animals. Eighteen unsymmetrical methylene derivatives of indoles were prepared by reaction of Mannich bases of 7-hydroxycoumarins with substituted indoles in acetic or propionic anhydride. The synthesised molecules were tested in vitro against the MCF7 and MDA-MB-231 breast cancer cell lines by MTT and cell count assays. Results from 16 tested compounds showed that 60% of them exerted some effects against the MDA-MB-231 compared to about 30% towards the MCF7. Among all, the 3-(7'-acetoxy-4-methylcoumarin-8'-yl)methyl-2-methylindole resulted the most effective in both cell lines, compared to indole-3-carbinol. In conclusion, these preliminary results report that some of these compounds might be promising potential antiproliferative agents.     

Intraperitoneal cytosine arabinoside administered in sequence with systemic cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer

After standard management of stage III-IV ovarian cancer patients by surgical reduction of tumor mass and subsequent cisplatin-based combination chemotherapy, eradication of residual intraabdominal disease remains a major clinical problem. In an effort to increase response to therapy without adding marrow toxicity, after laparotomy, 21 stage III-IV ovarian cancer patients were treated with systemic chemotherapy comprising cisplatin, doxorubicin, and cyclophosphamide (PAC) on Day 1 followed by intraperitoneal (ip) cytosine arabinoside (Ara-C) on either Day 8 or 14, every 28 days. Ara-C, an S-phase-specific drug, was administered ip to exploit the pharmacologic advantage of an ip regimen at a time when a possible PAC-induced recruitment of cells into the proliferative pool could further maximize cell kill. Kinetic features of ovarian neoplastic cells recovered from peritoneal washings were monitored during treatment by measurement of the thymidine labeling index (TLI): data from four patients indicate that there is an increase in proliferating cells on Days 8 and 14 after PAC treatment. Toxicity of treatment was acceptable. Although 95% of evaluable patients had more than 2 cm of residual disease, response was observed in 47% of patients. The therapeutic potential of this regimen should be tested in patients with small-volume disease after debulking surgery.     

In vitro cytotoxic activity of tri-<Emphasis Type="Italic">n</Emphasis>-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) and preliminary antitumor activity in vivo

Summary  The cytotoxicity in vitro and antitumor activity in vivo of the organotin compound tri-n-butyltin(IV)lupinylsulfide hydrogen fumarate (IST-FS 35) have been investigated. The IC50 values obtained in a panel of tumor cell lines were compared to those of the parental compound IST-FS 29 in the same cells. IST-FS 35 resulted significantly more active than IST-FS 29 with IC50 values in the range 0.16–1.8 μM. Toxicity studies in vivo, after intravenous administration of escalating concentrations of IST-FS 35, provided the identification of the maximal tolerated dose (3.5 mg/kg) which was employed as therapeutic dose in the antitumor activity experiments. Preliminary results, in transplanted murine tumor models, revealed that both the P388 myelomonocytic leukaemia and the B16-F10 melanoma, implanted subcutaneously in BDF1 mice, were inhibited about 96% in their tumor volume at day 11, following a single intravenous injection of the compound. Additional studies are mandatory to unravel the mechanism of action for the development of IST-FS 35 as potential antitumor drug.