The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

Specific and nonspecific effects of ethanol vapor on plasma corticosterone in mice.

The intent of this study was to determine whether chronic ethanol (EtOH) vapor inhalation, with or without adjunct pyrazole (PYR) administration, was stressful in mice, as defined by increases in plasma corticosterone (CORT) concentration. Mice were randomly assigned to groups differentiated both on the basis of EtOH vapor exposure and the presence or absence of PYR administration. Blood samples for blood EtOH concentration (BEC) and plasma CORT concentration were obtained from mice after 72-96 hours of treatment. Mice were sacrificed after 96 hours of treatment and body and adrenal weight determined. BEC was significantly higher in PYR-treated animals and animals treated with the higher EtOH vapor concentration. Plasma CORT was elevated in proportion to BEC; however, other nonspecific stresses, in particular that of PYR administration, also elevated plasma CORT. Nonspecific stresses associated with this protocol may reduce the generality of these observations. Nevertheless, the high correlation between BEC and plasma CORT concentration in the PYR groups indicates that, with suitable control groups, the PYR-EtOH vapor inhalation approach is viable for studies concerned with EtOH effects on hypothalamic-anterior pituitary-adrenocortical function.     

Traumatic infarction of the spinal cord in children

Infarction of the spinal cord in childhood is rarely due to trauma. During a 15-year period (1971 to 1985), eight children were admitted to The Hospital for Sick Children, Toronto, with a diagnosis of traumatic infarction of the spinal cord. All of these patients had delayed onset of neurological signs varying between 2 hours and 4 days after their initial trauma. No bone abnormalities were seen on plain spine x-ray films. Myelography was carried out in seven of these children and found to be normal in all seven. Six patients who were paraplegic at the time of admission remained permanently paraplegic, but two with incomplete cord signs did show some improvement.     

Day case stapled haemorrhoidopexy for prolapsing haemorrhoids

OBJECTIVE: Conventional surgical management of prolapsing haemorrhoids is by excisional haemorrhoidectomy. Postoperative pain has restricted the application of such procedures in the day case setting. These operations remain associated with a period of restricted activity. The use of circular stapling devices as an alternative to the excisional approach in the management of haemorrhoids has been described. This study reports our experience of stapled haemorrhoidopexy as a day case procedure. METHODS: Patients with third or fourth degree haemorrhoids were eligible for the procedure. Patients were considered suitable candidates for day case surgery based on conventional parameters. Symptoms were assessed using a previously validated symptom severity rating score. Stapled haemorrhoidopexy was carried out using a circular stapling device. Pain scores were obtained prior to discharge. Patients were admitted if pain was uncontrolled despite oral analgesia. Symptoms were re-scored at six-week follow-up. RESULTS: Over a 70-month period 168 consecutive stapled haemorrhoidopexies were performed or directly supervised by one consultant colorectal surgeon. One hundred and ten (65%) patients were considered appropriate candidates for day case surgery by conventional criteria. Ninety-six (87.3%) patients successfully underwent stapled haemorrhoidopexy on a day case basis. Fourteen (12.7%) patients required admission on the day of surgery (5 for early postoperative bleeding, 4 for pain necessitating continuing opiate analgesia, two for urinary retention and three for surgery performed late in the day). Six (5%) patients were re-admitted postoperatively; four for pain relief and two because of urinary retention. Of the day case patients, 91 (82.7%) and 56 (50.9%) had been seen for 6 week and 6 month review, respectively, at the time of analysis. Symptom scores were 6 (pre-operatively) vs 0 (postoperatively) (P < 0.01). 76/91 (83.5%) patients reviewed at 6/52 were asymptomatic. CONCLUSION: Stapled haemorrhoidopexy is a safe and effective procedure that can be carried out on selected patients on a day case basis. Complications are of a similar nature to excisional haemorrhoidectomy.     

Surgical treatment for temporomandibular joint problems.

Surgical intervention may be necessary for some patients with specific pathology or derangement of the temporomandibular joint as part of an overall management protocol. The current literature discusses the efficacy of arthroscopy, the treatment of the difficult problem of ankylosis, and the use of implants and autogenous and allogenic materials to replace the disk.     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

The role of still-frame parametric imaging in magnetic resonance assessment of left ventricular wall motion by non-cardiologists.

BACKGROUND: Cardiac magnetic resonance (MR) images are often reviewed by non-cardiologists who are not trained in the interpretation of regional left ventricular (LV) function. We hypothesized that the use of still-frame parametric MR images of wall motion could aid in the assessment of regional LV function. METHODS: Dynamic, electrocardiogram-gated, steady-state free precession (FIESTA) short-axis images were obtained in 6 to 10 slices in 18 consecutive patients. Each loop was used to automatically generate a still-frame image, in which each pixel is assigned a value equal to the amplitude of cyclic variation in local intensity, resulting in higher intensity in pixels that change between blood and tissue during the cardiac cycle. The dynamic images were reviewed by an expert cardiologist who provided gold standard grades for regional wall motion and by four radiologists. Then the radiologists reviewed and graded the same MR images in combination with parametric images. Grades assigned to each segment in the two sessions were compared with the gold standard. RESULTS: According to expert interpretation, 6 patients had normal wall motion, and 12 had wall motion abnormalities. Parametric images showed a bright band in the area spanned by endocardial motion, with reduced brightness and thickness in areas of hypokinesis. The agreement between the radiologists' grades and the gold standard significantly improved by adding parametric images (from 77% to 81%), which also resulted in reduced interobserver variability (from 52% to 33%). CONCLUSIONS: Still-frame parametric images aid in the assessment of regional wall motion by non-cardiologists who are required to interpret cardiac images.