The roles of von Willebrand factor and factor VIII in arterial thrombosis: studies in canine von Willebrand disease and hemophilia A

We have studied the roles of von Willebrand factor (vWF) and factor VIII in arterial thrombosis in four canine phenotypes: normal (n = 6), hemophilia A (n = 11), von Willebrand disease (vWD) (n = 9), and hemophilia A/vWD (n = 1). vWF activity was determined by botrocetin- induced agglutination of fixed human platelets and vWF antigen (vWF:Ag) by Laurell electroimmunoassay and crossed immunoelectrophoresis. Plasma from normal dogs and those with hemophilia A had vWF activity, vWF:Ag, and a full range of vWF:Ag multimers on gel electrophoresis equivalent to normal canine plasma pool. Platelet cytosol contents were isolated by freezing and thawing, triton X-100 solubilization, or sonication of washed platelets with and without protease inhibitors and inhibitors of platelet activation. Washed platelets were also stimulated with calcium ionophore and MgCl2. There was no measurable vWF activity or vWF:Ag in platelet lysates or releasates in any dog regardless of phenotype. All dogs were studied using a standard arterial stenosis and injury procedure to induce arterial thrombosis. Thromboses were detected by cyclic reductions in Doppler blood flow velocity. Vessels were examined by light and scanning electron microscopy. Thrombosis developed in the arteries of normal (9 of 10) and hemophilia A dogs (16 of 16) but in none of the vWD dogs (0 of 10). Infusion of canine vWF cryoprecipitate into vWD dogs markedly shortened bleeding time but did not support thrombosis as seen in dogs with vWF in the plasma and subendothelium. Thrombosis, then, fails to occur when vWF is absent from the plasma and subendothelial compartments or present only in the plasma compartment. These data are consistent with the hypothesis that vWF in the plasma and subendothelium supports thrombosis. Neither plasma FVIII nor platelet vWF is essential for thrombosis in this model.     

Surgical checklist application and its impact on patient safety in pediatric surgery

Background:

Surgical care is an essential component of health care of children worldwide. Incidences of congenital anomalies, trauma, cancers and acquired diseases continue to rise and along with that the impact of surgical intervention on public health system also increases. It then becomes essential that the surgical teams make the procedures safe and error proof. The World Health Organization (WHO) has instituted the surgical checklist as a global initiative to improve surgical safety.

Aims:

To assess the acceptance, application and adherence to the WHO Safe Surgery Checklist in Pediatric Surgery Practice at a university teaching hospital.

Materials and Methods:

In a prospective study, spanning 2 years, the checklist was implemented for all patients who underwent operative procedures under general anesthesia. The checklist identified three phases of an operation, each corresponding to a specific period in the normal flow of work: Before the induction of anesthesia (“sign in”), before the skin incision (“time out”) and before the patient leaves the operating room (“sign out”). In each phase, an anesthesiologist,-“checklist coordinator”, confirmed that the anesthesia, surgery and nursing teams have completed the listed tasks before proceeding with the operation and exit. The checklist was used for 3000 consecutive patients.

Results:

No major perioperative errors were noted. In 54 (1.8%) patients, children had the same names and identical surgical procedure posted on the same operation list. The patient identification tag was missing in four (0.1%) patients. Mention of the side of procedures was missing in 108 (3.6%) cases. In 0.1% (3) of patients there was mix up of the mention of side of operation in the case papers and consent forms. In 78 (2.6%) patients, the consent form was not signed by parents/guardians or the side of the procedure was not quoted. Antibiotic orders were missing in five (0.2%) patients. In 12 (0.4%) cases, immobilization of the patients was suboptimal, which led to displacement of diathermy grounding pad. In 54 (1.8%) patients, the checklist was not used at all. In 76 (2.5%) patients the checklist was found to be incompletely filled.

Conclusions:

Our study supports the use of the checklist as an essential safety tool and reinforcement of the same. The checklist may act as a valuable prompt to focus the team, to ensure that even the simple things have been cared for.KEY WORDS: Adverse events, checklist, communication, patient safety     

High serum and ascitic soluble interleukin-2 receptor alpha levels in advanced epithelial ovarian cancer [see comments]

This study was undertaken to determine if advanced epithelial ovarian cancer was associated with increased serum and ascitic levels of soluble interleukin-2 receptor alpha (sIL-2R alpha). Serum and ascitic fluid samples from 23 ovarian cancer patients were analyzed for sIL-2R alpha using an enzyme-linked immunosorbent assay and compared with the serum and peritoneal levels in 18 normal females. The samples were analyzed for CA-125 levels using a radioimmunoassay and the total protein was also measured. Normal individuals had low serum levels of sIL-2R alpha (367.5 +/- 44.6 U/mL), with similar levels of sIL-2R alpha in the normal peritoneal fluid (438.6 +/- 48.8 U/mL). In contrast, the serum and ascitic fluid levels in ovarian cancer patients were significantly higher (746.7 +/- 82.9 U/mL, P = .0006; 2,656.7 +/- 373.7 U/mL, P = .00002, respectively). The results for sIL-2R alpha were also significant when the levels were expressed per milligram of total protein. More importantly, in almost every ovarian cancer patient the ascitic sIL-2R alpha level far exceeded the serum level, a pattern also observed for CA-125. There was no correlation between the serum and ascitic sIL-2R alpha levels, or between the serum and ascitic CA-125 levels. Although the serum levels of sIL-2R alpha and CA-125 were elevated in the same patient, overall there was no correlation between the serum sIL-2R alpha and serum CA-125 levels, either when the levels were expressed in absolute units or per milligram of total protein. Similarly, there was no correlation between sIL-2R alpha and CA-125 levels in individual ascitic samples. While CA-125 levels may reflect an independent index of tumor burden, these results suggest that selective accumulation of sIL-2R alpha in the ascites may be one of the factors associated with the known nonresponsiveness of the infiltrating lymphocytes against ovarian carcinoma cells.     

Attitudes and treatment outcome of breast conservation therapy for stage I & II breast cancer using peroperative iridium‐192 implant boost to the tumour bed

Breast conservation therapy for early breast cancer is an established but grossly under‐utilized treatment option in India for various reasons. Breast conservation therapy was offered to 200 suitable breast cancer patients between June 1993 and June 1998. Fifty‐one patients (25%) opted for breast conservation and the remaining preferred mastectomy. In patients agreeing to conservation therapy, surgery was performed first along with peroperative implantation of iridium‐192 to deliver a boost. Whole breast irradiation of 45 Gy was delivered 3–4 weeks after the boost. Cosmesis was assessed at the end of 6 months from completion of therapy. The main reason for refusal of breast conservation therapy was fear of recurrence in the remaining breast (60%). There were no locoregional failures in our study at a median follow up of 42 months; one patient experienced a systemic relapse. Cosmesis was good to excellent in 80% of patients. Breast conservation therapy using peroperative iridium‐192 implant provides excellent locoregional disease control and cosmesis. The results of our study indicate that patient preference for mastectomy is an important reason for the under‐utilization of breast conservation therapy in India.     

Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype

Background  

According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI), ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI), and ADHD combined type (ADHD-C). These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI).