Doxorubicin-conjugated biodegradable polymeric micelles having acid-cleavable linkages.

Doxorubicin was chemically conjugated to the terminal end of a di-block copolymer composed of poly(L-lactic acid) (PLLA) and methoxy-poly(ethylene glycol) (mPEG) via two acid-cleavable linkages. A hydrazone bond and a cis-acotinyl bond were formed between doxorubicin and the terminal group of PLLA segment in the block copolymer. Doxorubicin-conjugated PLLA-mPEG di-block copolymers self-assembled to form micelles in aqueous solution. The doxorubicin-conjugated micelles were about 89.1 nm in diameter and their critical micelle concentration was 1.3 microg/ml. These values were comparable with those of unconjugated micelles. In an acidic condition, the conjugated doxorubicin in the hydrazone linkage was readily cleaved, releasing doxorubicin in an intact structure. Doxorubicin-conjugated PLLA-mPEG micelles were more potent in cell cytotoxicity than free doxorubicin, suggesting that they were more easily taken up within cells with concomitant rapid release of cleaved doxorubicin into the cytoplasm from acidic endosomes.     

Susceptibility of mast cell-deficient W/Wv mice to Cryptosporidium parvum.

Mast cell-deficient W/Wv infant mice were similar to normal mice in their susceptibility to and recovery from infection with the intestinal protozoan Cryptosporidium parvum. W/Wv adult mice were significantly more susceptible to primary infection than were normal adult mice, but both groups recovered at a similar rate.     

The relationship of the extrinsic blood supply to regeneration in graft reconstructed peripheral nerves

Median nerves of rats were reconstructed with conventional or vascular nerve grafts. After 2, 3 and 4 weeks, Allen Video-Enhanced Contrast, Differential Interference Contrast (AVEC-DIC) microscopy revealed axonal transport in most preparations, with varying degrees of myelination. Radio-isotope tracer was measured in the nerve. Two and 4 week measurements revealed no difference between the graft types. At 3 weeks the vascular graft group exhibited transport along the entire length of the nerve in contrast to a relatively abbreviated path length in the conventional graft group. Nerve conduction velocities (NCV) were measured proximal to, within and distal to the grafts. Three week NCV showed no difference between the graft types. The 4 week NCV revealed normal values in the vascular graft group at points distal to and within the graft. Significant slowing was seen in the conventional grafts at both points.     

Umbilical portion of recipient's left portal vein: a useful vascular conduit in dual living donor liver transplantation for the thrombosed portal vein.

We considered performing living donor liver transplantation (LDLT) in a larger-size recipient. When the recipient was large-sized, or when the donor liver was severely steatotic or had a right-to-left volume discrepancy. We devised dual living donor liver transplantation (DLDLT) to make up for graft size insufficiency and to secure the donor's safety. However, portal vein thrombosis (PVT) presented a challenge for DLDLT because of the need for intact right and left portal veins for the implantation of both liver grafts. Our 52-year-old male patient with hepatitis B cirrhosis had suffered from repeated esophageal and gastric variceal bleeding and underwent 2 trials of a transjugular intrahepatic portosystemic shunt (TIPS). He developed TIPS occlusion and PVT involving the area just above the spleno-mesenteric confluence to the right and left PV. Also, the right PV orifice was destructed and difficult to isolate because of severe periportal inflammation and neointima growth in the TIPS mesh. The patient's two sons were inadequate for donation because of right-to-left volume discrepancy. Therefore, DLDLT using 2 left lobes was necessary to compensate for graft-size insufficiency and to secure donor safety, and we substituted an intact umbilical portion of recipient's left PV for the destroyed right PV. The patient recovered well, and liver function has been normal for more than a year. In conclusion, the umbilical portion of recipient's left PV can be a useful vascular substitute for the reconstruction of a thrombosed main portal branch in DLDLT.     

Cyclin E, p27 and mutant p53 do not predict the prognosis in AJCC stage II colorectal carcinomas.

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.     

Plasma C-peptide and cognitive performance in older men without diabetes.

BACKGROUND: Emerging evidence suggests that type 2 diabetes may be related to diminished cognition, but little data are available directly regarding the role of insulin levels. OBJECTIVE: The objective of this prospective cohort study was to examine the relation of insulin secretion to cognitive function among men without diabetes. SETTING: The study setting was the Physicians' Health Study-U.S. male physicians. PARTICIPANTS: Three hundred sixty-seven men who provided blood samples in 1982, when they had no lifetime history of diabetes and ranged in age from 47-65 years (mean age: 57 years). MEASUREMENTS: The authors assayed plasma C-peptide, reflecting insulin secretion, in the stored blood samples. Beginning in 2001, an average 18 years after blood collection, the authors administered telephone interviews, including tests of general cognition (Telephone Interview of Cognitive Status [TICS]), verbal memory, and category fluency. The authors used regression models to estimate mean differences in cognitive performance across levels of C-peptide controlling for a wide variety of potential confounding factors. RESULTS: On the TICS, men in the top tertile of C-peptide performed significantly worse than those in the bottom (multivariable-adjusted mean difference: -1.01 points, 95% confidence interval: -1.78 to -0.24); this apparent impact of C-peptide on cognition was equivalent to the cognitive differences the authors observed between men 6 years apart in age. Performance on the global score (combining results from all the individual tests) and verbal memory score (combining results from four tests of verbal memory) appeared lower among men in the highest C-peptide tertile, but results were not statistically significant. CONCLUSION: Higher midlife insulin secretion may be related to decreased later-life cognitive function, even among men without diabetes.     

Benign osteoblastoma of the occipital bone: Case report and literature review

We present a case of benign osteoblastoma of the occipital bone. Benign osteoblastoma is an uncommon primary bone tumor, which usually involves the vertebrae and the long bones. This tumor rarely develops in the calvaria, showing a preference for the temporal and frontal bones when it does. To the best of our knowledge, this case is only the eighth reported case of benign osteoblastoma confined to the occipital bone. A 20‐year‐old male presented with a mild tender mass lesion of the occipital area, just below the lambda. Plain X‐ray films and CT scans demonstrated an osteolytic mass surrounded by the sclerotic rim within the diploic space. MRI proved to be effective for the evaluation of the intracranial and intraosseous extensions of the tumor. However, it was very difficult to formulate a differential diagnosis against other osteoblastic tumors, or osteoid osteoma, in view of its radiological appearance. The final diagnosis was obtained by careful consideration of the histopathological characteristics of the tumor combined with its clinical and radiological features. Although generally regarded as benign, a complete resection is preferred over conventional curettage as this can guard against possible recurrence and malignant transformation.     

Reproducibility of angiotensin converting enzyme inhibitor induced cough: A double-blind randomised study

1 The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect.

2 Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out.

3 Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made.

4 Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.