Effect of platelet-derived growth factor on rabbit corneal wound healing

Human recombinant platelet-derived growth factor was evaluated with the use of wound healing models in New Zealand albino rabbits. The efficacy of the platelet-derived growth factor dimers, AA, AB, and BB, was determined in corneal reepithelialization and anterior keratectomy models which examined the healing response in the presence or absence of the basement membrane. All dimers increased the rate of wound healing in both models at 100 µg/ml when compared with control; however, the platelet-derived growth factor-BB isoform showed the most dramatic increase in both studies. The strength of the healing stroma after incision was evaluated by means of a tensile strength model. Histologic evaluation of the stromal wound area after 9 days of healing showed a marked increase in the number of keratocytes within the wound bed of the corneas treated with platelet-derived growth factor-BB when compared with control corneas. In addition, at 9 days, the epithelial plug was still present in the control corneas but had been extruded to the surface by the granulation tissue in the platelet-derived growth factor-BB—treated corneas. These results are indicative of a more advanced stage of healing in treated versus control wounds at 9 days after the operation. A 30% increase in corneal tensile strength versus control was noted after 21 days of healing. Finally, in an in vitro gel contraction assay, platelet-derived growth factor exhibited a dose-dependent effect on the contraction of fibroblasts for doses ranging from 0.01 to 10 ng/ml. These results indicate that platelet-derived growth factor is active in the corneal wound healing process.     

Cisplatin and protracted venous infusion 5-fluorouracil (CF) -- good symptom relief with low toxicity in advanced pancreatic carcinoma

Purpose: The combination of protracted venous infusion (PVI)5-FU with moderate dose cisplatin was evaluated in patientswith advanced pancreatic cancer Patients and methods: Sixty-three patients with locally advancedor metastatic disease were treated with cisplatin (60 mg/m²every 21 days) and PVI 5-FU (300 mg/m²/day) for a maximum of24 weeks. All patients had histologkally/ cytologically confirmedtumour. Radiological response was assessed by CT scanning andtoxicity, performance status and symptomatic response were assessed3 weekly Results: The objective response rate was 16% with two radiologicalcomplete responses. The median survival was 7.6 months witha 1-year survival of 33% and a median progression-free survivalof 6.6 months. Patients who had local disease only had a mediansurvival of 14.8 months with a 1-year survival of 52%. Thirty-fourpercent of patients had an improvement in performance statuson treatment and specific symptom response rates were weightloss 71%, dysphagia 100%, nausea and vomiting 70%, pain 60%,anorexia 50% and reflux 81%. Chemotherapy was well toleratedwith grade 3 or 4 toxicity being nausea/vomiting 5%, diarrhoea7%, infection 4%, stomatitis 2%, plantar palmar syndrome 2%,anaemia 14%, leucopenia 5%, neutro-penia 10% and thrombocytopenia8% Conclusions: The CF regimen provides good symptomatic palliationwith low toxicity in patients with advanced pancreatic cancer pancreatic cancer, 5-fluorouracil, cisplatin     

EPIC: an effective low toxicity regimen for relapsing lymphoma.

We have treated 40 patients was relapsed or resistant lymphoma with the combination of Etoposide, Prednisolone, Ifosfamide and Cisplatin (EPIC). Complete response was obtained in 11 patients (28%) with an overall response of 58%. The presence of bulky disease (P < 0.005), elevated LDH serum levels (P < 0.005), response to prior chemotherapy (P < 0.01) and B symptoms (P < 0.005) were significantly associated with response. However on multivariate analysis only the presence of bulky disease and of B symptoms were independent adverse factors for response and for survival. The regimen was well tolerated with myelosuppression being the most common toxicity. Leucopenia < or 1,000 microliters-1 and thrombocytopenia < or = 25,000 microliters-1 developed in 27% and 4% of cycles respectively. There were no treatment related deaths. The EPIC regimen has equivalent activity to other reported cisplatin based regimens used in the treatment of recurrent lymphoma, but is associated with lower treatment related morbidity and mortality.     

Anteroseptal or apical myocardial infarction: a controversy addressed using delayed enhancement cardiovascular magnetic resonance imaging.

AIM: Delayed enhancement MRI (DE-MRI) of the heart has been shown to reliably identify areas of irreversible myocardial damage. We sought to determine if the term anteroseptal MI is appropriate by correlating electrocardiographic, angiographic, cine MRI and DE-MRI findings. METHODS AND RESULTS: Nineteen patients admitted to our hospital with their first acute anterior MI and whose ECG showed new Q waves in leads V1-V4 were studied. All patients underwent cardiac catheterization, cine MRI, and DE-MRI. The mean left ventricular ejection fraction was 53%+/-16%. All 19 patients had evidence of delayed hyperenhancement in one or more myocardial segments (mean number of affected segments 5.5+/-2.1). The mean mass of hyperenhanced myocardium was 14+/-8 grams, or 10%+/-6% of absolute LV mass. Nineteen (100%) and 15 (79%) patients showed evidence of delayed hyperenhancement of the apex and apical anterior segments respectively. Seven (37%) patients showed evidence of mid ventricular anteroseptal hyperenhancement and none had any hyperenhancement of basal anteroseptal segments. CONCLUSION: High resolution cardiac MRI applied in patients with acute infarction and new Q waves in leads V1-V4 demonstrates the presence of predominantly apical, but not isolated septal or anteroseptal infarction.     

Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia

Neurodevelopmental models for the pathology of schizophrenia propose both polygenetic and environmental risks, as well as early (pre/perinatal) and late (usually adolescent) developmental brain abnormalities. With the use of brain mapping algorithms, we detected striking anatomical profiles of accelerated gray matter loss in very early-onset schizophrenia; surprisingly, deficits moved in a dynamic pattern, enveloping increasing amounts of cortex throughout adolescence. Early-onset patients were rescanned prospectively with MRI, at 2-year intervals at three time points, to uncover the dynamics and timing of disease progression during adolescence. The earliest deficits were found in parietal brain regions, supporting visuospatial and associative thinking, where adult deficits are known to be mediated by environmental (nongenetic) factors. Over 5 years, these deficits progressed anteriorly into temporal lobes, engulfing sensorimotor and dorsolateral prefrontal cortices, and frontal eye fields. These emerging patterns correlated with psychotic symptom severity and mirrored the neuromotor, auditory, visual search, and frontal executive impairments in the disease. In temporal regions, gray matter loss was completely absent early in the disease but became pervasive later. Only the latest changes included dorsolateral prefrontal cortex and superior temporal gyri, deficit regions found consistently in adult studies. These emerging dynamic patterns were (i) controlled for medication and IQ effects, (ii) replicated in independent groups of males and females, and (iii) charted in individuals and groups. The resulting mapping strategy reveals a shifting pattern of tissue loss in schizophrenia. Aspects of the anatomy and dynamics of disease are uncovered, in a changing profile that implicates genetic and nongenetic patterns of deficits.